Performance of a Genomic Classifier (GC) Within a Phase 3 Randomized Trial of Dose Escalated Salvage Radiotherapy (SRT) After Radical Prostatectomy (RP).

PURPOSE/OBJECTIVE(S) Presalvage PSA is an important prognostic and a predictive factor for salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) post-prostatectomy. GC can independently prognosticate prostate cancer outcomes and may help individualize treatment intervention. Herein, we assessed the role of the GC in patients treated within a contemporary phase 3 trial. MATERIALS/METHODS The SAKK 09/10 trial (NCT01272050) is an open-label, multicenter, randomized phase 3 trial performed in 24 centers in Switzerland, Germany, and Belgium. Patients with biochemical progression (PSA > 0.1 to 2 ng/mL at randomization) were randomized to 64 Gy vs 70 Gy to the prostate bed. No patients received ADT or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. GC score range is 0 to 1, with locked cut points of 0.6 for low, intermediate, and high, respectively. In this sub-analysis, the primary endpoint was freedom from biochemical progression (FFBP) according to PSA at randomization (≤0.5 vs > 0.5, a trial stratification variable). Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, and randomization arm were performed. Secondary endpoints included clinical progression-free survival (CPFS) and time to salvage ADT. RESULTS Of 233 patients with tissue available, 1 was ineligible and 6 failed QC. The remaining 226 were included for analysis with a median follow-up of 6.3 years (IQR 6.0-7.2). High- vs. low/intermediate-GC had an HR of 2.22 (95% CI 1.37-3.58, P = 0.001) for FFBP, 2.29 (95% CI 1.32-3.98, P = 0.003) for CPFS, and 2.99 (95% CI 1.50-5.95, P = 0.002) for use of salvage ADT. In patients with PSA ≤0.5 ng/mL (165/226, 73%), the 5-year FFBP was 74% [95% CI 66-82] for low-intermediate GC compared to 59% [95% CI 43-74] in patients with high-GC. High-GC patients had 5-year FFBP of 13% [95% CI 0-32] when SRT was delivered at PSA > 0.5 ng/mL compared to 59% [95% CI 43-74] when PSA ≤0.5 ng/mL. CONCLUSION In a contemporary phase 3 trial, patients with a high-GC were more than twice as likely than patients with low/intermediate-GC to experience biochemical and clinical progression and receive salvage ADT. High-GC patients who received SRT with PSA > 0.5 ng/mL had nearly 90% risk of recurrence by 5-years post-SRT. This data validates the clinical utility of the GC for tailoring treatment in the salvage setting.