Purpose: To determine whether prostate-specific antigen (PSA) measurement after initiation of androgen deprivation therapy (ADT) but prior to the start of radiotherapy (RT) pPSA is an independent predictor of biochemical relapse-free survival (bRFS). We also sought to determine the effect, if any, of factors affecting bRFS for patients who did not achieve pPSA<0.5. ng/mL. Methods and materials: A total of 105 patients with National Comprehensive Cancer Network intermediate- or high-risk prostate cancer treated with neoadjuvant ADT (median = 3.9. mo) and external beam RT had pPSA data available and met the inclusion criteria. Pretreatment and treatment characteristics were included in a Cox proportional hazards model to determine effect on bRFS. Results: Median follow-up was 5.4 years. On multivariable analysis, pPSA≥0.5. ng/mL was associated with worsened bRFS (hazard ratio [HR] = 2.7, P = 0.013). For the subgroup of patients with at most 1 high-risk factor, pPSA remained a statistically significant prognostic factor. For patients within this subgroup who had pPSA≥0.5. ng/mL, the addition of pelvic RT was associated with a trend toward improved outcome (HR = 0.609, P = 0.083). Conclusion: For patients with intermediate- or high-risk prostate cancer receiving neoadjuvant ADT, achieving pPSA<0.5. ng/mL was associated with improved rates of bRFS. Additionally, pPSA measurement may identify patients who may be able to benefit from escalated treatment such as pelvic RT. © 2014 Elsevier Inc.