Marker for prostate cancer death can identify need for more aggressive Tx

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A prostate specific antigen (PSA) nadir value of greater than 0.5 ng/mL following radiation and androgen deprivation therapy appears to identify men prior to PSA failure who are at high-risk for death.

Prostate cancer (PC) is the second leading cause of male cancer death in the US with an estimated 26,000 deaths in 2016. Two-thirds of all PC deaths observed in the US are men with localised disease who developed metastasis. Several markers for dying from prostate cancer exist, but whether these are markers for telling who is likely to die early from any cause, and how their performance compares, is unknown. Identifying such a marker is important because we can then identify which men may benefit from new, more aggressive treatments for prostate cancer.

Researchers at Brigham and Women’s Hospital found that a prostate specific antigen (PSA) nadir (the lowest level a PSA drops after treatment) greater than 0.5 ng/mL following radiation and androgen deprivation therapy (anti-hormone therapy), appears to identify men prior to PSA failure who are at high-risk for dying early as a result of treatment failure for their prostate cancer.

“By identifying and enrolling these men in clinical trials immediately, the hope is to take a prostate cancer that appears to be incurable and make it curable” stated Dr Trevor J Royce, senior resident in the department of radiation oncology at BWH, and corresponding author of the study.

Using data from a randomised trial of 206 men treated with either radiation or, radiation and six months of hormonal therapy, researchers compared early markers of prostate cancer death to identify men at risk of dying early.

“This study’s results can have practice changing implications on how future prostate cancer trials are designed in terms of identifying the men for these studies who are at high risk for early death due to ineffective initial treatment for their prostate cancer,” stated Dr Anthony Victor D’Amico, chief, genitourinary radiation oncology, Brigham and Women’s Hospital and senior author of the study.


Importance: Several surrogates for prostate cancer–specific mortality satisfying the Prentice criteria exist, but whether these are surrogates for all-cause mortality, and how their performance compares, is unknown.
Objective: To ascertain and compare the performance of 4 candidate surrogates (prostate-specific antigen [PSA] failure, PSA nadir >0.5 ng/mL, PSA doubling time Design, Setting, and Participants: For this randomized clinical trial, 206 men with unfavorable-risk prostate cancer who were seen at a Harvard-affiliated academic hospital or an associated community hospital between December 1, 1995, to April 15, 2001, were identified, randomized to radiation therapy alone or radiation therapy followed by 6 months of androgen deprivation therapy, and followed for a median 16.62 years. This analysis looks at the subgroup of 157 men with minimal comorbidities or no comorbidity (median follow-up, 16.49 months).
Interventions: Patients were previously randomized to receive radiation therapy or radiation and 6 months of androgen deprivation therapy.
Main Outcomes and Measures: Risk of all-cause mortality.
Results: Overall, a cohort of 157 men (median [interquartile range] age, 72.43 [68.75-75.53]) with unfavorable-risk prostate cancer and minimal or no comorbidities were selected for this study. Three tested metrics met all 4 Prentice criteria for surrogacy for the surrogate covariate in the adjusted model for all-cause mortality: PSA nadir greater than 0.5 ng/mL (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.17-2.52; P = .01), PSA doubling time less than 9 months (aHR, 2.06; 95% CI, 1.29-3.28; P = .003), and interval to PSA failure less than 30 months (aHR, 1.76; 95% CI, 1.06-2.92; P = .03); while PSA failure did not. For the 3 successful surrogates, the proportion of treatment effect values were 103.86%, 43.09%, and 41.26%, respectively.
Conclusions and Relevance: A PSA nadir value of greater than 0.5 ng/mL following radiation and androgen deprivation therapy appears to identify men prior to PSA failure who are at high-risk for death. This could be used to select men for entry at the time of PSA nadir onto randomized trials evaluating the impact on survival of salvage androgen deprivation therapy with or without agents shown to prolong survival in men with castrate-resistant metastatic prostate cancer.

Trevor J Royce; Ming-Hui Chen; Jing Wu; Marian Loffredo; Andrew A Renshaw; Philip W Kantoff; Anthony V D’Amico

Brigham and Womens Hospital material
JAMA Oncology abstract

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