Men being treated for prostate cancer who are at higher risk of dying as a result of treatment failure can be identified prior to PSA recurrence using a surrogate endpoint, according to a study published in JAMA Oncology.
Prostate cancer is one of the leading causes of death for men in the US. Identifying patients’ mortality risk is important in order to determine which men may benefit from more aggressive treatments for prostate cancer. Although several surrogates for mortality have been identified for patients with prostate cancer, it is unknown whether they are appropriate surrogates for all-cause mortality nor how they compare to one another.
Trevor J Royce, MD, MS, Brigham and Women’s Hospital (Boston, MA), and colleagues studied 157 men who underwent radiation therapy alone or radiation therapy followed by 6-months of androgen deprivation therapy for localized unfavorable-risk prostate cancer and who had minimal comorbidities or no comorbidity (median follow-up, 16.49 months). They compared the performance of four potential surrogate endpoints for all-cause mortality: PSA failure; PSA nadir (the lowest level a PSA drops after treatment) > 0.5 ng/mL; PSA doubling time < 9 months; and interval PSA failure < 30 months.
Results of the study showed a PSA nadir value of > 0.5 ng/mL following radiation and androgen deprivation therapy identifies men prior to PSA failure who are at high-risk for death. PSA nadir > 0.5 ng/mL met all of the criteria for surrogacy for all-cause mortality (adjusted hazard ratio, 1.72; 95% CI, 1.17-2.52; P = .01), and the proportion of treatment effect value was 103.86%.
Interestingly, PSA failure was not a surrogate for all-cause mortality in the studied patients. This finding has potential implications for how such men should be managed at the time of PSA failure.
"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," said the study’s senior author Anthony Victor D'Amico, MD, PhD, Chief of Genitourinary Radiation Oncology, Brigham and Women's Hospital.
