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Calım Gurbuz B, Devecioglu Gursen EG, Ugur R, Kulac I, Ertoy Baydar D. Letter to the Editor Regarding "Primary Well-Differentiated Neuroendocrine Tumor/Carcinoid of the Prostate: Case Report and Review of Literature". Int J Surg Pathol 2025:10668969241308203. [PMID: 39773221 DOI: 10.1177/10668969241308203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Affiliation(s)
- Begum Calım Gurbuz
- Department of Pathology, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | | | - Ramazan Ugur
- Department of Urology, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Ibrahim Kulac
- Department of Pathology, Koc University School of Medicine, Istanbul, Turkey
| | - Dilek Ertoy Baydar
- Department of Pathology, Koc University School of Medicine, Istanbul, Turkey
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Alhamar M, Sethi S, Reuter VE, Fine SW. Primary Well-Differentiated Neuroendocrine Tumor/Carcinoid of the Prostate: Case Report and Review of Literature. Int J Surg Pathol 2024; 32:1374-1378. [PMID: 38303155 PMCID: PMC11808340 DOI: 10.1177/10668969241228297] [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: 02/03/2024]
Abstract
Primary well-differentiated neuroendocrine tumor (WDNT)/carcinoid of the genitourinary tract is rare. Many WDNT reported in the prostate gland have been seen in close association with conventional prostatic adenocarcinoma and/or label for prostate-specific immunohistochemical markers and are best considered prostatic adenocarcinomas with "carcinoid-like" features. We present a case of primary WDNT/carcinoid incidentally detected in a 67-year-old man who underwent radical prostatectomy for Grade group 2 prostatic adenocarcinoma. Morphologically, the neuroendocrine (NE) lesion appeared distinct from the prostatic adenocarcinoma, labeled for NE markers, was negative for prostatic markers (NKX3.1, PSA, and ERG), and showed an overall low Ki-67 proliferation index (<1%). Follow-up was uneventful with no evidence of residual disease or metastasis.
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Affiliation(s)
- Mohamed Alhamar
- Department of Pathology & Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Shenon Sethi
- Department of Pathology & Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Victor E Reuter
- Department of Pathology & Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Samson W Fine
- Department of Pathology & Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Butler W, Huang J. Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms. PRECISION CLINICAL MEDICINE 2021; 4:25-34. [PMID: 33842835 PMCID: PMC8023015 DOI: 10.1093/pcmedi/pbab003] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 01/23/2021] [Accepted: 01/24/2021] [Indexed: 12/12/2022] Open
Abstract
Prostate cancer (PCa) is a common cause of cancer-related mortality in men worldwide. Although most men are diagnosed with low grade, indolent tumors that are potentially curable, a significant subset develops advanced disease where hormone therapy is required to target the androgen receptor (AR). Despite its initial effect, hormone therapy eventually fails and the tumor progresses to lethal stages even through continued inhibition of AR. This review article focuses on the role of PCa cellular heterogeneity in therapy resistance and disease progression. Although AR-positive luminal-type cells represent the vast majority of PCa cells, there exists a minor component of AR-negative neuroendocrine (NE) cells that are resistant to hormonal therapy and are enriched by the treatment. In addition, it is now well accepted that a significant subset of hormonally treated tumors recur as small cell neuroendocrine carcinoma (SCNC), further highlighting the importance of targeting NE cells in addition to the more abundant luminal-type cancer cells. Although it has been long recognized that NE cells are present in PCa, their underlying function in benign prostate and molecular mechanisms contributing to PCa progression remains poorly understood. In this article, we review the morphology and function of NE cells in benign prostate and PCa as well as underlying molecular mechanisms. In addition, we review the major reported mechanisms for transformation from common adenocarcinoma histology to the highly lethal SCNC, a significant clinical challenge in the management of advanced PCa.
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Affiliation(s)
- William Butler
- Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Jiaoti Huang
- Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
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Rodriguez Pena MDC, Salles DC, Epstein JI, Canete-Portillo S, Tregnago AC, Ramirez J, Meliti A, Netto GJ. Well-differentiated neuroendocrine tumors of the lower urinary tract: biologic behavior of a rare entity. Hum Pathol 2020; 109:53-58. [PMID: 33301750 DOI: 10.1016/j.humpath.2020.11.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 11/30/2020] [Indexed: 11/25/2022]
Abstract
The spectrum of neuroendocrine (NE) tumors in the genitourinary tract ranges from the aggressive large and small cell carcinomas to the often benign paraganglioma and well-differentiated neuroendocrine tumor (WD-NET). At least 15 pure lower urinary tract (LUT) WD-NETs have been described. Owing to the rarity of WD-NET in the LUT and the limited number of reported cases, a better definition of their biologic long-term behavior is warranted. Herein, we aim to describe 10 new cases of WD-NET arising in the LUT and expand on follow-up findings. Ten consultation cases were identified and included 6 men and 4 women who ranged from 45 to 73 years of age. Seven cases arose in the bladder with one located in the bladder neck, 1 arose in the prostatic urethra, 1 arose in the female urethra, and 1 arose in the left ureteral orifice. All lesions were confined to the lamina propria, and tumor architecture was pseudoglandular in all cases. Associated cystitis cystica et glandularis was identified in 5 cases; urothelial papilloma and florid von Brunn's nests were found in 2 additional cases. Immunohistochemical staining for synaptophysin and chromogranin was diffusely positive in 9 cases and focal in 1 case, and the Ki-67 proliferation index was 5% or less in all tumors. Follow-up ranged from 37 to 137 months (mean = 82; median = 77), and there was no evidence of residual disease or recurrence in any of the 10 patients during the follow-up period.
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Affiliation(s)
- Maria Del Carmen Rodriguez Pena
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA
| | - Daniela C Salles
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA
| | - Jonathan I Epstein
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA
| | - Sofia Canete-Portillo
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA
| | - Aline C Tregnago
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA
| | - July Ramirez
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA
| | - Abdelrazak Meliti
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA
| | - George J Netto
- Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
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Shehabeldin AN, Ro JY. Neuroendocrine tumors of genitourinary tract: Recent advances. Ann Diagn Pathol 2019; 42:48-58. [DOI: 10.1016/j.anndiagpath.2019.06.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 06/15/2019] [Indexed: 01/25/2023]
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Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate. Oncotarget 2019; 10:17-29. [PMID: 30713600 PMCID: PMC6343754 DOI: 10.18632/oncotarget.26523] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 12/10/2018] [Indexed: 12/21/2022] Open
Abstract
Background Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited. Methods Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017. Results Of 46 identified patients 39.1 % had a prior diagnosis of prostatic adenocarcinoma only, 43.5 % had a mixed differentiation at NEPC diagnosis, 67.4 % developed visceral metastases, 10.9 % showed paraneoplastic syndromes. Overall survival (OS) from NEPC diagnosis was 15.5 months, and significantly shorter in patients with a prior prostatic adenocarcinoma (5.4 vs. 32.7 months, p=0.005). 34 patients received palliative first-line systemic therapy with a median progression-free survival (PFS) of 6.6 months, mostly PE. Overall response rate (ORR) for PE was 48.1 %. 19 patients received second-line therapy, mostly with poor responses. Active regimens were topotecan (1 PR, 3 PD), enzalutamide (1 SD), abiraterone (1 SD), FOLFIRI (1 SD), and ipilimumab+nivolumab (1 PR). One patient with prostatic carcinoid was sequentially treated with octreotide, peptide receptor radionuclide therapy and everolimus, and survived for over 9 years. Conclusions EP in first-line shows notable ORR, however limited PFS. For second-line therapy, topotecan, FOLFIRI, enzalutamide, abiraterone and immune checkpoint blockade are treatment options. Prostatic carcinoids can be treated in analogy to well differentiated gastrointestinal NETs.
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Yossi S, Brahmi T, Enachescu C, Selmaji I, Lapierre A, Samlali H, Chapet O. [Management of neuroendocrine prostate carcinoma: Literature review]. Cancer Radiother 2016; 20:330-5. [PMID: 27340027 DOI: 10.1016/j.canrad.2016.02.013] [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: 12/20/2015] [Revised: 02/02/2016] [Accepted: 02/24/2016] [Indexed: 10/21/2022]
Abstract
Neuroendocrine prostate carcinoma is a rare entity causing both diagnostic and therapeutic issues. There are basically four histological forms (adenocarcinoma with neuroendocrine differentiation, carcinoid tumors, small cell neuroendocrine carcinomas, large cell neuroendocrine carcinomas), which can be pure or mixed associated with prostatic carcinoma. There is no consensus on the management or the prognosis of these various tumor subtypes. We conducted a literature review aiming to determine the potential therapeutic implications.
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Affiliation(s)
- S Yossi
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France.
| | - T Brahmi
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France
| | - C Enachescu
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France
| | - I Selmaji
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; Département de radiothérapie, CHU de Marrakech, Marrakech, Maroc
| | - A Lapierre
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France
| | - H Samlali
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; Département de radiothérapie, CHU de Casablanca, Casablanca, Maroc
| | - O Chapet
- Département de radiothérapie, CHU Lyon Sud, 195, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France
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Priemer DS, Montironi R, Wang L, Williamson SR, Lopez-Beltran A, Cheng L. Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification. Endocr Pathol 2016; 27:123-35. [PMID: 26885643 DOI: 10.1007/s12022-016-9421-z] [Citation(s) in RCA: 52] [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: 01/30/2023]
Abstract
Neuroendocrine neoplasms of the prostate represent a multifarious group of tumors that exist both in pure forms and associated with prostatic adenocarcinoma. Morphologically, neuroendocrine cells in prostate neoplasms can range from being indistinguishable from surrounding prostate adenocarcinoma cells to having high-grade neuroendocrine appearances similar to neuroendocrine malignancies of other organs. On the molecular level, neuroendocrine malignancies arising in the setting of prostate adenocarcinoma have been the subject of a large amount of recent research, most of which has supported the conclusion that neuroendocrine malignancy within the prostate develops as a transdifferentiation from prostate adenocarcinoma. There has not, however, been substantial investigation into rare, pure neuroendocrine malignancies and the possibility that these tumors may have a different cell of origin and molecular genesis. Here, we discuss the morphologic spectrum of malignant neuroendocrine prostate neoplasms and review the most recent molecular data on the subject of malignant neuroendocrine differentiation in prostatic adenocarcinoma. In reflection of the most recent data, we also discuss diagnostic classification of prostate neuroendocrine tumors with reference to the 2016 World Health Organization (WHO) classification. We discuss the reporting of these tumors, placing emphasis on the differentiation between pure and mixed neuroendocrine malignancies so that, in the least, they can be easily identified for the purposes of future clinical and laboratory-based investigation. Finally, we suggest a designation for an unclassifiable (or not otherwise specified) high-grade neuroendocrine prostate malignancy whose features do not easily place it into one of the WHO diagnostic entities.
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Affiliation(s)
- David S Priemer
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IU Health Pathology Laboratory Room 4010, Indianapolis, IN, 46202, USA
| | - Rodolfo Montironi
- Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy
| | - Lisha Wang
- Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Sean R Williamson
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA
- Josephine Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA
- Wayne State University School of Medicine, Detroit, MI, USA
| | - Antonio Lopez-Beltran
- Department of Surgery, Faculty of Medicine, Cordoba University, Cordoba, Spain
- Champalimaud Clinical Center, Lisbon, Portugal
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IU Health Pathology Laboratory Room 4010, Indianapolis, IN, 46202, USA.
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
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Dagur G, Warren K, Singh N, Khan SA. Detecting diseases of neglected seminal vesicles using imaging modalities: A review of current literature. Int J Reprod Biomed 2016. [DOI: 10.29252/ijrm.14.5.293] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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10
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Adeniran AJ, Humphrey PA. Morphologic Updates in Prostate Pathology. Surg Pathol Clin 2015; 8:539-60. [PMID: 26612214 DOI: 10.1016/j.path.2015.08.002] [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: 10/22/2022]
Abstract
In the past several years, modifications have been made to the original Gleason system with resultant therapeutic and prognostic implications. Several morphologic variants of prostatic adenocarcinoma have also been described. Prostate pathology has also evolved over the years with the discovery and utility of new immunohistochemical stains. The topics discussed in this update include the Gleason grading system, prognostic grade grouping, variants of prostatic adenocarcinoma, and the application of immunohistochemistry to prostate pathology.
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Affiliation(s)
- Adebowale J Adeniran
- Department of Pathology, Yale University School of Medicine, 310 Cedar Street, LH 108, New Haven, CT 06520, USA.
| | - Peter A Humphrey
- Department of Pathology, Yale University School of Medicine, 310 Cedar Street, LH 108, New Haven, CT 06520, USA
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He HQ, Fan SF, Xu Q, Chen ZJ, Li Z. Diagnosis of prostatic neuroendocrine carcinoma: Two cases report and literature review. World J Radiol 2015; 7:104-109. [PMID: 26029353 PMCID: PMC4444603 DOI: 10.4329/wjr.v7.i5.104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2015] [Revised: 04/07/2015] [Accepted: 04/30/2015] [Indexed: 02/07/2023] Open
Abstract
Two cases of prostatic neuroendocrine carcinoma (PNEC) imaged by computed tomography (CT) and magnetic resonance imaging (MRI), and literature review are presented. Early enhanced CT, MRI, especially diffusion-weighted image were emphasized, the complementary roles of ultrasound, CT, MRI, clinical and laboratory characteristic’s features in achieving accurate diagnosis were valued in the preoperative diagnosis of PNEC.
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12
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Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol 2014; 38:756-67. [PMID: 24705311 DOI: 10.1097/pas.0000000000000208] [Citation(s) in RCA: 405] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.
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Arenas Reyes NJ, Manuel Moreno LA, Carrillo Rodríguez AP, Fonseca Buitrago CL, Pompilio Daza Almendrales F. Diferenciación neuroendocrina en cáncer de próstata. Revisión de la literatura. UROLOGÍA COLOMBIANA 2014. [DOI: 10.1016/s0120-789x(14)50007-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Review of small cell carcinomas of the prostate. Prostate Cancer 2011; 2011:543272. [PMID: 22110988 PMCID: PMC3200299 DOI: 10.1155/2011/543272] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2011] [Revised: 05/16/2011] [Accepted: 05/30/2011] [Indexed: 12/21/2022] Open
Abstract
Small cell carcinoma of the prostate is a rare neoplasm, with only a few series hitherto reported. A little less than half of the cases are associated with conventional acinar adenocarcinoma, which are usually high grade. Although consensus has not been reached, the majority of patients with small cell neuroendocrine carcinoma of the prostate have advanced disease at diagnosis and disproportionally low PSA levels compared to patients with conventional acinar adenocarcinoma. Treatment consists mainly of chemotherapy associated with surgery. Radiation therapy is reserved for selected cases. This study reviews the most up-to-date information on small cell carcinomas of the prostate.
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