Dose Escalation Reduces Need for Salvage Therapy in Localized Prostate Cancer

The phase 3 NRG Oncology/RTOG 0126 trial compared the efficacy of standard and dose-escalated radiotherapy (RT) administered with 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT) for intermediate-risk prostate cancer (PCa). Long-term results of the trial were presented at the American Society for Radiation Oncology 2023 Annual Meeting.

Eligible patients had clinical stage T1b-T2b localized PCa and either Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) <20 or GS 7 and PSA <15. Patients were randomized to receive either 79.2Gy in 44 fractions or 70.2Gy in 39 fractions through 3DCRT/IMRT to the planning target volume encompassing the prostate and seminal vesicles.

The trial cohort included 1499 eligible patients, with 748 assigned to receive 79.2Gy and 751 assigned to receive 70.2Gy. The median cohort age was 71 years, and 70% of patients had PSA <10 ng/ml. A total of 84% of patients had GS 7, 57% had T1 disease, and 66% were treated with 3DCRT.

With a median follow-up of 12 years, no significant difference in overall survival (OS) was noted. In the 79.2Gy arm, there was a statistically significant decrease in the cumulative incidence of ABF, PBF, distant metastases (DM), local progression (LP), and salvage therapies. There were also significantly higher rates of grade 2 and higher gastrointestinal (GI) and genitourinary (GU) toxicity. No significant differences were seen in the rates of grade 3 and higher GI or GU toxicity between either arm.

Long-term follow-up confirmed there was no improvement in OS with dose escalation in this study population, but significant improvements occurred in ABF, PBF, DM, LP, and the need for salvage therapy. Patients receiving dose escalation experienced a higher rate of grade 2 and higher GU and GI toxicities, but no grade 3 and higher toxicities. While the low-dose arm required more salvage therapy, dose-escalated RT resulted in lower rates of DM.