Absolute Benefit of Androgen Deprivation Therapy With Radiotherapy for Localized Prostate Cancer

Objectives: To estimate the absolute benefit of adding and prolonging androgen deprivation therapy (ADT) to radiation therapy (RT) for men with localized prostate cancer by integrating cancer-specific risk, other-cause mortality (OCM) risk, and relative treatment efficacy. Subjects and Methods: Individualized risks were estimated by integrating cause-specific hazard estimates from a validated staging system (STAR-CAP) with those from a validated non-cancer mortality model (OCCAM). ADT treatment efficacy was then incorporated using published hazard ratio estimates from the MARCAP meta-analysis. Model utility was illustrated using the Prostate, Lung, Colon, and Ovarian (PLCO) cancer screening trial cohort (n=5468 prostate cancer patients with complete covariates). The primary outcome was the estimated 10-year absolute risk reduction (ARR) in distant metastasis (DM) from adding short-term ADT (STADT) to RT or extending STADT to long term ADT (LTADT). Results: Within PLCO, model estimated risk of DM at 10 years ranged from <1% to 56% under guideline concordant care and OCM risk ranged from 3% to 80% independent of treatment. For patients with NCCN unfavorable intermediate-risk (n=1814), adding STADT to RT reduced estimated 10 year DM risk by a median of 4%, but the ARR estimates for individuals ranged from <1% to almost 15%. Similar variation was seen within NCCN high-risk patients (n=1289) with a median ARR of 9% [Range: 0.4%-17.2%] when prolonging ADT treatment. Moreover, 25% of NCCN unfavorable intermediate-risk patients have less than a 2.4% ARR while 25% of NCCN high-risk patients experience less than a 5% ARR. Conclusion: An integrated model accounting for both prostate cancer aggressiveness and comorbidities demonstrates substantial heterogeneity in the estimated absolute benefit of ADT within conventional risk groups. This approach provides individualized estimates to support treatment discussions; external validation is needed before clinical implementation.