Early adverse events and patient-reported outcomes after salvage radiotherapy following prostatectomy according to fractionation schedule: Interim analysis of the phase III URONCOR 06–24 trial

Background and purpose Moderate hypofractionation is increasingly used in salvage radiotherapy (SRT) after radical prostatectomy, although prospective data in the postoperative setting remain limited. We evaluated early adverse events and patient-reported outcomes (PROs) according to fractionation schedule within a prospective multicenter phase III trial. Materials and methods This prespecified interim analysis included the first 250 patients enrolled in the URONCOR 06–24 randomized trial (NCT05781217). SRT was delivered using moderate hypofractionation ( n = 175), most commonly 62.5 Gy in 25 fractions (80.5%), followed by 65.25 Gy in 29 fractions (7.5%), 60 Gy in 24 fractions (4.6%), and 52.5 Gy in 20 fractions (2.9%), corresponding to a biologically equivalent dose (EQ.D2) of approximately 65–71 Gy (α/β = 1.5), or conventional fractionation ( n = 75; 66–70 Gy in 33–35 fractions). Adverse events were assessed using CTCAE v5.0. PROs were evaluated using EPIC-26 and EORTC QLQ-C30 at baseline, 3, and 6 months. Results With a median follow-up of 12.7 months, grade ≥ 2 genitourinary (GU) adverse events occurred in 21.7% of patients treated with hypofractionation versus 17.3% with conventional fractionation ( p = 0.431). Grade ≥ 2 gastrointestinal (GI) adverse events occurred in 10.8% and 4.0%, respectively ( p = 0.079). Pelvic nodal irradiation was more frequent in the hypofractionation group (39.4% vs 13.3%, p = 0.001). On multivariable analysis, age was associated with increased risk of GU ≥2 adverse events, while pelvic nodal irradiation was associated with increased risk of GI ≥2 adverse events. No clinically meaningful differences were observed in PROs. Conclusion Early adverse events after SRT were low and comparable between fractionation schedules, and moderate hypofractionation showed a similar safety profile despite more frequent pelvic irradiation. However, given the non-randomized nature of the fractionation schedules, longer follow-up and robust adjustment for treatment-selection biases are needed before drawing definitive conclusions regarding comparative safety.