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Okhawere KE, Razdan S, Beksac AT, Saini I, Zuluaga L, Meilika K, Ucpinar B, Sheu RD, Mehrazin R, Sfakianos J, Tewari A, Stock RG, Badani K. Novel bioabsorbable, low-dose rate brachytherapy device (CivaSheet ®) with radical prostatectomy and adjuvant external beam radiation for the management of prostate cancer. BJU Int 2025; 135:782-791. [PMID: 39654390 DOI: 10.1111/bju.16617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2025]
Abstract
OBJECTIVE To investigate the safety and cancer control of a novel bioabsorbable, low-dose rate brachytherapy device, CivaSheet® (CivaTech Oncology Inc., Durham, NC, USA), in combination with radical prostatectomy (RP) with or without adjuvant external beam radiation therapy (EBRT) for the management of prostate cancer (PCa). PATIENTS AND METHODS This is an initial, single-centre experience, two-dose level, two-stage study conducted on patients with intermediate- and high-risk PCa. The CivaSheet was implanted during RP, followed by adjuvant EBRT in patients with adverse pathological features. Toxicities and peri- and postoperative complications were assessed. Biochemical recurrence (BCR) at the 6-month follow-up after EBRT was also evaluated. RESULTS Six patients were enrolled, with a median (range) age of 56 (53-71) years. No intraoperative complications occurred. No dose-limiting toxicities were observed at a maximum tested dose of 75 Gy. BCR occurred in one patient at 6 months, while another patient had residual disease and metastasis at 6 months. All patients reported having postoperative erectile dysfunction and one patient experienced urinary incontinence after EBRT. CONCLUSIONS This study demonstrated the feasibility and safety of CivaSheet combined with RP and adjuvant EBRT for high-risk PCa. The short-term toxicity profile was well-tolerated, supporting further prospective evaluation with clinical trials.
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Affiliation(s)
- Kennedy E Okhawere
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shirin Razdan
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alp Tuna Beksac
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Indu Saini
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Laura Zuluaga
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kirolos Meilika
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Burak Ucpinar
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ren-Dih Sheu
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Reza Mehrazin
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - John Sfakianos
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ashutosh Tewari
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Richard G Stock
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ketan Badani
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Schott D, Pizon M, Drozdz S, Mäurer I, Wurschi G, Pachmann K, Mäurer M. Circulating Epithelial Tumor Cells (CETC/CTC) in Prostate Cancer: Potential Prognostic Marker for the Risk of Recurrence During Radiotherapy. Int J Mol Sci 2025; 26:1548. [PMID: 40004014 PMCID: PMC11855499 DOI: 10.3390/ijms26041548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/04/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Prostate cancer is a leading cause of cancer-related mortality in men, with radiotherapy (RT) playing a pivotal role in treatment. However, reliable biomarkers for assessing relapse risk following RT remain scarce. This study aimed to evaluate circulating epithelial tumor cells (CETC/CTC) as potential biomarkers for assessing relapse risk in prostate cancer patients undergoing RT. Peripheral blood samples were collected from 52 prostate cancer patients, and CETC/CTC were detected using the EpCAM surface marker. Patients received definitive, adjuvant, or salvage RT, and CETC/CTC counts were measured before, at mid-treatment, and at the end of RT. The association between changes in CETC/CTC counts and relapse risk was examined. CETC/CTC were detected in 96% of patients prior to RT. A significant reduction in CETC/CTC counts during RT, particularly in patients who had undergone surgery, was associated with a lower relapse risk. In contrast, an increase in CETC/CTC counts during or after RT was associated with a higher relapse risk (hazard ratio = 8.8; p = 0.002). Furthermore, 36% of patients receiving adjuvant RT and 14% of those receiving definitive RT relapsed, with a higher risk observed in patients showing increasing CETC/CTC counts during RT. Among patients receiving salvage RT, 18% relapsed, though changes in CETC/CTC counts were less significantly associated with relapse. Monitoring CETC/CTC levels during RT offers important prognostic insights into relapse risk in prostate cancer patients. While changes in CETC/CTC counts correlated with relapse, PSA levels measured during the study did not reliably reflect relapse risk in this cohort. CETC/CTC shows promise as a prognostic marker, though further studies are required to validate its clinical superiority over PSA.
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Affiliation(s)
- Dorothea Schott
- Transfusion Medicine Center Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany; (M.P.); (K.P.)
| | - Monika Pizon
- Transfusion Medicine Center Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany; (M.P.); (K.P.)
| | - Sonia Drozdz
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany; (S.D.); (M.M.)
| | - Irina Mäurer
- Department of Neurology, Neurooncology Center, University Hospital, Am Klinikum 1, 07747 Jena, Germany;
| | - Georg Wurschi
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany; (S.D.); (M.M.)
- Clinician Scientist Program, Interdisciplinary Center for Clinical Research (IZKF), Jena Hospital, 07747 Jena, Germany
| | - Katharina Pachmann
- Transfusion Medicine Center Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany; (M.P.); (K.P.)
| | - Matthias Mäurer
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany; (S.D.); (M.M.)
- Clinician Scientist Program OrganAge, Interdisciplinary Center for Clinical Research (IZKF), Jena Hospital, 07747 Jena, Germany
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Minami T, Fujimoto S, Fujita K. Iodine-125 low-dose rate prostate brachytherapy. Int J Urol 2025; 32:130-137. [PMID: 39415463 DOI: 10.1111/iju.15609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/03/2024] [Indexed: 10/18/2024]
Abstract
Robotic-assisted laparoscopic radical prostatectomy and intensity-modulated radiation therapy are the most common radical treatments for localized prostate cancer, and brachytherapy (BT) also plays a role in this field. Iodine-125 (I-125) low-dose rate (LDR) prostate BT is an established treatment. However, it remains controversial. Specifically, there are a variety of issues, such as indications for combined treatment with external beam radiotherapy and androgen deprivation therapy, prostate-specific antigen follow-up, the significance of postimplant biopsy, the usefulness of salvage BT and focal therapy, reduction of toxicities, and bladder cancer after BT. In this review, we summarize the recent developments in I-125 LDR BT.
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Affiliation(s)
- Takafumi Minami
- Department of Urology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan
| | - Saizo Fujimoto
- Department of Urology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan
| | - Kazutoshi Fujita
- Department of Urology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan
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4
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Swensen S, Liao JJ, Chen JJ, Kim K, Ma TM, Weg ES. The expanding role of radiation oncology across the prostate cancer continuum. Abdom Radiol (NY) 2024; 49:2693-2705. [PMID: 38900319 DOI: 10.1007/s00261-024-04408-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/23/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024]
Abstract
Radiotherapy is used in the treatment of prostate cancer in a variety of disease states with significant reliance on imaging to guide clinical decision-making and radiation delivery. In the definitive setting, the choice of radiotherapy treatment modality, dose, and fractionation for localized prostate cancer is determined by the patient's initial risk stratification and other clinical considerations. Radiation is also an option as salvage therapy in patients with locoregionally recurrent disease after prior definitive radiation or surgery. In recent years, the role of radiation has expanded for patients with metastatic disease, including prostate-directed radiotherapy in de novo low volume metastatic disease, metastasis-directed therapy for oligorecurrent disease, and palliative management of symptomatic metastases in the advanced setting. Here we review the expanding role of radiation in the treatment of prostate cancer in the definitive, locoregionally recurrent, and metastatic settings, as well as highlight the role of imaging in clinical reasoning, radiation planning, and treatment delivery.
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Affiliation(s)
- Sasha Swensen
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Jay J Liao
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Jonathan J Chen
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Katherine Kim
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Ting Martin Ma
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Emily S Weg
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, 1959 NE Pacific St, Seattle, WA, 98195, USA.
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Gogineni E, Chen H, Cruickshank IK, Koempel A, Gogineni A, Li H, Deville C. In Silico Comparison of Three Different Beam Arrangements for Intensity-Modulated Proton Therapy for Postoperative Whole Pelvic Irradiation of Prostate Cancer. Cancers (Basel) 2024; 16:2702. [PMID: 39123430 PMCID: PMC11311848 DOI: 10.3390/cancers16152702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 07/17/2024] [Accepted: 07/23/2024] [Indexed: 08/12/2024] Open
Abstract
Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT2B) (opposed laterals), three-field (IMPT3B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT4B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT3B and IMPT4B plans, while several rectum objectives were exceeded by IMPT2B plans. IMPT4B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT2B +/- IMPT3B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.
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Affiliation(s)
- Emile Gogineni
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (A.K.); (A.G.)
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (H.C.); (I.K.C.J.); (H.L.); (C.D.J.)
| | - Hao Chen
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (H.C.); (I.K.C.J.); (H.L.); (C.D.J.)
| | - Ian K. Cruickshank
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (H.C.); (I.K.C.J.); (H.L.); (C.D.J.)
| | - Andrew Koempel
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (A.K.); (A.G.)
| | - Aarush Gogineni
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (A.K.); (A.G.)
| | - Heng Li
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (H.C.); (I.K.C.J.); (H.L.); (C.D.J.)
| | - Curtiland Deville
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (H.C.); (I.K.C.J.); (H.L.); (C.D.J.)
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Parker CC, Petersen PM, Cook AD, Clarke NW, Catton C, Cross WR, Kynaston H, Parulekar WR, Persad RA, Saad F, Bower L, Durkan GC, Logue J, Maniatis C, Noor D, Payne H, Anderson J, Bahl AK, Bashir F, Bottomley DM, Brasso K, Capaldi L, Chung C, Cooke PW, Donohue JF, Eddy B, Heath CM, Henderson A, Henry A, Jaganathan R, Jakobsen H, James ND, Joseph J, Lees K, Lester J, Lindberg H, Makar A, Morris SL, Oommen N, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Ramani V, Røder A, Sayers I, Simms M, Srinivasan V, Sundaram S, Tarver KL, Tran A, Wells P, Wilson J, Zarkar AM, Parmar MKB, Sydes MR. Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047). Ann Oncol 2024; 35:656-666. [PMID: 38583574 PMCID: PMC7617161 DOI: 10.1016/j.annonc.2024.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 03/25/2024] [Accepted: 03/27/2024] [Indexed: 04/09/2024] Open
Abstract
BACKGROUND The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.
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Affiliation(s)
- C C Parker
- Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Sutton, UK.
| | - P M Petersen
- Department of Oncology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - A D Cook
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London
| | - N W Clarke
- Department of Urology, The Christie NHS Foundation Trust, Manchester; Manchester Cancer Research Centre, The University of Manchester, Manchester; Department of Urology, Salford Royal NHS Foundation Trust, Manchester, UK, Department of Urology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
| | - C Catton
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
| | - W R Cross
- Department of Urology, St James's University Hospital, Leeds
| | - H Kynaston
- Division of Cancer and Genetics, Cardiff University, Cardiff, UK
| | - W R Parulekar
- Canadian Cancer Trials Group, Queen's University, Kingston, Canada
| | - R A Persad
- Department of Urology, Bristol Urological Institute, Bristol, UK
| | - F Saad
- Department of Urology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada
| | - L Bower
- Guy's and St Thomas' NHS Foundation Trust, London; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK
| | - G C Durkan
- Department of Urology, University Hospital Galway, Galway, Ireland
| | - J Logue
- Department of Oncology, The Christie Hospital NHS FT, Wilmslow Road, Manchester
| | - C Maniatis
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London
| | - D Noor
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London
| | | | | | - A K Bahl
- Bristol Haematology and Oncology Centre, University Hospitals Bristol & Weston NHS Trust, Bristol
| | - F Bashir
- Queen's Centre for Oncology, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, Cottingham, UK
| | | | - K Brasso
- Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - L Capaldi
- Worcester Oncology Centre, Worcestershire Acute NHS Hospitals Trust, Worcester
| | - C Chung
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London
| | - P W Cooke
- Department of Urology, The Royal Wolverhampton NHS Trust, Wolverhampton
| | - J F Donohue
- Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone
| | - B Eddy
- East Kent University Hospitals Foundation Trust, Kent
| | - C M Heath
- Department of Clinical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton
| | - A Henderson
- Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone
| | - A Henry
- Leeds Institute of Medical Research, University of Leeds, Leeds
| | - R Jaganathan
- Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - H Jakobsen
- Department of Urology, Herlev University Hospital, Herlev, Denmark
| | - N D James
- Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK
| | - J Joseph
- Leeds Teaching Hospitals; York and Scarborough Teaching Hospitals, York
| | - K Lees
- Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Maidstone
| | - J Lester
- South West Wales Cancer Centre, Singleton Hospital, Swansea, UK
| | - H Lindberg
- Department of Oncology, Herlev University Hospital, Herlev, Denmark
| | - A Makar
- Department of Urology, Worcestershire Acute Hospitals Trust, Worcester
| | - S L Morris
- Guy's and St Thomas' NHS Foundation Trust, London
| | - N Oommen
- Wrexham Maelor Hospital, Wrexham
| | - P Ostler
- Department of Urology, Hillingdon Hospitals NHS Foundation Trust, Hillingdon, London
| | - L Owen
- Bradford Royal Infirmary, Bradford; Leeds Cancer Centre, Leeds
| | - P Patel
- Department of Urology, University College London Hospitals, London
| | - A Pope
- Department of Urology, Hillingdon Hospitals NHS Foundation Trust, Hillingdon, London
| | - R Popert
- Guy's and St Thomas' NHS Foundation Trust, London
| | - R Raman
- Kent Oncology Centre, Kent & Canterbury Hospital, Canterbury
| | - V Ramani
- Department of Urology, The Christie NHS Foundation Trust, Manchester
| | - A Røder
- Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen
| | - I Sayers
- Deanesly Centre, New Cross Hospital, Wolverhampton
| | - M Simms
- Department of Urology, Hull University Hospitals NHS Trust, Hull
| | - V Srinivasan
- Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Rhyl
| | - S Sundaram
- Department of Urology, Mid Yorkshire Teaching Hospital, Wakefield
| | - K L Tarver
- Department of Oncology, Queen's Hospital, Romford
| | - A Tran
- Department of Oncology, The Christie Hospital NHS FT, Wilmslow Road, Manchester
| | - P Wells
- Barts Cancer Centre, St Bartholomews Hospital, London
| | | | - A M Zarkar
- Department of Oncology, University Hospitals Birmingham, Birmingham, UK
| | - M K B Parmar
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London
| | - M R Sydes
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London.
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7
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Sayan M, Tuac Y, Kucukcolak S, Rowan MD, Pratt GK, Aktan C, Tjio E, Akbulut D, Moningi S, Leeman JE, Orio PF, Nguyen PL, D’Amico AV, Akgul M. Histologically Overt Stromal Response and the Risk of Progression after Radical Prostatectomy for Prostate Cancer. Cancers (Basel) 2024; 16:1871. [PMID: 38791950 PMCID: PMC11119771 DOI: 10.3390/cancers16101871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 05/06/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
PURPOSE Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. METHODS This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. RESULTS Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. CONCLUSIONS HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial.
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Affiliation(s)
- Mutlay Sayan
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Yetkin Tuac
- Department of Statistics, Ankara University, 06100 Ankara, Türkiye
| | - Samet Kucukcolak
- Department of Pathology and Laboratory Medicine, Rutgers University, New Brunswick, NJ 07102, USA
| | - Mary D. Rowan
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Grace K. Pratt
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Cagdas Aktan
- Department of Medical Biology, Faculty of Medicine, Bandirma Onyedi Eylul University, 10250 Balikesir, Türkiye
| | - Elza Tjio
- Histopathology Department, Harrogate District Hospital, Harrogate HG2 7SX, UK
| | - Dilara Akbulut
- Laboratory of Pathology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA
| | - Shalini Moningi
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Jonathan E. Leeman
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Peter F. Orio
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Paul L. Nguyen
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Anthony V. D’Amico
- Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Mahmut Akgul
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, USA
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Gao Y, Yoon S, Ma TM, Yang Y, Sheng K, Low DA, Ballas L, Steinberg ML, Kishan AU, Cao M. Intra-fractional geometric and dose/volume metric variations of magnetic resonance imaging-guided stereotactic radiotherapy of prostate bed after radical prostatectomy. Phys Imaging Radiat Oncol 2024; 30:100573. [PMID: 38585371 PMCID: PMC10997948 DOI: 10.1016/j.phro.2024.100573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 03/22/2024] [Accepted: 03/22/2024] [Indexed: 04/09/2024] Open
Abstract
Background and purpose Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methods Nineteen patients who received 30-34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. Results Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9-76.8 %) and a median MDA of 5.1 mm (IQR 3.4-7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0-4.8 %). DSC was 0.97 (IQR 0.94-0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8-100 %) to 99.6 % (IQR 93.9-100 %). Conclusion Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.
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Affiliation(s)
- Yu Gao
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Radiation Oncology, Stanford University, Palo Alto, CA, USA
| | - Stephanie Yoon
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Radiation Oncology, City of Hope, Duarte, CA, USA
| | - Ting Martin Ma
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Yingli Yang
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Radiation Oncology, Shanghai Ruijin Hospital, China
| | - Ke Sheng
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA
| | - Daniel A. Low
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Leslie Ballas
- Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Michael L. Steinberg
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Amar U Kishan
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Minsong Cao
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA
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Sigg S, Arnold W, Grossmann NC, Baumeister P, Fankhauser CD, Wenzel M, Mattei A, Würnschimmel C. Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey. Urol Int 2024; 108:211-218. [PMID: 38325350 DOI: 10.1159/000536609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 01/27/2024] [Indexed: 02/09/2024]
Abstract
INTRODUCTION The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD). METHODS In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into "adherent" (aRT performed) and "non-adherent" groups (aRT not performed). RESULTS Of 55 patients receiving a recommendation for aRT (7.5% of all RP patients), 24 (44%) were non-adherent. Baseline tumour characteristics were comparable among the groups. "Fear of radiation damage" was the most common reason for rejection, followed by "lack of information," "feeling that the treating physician does not support the recommendation" and "the impression that aRT is not associated with improved oncological outcome." Salvage radiotherapy was performed in 25% of non-adherent patients. CONCLUSION High rates of non-adherence to aRT after RP were observed, and reasons for this phenomenon are most likely multifactorial. Multidisciplinary and individualized patient counselling might be a key for increasing adherence rates.
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Affiliation(s)
- Silvan Sigg
- Department of Urology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
| | - Winfried Arnold
- Department of Radio-oncology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
| | - Nico Christian Grossmann
- Department of Urology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
- University of Lucerne, Lucerne, Switzerland
- Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
| | - Philipp Baumeister
- Department of Urology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
| | - Christian Daniel Fankhauser
- Department of Urology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
- University of Lucerne, Lucerne, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Mike Wenzel
- Department of Urology, University Hospital Frankfurt, Goethe Universität Frankfurt, Frankfurt, Germany
| | - Agostino Mattei
- Department of Urology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
- Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
| | - Christoph Würnschimmel
- Department of Urology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
- Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
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10
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Mathier E, Althaus A, Zwahlen D, Lustenberger J, Zamboglou C, De Bari B, Aebersold DM, Guckenberger M, Zilli T, Shelan M. HypoFocal SRT Trial: Ultra-hypofractionated focal salvage radiotherapy for isolated prostate bed recurrence after radical prostatectomy; single-arm phase II study; clinical trial protocol. BMJ Open 2024; 14:e075846. [PMID: 38296279 PMCID: PMC10828884 DOI: 10.1136/bmjopen-2023-075846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 01/08/2024] [Indexed: 02/03/2024] Open
Abstract
INTRODUCTION Despite radical prostatectomy (RP) and radiotherapy (RT) being established treatments for localised prostate cancer, a significant number of patients experience recurrent disease. While conventionally fractionated RT is still being used as a standard treatment in the postoperative setting, ultra-hypofractionated RT has emerged as a viable option with encouraging results in patients with localised disease in the primary setting. In addition, recent technological advancements in RT delivery and precise definition of isolated macroscopic recurrence within the prostate bed using prostate-specific membrane antigen-positron emission tomography (PSMA-PET) and multiparametric MRI (mpMRI) allow the exploration of ultra-hypofractionated schedules in the salvage setting using five fractions. METHODS AND ANALYSIS In this single-arm prospective phase II multicentre trial, 36 patients with node-negative prostate adenocarcinoma treated with RP at least 6 months before trial registration, tumour stage pT2a-3b, R0-1, pN0 or cN0 according to the UICC TNM 2009 and evidence of measurable local recurrence within the prostate bed detected by PSMA PET/CT and mpMRI within the last 3 months, will be included. The patients will undergo focal ultra-hypofractionated salvage RT with 34 Gy in five fractions every other day to the site of local recurrence in combination with 6 months of androgen deprivation therapy. The primary outcome of this study is biochemical relapse-free survival at 2 years. Secondary outcomes include acute side effects (until 90 days after the end of RT) of grade 3 or higher based on Common Terminology Criteria for Adverse Events V.5, progression-free survival, metastasis-free survival, late side effects and the quality of life (based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, QLQ-PR25). ETHICS AND DISSEMINATION The study has received ethical approval from the Ethics Commission of the Canton of Bern (KEK-BE 2022-01026). Academic dissemination will occur through publications and conference presentations. TRIAL REGISTRATION NUMBER NCT05746806.
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Affiliation(s)
- Etienne Mathier
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Alexander Althaus
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Daniel Zwahlen
- Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland
| | - Jens Lustenberger
- Department of Radiation Oncology, University Hospital Basel, Basel, Switzerland
| | | | - Berardino De Bari
- Department of Radiation Oncology, Réseau hospitalier neuchâtelois, Neuchatel, Switzerland
| | - Daniel M Aebersold
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | - Thomas Zilli
- Department of Radiation Oncology, Oncological Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
- Università della Svizzera italiana, Lugano, Switzerland
| | - Mohamed Shelan
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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11
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Esen T, Esen B, Yamaoh K, Selek U, Tilki D. De-Escalation of Therapy for Prostate Cancer. Am Soc Clin Oncol Educ Book 2024; 44:e430466. [PMID: 38206291 DOI: 10.1200/edbk_430466] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
Prostate cancer (PCa) is the second most commonly diagnosed cancer in men with around 1.4 million new cases every year. In patients with localized disease, management options include active surveillance (AS), radical prostatectomy (RP; with or without pelvic lymph node dissection), or radiotherapy to the prostate (with or without pelvic irradiation) with or without hormonotherapy. In advanced disease, treatment options include systemic treatment(s) and/or treatment to primary tumour and/or metastasis-directed therapies (MDTs). Specifically, in advanced stage, the current trend is earlier intensification of treatment such as dual or triple combination systemic treatments or adding treatment to primary and MDT to systemic treatment. However, earlier treatment intensification comes with the cost of increased morbidity and mortality resulting from drug-/treatment-related side effects. The main goal is and should be to provide the best possible care and oncologic outcomes with minimum possible side effects. This chapter will explore emerging possibilities to de-escalate treatment in PCa driven by enhanced insights into disease biology and the natural course of PCa such as AS in intermediate-risk disease or salvage versus adjuvant radiotherapy in post-RP patients. Considerations arising from advancements in PCa imaging and technological advancements in surgical and radiation therapy techniques including omitting pelvic lymph node dissection in the era of prostate-specific membrane antigen positron emitting tomography, the potential of MDT to delay/omit systemic treatment in metachronous oligorecurrence, and the efficacy of hypofractionation schemes compared with conventional fractionated radiotherapy will be discussed.
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Affiliation(s)
- Tarik Esen
- Department of Urology, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Esen
- Department of Urology, Koc University School of Medicine, Istanbul, Turkey
| | - Kosj Yamaoh
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL
| | - Ugur Selek
- Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey
| | - Derya Tilki
- Department of Urology, Koc University School of Medicine, Istanbul, Turkey
- Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
- Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
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12
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Meyers SM, Winter JD, Obeidi Y, Chung P, Menard C, Warde P, Fong H, McPartlin A, Parameswaran S, Berlin A, Bayley A, Catton C, Craig T. A feasibility study of adaptive radiation therapy for postprostatectomy prostate cancer. Med Dosim 2023; 49:150-158. [PMID: 37985297 DOI: 10.1016/j.meddos.2023.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 10/13/2023] [Accepted: 10/21/2023] [Indexed: 11/22/2023]
Abstract
Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART. Twenty-one patients were treated with single-adaptation ART. Conventional treatments were delivered for fractions 1 to 6 and adapted plans for the remaining 27 fractions. Clinical target volumes (CTVs) and small bowel delineated on fraction 1 to 4 CBCT were used to generate adapted PTVs and planning organ-at-risk (OAR) volumes for adapted plans. PTV volume and OAR dose were compared between ART and conventional using Wilcoxon signed-rank tests. Weekly CBCT were used to assess the fraction of CTV covered by PTV, CTV D99, and small bowel D1cc. Clinical metrics were compared using a Student's t-test (p < 0.05 significant). Offline adaptive planning required 1.9 ± 0.4 days (mean ± SD). ART decreased mean adapted PTV volume 61 ± 37 cc and bladder wall D50 compared with conventional treatment (p < 0.01). The CTV was fully covered for 96% (97%) of fractions with ART (conventional). Reconstructing dose on weekly CBCT, a nonsignificant reduction in CTV D99 was observed with ART (94%) compared to conventional (96%). Reduced CTV D99 with ART was significantly correlated with large anterior-posterior rectal diameter on simulation CT. ART reduced the number of fractions exceeding our institution's small bowel D1c limit from 14% to 7%. This study has demonstrated the feasibility of offline ART for post-prostatectomy cancer. ART facilitates PTV volume reduction while maintaining reasonable CTV coverage and can reduce the dose to adjacent normal tissues.
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Affiliation(s)
- Sandra M Meyers
- Department of Radiation Medicine and Applied Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Jeff D Winter
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | | | - Peter Chung
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Cynthia Menard
- Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada
| | - Padraig Warde
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Heng Fong
- The Ministry of Health Malaysia, Daerah Timur Laut, Penang, Malaysia
| | - Andrew McPartlin
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | | | - Alejandro Berlin
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Andrew Bayley
- Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada
| | - Charles Catton
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Tim Craig
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
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13
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Aizawa T, Maebayashi T, Ishibashi N, Sakaguchi M, Sato A, Yamaguchi K. Study of prostate-specific antigen levels during salvage radiotherapy after prostate cancer surgery. BMC Urol 2023; 23:157. [PMID: 37794380 PMCID: PMC10552428 DOI: 10.1186/s12894-023-01323-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 09/13/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND Administration of adjuvant or salvage radiotherapy (RT) after prostate cancer (PCa) surgery is supported by clinical evidence and is a widely adopted strategy. On occasion, we detect changes in prostate-specific antigen (PSA) levels, such as a transient elevation or decline, during RT. Thus, we retrospectively investigated the frequency of changes in PSA levels, their associations with histopathological parameters, PSA doubling time (PSADT), and biochemical recurrence (BR) of PCa. METHODS This study included 23 consecutive patients who underwent surgery for PCa between 2012 and 2019, received salvage RT without hormone therapy, and exhibited changes in PSA levels during RT. The prostatic bed was irradiated with a total dose of 64 to 66 Gy. BR was defined as consecutive PSA levels exceeding 0.2 ng/mL or having to start hormone therapy because of PSA elevation after salvage RT. RESULTS During salvage RT after PCa surgery, PSA levels transiently increased in 11 patients (47.8%) and decreased in 12 (52.2%). When factors associated with BR were examined in patients with transient PSA elevation, seminal vesicle invasion and preoperative PSA values were identified as being statistically significant. When factors for BR were examined in patients with a decline in PSA levels, the Gleason score and PSADT were identified as being significant. Among the cases of a decline in PSA levels during salvage RT, those who received a radiation dose of less than 36 Gy did not experience BR. Similarly, patients who exhibited changes in PSA levels during salvage RT and did not have perineural invasion did not experience BR. CONCLUSION This is the first study to examine the histopathological factors possibly affecting BR in patients undergoing salvage RT after PCa surgery. The results indicate that in patients with transient PSA elevation, seminal vesicle invasion is a significant risk factor. On the other hand, in patients with a decline in PSA levels during irradiation, the Gleason score and perineural invasion were found to be potential risk factors for BR. These findings suggest that a thorough examination of postoperative histopathological results may be necessary for the optimal management of patients with PCa.
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Affiliation(s)
- Takuya Aizawa
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Toshiya Maebayashi
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Naoya Ishibashi
- Department of Radiology, Nihon University Hospital, Chiyoda-ku, Tokyo, 101- 8309, Japan
| | - Masakuni Sakaguchi
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Akahiko Sato
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Kenya Yamaguchi
- Department of Urology, Nihon University Hospital, Chiyoda-ku, Tokyo, 101-8309, Japan
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14
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ESTRO-ACROP recommendations for evidence-based use of androgen deprivation therapy in combination with external-beam radiotherapy in prostate cancer. Radiother Oncol 2023; 183:109544. [PMID: 36813168 DOI: 10.1016/j.radonc.2023.109544] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/03/2023] [Accepted: 02/04/2023] [Indexed: 02/22/2023]
Abstract
BACKGROUND AND PURPOSE There is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. MATERIAL AND METHODS A literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D'Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. RESULTS Key issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. CONCLUSION These ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.
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15
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Muralidhar A, Potluri HK, Jaiswal T, McNeel DG. Targeted Radiation and Immune Therapies-Advances and Opportunities for the Treatment of Prostate Cancer. Pharmaceutics 2023; 15:252. [PMID: 36678880 PMCID: PMC9863141 DOI: 10.3390/pharmaceutics15010252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/03/2023] [Accepted: 01/06/2023] [Indexed: 01/12/2023] Open
Abstract
Prostate cancer is the most diagnosed malignancy in men in the United States and the second leading cause of cancer-related death. For localized disease, radiation therapy is a standard treatment that is often curative. For metastatic disease, radiation therapy has been primarily used for palliation, however, several newer systemic radiation therapies have been demonstrated to significantly improve patient outcomes and improve survival. In particular, several targeted radionuclide therapies have been approved for the treatment of advanced-stage cancer, including strontium-89, samarium-153, and radium-223 for bone-metastatic disease, and lutetium-177-labeled PSMA-617 for patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castration-resistant prostate cancer (mCRPC). Contrarily, immune-based treatments have generally demonstrated little activity in advanced prostate cancer, with the exception of the autologous cellular vaccine, sipuleucel-T. This has been attributed to the presence of an immune-suppressive prostate cancer microenvironment. The ability of radiation therapy to not only eradicate tumor cells but also potentially other immune-regulatory cells within the tumor immune microenvironment suggests that targeted radionuclide therapies may be well poised to combine with immune-targeted therapies to eliminate prostate cancer metastases more effectively. This review provides an overview of the recent advances of targeted radiation agents currently approved for prostate cancer, and those being investigated in combination with immunotherapy, and discusses the challenges as well as the opportunities in this field.
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Affiliation(s)
- Anusha Muralidhar
- University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, Madison, WI 53705, USA
| | - Hemanth K. Potluri
- University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, Madison, WI 53705, USA
| | - Tanya Jaiswal
- University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, Madison, WI 53705, USA
| | - Douglas G. McNeel
- University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, Madison, WI 53705, USA
- 7007 Wisconsin Institutes for Medical Research, 1111 Highland Avenue, Madison, WI 53705, USA
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16
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Kim WT, Kim J, Kim WJ. How can we best manage biochemical failure after radical prostatectomy? Investig Clin Urol 2022; 63:592-601. [PMID: 36347548 PMCID: PMC9643724 DOI: 10.4111/icu.20220294] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/27/2022] [Accepted: 09/29/2022] [Indexed: 11/25/2022] Open
Abstract
Biochemical recurrence (BCR) is common after radical prostatectomy, but effective treatment options for men with BCR after curative treatment remain controversial. Although prostate-specific antigen is widely used as a surrogate marker for prostate cancer survival, it cannot fully differentiate between prostate-cancer-specific survival and overall survival. Thus, it is challenging for physicians to determine the timing of treatment to halt or slow the clinical progression of disease in patients with BCR while avoiding overtreatment for patients whose disease may not progress beyond BCR. Adjuvant therapy for radical prostatectomy or radiotherapy in intermediate- or high-risk localized prostate cancer has a benefit in terms of disease progression and survival but is not recommended in low-risk prostate cancer because of the significant adverse effects related to radiotherapy and androgen-deprivation therapy (ADT). Salvage radiotherapy (SRT) is also recommended for patients with BCR after radical prostatectomy. Several options for management of BCR after radical prostatectomy include SRT to the prostatic bed and/or pelvis, continuous or intermittent ADT, or observation. Patients' comorbidity, preferences, and cancer-related factors must be considered when deciding the best management strategy. Modern imaging technology such as positron emission tomography imaging of prostate-specific membrane antigen-positive regions enables earlier detection of disease progression, thus enhancing decision making for future disease management.
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Affiliation(s)
- Won Tae Kim
- Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jiyeon Kim
- Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wun-Jae Kim
- Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.,Institute of Urotech, Cheongju, Korea
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Moll M, D'Andrea D, Zaharie A, Grubmüller B, Paschen C, Zehetmayer S, Shariat SF, Widder J, Goldner G. Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy. Strahlenther Onkol 2022; 198:719-726. [PMID: 35284951 PMCID: PMC9300528 DOI: 10.1007/s00066-022-01909-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 02/04/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy. METHODS Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65-72 Gy, single fraction 1.8-2 Gy) in 572 patients and HF (total dose 62.5-63.75 Gy, single fraction 2.5-2.55 Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis. RESULTS There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; p = 0.20). OS estimates after 5 years: 95% versus 93% (p = 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (p = 0.03 and p = 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (p < 0.001). CONCLUSION For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (n = 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited.
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Affiliation(s)
- Matthias Moll
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - David D'Andrea
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Alexandru Zaharie
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Bernhard Grubmüller
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Christopher Paschen
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Sonja Zehetmayer
- Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- Departments of Urology, Weill Cornell Medical College, New York, NY, USA
- Department of Urology, University of Texas Southwestern, Dallas, TX, USA
- Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
- Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
- Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
| | - Joachim Widder
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Gregor Goldner
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
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18
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Luo D, Wang X, Walker E, Springer S, Ramamurthy G, Burda C, Basilion JP. Targeted Chemoradiotherapy of Prostate Cancer Using Gold Nanoclusters with Protease Activatable Monomethyl Auristatin E. ACS APPLIED MATERIALS & INTERFACES 2022; 14:14916-14927. [PMID: 35316026 PMCID: PMC9153066 DOI: 10.1021/acsami.1c23780] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Combined radiotherapy (RT) and chemotherapy are prescribed to patients with advanced prostate cancer (PCa) to increase their survival; however, radiation-related side effects and systematic toxicity caused by chemotherapeutic drugs are unavoidable. To improve the precision and efficacy of concurrent RT and chemotherapy, we have developed a PCa-targeted gold nanocluster radiosensitizer conjugated with a highly potent cytotoxin, monomethyl auristatin E, PSMA-AuNC-MMAE, for RT and chemotherapy of PCa. This approach resulted in enhanced uptake of NCs by PSMA-positive cancer cells, targeted chemotherapy, and increased efficacy of RT both in vitro and in vivo. In addition, the combination of gold and MMAE further increased the efficacy of either of the agents delivered alone or simultaneously but not covalently linked. The PSMA-AuNC-MMAE conjugates improve the specificity and efficacy of radiation and chemotherapy, potentially reducing the toxicity of each therapy and making this an attractive avenue for clinical treatment of advanced PCa.
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19
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Asso R, Degrande F, Fernandes da Silva J, Leite E. Postoperative radiotherapy in prostate cancer: When and how? – An update review. Cancer Radiother 2022; 26:742-748. [DOI: 10.1016/j.canrad.2021.10.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/15/2021] [Accepted: 10/12/2021] [Indexed: 11/17/2022]
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20
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Terlizzi M, Limkin EJ, Moukasse Y, Blanchard P. Adjuvant or Salvage Radiation Therapy for Prostate Cancer after Prostatectomy: Current Status, Controversies and Perspectives. Cancers (Basel) 2022; 14:cancers14071688. [PMID: 35406460 PMCID: PMC8996903 DOI: 10.3390/cancers14071688] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 03/18/2022] [Accepted: 03/23/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary The management of patients with biochemical recurrence after prostatectomy has undergone significant changes in recent years. Currently, close monitoring of prostate-specific antigen (PSA) with early salvage radiotherapy (RT) in case of recurrence is the standard of care based on several randomized trials and a meta-analysis that has demonstrated its non-inferiority to adjuvant RT. Uncertainties remain regarding the management of patients at very high risk of recurrence, including appropriate selection criteria for adjuvant hormone therapy, and the role of imaging in refining the treatment strategy. This review explains this paradigm shift, raises points of controversy, and suggests ways to think about the future. Abstract Nearly one-third of the patients who undergo prostatectomy for prostate cancer have a biochemical recurrence (BCR) during follow-up. While several randomized trials have shown that adjuvant radiation therapy (aRT) improves biochemical control, this strategy has not been widely used because of the risk of toxicity and the fear of overtreating patients who would not have relapsed. In addition, the possibility of close PSA monitoring in the era of ultrasensitive assays enables to anticipate early salvage strategies (sRT). Three recent randomized trials and their meta-analysis have confirmed that aRT does not improve event-free survival compared to sRT, imposing the latter as the new standard of treatment. The addition of androgen deprivation therapy (ADT) to RT has been shown to improve biochemical control and metastasis-free survival, but the precise definition of to whom it should be proposed is still a matter of debate. The development of genomic tests or the use of artificial intelligence will allow more individualized treatment in the future. Therapeutic intensification with the combination of new-generation hormone therapy and RT is under study. Finally, the growing importance of metabolic imaging (PET/CT) due to its performance especially for low PSA levels will help in further personalizing management strategies.
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21
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Kurose H, Ueda K, Ogasawara N, Chikui K, Nakiri M, Nishihara K, Matsuo M, Suekane S, Kusano H, Akiba J, Yano H, Igawa T. Impact of Gleason score of the tumor at the positive surgical margin as a prognostic factor. Mol Clin Oncol 2022; 16:82. [PMID: 35251633 PMCID: PMC8892462 DOI: 10.3892/mco.2022.2515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 10/27/2021] [Indexed: 11/19/2022] Open
Abstract
Although numerous studies have reported that a positive surgical margin (PSM) is the most important predictive factor for biochemical recurrence (BCR) of prostate cancer (PCa), only a small number of studies have evaluated the predictive value of the Gleason score (GS) of the tumor at the margin in radical prostatectomy (RP). The present study aimed to investigate the preoperative factors that predict PSM and the significant predictive factors for BCR in cases with PSM. In addition, it was examined whether documenting the GS of the tumor at the margin in pathological reports is useful as a predictive factor for BCR. Data of 241 patients with PCa who underwent RP at Kurume University Hospital (Kurume, Japan) between January 2007 and December 2011 were retrospectively reviewed. The median follow-up period was 72 months and 122 patients had at least one PSM. The time to BCR was significantly shorter in patients with PSM than in those with a negative surgical margin. Multivariate analysis demonstrated that >10 ng/ml prostate-specific antigen at diagnosis (P=0.024) and >25% positive core at biopsy (P=0.041) were independent prognostic preoperative factors for PSM. The GS of the tumor at the margin was equal, lower and higher than those of the main tumor in 74 (60.7%), 16 (13.1%) and 32 (26.2%) RPs, respectively. The BCR rates were 35.7, 55.1 and 82.1% in patients whose GS of the tumor at the margin was 6, 7 and 8-10, respectively (P=0.0017). The GS of the tumor at the PSM (P=0.038) and anatomic location of the PSM (P=0.04) were identified as independent prognostic preoperative factors for BCR, whereas the GS of the main tumor and margin length were not. These results suggest that documenting the GS at the margin in pathological reports is useful as a predictive factor for BCR.
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Affiliation(s)
- Hirofumi Kurose
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Kosuke Ueda
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Naoyuki Ogasawara
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Katsuaki Chikui
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Makoto Nakiri
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Kiyoaki Nishihara
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Mitsunori Matsuo
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Shigetaka Suekane
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Hironori Kusano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Jun Akiba
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
| | - Tsukasa Igawa
- Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
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22
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Stone NN, Unger PD, Sheu R, Rosenstein BS, Stock RG. Factors associated with late local failure and its influence on survival in men undergoing prostate brachytherapy. Brachytherapy 2022; 21:460-467. [DOI: 10.1016/j.brachy.2022.01.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 11/26/2021] [Accepted: 01/05/2022] [Indexed: 11/30/2022]
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23
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Schröder C, Tang H, Windisch P, Zwahlen DR, Buchali A, Vu E, Bostel T, Sprave T, Zilli T, Murthy V, Förster R. Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review. Cancers (Basel) 2022; 14:cancers14030696. [PMID: 35158961 PMCID: PMC8833497 DOI: 10.3390/cancers14030696] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 01/22/2022] [Accepted: 01/26/2022] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Stereotactic body radiotherapy, a type of high-precision radiotherapy delivering high doses within few treatment sessions has proven to be effective and well tolerated in prostate cancer patients treated with definite radiotherapy. This systematic review summarizes the available data and analyzes whether this modern treatment may routinely be offered to prostate cancer patients after radical prostatectomy. Abstract (1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown. (2) Methods: We searched the PubMed and Embase databases with the following full-text queries in August 2021 for any combination of the terms “SBRT”, “prostate”, “adjuvant”, “postoperative”, “salvage”, “stereotactic radiotherapy”, “prostate bed”. There were no limitations regarding publication date or language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. (3) Results: We identified 11 individual studies that were included in this systematic review. Three publications included patients without prior radiotherapy and the remaining eight patients with prior radiotherapy. In all but two publications the radiation target was the macroscopic recurrence. SBRT was overall well tolerated with acceptable rates of acute and late gastrointestinal or genitourinary toxicity. Quality of life was published for two phase I trials with good results. There was a very heterogeneous reporting on biochemical control after SBRT. (4) Conclusions: At this point, ultra-hypofractionated RT using SBRT to the prostate bed remains experimental and its use should be restricted to clinical trials. Given the biological rationale for extreme hypofractionation in patients with prostate cancer and the acceptable toxicity rates that have been reported, further exploration of this field is warranted.
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Affiliation(s)
- Christina Schröder
- Institute for Radiation Oncology, Cantonal Hospital Winterthur (KSW), 8400 Winterthur, Switzerland; (C.S.); (H.T.); (P.W.); (D.R.Z.)
| | - Hongjian Tang
- Institute for Radiation Oncology, Cantonal Hospital Winterthur (KSW), 8400 Winterthur, Switzerland; (C.S.); (H.T.); (P.W.); (D.R.Z.)
| | - Paul Windisch
- Institute for Radiation Oncology, Cantonal Hospital Winterthur (KSW), 8400 Winterthur, Switzerland; (C.S.); (H.T.); (P.W.); (D.R.Z.)
| | - Daniel Rudolf Zwahlen
- Institute for Radiation Oncology, Cantonal Hospital Winterthur (KSW), 8400 Winterthur, Switzerland; (C.S.); (H.T.); (P.W.); (D.R.Z.)
| | - André Buchali
- Department of Radiation Oncology, Ruppiner Kliniken GmbH, Brandenburg Medical School (MHB), 16816 Neuruppin, Germany;
| | - Erwin Vu
- Department of Radiation Oncology, Cantonal Hospital St. Gallen (KSSG), 9000 St. Gallen, Switzerland;
| | - Tilman Bostel
- Department of Radiation Oncology, University Hospital Mainz, 55131 Mainz, Germany;
| | - Tanja Sprave
- Department of Radiation Oncology, University Hospital Freiburg, 79106 Freiburg im Breisgau, Germany;
| | - Thomas Zilli
- Department of Radiation Oncology, University Hospital Geneva (HUG), 1205 Geneva, Switzerland;
| | - Vedang Murthy
- Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai 400012, India;
| | - Robert Förster
- Institute for Radiation Oncology, Cantonal Hospital Winterthur (KSW), 8400 Winterthur, Switzerland; (C.S.); (H.T.); (P.W.); (D.R.Z.)
- Correspondence: ; Tel.: +41-52-266-31-40
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24
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Management of patients with a persistently elevated PSA after radical prostatectomy: a narrative review. World J Urol 2022; 40:965-972. [PMID: 35024944 DOI: 10.1007/s00345-021-03923-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/28/2021] [Indexed: 10/19/2022] Open
Abstract
INTRODUCTION The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (SRT) with or without the addition of a variable duration of hormone therapy (HT). The indications for SRT +/- HT are established in the setting of a rising PSA level after a period where an undetectable PSA was achieved. However, in case of detectable PSA immediately after radical prostatectomy, the treatment options and prognosis are still unclear. MATERIALS AND METHODS We conducted a narrative review based on an analysis of the literature focusing on articles targeting the population of patients with postoperative persistently detectable PSA level. Case reports, original articles, clinical trials, and published reviews were studied for this purpose. CONCLUSION This article will describe current management of patients with detectable PSA immediately after radical prostatectomy, notably the contribution of modern imaging and new treatment options involving the combination of RT and HT.
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25
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Cailleteau A, Sargos P, Saad F, Latorzeff I, Supiot S. Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients. Front Oncol 2021; 11:780507. [PMID: 35004302 PMCID: PMC8739777 DOI: 10.3389/fonc.2021.780507] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/30/2021] [Indexed: 12/26/2022] Open
Abstract
Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment may help increase the response to prostate bed irradiation while minimizing potential side effects. This perspective review focuses on the most relevant molecules that may have an impact when combined with salvage radiotherapy, and underlines the strategies that need to be developed to increase the efficacy of salvage post-prostatectomy radiotherapy in prostate cancer patients.
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Affiliation(s)
- Axel Cailleteau
- Department of Radiation Oncology, Institut de Cancérologie de l’Ouest, Nantes Saint-Herblain, France
| | - Paul Sargos
- Department of Radiation Oncology, Institut Bergonié, Bordeaux, France
| | - Fred Saad
- Department of Urology, Université de Montréal, Montreal, QC, Canada
| | - Igor Latorzeff
- Department of Radiation Oncology, Oncorad Clinique Pasteur, Toulouse, France
| | - Stéphane Supiot
- Department of Radiation Oncology, Institut de Cancérologie de l’Ouest, Nantes Saint-Herblain, France
- University of Nantes, CRCINA (CNRS, Inserm), Nantes, France
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26
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Shimoyachi N, Yoshioka Y, Sasamura K, Yonese J, Yamamoto S, Yuasa T, Soyano T, Kozuka T, Oguchi M. Comparison Between Dose-Escalated Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy for Salvage Radiation Therapy After Prostatectomy. Adv Radiat Oncol 2021; 6:100753. [PMID: 34934854 PMCID: PMC8655408 DOI: 10.1016/j.adro.2021.100753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/07/2021] [Indexed: 11/26/2022] Open
Abstract
Purpose To compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy. Methods and Materials A total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first. Results The median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively. Conclusions Dose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.
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Affiliation(s)
- Nana Shimoyachi
- Departments of Radiation Oncology and
- Corresponding author: Nana Shimoyachi, MD
| | | | | | - Junji Yonese
- Urology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shinya Yamamoto
- Urology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Yuasa
- Urology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Soyano
- Department of Radiology, Japan Self-Defense Forces Central Hospital, Tokyo, Japan
| | - Takuyo Kozuka
- Department of Radiology, University of Tokyo Hospital, Tokyo, Japan
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27
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Giraud N, Benziane-Ouaritini N, Schick U, Beauval JB, Chaddad A, Niazi T, Faye MD, Supiot S, Sargos P, Latorzeff I. Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach? Front Oncol 2021; 11:781040. [PMID: 34881187 PMCID: PMC8647553 DOI: 10.3389/fonc.2021.781040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 10/27/2021] [Indexed: 11/23/2022] Open
Abstract
Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64–66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.
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Affiliation(s)
- Nicolas Giraud
- Radiation Oncology Department, Institut Bergonié, Bordeaux, France
| | | | - Ulrike Schick
- Radiation Oncology Department, University Hospital, Brest, France
| | | | - Ahmad Chaddad
- School of Artificial Intelligence, Guilin University of Electronic Technology, Guilin, China
| | - Tamim Niazi
- Division of Radiation Oncology, Department of Oncology, McGill University, Montreal, QC, Canada
| | - Mame Daro Faye
- Division of Radiation Oncology, Department of Oncology, McGill University, Montreal, QC, Canada
| | - Stéphane Supiot
- Radiation Oncology Department, Institut de Cancérologie de l'Ouest, Nantes Saint-Herblain, France
| | - Paul Sargos
- Radiation Oncology Department, Institut Bergonié, Bordeaux, France
| | - Igor Latorzeff
- Radiation Oncology Department, Clinique Pasteur, Toulouse, France
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28
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Garriga M, Feng FY, Lee WR, Hong JC. Early salvage versus adjuvant therapy for treatment of prostate cancer following prostatectomy. BMJ Evid Based Med 2021; 26:e8. [PMID: 33361287 DOI: 10.1136/bmjebm-2020-111592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/02/2020] [Indexed: 11/04/2022]
Affiliation(s)
- Meera Garriga
- School of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Felix Y Feng
- Department of Radiation Oncology, University of California San Francisco, San Francisco, California, USA
| | - W Robert Lee
- Department of Radiation Oncology, Duke University, Durham, North Carolina, USA
| | - Julian C Hong
- Department of Radiation Oncology, University of California San Francisco, San Francisco, California, USA
- Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA
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Zaharie AT, Moll M, Goldner G. Biochemical control after adjuvant radiation therapy for prostate cancer: a unicentric, retrospective analysis. Strahlenther Onkol 2021; 197:971-975. [PMID: 33502568 PMCID: PMC8545725 DOI: 10.1007/s00066-020-01742-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 12/31/2020] [Indexed: 11/29/2022]
Abstract
PURPOSE To retrospectively evaluate the biochemical no evidence of disease (bNED) and late side effects after adjuvant radiotherapy in prostate cancer patients. METHODS Patients (n = 85) treated with external beam radiotherapy between 1997 and 2013 following radical prostatectomy (RPE) with pathological tumour stage pT2c with positive surgical margins or pT3 and pT4 tumours with or without positive margins who presented with a postoperative and a preradiation prostate-specific antigen (PSA) level below 0.1 ng/ml. The mean dose applied was 66 Gy with conventional fractionation (4 field box-technique). No androgen deprivation therapy was administered, and patients with incomplete data (missing Gleason score, pT stage, or PSA values postoperatively and/or prior to radiation at the presentation at our department) have been excluded from the analysis. Biochemical recurrence was defined as reaching a PSA level > 0.2 ng/ml during follow-up and bNED rates were assessed. In addition, patients were divided into two groups according to the Roach formula for predicting the risk of pelvic node involvement at a cut-off value of 15%. Late urogenital and gastrointestinal side effects (EORTC/RTOG) were assessed. RESULTS After a median follow-up of 60 months the bNED rate was 88% at 5 years and 72% at 10 years for all patients. Patients with low risk of lymph node involvement (group < 15%) had a 5 year and 10 year bNED of 97% and 85%, while patients with high risk of positive lymph node involvement (group > 15%) showed corresponding bNED rates of 77% and 52%, respectively. A significant difference according to the Roach stratification was detected (p ≤ 0.002). Late urogenital (UG) and gastrointestinal (GI) grade ≥ 2 side effects were detected in 10% and 15%, respectively. CONCLUSION Postoperative radiotherapy with an average dose of 66 Gy to the prostatic fossa following RPE provides excellent tumour control rates with acceptable side effects. Patients with a higher risk of positive lymph nodes (> 15%) according to the Roach formula show significant worse tumour control rates.
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Affiliation(s)
| | - Matthias Moll
- Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
| | - Gregor Goldner
- Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
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Latorzeff I, Ploussard G, Schick U, Benziane N, Pasquier D, Sargos P. [Salvage radiotherapy after prostatectomy - what do do in case of elevated post operative PSA or macroscopic relapse?]. Cancer Radiother 2021; 25:822-829. [PMID: 34702645 DOI: 10.1016/j.canrad.2021.08.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/12/2021] [Accepted: 08/13/2021] [Indexed: 02/03/2023]
Abstract
The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (RT) and a variable duration of hormone therapy (HT) in addition. The indications for RT±HT become more consensual for the adjuvant postoperative situation or in the event of a rising PSA level after a period where an undetectable PSA level was achieved. On the other hand, in the event of detectable PSA immediately postoperatively or in the event of a biological recurrence with macroscopic relapse in the prostate bed seen on conventional imaging assessment, the treatment options are still being evaluated. This article will describe these 2 situations and their current management but also will come through assessments with the contribution of modern imaging and new treatment options in terms of RT dose and RT±HT combination.
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Affiliation(s)
- I Latorzeff
- Département de radiothérapie-oncologie, Bât Atrium, clinique Pasteur, 1, rue de la Petite-Vitesse, 31300 Toulouse, France.
| | - G Ploussard
- Département d'urologie, clinique La Croix du Sud, Quint-Fonsegrives, France
| | - U Schick
- Département de radiothérapie-oncologie, CHU de Brest, Brest, France
| | - N Benziane
- Département de radiothérapie, institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux cedex, France
| | - D Pasquier
- Département universitaire de radiothérapie, centre O.-Lambret, 3, rue F.-Combemale, 59020 Lille, France
| | - P Sargos
- Département de radiothérapie, institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux cedex, France
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Remmers S, Hollemans E, Nieboer D, Luiting HB, van Leenders GJLH, Helleman J, Roobol MJ. Improving the prediction of biochemical recurrence after radical prostatectomy with the addition of detailed pathology of the positive surgical margin and cribriform growth. Ann Diagn Pathol 2021; 56:151842. [PMID: 34717190 DOI: 10.1016/j.anndiagpath.2021.151842] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/08/2021] [Accepted: 10/14/2021] [Indexed: 11/15/2022]
Abstract
The risk on biochemical recurrence (BCR) after radical prostatectomy (RP) is usually estimated using PSA and pathological stage and grading including the presence of positive surgical margins (PSM). Objective was to investigate whether the presence of cribriform growth in the primary tumor, Grade Group (GG) at the PSM, and length of the PSM have added value in the prognostication. We analyzed data of 835 patients initially treated with RP between 2000 and 2017. Cox regression models were developed to compare the baseline model (PSA, pT-stage, pN-stage, GG at RP, and presence of PSM) with an extended model (adding the presence of cribriform growth, length and GG at the PSM) using the likelihood ratio test. Discrimination was assessed at internal validation by the time-dependent area under the receiver operating characteristic curve (AUC) at 3- and 5-year. A total of 224 men experienced BCR. Median follow-up for men without BCR was 50.4 months (interquartile range, IQR 11.9-95.5). The extended model had a significant better fit, χ2(4) = 31.0, p < 0.001 than the baseline model. The AUC of the 3- and 5-year extended model was 0.85 (95% CI 0.81-0.88) compared to 0.83 (95% CI 0.79-0.87) for the baseline model. Importantly, the presence of cribriform growth in the primary tumor, and GG ≥ 2 at PSM were associated with a higher risk on BCR. In conclusion, the addition of pathological variables improved the prediction of the risk on BCR after RP slightly. However, the clinical implications of this model are important.
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Affiliation(s)
- Sebastiaan Remmers
- Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands.
| | - Eva Hollemans
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Daan Nieboer
- Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands; Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Henk B Luiting
- Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Geert J L H van Leenders
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Jozien Helleman
- Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Monique J Roobol
- Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
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[Postoperative radiotherapy for prostate cancer: when to propose it? What is the place for androgen deprivation?]. Cancer Radiother 2021; 25:667-673. [PMID: 34391651 DOI: 10.1016/j.canrad.2021.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 11/22/2022]
Abstract
PURPOSE While there is no high-level evidence showing superiority of surgery over radiation treatment, radical prostatectomy is the most common treatment option for patients with localized, non-metastatic disease. Nearly 30% of all patients undergoing surgery will develop a biochemical recurrence in 10 years. In fact, more than 30% of contemporary patients treated with RP will harbor aggressive disease characteristics at final pathology. MATERIAL AND MEHODS We conducted a review of the literature evaluating the timing of radiotherapy and the place of androgen deprivation after prostatectomie totale. RESULTS Four trials randomizing adjuvant radiotherapy and surveillance found an advantage in biochemical relapse-free survival in favor of immediate irradiation after radical prostatectomy, called adjuvant. However, in these studies, more than 40% of patients in the arm without adjuvant radiotherapy did not relapse at 10 years of follow-up. More recently, the question of the optimal time of this post-operative, adjuvant RT or during biological relapse has arisen through three trials (RADICALS-RT, RAVES, GETUG-AFU 17). These trials did not show a benefit for adjuvant radiotherapy in terms of event-free survival, a PSA-based endpoint, while confirming the toxicities observed during irradiation immediately after surgery. The optimal duration of hormonal therapy when associated with post-prostatectomy radiation therapy remains controversial. CONCLUSION Early salvage radiotherapy is a new standard of treatment and adjuvant radiotherapy could be reserved for very selected patients. The role of hormone therapy is well defined in salvage situation, but its duration is still being studied.
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Kwon YS, Wang W, Srivastava A, Jang TL, Singer EA, Parikh RR, Kim WJ, Kim IY. Observation with or without late radiotherapy is equivalent to early radiotherapy in high-risk prostate cancer after radical prostatectomy: A SEER-Medicare analysis on trends, survival outcomes, and complications. Prostate Int 2021; 9:82-89. [PMID: 34386450 PMCID: PMC8322776 DOI: 10.1016/j.prnil.2020.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/12/2020] [Accepted: 10/20/2020] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND We aimed to illustrate national trends of post-radical prostatectomy (RP) radiotherapy (RT) and compare outcomes and toxicities in patients receiving eRT versus observation with or without late radiotherapy (lRT). METHODS Utilizing the Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2001 to 2011, we identified 7557 patients with high-risk pathologic features after RP (≥pT3N0 and/or positive surgical margins). Our study cohort consisted of patients receiving RT within 6 months of surgery (eRT), those receiving RT after 6 months (lRT), and those never receiving RT (observation). Another subcohort, delayed RT (dRT), encompassed both lRT and observation. Trends of post-RP RT were compared using the Cochran-Armitage trend test. Cox regression models identified factors predictive of worse survival outcomes. Kaplan-Meier analyses compared the eRT and the dRT groups. RESULTS Among those with pathologically confirmed high-risk prostate cancer (PCa) after RP, 12.7% (n = 959), 13.2% (n = 1710), and 74.1% (n = 4888) underwent eRT, lRT, and observation without RT, respectively. Of these strategies, the proportion of men on observation without RT increased significantly over time (p = 0.004). The multivariable Cox regression model demonstrated similar outcomes between the eRT and the dRT groups. At a median follow-up of 5.9 years, five-year overall and cancer-specific survival outcomes were more favorable in the dRT group, when compared to the eRT group. CONCLUSIONS A blanket adoption of the eRT in high-risk PCa based on clinical trials with limited follow-up may result in overtreatment of a significant number of men and expose them to unnecessary radiation toxicity.
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Affiliation(s)
- Young Suk Kwon
- Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
| | - Wei Wang
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, USA
| | - Arnav Srivastava
- Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
| | - Thomas L. Jang
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Division of Urology, New Brunswick, New Jersey, USA
| | - Eric A. Singer
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Division of Urology, New Brunswick, New Jersey, USA
| | - Rahul R. Parikh
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Division of Urology, New Brunswick, New Jersey, USA
| | - Wun-Jae Kim
- Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Isaac Yi Kim
- Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Division of Urology, New Brunswick, New Jersey, USA
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López Campos F, Sancho Pardo G, Maldonado Pijoan X, Zilli T, Couñago Lorenzo F, Hervás Morón A. Is hypofractionation acceptable for prostate bed radiotherapy? Urol Oncol 2021; 39:346-350. [PMID: 34049781 DOI: 10.1016/j.urolonc.2021.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/02/2021] [Indexed: 11/15/2022]
Abstract
Approximately 30% of patients who undergo radical prostatectomy for prostate cancer develop disease progression. The only potentially curative treatment in these patients is postoperative radiotherapy with or without hormonotherapy. One of the standards of care in nonsurgical patients is hypofractionated radiotherapy. However, the current evidence based is insufficient to define the optimal dose and fractionation schedule for postoperative radiotherapy. In this context, the aim of this editorial is to assess the main efficacy and toxicity data for postoperative hypofractionated radiotherapy and discuss the potential to implement this fractionation in routine clinical practice.
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Affiliation(s)
| | - Gemma Sancho Pardo
- Radiation Oncology Department. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Thomas Zilli
- Radiation Oncology Department. Geneva University Hospital, Geneva, Switzerland
| | - Felipe Couñago Lorenzo
- Radiation Oncology Department. Hospital Universitario Quirónsalud Madrid, Madrid, Spain.
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Murgic J, Jaksic B, Prpic M, Kust D, Bahl A, Budanec M, Prgomet Secan A, Franco P, Kruljac I, Spajic B, Babic N, Kruslin B, Zovak M, Zubizarreta E, Rosenblatt E, Fröbe A. Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience. Radiat Oncol 2021; 16:88. [PMID: 33980277 PMCID: PMC8115388 DOI: 10.1186/s13014-021-01808-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/18/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.
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Affiliation(s)
- Jure Murgic
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Blanka Jaksic
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Marin Prpic
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
- School of Dental Medicine, University of Zagreb, Gunduliceva 5, 10000, Zagreb, Croatia
| | - Davor Kust
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Amit Bahl
- University Hospitals Bristol NHS Foundation Trust, Marlborough Street, Bristol, BS13NU, UK
| | - Mirjana Budanec
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Angela Prgomet Secan
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Pierfrancesco Franco
- Department of Translational Medicine, University of Eastern Piedmont, 28100, Novara, Italy
- Department of Radiation Oncology, 'Maggiore della Carità' University Hospital, 28100, Novara, Italy
| | - Ivan Kruljac
- Department of Endocrinology, Diabetes and Metabolic Diseases "Mladen Sekso", University Hospital Center Sestre Milosrdnice, University of Zagreb School of Medicine, Vinogradska 29, 10000, Zagreb, Croatia
| | - Borislav Spajic
- Department of Urology, University Hospital Center Sestre Milosrdnice, 10000, Zagreb, Croatia
| | - Nenad Babic
- Department of Radiology, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Bozo Kruslin
- Ljudevit Jurak Department of Pathology and Cytology, Sestre Milosrdnice University Hospital Centre, Vinogradska 29, 10000, Zagreb, Croatia
| | - Mario Zovak
- Department of Surgery, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia
| | - Eduardo Zubizarreta
- Division of Human Health, International Atomic Energy Agency (IAEA), Wagramer Str. 5, 1220, Vienna, Austria
| | - Eduardo Rosenblatt
- Division of Human Health, International Atomic Energy Agency (IAEA), Wagramer Str. 5, 1220, Vienna, Austria
| | - Ana Fröbe
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Vinogradska 29, 10000, Zagreb, Croatia.
- School of Dental Medicine, University of Zagreb, Gunduliceva 5, 10000, Zagreb, Croatia.
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Su SH, Chang YH, Huang LK, Chu YC, Kan HC, Liu CY, Lin PH, Yu KJ, Wu CT, Pang ST, Chuang CK, Shao IH. Clinical predictors for biochemical failure in patients with positive surgical margin after robotic-assisted radical prostatectomy. TUMORI JOURNAL 2021; 108:270-277. [PMID: 33845702 DOI: 10.1177/03008916211007928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Patients with positive surgical margins (PSMs) after radical prostatectomy for localized prostate cancer have a higher risk of biochemical failure (BCF). We investigated the risk factors of BCF in patients with PSMs after robotic-assisted radical prostatectomy (RARP). METHODS We evaluated 462 patients who underwent RARP in a single medical center from 2006 through 2013. Of them, 61 with PSMs did not receive any treatment before BCF. Kaplan-Meier curve and Cox regression analysis were used to compare patients with (n = 19) and without (n = 41) BCF. RESULTS Overall, 13.2% of patients had PSMs, and of those, 31.7% experienced BCF during follow-up. The mean follow-up duration was 43.7 months (42.4 [non-BCF] vs 46.35 (BCF], p = 0.51). In univariant analyses, the platelet to lymphocyte ratio (6.26 [non-BCF] vs 8.02 [BCF], p = 0.04) differed statistically. When patients were grouped by pathologic grade ≦2 or ≧3 (p = 0.004), the BCF-free survival rates differed significantly. Seminal vesicle invasion also differed significantly (5 [non-BCF] vs 7 [BCF], p = 0.005). Patients with undetectable nadir prostate-specific antigen (PSA) after RARP (BCF rate 4/34) differed statistically from those with detectable PSA after RARP (BCF rate 15/26) (p < 0.001). In the multivariate analysis, the platelet/lymphocyte (P/L) ratio, pathologic grade, and undetectable nadir PSA remained statistically significant. CONCLUSIONS In patients who undergo RARP and have PSMs, P/L ratio >9 preoperatively, pathologic grade ⩾3, and detectable nadir PSA after RARP should be considered adverse features. Early intervention such as salvage radiation therapy or androgen deprivation therapy should be offered to these patients.
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Affiliation(s)
- Shih-Huan Su
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ying-Hsu Chang
- Department of Urology, New Taipei City TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei Municipal, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Liang-Kang Huang
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yuan-Cheng Chu
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hung-Cheng Kan
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chung-Yi Liu
- Department of Urology, New Taipei City TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei Municipal, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Po-Hung Lin
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kai-Jie Yu
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Te Wu
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Keelung Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - See-Tong Pang
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Keng Chuang
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - I-Hung Shao
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.,Department of Medicine, Chang Gung University, Taoyuan, Taiwan.,Cancer Genome Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
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Gao XS, Qi X, Wang D. In Reply to Zilli et al. Int J Radiat Oncol Biol Phys 2021; 109:1128. [PMID: 33610297 DOI: 10.1016/j.ijrobp.2020.11.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 11/02/2020] [Indexed: 11/16/2022]
Affiliation(s)
- Xian-Shu Gao
- Department of Radiation Oncology, Peking University First Hospital, Beijing, China
| | - Xin Qi
- Department of Radiation Oncology, Peking University First Hospital, Beijing, China
| | - Dian Wang
- Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois
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Hirth CG, Vasconcelos GR, Lima MVA, da Cunha MDPSS, Frederico IKS, Dornelas CA. Prognostic value of FUS immunoexpression for Gleason patterns and prostatic adenocarcinoma progression. Ann Diagn Pathol 2021; 52:151729. [PMID: 33713944 DOI: 10.1016/j.anndiagpath.2021.151729] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 01/28/2021] [Accepted: 02/26/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Risk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. PATIENTS AND METHODS Non-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. RESULTS Our cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203-2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878-1.499]; p = 0.313). CONCLUSION Non-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.
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Affiliation(s)
- Carlos Gustavo Hirth
- Department of Pathology and Forensic Medicine, Postgraduate Program in Medical-Surgical Sciences of the Department of Surgery of the Federal University of Ceará, Hospital Haroldo Juaçaba, Ceará Cancer Institute, Brazil.
| | - Gislane Rocha Vasconcelos
- Hospital Haroldo Juaçaba, Ceará Cancer Institute, Pathology Laboratory, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil
| | - Marcos Venício Alves Lima
- Hospital Haroldo Juaçaba, Ceará Cancer Institute, Rodolfo Teófilo College, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil
| | - Maria do Perpétuo Socorro Saldanha da Cunha
- Hospital Haroldo Juaçaba, Ceará Cancer Institute, Urology Clinical, Rodolfo Teófilo College, Albert Sabin Hospital, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil
| | - Ingrid Kellen Sousa Frederico
- Hospital Haroldo Juaçaba, Ceará Cancer Institute, Pathology Laboratory, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil
| | - Conceição Aparecida Dornelas
- Department of Pathology and Forensic Medicine and Department of Surgery, Postgraduate Program in Medical-Surgical Sciences of the Department of Surgery of the Federal University of Ceará, Departamento de Patologia e Medicina Legal, Universidade Federal do Ceará, Rua Monsenhor Furtado, s/n, Rodolfo Teófilo, Fortaleza, Ceará 60441-750, Brazil
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Ploussard G, Fossati N, Wiegel T, D'Amico A, Hofman MS, Gillessen S, Mottet N, Joniau S, Spratt DE. Management of Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy: A Systematic Review of the Literature. Eur Urol Oncol 2021; 4:150-169. [PMID: 33574012 DOI: 10.1016/j.euo.2021.01.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/03/2020] [Accepted: 01/06/2021] [Indexed: 10/22/2022]
Abstract
CONTEXT The prognosis and optimal management of pN0/pN1 patients with persistently elevated prostate-specific antigen (PSA) 6-8 wk after radical prostatectomy (RP) remain unclear. OBJECTIVE To perform a systematic review of oncologic outcomes and effectiveness of salvage therapies in men with a detectable PSA level after RP. EVIDENCE ACQUISITION A systematic review was performed in May 2020. A total of 2374 articles were screened, and 25 studies including 5217 men were selected and included in the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. EVIDENCE SYNTHESIS PSA persistence was most commonly defined as PSA >0.1 ng/ml. PSA persistence was significantly correlated with disease aggressiveness and associated with worse oncologic outcomes than in men with undetectable PSA levels. The 5-yr recurrence-free survival rates varied from 21.5% to 67.0%. The ≥10-yr cancer-specific survival was 75-88%. Salvage radiotherapy ± androgen deprivation therapy was associated with improved survival outcomes. Risk stratification according to pathologic features, PSA levels/kinetics, and genomic classifier may aid in personalization of treatment. The usefulness of molecular imaging in this setting remains underevaluated. Main limitations of this systematic review are the retrospective design of the included studies and the lack of randomized controlled trials (RCTs) focusing on this specific population. CONCLUSIONS PSA persistence after RP is strongly correlated with poor oncologic outcomes. Our review suggests a benefit from immediate radiotherapy; however, current evidence is still low. Indication of subsequent therapies should be based on individual discussions, taking into account all the prognostic factors and the efficacy/toxicity imbalance of proposed treatment. Results from ongoing RCTs are awaited to state on the role of more intensified systemic therapy in this population. PATIENT SUMMARY Patients with a detectable prostate-specific antigen level after surgery are at high risk of subsequent progression. Immediate radiotherapy might improve survival outcomes. Further research into the role of molecular imaging and genomic classifier is needed in this patient population.
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Affiliation(s)
- Guillaume Ploussard
- Department of Urology, La Croix du Sud Hospital, Toulouse, France and Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
| | - Nicola Fossati
- Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Thomas Wiegel
- Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany
| | - Anthony D'Amico
- Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Michael S Hofman
- Prostate Theranostics and Imaging Centre of Excellence (ProsTIC), Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, VIC, Australia
| | - Silke Gillessen
- Department of Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland; University of Bern, Bern, Switzerland; Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Nicolas Mottet
- Department of Urology, University Hospital, St. Etienne, France
| | - Steven Joniau
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
| | - Daniel E Spratt
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
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Barbas Bernardos G, Herranz Amo F, González San Segundo C, Caño Velasco J, Subirá Ríos D, Moralejo Gárate M, Mayor de Castro J, Aragón Chamizo J, Hernández Fernández C. Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence. Actas Urol Esp 2020; 44:701-707. [PMID: 32595092 DOI: 10.1016/j.acuro.2020.02.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 01/25/2020] [Accepted: 02/03/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Survival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODS Retrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTS Mean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15years were 99.1%, 98.1% and 96.6%. Only time to BR <24months (HR=2.55, P=.01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONS In these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24months responded better to rescue treatment.
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Affiliation(s)
| | - F Herranz Amo
- Servicio de Urología, H.G.U. Gregorio Marañón, Madrid, España
| | | | - J Caño Velasco
- Servicio de Urología, H.G.U. Gregorio Marañón, Madrid, España
| | - D Subirá Ríos
- Servicio de Urología, H.G.U. Gregorio Marañón, Madrid, España
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Rans K, Berghen C, Joniau S, De Meerleer G. Salvage Radiotherapy for Prostate Cancer. Clin Oncol (R Coll Radiol) 2020; 32:156-162. [PMID: 32035581 DOI: 10.1016/j.clon.2020.01.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 12/23/2019] [Accepted: 01/08/2020] [Indexed: 02/07/2023]
Abstract
For patients experiencing biochemical recurrence in the absence of distant metastasis, salvage radiotherapy (SRT) with or without androgen deprivation therapy (ADT) is currently the only possible curative treatment option. Prostate-specific antigen (PSA) monitoring and the selected use of SRT has some advantages when compared with adjuvant radiotherapy. The most important one is avoidance of a potential overtreatment of patients who would never have disease progression, even in the presence of high-risk pathological features. The identification of a specific PSA cut-off seems to be incorrect. In patients with more adverse pathological features, early SRT administered at the very first sign of a PSA rise granted better disease control. Dose-intensified SRT is feasible and well tolerated with no significant difference in grade 2 or more acute and late toxicity. At least 66 Gy must be given in the salvage setting. ADT has a radio-sensitising effect on the radiotherapy by inhibiting the repair of DNA double-strand breaks. The use of ADT in the salvage setting results in a better oncological outcome. Hormonal therapy is associated with a decrease in quality of life and side-effects depending on the duration of hormone therapy. The oncological benefit of hormone therapy duration depends on their clinical and pathological characteristics. 68-Ga-prostate-specific membrane antigen positron emission tomography-computed tomography is the gold standard in staging prostate cancer patients with biochemical persistence or recurrence after radical prostatectomy. The implementation of 18F-labelled PSMA tracers can provide a further improvement.
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Affiliation(s)
- K Rans
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium.
| | - C Berghen
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium
| | - S Joniau
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
| | - G De Meerleer
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium
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Carrion A, Ingelmo-Torres M, Lozano JJ, Montalbo R, D'Anna M, Mercader C, Velez E, Ribal MJ, Alcaraz A, Mengual L. Prognostic classifier for predicting biochemical recurrence in localized prostate cancer patients after radical prostatectomy. Urol Oncol 2020; 39:493.e17-493.e25. [PMID: 33189527 DOI: 10.1016/j.urolonc.2020.10.075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/23/2020] [Accepted: 10/29/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVE The purpose of the study was to develop an improved classifier for predicting biochemical recurrence (BCR) in clinically localized PCa patients after radical prostatectomy. METHODS AND MATERIALS Retrospective study including 122 PCa patients who attended our department between 2000 and 2007. Gene expression patterns were analyzed in 21 samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in 101 independent PCa patients who underwent radical prostatectomy. Logistic regression analysis was used to identify individual predictors of BCR. A risk score for predicting BCR including clinicopathological and gene expression variables was developed. Interaction networks were built by GeneMANIA Cytoscape plugin. RESULTS A total of 37 patients developed BCR (36.6%) in a median follow-up of 120 months. Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR < 0.1). We found that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion, and positive margins were independent prognostic factors of BCR. A risk score generated using these variables was able to discriminate between 2 groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, P< 0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the 2 genes of the model were not found. CONCLUSION Combination of gene expression patterns and clinicopathological variables in a robust, easy-to-use, and reliable classifier may contribute to improve PCa risk stratification.
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Affiliation(s)
- Albert Carrion
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Mercedes Ingelmo-Torres
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Juan José Lozano
- CIBERehd. Plataforma de Bioinformática, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Spain
| | - Ruth Montalbo
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Maurizio D'Anna
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Clàudia Mercader
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Elena Velez
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Maria José Ribal
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Antonio Alcaraz
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Lourdes Mengual
- Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
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Abstract
High-risk prostate cancer is a heterogeneous disease that lacks clear consensus on its ideal management. Historically, non-surgical treatment was the preferred strategy, and several studies demonstrated improved survival among men with high-risk disease managed with the combination of radiotherapy and androgen deprivation therapy (ADT) compared with ADT alone. However, practice trends in the past 10-15 years have shown increased use of radical prostatectomy with pelvic lymph node dissection for primary management of high-risk, localized disease. Radical prostatectomy, as a primary monotherapy, offers the potential benefits of avoiding ADT, reducing rates of symptomatic local recurrence, enabling full pathological tumour staging and potentially reducing late adverse effects such as secondary malignancy compared with radiation therapy. Retrospective studies have reported wide variability in short-term (pathological) and long-term (oncological) outcomes of radical prostatectomy. Surgical monotherapy continues to be appropriate for selected patients, whereas in others the best treatment strategy probably involves a multimodal approach. Appropriate risk stratification utilizing clinical, pathological and potentially also genomic risk data is imperative in the initial management of men with prostate cancer. However, data from ongoing and planned prospective trials are needed to identify the optimal management strategy for men with high-risk, localized prostate cancer.
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Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, Sargos P, Sydes MR, Brawley C, Brihoum M, Brown C, Chabaud S, Cook A, Forcat S, Fraser-Browne C, Latorzeff I, Parmar MKB, Tierney JF. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet 2020; 396:1422-1431. [PMID: 33002431 PMCID: PMC7611137 DOI: 10.1016/s0140-6736(20)31952-8] [Citation(s) in RCA: 264] [Impact Index Per Article: 52.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 07/13/2020] [Accepted: 07/27/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches. METHODS We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing. RCTs were eligible if they aimed to compare immediate adjuvant radiotherapy versus early salvage radiotherapy, following radical prostatectomy in men (age ≥18 years) with intermediate-risk or high-risk, localised or locally advanced prostate cancer. We searched trial registers and conference proceedings until July 8, 2020, to identify eligible RCTs. By establishing the ARTISTIC collaboration with relevant trialists, we were able to anticipate when eligible trial results would emerge, and we developed and registered a protocol with PROSPERO before knowledge of the trial results (CRD42019132669). We used a harmonised definition of event-free survival, as the time from randomisation until the first evidence of either biochemical progression (prostate-specific antigen [PSA] ≥0·4 ng/mL and rising after completion of any postoperative radiotherapy), clinical or radiological progression, initiation of a non-trial treatment, death from prostate cancer, or a PSA level of at least 2·0 ng/mL at any time after randomisation. We predicted when we would have sufficient power to assess whether adjuvant radiotherapy was superior to early salvage radiotherapy. Investigators supplied results for event-free survival, both overall and within predefined patient subgroups. Hazard ratios (HRs) for the effects of radiotherapy timing on event-free survival and subgroup interactions were combined using fixed-effect meta-analysis. FINDINGS We identified three eligible trials and were able to obtain updated results for event-free survival for 2153 patients recruited between November, 2007, and December, 2016. Median follow-up ranged from 60 months to 78 months, with a maximum follow-up of 132 months. 1075 patients were randomly assigned to receive adjuvant radiotherapy and 1078 to a policy of early salvage radiotherapy, of whom 421 (39·1%) had commenced treatment at the time of analysis. Patient characteristics were balanced within trials and overall. Median age was similar between trials at 64 or 65 years (with IQRs ranging from 59 to 68 years) across the three trials and most patients (1671 [77·6%]) had a Gleason score of 7. All trials were assessed as having low risk of bias. Based on 270 events, the meta-analysis showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy (HR 0·95, 95% CI 0·75-1·21; p=0·70), with only a 1 percentage point (95% CI -2 to 3) change in 5-year event-free survival (89% vs 88%). Results were consistent across trials (heterogeneity p=0·18; I2=42%). INTERPRETATION This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localised or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy as it offers the opportunity to spare many men radiotherapy and its associated side-effects. FUNDING UK Medical Research Council.
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Affiliation(s)
- Claire L Vale
- MRC Clinical Trials Unit, University College London, London, UK.
| | - David Fisher
- MRC Clinical Trials Unit, University College London, London, UK
| | | | - Christopher Parker
- Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK
| | | | | | | | - Matthew R Sydes
- MRC Clinical Trials Unit, University College London, London, UK
| | | | | | - Chris Brown
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
| | | | - Adrian Cook
- MRC Clinical Trials Unit, University College London, London, UK
| | - Silvia Forcat
- MRC Clinical Trials Unit, University College London, London, UK
| | | | | | | | - Jayne F Tierney
- MRC Clinical Trials Unit, University College London, London, UK
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Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, Persad R, Pickering H, Saad F, Anderson J, Bahl A, Bottomley D, Brasso K, Chahal R, Cooke PW, Eddy B, Gibbs S, Goh C, Gujral S, Heath C, Henderson A, Jaganathan R, Jakobsen H, James ND, Kanaga Sundaram S, Lees K, Lester J, Lindberg H, Money-Kyrle J, Morris S, O'Sullivan J, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Røder MA, Sayers I, Simms M, Wilson J, Zarkar A, Parmar MKB, Sydes MR. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet 2020; 396:1413-1421. [PMID: 33002429 PMCID: PMC7616947 DOI: 10.1016/s0140-6736(20)31553-1] [Citation(s) in RCA: 257] [Impact Index Per Article: 51.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/26/2020] [Accepted: 06/12/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.
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Affiliation(s)
- Christopher C Parker
- Department of Oncology, Royal Marsden NHS Foundation Trust, Sutton, UK; Institute of Cancer Research, Sutton, UK
| | - Noel W Clarke
- Department of Oncology, Genito-Urinary Cancer Research Group, The Christie Hospital, Manchester, UK; Department of Surgery, The Christie Hospital, Manchester, UK; Department of Urology, Salford Royal Hospitals, Manchester, UK
| | - Adrian D Cook
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK
| | - Howard G Kynaston
- Department of Urology, Cardiff University School of Medicine, Cardiff University, Cardiff, UK
| | - Peter Meidahl Petersen
- Department of Oncology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Charles Catton
- Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
| | - William Cross
- Department Of Urology, St James's University Hospital, Leeds, UK
| | - John Logue
- Department of Oncology, The Christie Hospital, Manchester, UK
| | - Wendy Parulekar
- Department of Oncology, Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada
| | - Heather Payne
- Department of Oncology, University College London Hospitals, London, UK
| | - Rajendra Persad
- Department of Urology, Bristol Urological Institute, North Bristol Hospitals, Bristol, UK
| | - Holly Pickering
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK
| | - Fred Saad
- Department of Urology, Centre Hospitalier de l'Université de Montreal, Montreal, QC, Canada
| | - Juliette Anderson
- Department of Oncology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
| | - Amit Bahl
- Department of Oncology, Bristol Cancer Institute, University Hospitals Bristol, Bristol, UK
| | | | - Klaus Brasso
- Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Rohit Chahal
- Department of Urology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Peter W Cooke
- Department of Urology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Ben Eddy
- Department of Urology, East Kent Hospitals University Foundation Trust, Canterbury, UK
| | - Stephanie Gibbs
- Department of Oncology, Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK
| | - Chee Goh
- Department of Oncology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
| | - Sandeep Gujral
- Department of Urology, Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK
| | - Catherine Heath
- Department of Clinical Oncology, University Hospital Southampton, Southampton, UK
| | - Alastair Henderson
- Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK
| | - Ramasamy Jaganathan
- Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Henrik Jakobsen
- Department of Urology, Herlev University Hospital, Herlev, Denmark
| | - Nicholas D James
- Institute of Cancer Research, London, UK; Department of Oncology, Royal Marsden NHS Foundation Trust, London, UK
| | | | - Kathryn Lees
- Kent Oncology Centre, Maidstone Hospital, Kent, UK
| | - Jason Lester
- Department of Oncology, South West Wales Cancer Centre, Swansea, UK
| | | | - Julian Money-Kyrle
- Department of Oncology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
| | - Stephen Morris
- Department of Clinical Oncology, Guys Hospital, London, UK
| | - Joe O'Sullivan
- Department of Clinical Oncology, Belfast Health and Social Care Trust, Belfast, UK
| | | | - Lisa Owen
- Department of Oncology, Leeds Cancer Centre, St James's University Hospital, Leeds, UK
| | - Prashant Patel
- Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Alvan Pope
- Department of Urology, Hillingdon Hospital, Middlesex, UK; Mount Vernon Hospital, Northwood, UK; Mount Vernon Cancer Centre, Northwood, UK
| | | | - Rakesh Raman
- Department of Clinical Oncology, Kent Oncology Centre, Canterbury, UK
| | - Martin Andreas Røder
- Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Ian Sayers
- Department of Oncology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Matthew Simms
- Department of Urology, Hull University Hospitals NHS Trust, Hull, UK
| | - Jim Wilson
- Department of Urology, Anuerin Bevan University Health Board, Newport, UK
| | - Anjali Zarkar
- Department of Oncology, University Hospital Birmingham, Birmingham, UK
| | - Mahesh K B Parmar
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK
| | - Matthew R Sydes
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK.
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Abstract
BACKGROUND F-Fluciclovine is the most recent prostate cancer (PCa)-directed PET radiotracer approved by the US Food and Drug Administration for detection of recurrent PCa. We report the treatments and outcomes of patients at our institution with PCa recurrences detected on F-fluciclovine PET/CT. METHODS We identified men with recurrent PCa detected on F-fluciclovine PET/CT performed between 2017 and 2018 who were previously treated definitively and analyzed their patterns of care and cancer-specific outcomes. RESULTS We identified 28 men with recurrent PCa detected on F-fluciclovine PET/CT. Twenty-three were initially treated with surgery and 13 also received postoperative radiation therapy (RT). Five patients were initially treated with definitive radiation. After surgery, the median time to F-fluciclovine PET/CT was 67 months (median prostate-specific antigen [PSA] of 1.63 ng/mL). After RT, the median time to F-fluciclovine PET/CT was 95 months with median PSA of 13.31 ng/mL. Six men recurred locally, 9 recurred in the pelvic nodes, 9 had distant nodal recurrences, and 4 had osseous metastases. Of the patients initially treated with surgery, 4 received salvage radiation and 3 received androgen deprivation therapy (ADT). Of the patients initially treated with surgery and postoperative RT, 3 received salvage pelvic nodal dissection, 4 received salvage radiation, and 2 received ADT. Of the patients initially treated with radiation, 4 received salvage ADT. All had PSA decline after salvage therapy. CONCLUSIONS F-fluciclovine PET/CT can localize PCa recurrences, and subsequent salvage therapies appear effective with decreasing PSA. Longer follow-up will reveal if these diagnostic tests and subsequent therapies will improve PCa survival.
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Mahase S, Nagar H. Hypofractionated Postoperative Radiotherapy for Prostate Cancer: Is the Field Ready Yet? EUR UROL SUPPL 2020; 22:9-16. [PMID: 34337473 PMCID: PMC8317782 DOI: 10.1016/j.euros.2020.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2020] [Indexed: 12/30/2022] Open
Abstract
Context Radiotherapy (RT) is a valid adjuvant treatment for men with high-risk pathological features after radical prostatectomy and a salvage treatment for biochemical recurrence. A major inconvenience is that RT takes course over 7–8 wk in these settings, which has been shown to limit its use. Retrospective and pilot prospective investigations suggest that hypofractionation may provide noninferior outcomes but report variable results regarding toxicities. Additionally, our evolving understanding of prostate cancer radiobiology suggests that hypofractionated regimens may not increase toxicity. Objective We examine and review the rationale and clinical evidence of hypofractionated RT in the adjuvant and salvage settings for prostate cancer. Evidence acquisition We reviewed relevant literature, with a particular focus on recent studies employing hypofractionated RT. Evidence synthesis Hypofractionated RT in the adjuvant or salvage setting is not a standard option for prostate cancer RT outside of an investigational trial. While smaller studies show conflicting data regarding toxicity, initial evidence from larger clinical trials appears to demonstrate that hypofractionated postoperative RT is as effective and safe as conventionally fractionated courses. Conclusions With the growing acceptance of hypofractionation across other cancer sites and the rise of extreme hypofractionation for definitive prostate cancer treatment, hypofractionated postoperative therapy for prostate cancer is poised to become an option, as it may reduce the burden on men and treatment centers while maintaining clinical efficacy and safety. Prospective trials are currently ongoing to address efficacy and safety concerns. Patient summary Postoperative radiotherapy is a potentially curative treatment for patients with high-risk disease or recurrence after surgery. Shortening of the treatment regimen with the availability of modern treatment delivery techniques in conjunction with the integration of molecular imaging information to refine treatment volumes may improve therapeutic benefit without increasing toxicity.
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Shelan M, Aebersold D, Ghadjar P. [Early salvage radiation therapy of the prostate bed appears to be equally effective compared to adjuvant radiation therapy after radical prostatectomy]. Strahlenther Onkol 2020; 196:406-409. [PMID: 32060583 DOI: 10.1007/s00066-020-01591-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- M Shelan
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Schweiz
| | - D Aebersold
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Schweiz
| | - P Ghadjar
- Klinik für Radioonkologie und Strahlentherapie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, Augustenburger Platz 1, 13353, Berlin, Deutschland.
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Sargos P, Chabaud S, Latorzeff I, Magné N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulié M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol 2020; 21:1341-1352. [PMID: 33002438 DOI: 10.1016/s1470-2045(20)30454-x] [Citation(s) in RCA: 209] [Impact Index Per Article: 41.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/29/2020] [Accepted: 07/03/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. METHODS GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. FINDINGS Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50-100), 74 months (47-100) in the adjuvant radiotherapy group and 78 months (52-101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86-95) in the adjuvant radiotherapy group and 90% (85-94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48-1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). INTERPRETATION Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. FUNDING French Health Ministry and Ipsen.
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Affiliation(s)
| | | | | | - Nicolas Magné
- Institut de Cancérologie de la Loire, Saint-Priest-en-Jarèz, France
| | | | - Stéphane Supiot
- Institut de Cancérologie de l'Ouest, Site René Gauducheau, Saint-Herblain, France
| | - David Pasquier
- Centre Oscar Lambret and Lille University, Lille, France
| | | | | | | | | | - Philippe Bergerot
- Clinique Mutualiste de l'Estuaire, Cité Sanitaire, Saint-Nazaire, France
| | | | - Yazid Belkacemi
- Hôpitaux Universitaires Henri Mondor, Université Paris Est Créteil, Creteil, France
| | - David Azria
- Institut Régional du Cancer de Montpellier Val d'Aurelle, Montpellier, France
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Luo D, Johnson A, Wang X, Li H, Erokwu BO, Springer S, Lou J, Ramamurthy G, Flask CA, Burda C, Meade TJ, Basilion JP. Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer. NANO LETTERS 2020; 20:7159-7167. [PMID: 32845644 PMCID: PMC9109254 DOI: 10.1021/acs.nanolett.0c02487] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd(III) complexes and prostate-specific membrane antigen (PSMA) targeting ligands to AuNP surfaces, we found enhanced uptake of AuNPs by PSMA-expressing cancer cells with excellent MR contrast and radiation therapy outcome in vitro and in vivo. The AuNPs binding affinity and r1 relaxivity were dramatically improved and the combination of Au and Gd(III)provided better tumor suppression after radiation. The precise tumor localization by MR and selective tumor targeting of the PSMA-1-targeted AuNPs could enable precise radiotherapy, reduction in irradiating dose, and minimization of healthy tissue damage.
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Affiliation(s)
- Dong Luo
- Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Andrew Johnson
- Department of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, Illinois 60208, United States
| | - Xinning Wang
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Hao Li
- Department of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, Illinois 60208, United States
| | - Bernadette O Erokwu
- Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Sarah Springer
- Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Jason Lou
- Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | | | - Chris A Flask
- Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States
- Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Clemens Burda
- Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Thomas J Meade
- Department of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, Illinois 60208, United States
| | - James P Basilion
- Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
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