Toxicity and Biochemical Outcomes of Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Results of a Randomized Phase III Trial

Abstract

Our purpose was to compare toxicity and biochemical control in postprostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiation therapy. Patients who had stage pT3-4, positive surgical margins, or rising prostate-specific antigen ≥ 0.2 ng/mL after radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these 2 cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic toxicities between these 2 cohorts. bPFS was estimated by the Kaplan-Meier method and toxicities were compared using the χ2 test. Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range, 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs 82.6%; P = .299). However, in patients with a higher Gleason score (8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs 55.7%; P = .049). Toxicity analysis showed no difference in ≥2 acute or late GI or GU toxicities between these 2 cohorts. A total of 48 patients were scored as urinary incontinence before radiation therapy, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, and only 9 (18.8%) patients reported worsening. There was no difference between the 2 cohorts in urinary incontinence either at baseline or at 1-year follow-up. Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities and did not increase urinary incontinence.