ASCO 2017: Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients

Chicago, IL (UroToday.com) Dr. David Yang and colleagues presented results from their study assessing patients with low PSA and high Gleason score prostate cancer as a unique hormone-resistant entity with poor survival at the prostate cancer poster sessions at the ASCO 2017 annual meeting. This is an understudied area and the outcomes of these patients are poorly described. The objective of this study was to examine the prognostic and predictive value of a low PSA in high-grade prostate cancer.

To perform this study, the authors used the National Cancer Database (n=491,505) and Surveillance, Epidemiology, and End Results program (n=151,470) to identify 642,975 patients with localized or locally advanced prostate cancer from 2004-2013. Men were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox proportional regression models were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. There were 5.6% of patients with Gleason 8-10 tumors diagnosed with a PSA ≤2.5 ng/mL. Using PSA 4.1-10.0 ng/mL among men with Gleason 8-10 disease as a referent, the adjusted hazard ratio AHR was 1.75 (95%CI 1.05-2.92) for PSA ≤2.5 ng/mL, compared to AHR 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively. Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95%CI 1.18-3.14; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA > 2.5 ng/mL (AHR 0.87, 95%CI 0.81-0.94) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95%CI 0.89-1.81, P = 0.194; PADT*PSA interaction= 0.026). In contrast, PCSM for Gleason ≤7 disease had an AHR of 0.32 (95%CI 0.10-1.00) for PSA ≤2.5 ng/mL vs. AHR of 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL (PGleason*PSA interaction< 0.001), respectively. This is a provocatively designed study with strong methodology and a large sample size. 

The authors conclude that low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Although prospective trials are warranted, based on these results these young patients should be considered for chemotherapy, novel systemic agents and/or clinical trials.

Presented By: David D. Yang, MD, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, USA

Co-Authors: Brandon Arvin Virgil Mahal, Christopher Sweeney, Quoc-Dien Trinh, Felix Yi-Chung Feng, Paul L. Nguyen

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
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