Less advanced disease at initiation of salvage androgen deprivation therapy is associated with decreased mortality following biochemical failure post-salvage radiation therapy

BACKGROUND: The optimal clinical context for initiation of salvage androgen deprivation therapy (SADT) following the biochemical recurrence of localized prostate cancer remains controversial. We chose to investigate if disease burden at time of SADT initiation is associated with clinical outcomes following biochemical failure (BF) post-salvage radiation therapy (SRT). METHODS: Medical records of 575 patients receiving SRT at a single institution from 1986–2010 were retrospectively reviewed. Of 250 patients experiencing BF post-SRT, 172 had a calculable prostate-specific antigen doubling time (PSADT) prior to SADT initiation. These patients comprise the analyzed cohort and were divided into four groups based on characteristics at SADT initiation: those with PSADTs >3 months without distant metastasis (DM) (group 1 [less advanced disease], n = 62), those with PSADTs <3 months without DM (group 2 [more advanced disease], n = 28), those with DM (group 3 [more advanced disease], n = 32), and those not receiving SADT during follow-up (group 4, n = 50). Endpoints included prostate cancer-specific mortality (PCSM) and overall mortality (OM). Kaplan-Meier methods were used to estimate survival, and Cox proportional hazards models were used for multivariate analysis. RESULTS: Median follow-up post-SRT was 7.9 years. Patients starting SADT with more advanced disease were at significantly increased risk for PCSM (hazard ratio [HR]:2.8, 95% confidence interval [CI]: 1.4–5.6, p = 0.005) and OM (HR:1.9, 95% CI: 1.0–3.5, p = 0.04) compared to those receiving SADT with less advanced disease. PCSM and OM did not significantly differ between groups 1 and 4 or groups 2 and 3. Of note, patients in group 4 had very long PSADTs (median = 27.0 months) that were significantly longer than those of group 1 (median = 6.0 months) (p < 0.001). Multivariate analysis including groups 1–3 found a pre-SADT PSADT <3 months to be the most significant predictor of PCSM (HR:4.2, 95% CI: 1.6–11.1, p = 0.004) and the only significant predictor of OM (HR:2.9, 95% CI: 1.3–6.7, p = 0.01). CONCLUSIONS: Less advanced disease at initiation of SADT is associated with decreased PCSM and OM following BF post-SRT; however, observation may be reasonable for patients with very long PSADTs. A PSADT <3 months prior to SADT initiation significantly predicts an increased risk of PCSM and OM in this patient demographic.