Prospective Study Evaluating Postoperative Radiotherapy Plus 2-year Androgen Suppression for Post-radical Prostatectomy Patients with PT3 and/or Positive Surgical Margins

Abstract

To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a Phase II study. Patients were assigned into 2 groups: Group 1: undetectable postoperative PSA (<0.2 ng/mL), and Group 2: persistently detectable postoperative PSA. AS started within 1 month after the completion of RT, and consisted of nilutamide for 4 weeks and buserelin acetate depot (LHRH analogue) subcutaneously every 2 months for 2 years. Relapse-free rate including the freedom from PSA relapse was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate predictive factors for relapse. A PSA relapse was defined as a PSA rise above 0.2 with two consecutive increases over a minimum of 3 months. The first date of these two consecutive PSA increases above 0.2 was regarded as the date of PSA relapse. Median age was 62 years at the time of RT. Median interval between RP and postoperative RT was 4.2 months. 49 patients were in Group 1 and 29 in Group 2. Median RT dose was 60 Gy for Group 1 and 66 Gy for Group 2 with 2 Gy/fraction. The RT was delivered with a 4-field technique and 18 MV photons. 61 patients completed 2-year AS, while 17 had a shorter duration of AS (median: 12 months). Distribution of Gleason score (GS) was: 6: 7: 8-10 = 10%: 64%: 26%. 36% had pT2, 32% with pT3a, and 32% with pT3b-T4. 85% had PSM. Group 2, in comparison with Group 1, had more patients with GS 8-10 (38% vs. 18%) and pre-RP PSA >10 (59% vs. 35%). Median pre-RT PSA for Group 2 was 1.2. Median follow-up from RT was 6.4 years. Actuarial relapse-free rates including the freedom from PSA relapse for the entire cohort were 94% at 5 years and 90% at 7 years. Relapse-free rate was much higher in Group 1 than Group 2 (100% vs. 85% at 5 years; 98% vs. 68% at 7 years). Actuarial survival rates for entire cohort were 96% at 5 years and 93% at 7 years. At the time of their last follow-up, only 1 in Group 1 had recurrence with PSA relapse alone, while 7 in Group 2 had recurrence (6 with PSA relapse alone, and 1 with distant metastasis). None had local recurrence. 4 died of other causes with none from prostate cancer. Significant predictors for relapse were Group 2 (vs. Group 1) and pT3b-4 in univariate analysis; only Group 2 (vs. Group 1) in multivariate model. The combined treatment of postoperative RT plus 2-year AS yielded an encouraging result for patients with pT3 and/or PSM after RP. Persistently detectable postoperative PSA and pT3b-T4 were associated with a higher risk of relapse.