Low testosterone at first PSA failure and assessment of the risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

Abstract

45 Background: Low testosterone at prostate cancer diagnosis has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at first PSA failure following definitive therapy and prior to the documentation of metastatic disease has not been elucidated and was studied. Methods: Between 1995 to 2001, 58 men with unfavorable-risk prostate cancer treated on clinical trials with radiation and androgen deprivation therapy (ADT) had testosterone levels at PSA failure available. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone at PSA failure was associated with the risk of prostate cancer-specific, other-cause and all-cause mortality (PCSM, OCM, ACM) adjusting for age, salvage ADT use and known prostate cancer prognostic factors. Results: After a median follow-up of 6.68 years following first PSA failure, 31 men (53.4%) died; 10 from prostate cancer (32.3%), of which 8/11 (72.7%) versus 2/47 (4.3%) occurred in men with low versus normal testosterone at PSA failure, respectively. A significant increase in the risk of ACM (adjusted hazard ratio, AHR [2.54, 95% CI 1.04-6.21]; P = 0.04) and PCSM (AHR [13.71, 95% CI 2.4-78.16]; P = 0.003), with a reciprocal trend toward decreased risk of OCM (AHR [0.18, 95% CI 0.02-1.55]; P = 0.12) was observed in men with low versus normal testosterone at first PSA failure. Conclusions: Low testosterone at first PSA failure confers a very poor prognosis. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic prostate cancer and possibly in men with localized high-risk prostate cancer provides rationale to support their use with ADT in men with low testosterone at PSA failure in the setting of a phase II trial.