First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH.

ABSTRACT

PURPOSE: We aimed to study the associations between androgen-deprivation therapy (ADT)-induced weight changes and prostate cancer (PC) progression and mortality in men who had undergone radical prostatectomy (RP). METHODS: Data from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort were used to study the associations between weight change approximately 1-year post-ADT initiation and metastases, castration-resistant prostate cancer (CRPC), all-cause mortality (ACM), and PC-specific mortality (PCSM) in 357 patients who had undergone RP between 1988 and 2014. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) using covariate-adjusted Cox regression models for associations between weight loss, and weight gains of 2.3 kg or more, and PC progression and mortality post-ADT. RESULTS: During a median (IQR) follow-up of 81 (46-119) months, 55 men were diagnosed with metastases, 61 with CRPC, 36 died of PC, and 122 died of any cause. In multivariable analysis, weight loss was associated with increases in risks of metastases (HR 3.13; 95% CI 1.40-6.97), PCSM (HR 4.73; 95% CI 1.59-14.0), and ACM (HR 2.16; 95% CI 1.25-3.74) compared with mild weight gains of ≤ 2.2. Results were slightly attenuated but remained statistically significant in analyses that accounted for competing risks of non-PC death. Estimates for the associations between weight gains of ≥ 2.3 kg and metastases (HR 1.58; 95% CI 0.73-3.42), CRPC (HR 1.33; 95% CI 0.66-2.66), and PCSM (HR 2.44; 95% CI 0.84-7.11) were elevated, but not statistically significant. CONCLUSIONS: Our results suggest that weight loss following ADT initiation in men who have undergone RP is a poor prognostic sign. If confirmed in future studies, testing ways to mitigate weight loss post-ADT may be warranted.