Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Onda T, Matsumoto K, Shibata T, Sato A, Fukuda H, Konishi I, Kamura T, Yoshikawa H. Phase III trial of upfront debulking surgery versus neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0602. Jpn J Clin Oncol 2008;38:74-7. [PMID: 18258715 DOI: 10.1093/jjco/hym145] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open

For:	Onda T, Matsumoto K, Shibata T, Sato A, Fukuda H, Konishi I, Kamura T, Yoshikawa H. Phase III trial of upfront debulking surgery versus neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0602. Jpn J Clin Oncol 2008;38:74-7. [PMID: 18258715 DOI: 10.1093/jjco/hym145] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open

Number

Cited by Other Article(s)

Shawky M, Choudhary C, Coleridge SL, Bryant A, Morrison J. Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2025;2:CD005343. [PMID: 39927569 PMCID: PMC11808835 DOI: 10.1002/14651858.cd005343.pub7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]

Abstract

RATIONALE

Epithelial ovarian cancer (EOC) presents at an advanced stage in the majority of women. These women require a combination of surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery.

OBJECTIVES

To assess the advantages and disadvantages of treating women with advanced EOC with chemotherapy before cytoreductive surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows cytoreductive surgery (primary cytoreductive surgery (PCRS)).

SEARCH METHODS

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 21 March 2024. We also checked the reference lists of relevant papers for further studies. We contacted the principal investigators of relevant trials for further information.

ELIGIBILITY CRITERIA

Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery.

OUTCOMES

We extracted data on overall (OS) and progression-free survival (PFS), adverse events, surgically related mortality and morbidity, and quality of life outcomes.

RISK OF BIAS

We used the Cochrane RoB 1 tool to assess risk of bias in RCTs.

SYNTHESIS METHODS

We conducted meta-analyses using random-effects models (due to heterogeneity between studies) to calculate hazard ratios (HR), risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) for all outcomes. We assessed the certainty of evidence according to the GRADE approach.

INCLUDED STUDIES

We identified a further 1022 titles and abstracts through our searches in this update (958 unique records after further de-duplication), adding to the 2227 titles and abstracts identified in previous versions of this review. A total of five RCTs of varying quality and size met the inclusion criteria. We identified no new completed studies in this update, but we did include additional data from existing studies. The studies assessed a total of 1774 women with stage III/IV ovarian cancer randomised to NACT followed by interval cytoreductive surgery (ICRS) or PCRS followed by chemotherapy. We included data from four studies in the meta-analyses (1692 participants).

SYNTHESIS OF RESULTS

Survival We found little or no difference between groups in OS (HR 0.96, 95% CI 0.86 to 1.08; P = 0.49; I2 = 0%; 4 studies; 1692 women; high-certainty evidence) and likely little or no difference between groups in PFS (HR 0.98, 95% CI 0.88 to 1.08; P = 0.62; I2 = 0%; 4 studies; 1692 women; moderate-certainty evidence). Adverse events Adverse events, surgical morbidity, and quality of life outcomes were variably and incompletely reported across studies. NACT reduces postoperative mortality (0.4% in the NACT group versus 3.3% in the PCRS group) (RR 0.18, 95% CI 0.06 to 0.52; P = 0.002; I2 = 0%; 4 studies; 1542 women; high-certainty evidence). There are probably clinically meaningful differences in favour of NACT compared to PCRS in overall surgically related adverse effects (grade 3+ (G3+)) (6% in the NACT group versus 29% in the PCRS group) (RR 0.22, 95% CI 0.13 to 0.38; P < 0.001; I2 = 0%; 2 studies; 435 women; moderate-certainty evidence). Organ resection NACT probably results in a large reduction in the need for stoma formation (5.8% in the NACT group versus 20.4% in the PCRS group) (RR 0.29, 95% CI 0.12 to 0.74; P = 0.009; I2 = 70%; 2 studies; 632 women; moderate-certainty evidence) and probably reduces the risk of needing bowel resection at the time of surgery (13.0% in the NACT group versus 26.6% in the PCRS group) (RR 0.47, 95% CI 0.27 to 0.81; P = 0.007; I2 = 84%; 4 studies; 1578 women; moderate-certainty evidence). Quality of life Global quality of life on the EORTC QLQ-C30 produced imprecise results in three studies, with high levels of heterogeneity (quality of life at six months: MD 6.62, 95% CI -2.89 to 16.13; P = 0.17; I2 = 92%; 3 studies; 559 women; low-certainty evidence). Overall, functional and symptom scores may be slightly improved for NACT at 6 months, but similar by 12 months, although the differences might not be clinically meaningful.

AUTHORS' CONCLUSIONS

The available high- to moderate-certainty evidence shows there is likely little or no difference in primary survival outcomes between PCRS and NACT for those with advanced EOC who are suitable for either treatment option. NACT reduces the risk of postoperative mortality and likely reduces the risk of serious adverse events, especially those around the time of surgery, and the need for stoma formation. These data should inform women and clinicians (involving specialist gynaecological multidisciplinary teams) and allow treatment to be tailored to the individual patient, taking into account surgical resectability, age, histology, stage, and performance status. Data from an unpublished study and ongoing studies are awaited.

FUNDING

This Cochrane review update had no dedicated funding.

REGISTRATION

Protocol (2005): DOI: 10.1002/14651858.CD005343 Original review (2007): DOI: 10.1002/14651858.CD005343.pub2 Review update (2012): DOI: 10.1002/14651858.CD005343.pub3 Review update (2019): DOI: 10.1002/14651858.CD005343.pub4 Review update (2021): DOI: 10.1002/14651858.CD005343.pub5 Review updated (2021a): DOI: 10.1002/14651858.CD005343.pub6.

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Lee EYP, Ip PPC, Tse KY, Chiu KWH, Chu MMY, Chai YK, Wu PY, Law JYP, Kwok ST, Chiu WK, Ngan HYS. Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer. Eur Radiol 2024;34:5911-5922. [PMID: 38460014 PMCID: PMC11364794 DOI: 10.1007/s00330-024-10674-y] [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: 10/26/2023] [Revised: 01/22/2024] [Accepted: 02/14/2024] [Indexed: 03/11/2024]

Abstract

OBJECTIVES

The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC).

MATERIALS AND METHODS

This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test.

RESULTS

In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05).

CONCLUSION

2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC.

CLINICAL RELEVANCE STATEMENT

2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery.

KEY POINTS

• Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

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Kawahara N, Yamanaka S, Sugimoto S, Kamibayashi J, Nishikawa K, Kawaguchi R, Kimura F. The Prognosis Predictive Score around Neo Adjuvant Chemotherapy (PPSN) Improves Diagnostic Efficacy in Predicting the Prognosis of Epithelial Ovarian Cancer Patients. Cancers (Basel) 2023;15:5062. [PMID: 37894429 PMCID: PMC10605019 DOI: 10.3390/cancers15205062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 10/07/2023] [Accepted: 10/13/2023] [Indexed: 10/29/2023] Open

Liu Y, Ni M, Huang F, Gu Q, Xiao Y, Du X. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer by histology: A SEER based survival analysis. Medicine (Baltimore) 2023;102:e32774. [PMID: 36705377 PMCID: PMC9875958 DOI: 10.1097/md.0000000000032774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open

Bryant A, Hiu S, Kunonga PT, Gajjar K, Craig D, Vale L, Winter-Roach BA, Elattar A, Naik R. Impact of residual disease as a prognostic factor for survival in women with advanced epithelial ovarian cancer after primary surgery. Cochrane Database Syst Rev 2022;9:CD015048. [PMID: 36161421 PMCID: PMC9512080 DOI: 10.1002/14651858.cd015048.pub2] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Abstract

BACKGROUND

Ovarian cancer is the seventh most common cancer among women and a leading cause of death from gynaecological malignancies. Epithelial ovarian cancer is the most common type, accounting for around 90% of all ovarian cancers. This specific type of ovarian cancer starts in the surface layer covering the ovary or lining of the fallopian tube. Surgery is performed either before chemotherapy (upfront or primary debulking surgery (PDS)) or in the middle of a course of treatment with chemotherapy (neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS)), with the aim of removing all visible tumour and achieving no macroscopic residual disease (NMRD). The aim of this review is to investigate the prognostic impact of size of residual disease nodules (RD) in women who received upfront or interval cytoreductive surgery for advanced (stage III and IV) epithelial ovarian cancer (EOC).

OBJECTIVES

To assess the prognostic impact of residual disease after primary surgery on survival outcomes for advanced (stage III and IV) epithelial ovarian cancer. In separate analyses, primary surgery included both upfront primary debulking surgery (PDS) followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Each residual disease threshold is considered as a separate prognostic factor.

SEARCH METHODS

We searched CENTRAL (2021, Issue 8), MEDLINE via Ovid (to 30 August 2021) and Embase via Ovid (to 30 August 2021).

SELECTION CRITERIA

We included survival data from studies of at least 100 women with advanced EOC after primary surgery. Residual disease was assessed as a prognostic factor in multivariate prognostic models. We excluded studies that reported fewer than 100 women, women with concurrent malignancies or studies that only reported unadjusted results. Women were included into two distinct groups: those who received PDS followed by platinum-based chemotherapy and those who received IDS, analysed separately. We included studies that reported all RD thresholds after surgery, but the main thresholds of interest were microscopic RD (labelled NMRD), RD 0.1 cm to 1 cm (small-volume residual disease (SVRD)) and RD > 1 cm (large-volume residual disease (LVRD)).

DATA COLLECTION AND ANALYSIS

Two review authors independently abstracted data and assessed risk of bias. Where possible, we synthesised the data in meta-analysis. To assess the adequacy of adjustment factors used in multivariate Cox models, we used the 'adjustment for other prognostic factors' and 'statistical analysis and reporting' domains of the quality in prognosis studies (QUIPS) tool. We also made judgements about the certainty of the evidence for each outcome in the main comparisons, using GRADE. We examined differences between FIGO stages III and IV for different thresholds of RD after primary surgery. We considered factors such as age, grade, length of follow-up, type and experience of surgeon, and type of surgery in the interpretation of any heterogeneity. We also performed sensitivity analyses that distinguished between studies that included NMRD in RD categories of < 1 cm and those that did not. This was applicable to comparisons involving RD < 1 cm with the exception of RD < 1 cm versus NMRD. We evaluated women undergoing PDS and IDS in separate analyses.

MAIN RESULTS

We found 46 studies reporting multivariate prognostic analyses, including RD as a prognostic factor, which met our inclusion criteria: 22,376 women who underwent PDS and 3697 who underwent IDS, all with varying levels of RD. While we identified a range of different RD thresholds, we mainly report on comparisons that are the focus of a key area of clinical uncertainty (involving NMRD, SVRD and LVRD). The comparison involving any visible disease (RD > 0 cm) and NMRD was also important. SVRD versus NMRD in a PDS setting In PDS studies, most showed an increased risk of death in all RD groups when those with macroscopic RD (MRD) were compared to NMRD. Women who had SVRD after PDS had more than twice the risk of death compared to women with NMRD (hazard ratio (HR) 2.03, 95% confidence interval (CI) 1.80 to 2.29; I2 = 50%; 17 studies; 9404 participants; moderate-certainty). The analysis of progression-free survival found that women who had SVRD after PDS had nearly twice the risk of death compared to women with NMRD (HR 1.88, 95% CI 1.63 to 2.16; I2 = 63%; 10 studies; 6596 participants; moderate-certainty). LVRD versus SVRD in a PDS setting When we compared LVRD versus SVRD following surgery, the estimates were attenuated compared to NMRD comparisons. All analyses showed an overall survival benefit in women who had RD < 1 cm after surgery (HR 1.22, 95% CI 1.13 to 1.32; I2 = 0%; 5 studies; 6000 participants; moderate-certainty). The results were robust to analyses of progression-free survival. SVRD and LVRD versus NMRD in an IDS setting The one study that defined the categories as NMRD, SVRD and LVRD showed that women who had SVRD and LVRD after IDS had more than twice the risk of death compared to women who had NMRD (HR 2.09, 95% CI 1.20 to 3.66; 310 participants; I2 = 56%, and HR 2.23, 95% CI 1.49 to 3.34; 343 participants; I2 = 35%; very low-certainty, for SVRD versus NMRD and LVRD versus NMRD, respectively). LVRD versus SVRD + NMRD in an IDS setting Meta-analysis found that women who had LVRD had a greater risk of death and disease progression compared to women who had either SVRD or NMRD (HR 1.60, 95% CI 1.21 to 2.11; 6 studies; 1572 participants; I2 = 58% for overall survival and HR 1.76, 95% CI 1.23 to 2.52; 1145 participants; I2 = 60% for progression-free survival; very low-certainty). However, this result is biased as in all but one study it was not possible to distinguish NMRD within the < 1 cm thresholds. Only one study separated NMRD from SVRD; all others included NMRD in the SVRD group, which may create bias when comparing with LVRD, making interpretation challenging. MRD versus NMRD in an IDS setting Women who had any amount of MRD after IDS had more than twice the risk of death compared to women with NMRD (HR 2.11, 95% CI 1.35 to 3.29, I2 = 81%; 906 participants; very low-certainty).

AUTHORS' CONCLUSIONS

In a PDS setting, there is moderate-certainty evidence that the amount of RD after primary surgery is a prognostic factor for overall and progression-free survival in women with advanced ovarian cancer. We separated our analysis into three distinct categories for the survival outcome including NMRD, SVRD and LVRD. After IDS, there may be only two categories required, although this is based on very low-certainty evidence, as all but one study included NMRD in the SVRD category. The one study that separated NMRD from SVRD showed no improved survival outcome in the SVRD category, compared to LVRD. Further low-certainty evidence also supported restricting to two categories, where women who had any amount of MRD after IDS had a significantly greater risk of death compared to women with NMRD. Therefore, the evidence presented in this review cannot conclude that using three categories applies in an IDS setting (very low-certainty evidence), as was supported for PDS (which has convincing moderate-certainty evidence).

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Thomas QD, Boussere A, Classe JM, Pomel C, Costaz H, Rodrigues M, Ray-Coquard I, Gladieff L, Rouzier R, Rouge TDLM, Gouy S, Barranger E, Sabatier R, Floquet A, Marchal F, Guillemet C, Polivka V, Martin AL, Colombo PE, Fiteni F. Optimal timing of interval debulking surgery for advanced epithelial ovarian cancer: A retrospective study from the ESME national cohort. Gynecol Oncol 2022;167:11-21. [PMID: 35970603 DOI: 10.1016/j.ygyno.2022.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 07/30/2022] [Accepted: 08/07/2022] [Indexed: 11/16/2022]

Affiliation(s)

Quentin Dominique Thomas Departement of Medical Oncology, Institut du Cancer de Montpellier, Montpellier University, Montpellier, France.
Amal Boussere Department of Biometry, Institut du Cancer de Montpellier, Montpellier University, Montpellier, France
Jean-Marc Classe Department of Surgical Oncology, Institut de Cancérologie de l'Ouest Centre René Gauducheau, Saint Herblain, France
Christophe Pomel Department of Surgical Oncology, Centre de Lutte Contre le Cancer Jean Perrin, Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, UMR INSERM-UCA, Clermont-Ferrand, France
Hélène Costaz Department of Surgical Oncology, Centre Georges-François Leclerc, Dijon, France
Manuel Rodrigues Department of Medical Oncology, Institut Curie, Paris, France
Isabelle Ray-Coquard Department of Medical Oncology, Centre Léon Bérard, Lyon, France
Laurence Gladieff Department of Medical Oncology, Institut Claudius Régaud IUCT-O, Toulouse, France
Roman Rouzier Department of Surgical Oncology, Centre François Baclesse, Caen, France
Thibault De La Motte Rouge Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
Sébastien Gouy Department of Surgery, Gustave Roussy, Villejuif, France
Emmanuel Barranger Departement of Surgery, Centre Antoine Lacassagne, Nice, France
Renaud Sabatier Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France
Anne Floquet Department of Medical Oncology, Institut Bergonié, Bordeaux, France
Frédéric Marchal Departement of Surgery, Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France
Cécile Guillemet Department of Medical Oncology, Centre Henri Becquerel, Rouen, France
Valentine Polivka Department of Biometry, Institut du Cancer de Montpellier, Montpellier University, Montpellier, France
Anne-Laure Martin Health Data and Partnership Department, Unicancer, Paris, France
Pierre-Emmanuel Colombo Departement of Surgery, Institut du Cancer de Montpellier, Montpellier University, Montpellier, France
Frédéric Fiteni Departement of Medical Oncology, University Hospital of Nîmes, University of Montpellier, UMR UA11 INSERM, IDESP Institut Desbrest d'Epidémiologie et de Santé Publique, Montpellier, France

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Ergasti R, Marchetti C, Tudisco R, Iervolino A, Naldini A, Oliva R, Inzani F, Scambia G, Fagotti A. BRCA status and platinum sensitivity in advanced ovarian cancer according to Chemotherapy Response Score. Int J Gynecol Cancer 2022;32:639-645. [PMID: 35246469 DOI: 10.1136/ijgc-2021-003116] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open

Evaluation of Surgical Morbidity After Hysterectomy During an Obesity Epidemic. Obstet Gynecol 2022;139:589-596. [DOI: 10.1097/aog.0000000000004699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 12/16/2021] [Indexed: 11/26/2022]

Moukarzel LA, Chi DS. Posterior pelvic exenteration, a crucial component in the surgeon’s toolbox for optimizing surgical cytoreduction for advanced ovarian cancer. J Gynecol Oncol 2022;33:e41. [PMID: 35320890 PMCID: PMC9024179 DOI: 10.3802/jgo.2022.33.e41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/08/2022] [Accepted: 02/08/2022] [Indexed: 11/30/2022] Open

Huang AB, Wu J, Chen L, Albright BB, Previs RA, Moss HA, Davidson BA, Havrilesky LJ, Melamed A, Wright JD. Neoadjuvant chemotherapy for advanced stage endometrial cancer: A systematic review. Gynecol Oncol Rep 2021;38:100887. [PMID: 34820496 PMCID: PMC8601999 DOI: 10.1016/j.gore.2021.100887] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/18/2021] [Accepted: 10/27/2021] [Indexed: 12/22/2022] Open

Abstract

OBJECTIVE

While primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS.

METHODS

We conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with "endometrial cancer" and "neoadjuvant chemotherapy". Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies.

RESULTS

The nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (<1 cm of residual disease) rates were similar across both treatment groups in three separate analyses, however pooled data suggest improved rates of optimal cytoreduction for NACT + ICS vs. PCS patients (81.9% vs. 51.5% respectively). Patients receiving NACT experienced significantly shorter hospital admissions and lower operative times compared to PCS counterparts.

CONCLUSIONS

NACT followed by ICS reduces perioperative morbidity while offering similar overall survival.

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Coleridge SL, Bryant A, Kehoe S, Morrison J. Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev 2021;7:CD005343. [PMID: 34328210 PMCID: PMC8406953 DOI: 10.1002/14651858.cd005343.pub6] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]

Abstract

BACKGROUND

Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require a combination of surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery.

OBJECTIVES

To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)).

SEARCH METHODS

We searched the following databases up to 9 October 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information.

SELECTION CRITERIA

Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery.

DATA COLLECTION AND ANALYSIS

Two review authors independently extracted data and assessed risk of bias in each included trial. We extracted data of overall (OS) and progression-free survival (PFS), adverse events, surgically-related mortality and morbidity and quality of life outcomes. We used GRADE methods to determine the certainty of evidence.

MAIN RESULTS

We identified 2227 titles and abstracts through our searches, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1774 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the four studies where data were available and found little or no difference with regard to overall survival (OS) (Hazard Ratio (HR) 0.96, 95% CI 0.86 to 1.08; participants = 1692; studies = 4; high-certainty evidence) or progression-free survival in four trials where we were able to pool data (Hazard Ratio 0.98, 95% CI 0.88 to 1.08; participants = 1692; studies = 4; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were variably and incompletely reported across studies. There are probably clinically meaningful differences in favour of NACT compared to PDS with regard to overall postoperative serious adverse effects (SAE grade 3+): 6% in NACT group, versus 29% in PDS group, (risk ratio (RR) 0.22, 95% CI 0.13 to 0.38; participants = 435; studies = 2; heterogeneity index (I2) = 0%; moderate-certainty evidence). NACT probably results in a large reduction in the need for stoma formation: 5.9% in NACT group, versus 20.4% in PDS group, (RR 0.29, 95% CI 0.12 to 0.74; participants = 632; studies = 2; I2 = 70%; moderate-certainty evidence), and probably reduces the risk of needing bowel resection at the time of surgery: 13.0% in NACT group versus 26.6% in PDS group (RR 0.49, 95% CI 0.30 to 0.79; participants = 1565; studies = 4; I2 = 79%; moderate-certainty evidence). NACT reduces postoperative mortality: 0.6% in NACT group, versus 3.6% in PDS group, (RR 0.16, 95% CI 0.06 to 0.46; participants = 1623; studies = 5; I2 = 0%; high-certainty evidence). QoL on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scale produced inconsistent and imprecise results in three studies (MD -0.29, 95% CI -2.77 to 2.20; participants = 524; studies = 3; I2 = 81%; very low-certainty evidence) but the evidence is very uncertain and should be interpreted with caution.

AUTHORS' CONCLUSIONS

The available high to moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT probably reduces the risk of serious adverse events, especially those around the time of surgery, and reduces the risk of postoperative mortality and the need for stoma formation. These data will inform women and clinicians (involving specialist gynaecological multidisciplinary teams) and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

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Hishida T, Masai K, Kaseda K, Asakura K, Asamura H. Debulking surgery for malignant tumors: the current status, evidence and future perspectives. Jpn J Clin Oncol 2021;51:1349-1362. [PMID: 34254145 DOI: 10.1093/jjco/hyab107] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/22/2021] [Indexed: 11/14/2022] Open

Nero C, Vizzielli G, Lorusso D, Cesari E, Daniele G, Loverro M, Scambia G, Sette C. Patient-derived organoids and high grade serous ovarian cancer: from disease modeling to personalized medicine. J Exp Clin Cancer Res 2021;40:116. [PMID: 33789687 PMCID: PMC8011220 DOI: 10.1186/s13046-021-01917-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 03/17/2021] [Indexed: 12/13/2022] Open

Abstract

BACKGROUND

High grade serous ovarian cancer (HGSOC) is among the deadliest human cancers and its prognosis remains extremely poor. Tumor heterogeneity and rapid acquisition of resistance to conventional chemotherapeutic approaches strongly contribute to poor outcome of patients. The clinical landscape of HGSOC has been radically transformed since the advent of targeted therapies in the last decade. Nevertheless, the lack of predictive biomarkers informing on the differential clinical benefit in select subgroups, and allowing patient-centric approaches, currently limits the efficacy of these novel therapies. Thus, rational selection of the best possible treatment for each patient represents a clinical priority in order to improve outcome, while limiting undesirable effects.

MAIN BODY

In this review, we describe the state of the art and the unmet needs in HGSOC management, illustrate the treatment options that are available and the biomarkers that are currently employed to orient clinical decisions. We also describe the ongoing clinical trials that are testing new therapeutic approaches for HGSOC. Next, we introduce the organoid technology as a promising, expanding strategy to study cancer and to develop personalized therapeutic approaches. In particular, we discuss recent studies that have characterized the translational potential of Patient's Derived Organoids (PDOs) to inform on drug sensitivity of HGSOC patients.

CONCLUSIONS

PDOs can predict the response of patients to treatments and may therefore guide therapeutic decisions. Although preliminary results appear encouraging, organoids still need to be generated and expanded efficiently to enable drug screening in a clinically meaningful time window. A new generation of clinical trials based on the organoid technology should guarantee tailored approaches to ovarian cancer management, as it is now clear that the one-size-fits-all approach cannot lead to efficient and meaningful therapeutic advancements.

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Onda T, Tanaka YO, Kitai S, Manabe T, Ishikawa M, Hasumi Y, Miyamoto K, Ogawa G, Satoh T, Saito T, Kasamatsu T, Nakanishi T. Stage III disease of ovarian, tubal and peritoneal cancers can be accurately diagnosed with pre-operative CT. Japan Clinical Oncology Group Study JCOG0602. Jpn J Clin Oncol 2021;51:205-212. [PMID: 33556170 DOI: 10.1093/jjco/hyaa145] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 08/11/2020] [Indexed: 11/14/2022] Open

Abstract

PURPOSE

Computed tomography of the abdomen and pelvis is a useful imaging modality for identifying origin and extent of ovarian cancer before primary debulking surgery. However, the International Federation of Gynecology and Obstetrics staging for ovarian cancer is determined based on surgico-pathological findings. The purpose of this study is to determine whether computed tomography staging can be the surrogate for surgico-pathological International Federation of Gynecology and Obstetrics staging in advanced ovarian cancer undergoing neoadjuvant chemotherapy.

METHODS

Computed tomography staging was compared with surgico-pathological International Federation of Gynecology and Obstetrics staging in primary debulking surgery arm patients in a randomized controlled trial comparing primary debulking surgery and neoadjuvant chemotherapy (JCOG0602). The cancer of primary debulking surgery arm was identically diagnosed regarding the origin and extent with the cancer of neoadjuvant chemotherapy arm before accrual, using imaging studies (computed tomography and/or magnetic resonance imaging), cytological examination (ascites, pleural effusion or tumor contents fluid) and tumor marker (CA125 > 200 U/mL and CEA < 20 ng/mL). Institutional computed tomography staging was also compared with computed tomography staging by central review.

RESULTS

Among 149 primary debulking surgery arm patients, 147 patients who underwent primary debulking surgery immediately were analyzed. Positive predictive values and sensitivity of computed tomography staging for surgical stage III disease (extra-pelvic peritoneal disease and/or retroperitoneal lymph node metastasis) were 99%. Meanwhile, positive predictive values for the presence of small (≤2 cm) extra-pelvic peritoneal disease were low; <20% in omentum. Accuracy of institutional computed tomography staging was comparable with computed tomography staging by central review.

CONCLUSIONS

Preoperative computed tomography staging in each institution can be the surrogate for surgico-pathological diagnosis in stage III disease of ovarian cancer patients undergoing neoadjuvant chemotherapy without diagnostic surgery, but reliability of diagnosis of stage IIIB disease is inadequate.Clinical trial registration: UMIN000000523(UMIN-CTR).

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Coleridge SL, Bryant A, Kehoe S, Morrison J. Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev 2021;2:CD005343. [PMID: 33543776 PMCID: PMC8094177 DOI: 10.1002/14651858.cd005343.pub5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Abstract

BACKGROUND

Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery.

OBJECTIVES

SEARCH METHODS

We searched the following databases on 11 February 2019: CENTRAL, Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information.

SELECTION CRITERIA

DATA COLLECTION AND ANALYSIS

Two review authors independently extracted data and assessed risk of bias in each included trial.

MAIN RESULTS

We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; Hazard Ratio (HR) 0.95, 95% CI 0.84 to 1.07; I2 = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 0.97, 95% CI 0.87 to 1.07; I2 = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred.

AUTHORS' CONCLUSIONS

The available moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT may reduce the risk of serious adverse events, especially those around the time of surgery, and the need for bowel resection and stoma formation. These data will inform women and clinicians and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

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Moschetta M, Boussios S, Rassy E, Samartzis EP, Funingana G, Uccello M. Neoadjuvant treatment for newly diagnosed advanced ovarian cancer: where do we stand and where are we going? ANNALS OF TRANSLATIONAL MEDICINE 2020;8:1710. [PMID: 33490222 PMCID: PMC7812234 DOI: 10.21037/atm-20-1683] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Nishio S, Ushijima K. Clinical significance of primary debulking surgery and neoadjuvant chemotherapy-interval debulking surgery in advanced ovarian cancer. Jpn J Clin Oncol 2020;50:379-386. [PMID: 32083282 DOI: 10.1093/jjco/hyaa015] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/18/2019] [Accepted: 01/25/2020] [Indexed: 11/15/2022] Open

Ogasawara A, Sato S, Hasegawa K. Current and future strategies for treatment of ovarian clear cell carcinoma. J Obstet Gynaecol Res 2020;46:1678-1689. [PMID: 32578333 DOI: 10.1111/jog.14350] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 05/23/2020] [Indexed: 01/04/2023]

Rethinking Radical Surgery in Interval Debulking Surgery for Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy. J Clin Med 2020;9:jcm9041235. [PMID: 32344611 PMCID: PMC7231092 DOI: 10.3390/jcm9041235] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/13/2020] [Accepted: 04/22/2020] [Indexed: 01/11/2023] Open

Onda T, Satoh T, Ogawa G, Saito T, Kasamatsu T, Nakanishi T, Mizutani T, Takehara K, Okamoto A, Ushijima K, Kobayashi H, Kawana K, Yokota H, Takano M, Kanao H, Watanabe Y, Yamamoto K, Yaegashi N, Kamura T, Yoshikawa H. Comparison of survival between primary debulking surgery and neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers in phase III randomised trial. Eur J Cancer 2020;130:114-125. [PMID: 32179446 DOI: 10.1016/j.ejca.2020.02.020] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 02/05/2020] [Accepted: 02/09/2020] [Indexed: 11/24/2022]

Abstract

BACKGROUND

Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS).

METHODS

Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300.

FINDINGS

Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour <1 cm) was achieved in 37% (55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum albumin ≤2·5, CA125 > 2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS.

INTERPRETATION

The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied.

FUNDING

Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan.

CLINICAL TRIAL INFORMATION

UMIN000000523.

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Affiliation(s)

Takashi Onda Department of Gynecology, Kitasato University School of Medicine, Sagamihara, Japan.
Toyomi Satoh Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
Gakuto Ogawa JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
Toshiaki Saito Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
Takahiro Kasamatsu Department of Gynecologic Oncology, National Cancer Center Hospital, Tokyo, Japan
Toru Nakanishi Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
Tomonori Mizutani JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
Kazuhiro Takehara Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
Kimio Ushijima Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan
Hiroaki Kobayashi Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Kei Kawana Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
Harushige Yokota Department of Gynecology, Saitama Cancer Center, Kita Adachi Gun, Japan
Masashi Takano Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Japan
Hiroyuki Kanao Department of Gynecological Oncology, Cancer Institute Hospital, Tokyo, Japan
Yoh Watanabe Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osakasayama, Japan
Kaichiro Yamamoto Department of Obstetrics and Gynecology, Faculty of Medicine, Kindai University, Sakai Hospital, Sakai, Japan
Nobuo Yaegashi Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan
Toshiharu Kamura Medical Care Education Research Foundation, Yanagawa Hospital, Yanagawa, Japan
Hiroyuki Yoshikawa Ibaraki Prefectural Central Hospital, Kasama, Japan

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Lee YJ, Kim HS, Rim JH, Lee JY, Nam EJ, Kim SW, Kim S, Kim YT. Germline BRCA, chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer. BMC Cancer 2020;20:185. [PMID: 32131779 PMCID: PMC7057666 DOI: 10.1186/s12885-020-6688-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 02/27/2020] [Indexed: 12/14/2022] Open

Coleridge SL, Bryant A, Lyons TJ, Goodall RJ, Kehoe S, Morrison J, Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev 2019;2019:CD005343. [PMID: 31684686 PMCID: PMC6822157 DOI: 10.1002/14651858.cd005343.pub4] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]

Abstract

BACKGROUND

OBJECTIVES

SEARCH METHODS

SELECTION CRITERIA

DATA COLLECTION AND ANALYSIS

Two review authors independently extracted data and assessed risk of bias in each included trial.

MAIN RESULTS

We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.94 to 1.19, I2 = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 1.02; 95% CI 0.92 to 1.13, I2 = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred.

AUTHORS' CONCLUSIONS

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Brown J, Drury L, Crane EK, Anderson WE, Tait DL, Higgins RV, Naumann RW. When Less Is More: Minimally Invasive Surgery Compared with Laparotomy for Interval Debulking After Neoadjuvant Chemotherapy in Women with Advanced Ovarian Cancer. J Minim Invasive Gynecol 2019;26:902-909. [DOI: 10.1016/j.jmig.2018.09.765] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 09/07/2018] [Accepted: 09/07/2018] [Indexed: 12/21/2022]

Davidson BA, Broadwater G, Crim A, Boccacio R, Bixel K, Backes F, Previs RA, Salinaro J, Salani R, Moore K, Secord AA. Surgical complexity score and role of laparoscopy in women with advanced ovarian cancer treated with neoadjuvant chemotherapy. Gynecol Oncol 2019;152:554-559. [DOI: 10.1016/j.ygyno.2018.12.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 12/10/2018] [Accepted: 12/10/2018] [Indexed: 10/27/2022]

Chen M, Chen Z, Xu M, Liu D, Liu T, He M, Yao S. Impact of the Time Interval from Neoadjuvant Chemotherapy to Surgery in Primary Ovarian, Tubal, and Peritoneal Cancer Patients. J Cancer 2018;9:4087-4091. [PMID: 30410613 PMCID: PMC6218782 DOI: 10.7150/jca.26631] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 08/02/2018] [Indexed: 12/26/2022] Open

Lee YJ, Lee IH, Kim YJ, Chung YS, Lee JY, Nam EJ, Kim S, Kim SW, Kim YT. Evaluation of various kinetic parameters of CA-125 in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy. PLoS One 2018;13:e0203366. [PMID: 30188915 PMCID: PMC6126869 DOI: 10.1371/journal.pone.0203366] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 08/20/2018] [Indexed: 11/18/2022] Open

Lee YJ, Chung YS, Lee JY, Nam EJ, Kim SW, Kim S, Kim YT. Impact of increased utilization of neoadjuvant chemotherapy on survival in patients with advanced ovarian cancer: experience from a comprehensive cancer center. J Gynecol Oncol 2018;29:e63. [PMID: 29770632 PMCID: PMC5981113 DOI: 10.3802/jgo.2018.29.e63] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 04/01/2018] [Accepted: 04/06/2018] [Indexed: 12/29/2022] Open

Lee YJ, Chung YS, Lee JY, Nam EJ, Kim SW, Kim S, Kim YT. Impact of the time interval from completion of neoadjuvant chemotherapy to initiation of postoperative adjuvant chemotherapy on the survival of patients with advanced ovarian cancer. Gynecol Oncol 2018;148:62-67. [DOI: 10.1016/j.ygyno.2017.11.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 11/13/2017] [Accepted: 11/17/2017] [Indexed: 02/09/2023]

Sakurai M, Matsumoto K, Gosho M, Sakata A, Hosokawa Y, Tenjimbayashi Y, Katoh T, Shikama A, Komiya H, Michikami H, Tasaka N, Akiyama-Abe A, Nakao S, Ochi H, Onuki M, Minaguchi T, Yoshikawa H, Satoh T. Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism. Int J Gynecol Cancer 2017;27:37-43. [PMID: 27755234 PMCID: PMC5181121 DOI: 10.1097/igc.0000000000000848] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 08/18/2016] [Accepted: 08/24/2016] [Indexed: 12/04/2022] Open

Affiliation(s)

Manabu Sakurai Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Koji Matsumoto Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Masahiko Gosho Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Akiko Sakata Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Yoshihiko Hosokawa Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Yuri Tenjimbayashi Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Takashi Katoh Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Ayumi Shikama Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Haruna Komiya Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Hiroo Michikami Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Nobutaka Tasaka Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Azusa Akiyama-Abe Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Sari Nakao Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Hiroyuki Ochi Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Mamiko Onuki Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Takeo Minaguchi Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Hiroyuki Yoshikawa Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan
Toyomi Satoh Faculty of Medicine, Departments of *Obstetrics and Gynecology and †Clinical Trial and Clinical Epidemiology, and ‡Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan

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Biswal BM, Yusoff Z. Application of Nanotechnology in Cancer Treatment. ENGINEERING APPLICATIONS OF NANOTECHNOLOGY 2017. [DOI: 10.1007/978-3-319-29761-3_11] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]

Onda T, Satoh T, Saito T, Kasamatsu T, Nakanishi T, Nakamura K, Wakabayashi M, Takehara K, Saito M, Ushijima K, Kobayashi H, Kawana K, Yokota H, Takano M, Takeshima N, Watanabe Y, Yaegashi N, Konishi I, Kamura T, Yoshikawa H. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. Eur J Cancer 2016;64:22-31. [PMID: 27323348 DOI: 10.1016/j.ejca.2016.05.017] [Citation(s) in RCA: 164] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 04/14/2016] [Accepted: 05/16/2016] [Indexed: 11/26/2022]

Abstract

BACKGROUND

We conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS.

METHODS

Patients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523).

RESULTS

Between November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively).

CONCLUSION

Our findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017.

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Affiliation(s)

Takashi Onda Department of Gynecology, Kitasato University School of Medicine, Japan.
Toyomi Satoh Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Japan
Toshiaki Saito Gynecology Service, National Kyushu Cancer Center, Japan
Takahiro Kasamatsu Department of Gynecologic Oncology, National Cancer Center Hospital, Japan
Toru Nakanishi Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Japan
Kenichi Nakamura JCOG Data Center/Operations Office, National Cancer Center, Japan
Masashi Wakabayashi JCOG Data Center/Operations Office, National Cancer Center, Japan
Kazuhiro Takehara Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Japan
Motoaki Saito Department of Obstetrics and Gynecology, Jikei University Hospital, Japan
Kimio Ushijima Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan
Hiroaki Kobayashi Department of Obstetrics and Gynecology, Kyushu University Hospital, Japan
Kei Kawana Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Japan
Harushige Yokota Department of Gynecologic Oncology, Saitama Cancer Center, Japan
Masashi Takano Department of Obstetrics and Gynecology, National Defense Medical College, Japan
Nobuhiro Takeshima Department of Gynecologic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan
Yoh Watanabe Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Japan
Nobuo Yaegashi Department of Obstetrics and Gynecology, Tohoku University Hospital, Japan
Ikuo Konishi Department of Obstetrics and Gynecology, Kyoto University Hospital, Japan
Toshiharu Kamura Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan
Hiroyuki Yoshikawa Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Japan

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Iwase H, Takada T, Iitsuka C, Nomura H, Abe A, Taniguchi T, Takizawa K. Clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery in advanced ovarian cancer patients. J Gynecol Oncol 2015. [PMID: 26197771 PMCID: PMC4620367 DOI: 10.3802/jgo.2015.26.4.303] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open

Poonawalla IB, Lairson DR, Chan W, Piller LB, Du XL. Cost-Effectiveness of Neoadjuvant Chemotherapy versus Primary Surgery in Elderly Patients with Advanced Ovarian Cancer. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2015;18:387-395. [PMID: 26091592 DOI: 10.1016/j.jval.2015.01.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 01/13/2015] [Accepted: 01/26/2015] [Indexed: 06/04/2023]

Abstract

BACKGROUND

The use of neoadjuvant chemotherapy (NAC) in the treatment of advanced ovarian cancer has increased in recent years. There is uncertainty about NAC's effectiveness and no study of its cost-effectiveness compared with that of standard primary debulking surgery (PDS).

OBJECTIVES

To seek answers to three important questions: 1) What is the lifetime cost of treating elderly patients with advanced ovarian cancer, based on the primary treatment received? 2) Are the extra costs expended by the NAC group worth any extra survival advantage? 3) Would NAC potentially benefit a particular subgroup and serve as a cost-effective first-line treatment approach?

METHODS

A cohort of elderly women (≥65 years) with stage III/IV ovarian cancer was identified from the Surveillance, Epidemiology and End Results-Medicare linked database from January 1, 2000, to December 31, 2009. Cost analysis was conducted from a payer perspective, and direct medical costs incurred by Medicare were integrated for each patient. Cumulative treatment costs were estimated with a phase-of-care approach, and effectiveness was measured as years of survival. Incremental cost-effectiveness ratio (ICER) and propensity-score-adjusted net monetary benefit regression was used to estimate the cost-effectiveness of NAC per life-year gained. Analyses were further stratified by risk group categorization on the basis of tumor stage, patient age, and comorbidity score.

RESULTS

Average lifetime cost for treatment with NAC was $17,417 more than with PDS. With only 0.1 incremental life-year gained, the ICER estimate was $174,173. Stratification, however, helped to delineate the treatment effect. Patients in the high-risk subgroup incurred $34,390 and 0.8 life-years more than did patients in the PDS subgroup, with a corresponding ICER of $42,987. In the non-high-risk subgroup, NAC use was dominated by PDS (more costly, less effective).

CONCLUSIONS

Administering NAC before surgery to patients in the high-risk subgroup was cost-effective at "normal" levels of willingness to pay, but not for the overall sample or for patients in the non-high-risk subgroup.

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Sakurai M, Satoh T, Matsumoto K, Michikami H, Nakamura Y, Nakao S, Ochi H, Onuki M, Minaguchi T, Yoshikawa H. High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor Extension. Int J Gynecol Cancer 2015;25:593-8. [PMID: 25756402 PMCID: PMC4406979 DOI: 10.1097/igc.0000000000000415] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 01/14/2015] [Accepted: 01/21/2015] [Indexed: 11/25/2022] Open

Onda T, Yoshikawa H. Neoadjuvant chemotherapy for advanced ovarian cancer: overview of outcomes and unanswered questions. Expert Rev Anticancer Ther 2014;11:1053-67. [DOI: 10.1586/era.11.24] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]

Clinical trials of neoadjuvant chemotherapy for ovarian cancer: what do we gain after an EORTC trial and after two additional ongoing trials are completed? Curr Oncol Rep 2013;15:197-200. [PMID: 23504482 DOI: 10.1007/s11912-013-0313-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]

Tangjitgamol S, Hanprasertpong J, Cubelli M, Zamagni C. Neoadjuvant chemotherapy and cytoreductive surgery in epithelial ovarian cancer. World J Obstet Gynecol 2013;2:153-166. [DOI: 10.5317/wjog.v2.i4.153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 02/06/2013] [Indexed: 02/05/2023] Open

Abstract

Ovarian cancer is one of the leading causes of death among gynecological cancers. This is because the majority of patients present with advanced stage disease. Primary debulking surgery (PDS) followed by adjuvant chemotherapy is still a mainstay of treatment. An optimal surgery, which is currently defined by leaving no gross residual tumor, is the goal of PDS. The extent of disease as well as the operative setting, including the surgeon’s skill, influences the likelihood of successful debulking. With extensive disease and a poor chance of optimal surgery or high morbidity anticipated, neoadjuvant chemotherapy (NACT) prior to primary surgery is an option. Secondary surgery after induction chemotherapy is termed interval debulking surgery (IDS). Delayed PDS or IDS is offered to patients who show some clinical response and are without progressive disease. NACT or IDS has become more established in clinical practice and there are numerous publications regarding its advantages and disadvantages. However, data on survival are limited and inconsistent. Only one large randomized trial could demonstrate that NACT was not inferior to PDS while the few randomized trials on IDS had inconsistent results. Without a definite benefit of NACT prior to surgery over PDS, one must carefully weigh the chances of safe and successful PDS against the morbidity and risks of suboptimal surgery. Appropriate selection of a patient to undergo PDS followed by chemotherapy or, preferably, to have NACT prior to surgery is very important. Some clinical characteristics from physical examination, serum tumor markers and/or findings from imaging studies may be predictive of resectability. However, no specific features have been consistently identified in the literature. This article will address the clinical data on prediction of surgical outcomes, the role of NACT, and the role of IDS.

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van Meurs HS, Tajik P, Hof MH, Vergote I, Kenter GG, Mol BWJ, Buist MR, Bossuyt PM. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. Eur J Cancer 2013;49:3191-201. [DOI: 10.1016/j.ejca.2013.06.013] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Revised: 06/11/2013] [Accepted: 06/13/2013] [Indexed: 10/26/2022]

Comparison of Platinum-based Neoadjuvant Chemotherapy and Primary Debulking Surgery in Patients with Advanced Ovarian Cancer. J Obstet Gynaecol India 2013;63:405-9. [PMID: 24431688 DOI: 10.1007/s13224-013-0425-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Accepted: 07/09/2013] [Indexed: 10/26/2022] Open

Kemp Z, Ledermann JA. Update on first-line treatment of advanced ovarian carcinoma. Int J Womens Health 2013;5:45-51. [PMID: 23378788 PMCID: PMC3558307 DOI: 10.2147/ijwh.s30231] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open

Morrison J, Haldar K, Kehoe S, Lawrie TA. Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev 2012;2012:CD005343. [PMID: 22895947 PMCID: PMC4050358 DOI: 10.1002/14651858.cd005343.pub3] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Abstract

BACKGROUND

Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment is to perform surgery first and then give chemotherapy. However, it is not yet clear whether there are any advantages to using chemotherapy before surgery.

OBJECTIVES

To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before cytoreductive surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows maximal cytoreductive surgery.

SEARCH METHODS

For the original review we searched, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006), MEDLINE (Silver Platter, from 1966 to 1 Sept 2006), EMBASE via Ovid (from 1980 to 1 Sept 2006), CANCERLIT (from 1966 to 1 Sept 2006), PDQ (search for open and closed trials) and MetaRegister (most current search Sept 2006). For this update randomised controlled trials (RCTs) were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2011) and the Cochrane Gynaecological Cancer Specialised Register (2011), MEDLINE (August week 1, 2011), EMBASE (to week 31, 2011), PDQ (search for open and closed trials) and MetaRegister (August 2011).

SELECTION CRITERIA

RCTs of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery.

DATA COLLECTION AND ANALYSIS

Data were extracted by two review authors independently, and the quality of included trials was assessed by two review authors independently.

MAIN RESULTS

One high-quality RCT met the inclusion criteria. This multicentre trial randomised 718 women with stage IIIc/IV ovarian cancer to NACT followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (670 women; HR 0.98; 95% CI 0.82 to 1.18) or progression-free survival (PFS) (670 women; HR 1.01; 95% CI 0.86 to 1.17).Significant differences occurred between the NACT and PDS groups with regard to some surgically related serious adverse effects (SAE grade 3/4) including haemorrhage (12 in NACT group vs 23 in PDS group; RR 0.50; 95% CI 0.25 to 0.99), venous thromboembolism (none in NACT group vs eight in PDS group; RR 0.06; 95% CI 0 to 0.98) and infection (five in NACT group vs 25 in PDS group; RR 0.19; 95% CI 0.07 to 0.50). Quality of life (QoL) was reported to be similar for the NACT and PDS groups.Three ongoing RCTs were also identified.

AUTHORS' CONCLUSIONS

We consider the use of NACT in women with stage IIIc/IV ovarian cancer to be a reasonable alternative to PDS, particularly in bulky disease. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account resectability, age, histology, stage and performance status. These results cannot be generalised to women with stage IIIa and IIIb ovarian cancer; in these women, PDS is the standard. We await the results of three ongoing trials, which may change these conclusions.

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Fujiwara K, Katsumata N, Onda T. Dose-dense chemotherapy and neoadjuvant chemotherapy for ovarian cancer. Am Soc Clin Oncol Educ Book 2012:349-54. [PMID: 24451762 DOI: 10.14694/edbook_am.2012.32.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]

Onda T, Konishi I, Yoshikawa H, Kamura T. The history of the Gynecologic Cancer Study Group (GCSG) of the Japan Clinical Oncology Group (JCOG). Jpn J Clin Oncol 2011;41:1156-61. [PMID: 21890655 DOI: 10.1093/jjco/hyr111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open

Weinberg LE, Rodriguez G, Hurteau JA. The role of neoadjuvant chemotherapy in treating advanced epithelial ovarian cancer. J Surg Oncol 2010;101:334-43. [PMID: 20187069 DOI: 10.1002/jso.21482] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Begum FD, Høgdall E, Christensen IJ, Kjaer SK, Blaakaer J, Christensen L, Høgdall C. Serum tetranectin is a significant prognostic marker in ovarian cancer patients. Acta Obstet Gynecol Scand 2010;89:190-8. [PMID: 20121334 DOI: 10.3109/00016340903530936] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]

Srivastava MK, Sinha P, Clements VK, Rodriguez P, Ostrand-Rosenberg S. Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 2009;70:68-77. [PMID: 20028852 DOI: 10.1158/0008-5472.can-09-2587] [Citation(s) in RCA: 707] [Impact Index Per Article: 44.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Onda T, Yoshikawa H, Yasugi T, Matsumoto K, Taketani Y. The optimal debulking after neoadjuvant chemotherapy in ovarian cancer: proposal based on interval look during upfront surgery setting treatment. Jpn J Clin Oncol 2009;40:36-41. [PMID: 19820253 DOI: 10.1093/jjco/hyp127] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open

Onda T, Yoshikawa H. A phase III randomized trial comparing neoadjuvant chemotherapy and upfront debulking surgery is indispensable as a basis for changing the standard treatment of advanced Müllerian cancer. Gynecol Oncol 2009. [DOI: 10.1016/j.ygyno.2009.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]

Krasner C, Duska L. Management of women with newly diagnosed ovarian cancer. Semin Oncol 2009;36:91-105. [PMID: 19332244 DOI: 10.1053/j.seminoncol.2008.12.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Onda T, Kobayashi H, Nakanishi T, Hatae M, Iwasaka T, Konishi I, Shibata T, Fukuda H, Kamura T, Yoshikawa H. Feasibility study of neoadjuvant chemotherapy followed by interval debulking surgery for stage III/IV ovarian, tubal, and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206. Gynecol Oncol 2009;113:57-62. [DOI: 10.1016/j.ygyno.2008.12.027] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2008] [Revised: 12/17/2008] [Accepted: 12/20/2008] [Indexed: 11/16/2022]