Top Line: Does moderate hypofractionation increase toxicity for postprostatectomy radiation?
The Study: While moderate hypofractionation is now common when treating intact prostate cancer, conventional fractionation is still considered the standard after prostatectomy. NRG GU003 was a randomized trial that sought to determine if hypofractionated postprostatectomy radiation resulted in non-inferior patient-reported GI and GU toxicity 2 years after treatment. It included 296 patients with a detectable PSA after prostatectomy (≥0.1 ng/mL) or undetectable PSA with pT3 disease or positive margins. The same prostate fossa target volume (RTOG consensus guidelines) and PTV margins were used in both arms, however elective lymph node RT was not permitted. Patients in the conventional arm received 66.6 Gy in 37 fractions, and patients in the hypofractionated arm received 62.5 Gy in 25 fractions. OAR constraints in the latter included rectum V36<55-60%, rectum V59<35-39%, bladder (minus CTV) V35<70-77%, bladder (minus CTV) V57<50-55%, and femoral heads V44<10-11%. At 2 years, there was no difference in patient-reported GU and GI symptoms between arms. At the end of radiation, patients in the hypofractionated arm reported more GI symptoms, but this resolved by 6 months and beyond. Treatment-related grade 3+ toxicity was low, and there was no difference between hypofractionation and conventional fractionation (9% v 6%). Freedom from biochemical failure at 2 years was also similar between groups (12.5% hypofrac, 8.6% conventional). This trial met its primary endpoint, but there will obviously be debate about how long is long enough follow up to feel comfortable that toxicity remains similar between arms. The same goes for long-term disease control and the coverage of elective pelvic lymph nodes with this regimen. Nevertheless, 62.5 Gy in 25 fractions to the prostate fossa appears to be a safe and effective option for postprostatectomy radiation.
TBL: In NRG GU003, there was no difference in patient-reported and clinician-reported toxicity at 2 years between moderate hypofractionation and conventional fractionation. | Buyyounouski, JAMA Oncol 2024
The Study: While moderate hypofractionation is now common when treating intact prostate cancer, conventional fractionation is still considered the standard after prostatectomy. NRG GU003 was a randomized trial that sought to determine if hypofractionated postprostatectomy radiation resulted in non-inferior patient-reported GI and GU toxicity 2 years after treatment. It included 296 patients with a detectable PSA after prostatectomy (≥0.1 ng/mL) or undetectable PSA with pT3 disease or positive margins. The same prostate fossa target volume (RTOG consensus guidelines) and PTV margins were used in both arms, however elective lymph node RT was not permitted. Patients in the conventional arm received 66.6 Gy in 37 fractions, and patients in the hypofractionated arm received 62.5 Gy in 25 fractions. OAR constraints in the latter included rectum V36<55-60%, rectum V59<35-39%, bladder (minus CTV) V35<70-77%, bladder (minus CTV) V57<50-55%, and femoral heads V44<10-11%. At 2 years, there was no difference in patient-reported GU and GI symptoms between arms. At the end of radiation, patients in the hypofractionated arm reported more GI symptoms, but this resolved by 6 months and beyond. Treatment-related grade 3+ toxicity was low, and there was no difference between hypofractionation and conventional fractionation (9% v 6%). Freedom from biochemical failure at 2 years was also similar between groups (12.5% hypofrac, 8.6% conventional). This trial met its primary endpoint, but there will obviously be debate about how long is long enough follow up to feel comfortable that toxicity remains similar between arms. The same goes for long-term disease control and the coverage of elective pelvic lymph nodes with this regimen. Nevertheless, 62.5 Gy in 25 fractions to the prostate fossa appears to be a safe and effective option for postprostatectomy radiation.
TBL: In NRG GU003, there was no difference in patient-reported and clinician-reported toxicity at 2 years between moderate hypofractionation and conventional fractionation. | Buyyounouski, JAMA Oncol 2024