Platinum sensitivity in metastatic prostate cancer: Does histology matter?

Michael S. Humeniuk, Rajan T. Gupta, Patrick Healy, Megan McNamara, Sundhar Ramalingam, Michael Harrison, Daniel George, Tian Zhang, Yuan Wu, Andrew J. Armstrong

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. Methods: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent. Data surrounding clinical features, histology, imaging, safety, and neuroendocrine transformation were collected. Scans were re-reviewed using RECIST v1.1 criteria to estimate responses as well as calculate radiographic progression-free survival (rPFS). Results: A database search identified 73 men with mCRPC treated with cisplatin, carboplatin, or oxaliplatin. There were three men with primary NEPC and small cell prostate cancer, and 14 with a NEPC transformation. In the first-line setting, 10 (63%) men with NEPC had a partial response (PR) compared with 14 (29%) of the men with adenocarcinoma (p = 0.017), with a median rPFS of 5.1 mo (3.1-7.8) and 4.3 mo (3.0-5.2 mo), respectively. The median overall survival was 8.5 mo (6.4-20.1 mo) for men with NEPC compared to 10.0 mo (8.0-14.4) in men with adenocarcinoma. Prostate-specific antigen (PSA) declines meeting >30%, >50%, and >90% criteria from baseline were observed in 64/57/29% of NEPC patients (n = 14) treated with platinum chemotherapy vs. 48/30/14% of men with prostate adenocarcinoma (n = 50), respectively. Conclusions: This study suggests that NEPC histology enriches for platinum sensitivity, but that an important minority group (20-30%) of men with adenocarcinoma have a clinical benefit with platinum-based chemotherapy. Molecular predictors, such as germline or somatic mutations in DNA repair enzymes, should be evaluated for platinum responsiveness.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalProstate Cancer and Prostatic Diseases
Volume21
Issue number1
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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