Prostate-Only vs Whole-Pelvic Radiation Therapy in High-Risk and Very High–Risk Prostate Cancer

Expansion of the field of treatment to include the pelvic lymph nodes among patients with clinically organ-confined prostate cancer at risk for nodal metastases has been well-established in the surgical literature. Among patients pathologically proven to have nodal positivity, a therapeutic lymphadenectomy cures 20% to 30%. Considerations for including the nodal basins in high-risk patients undergoing external beam radiotherapy makes intuitive sense. Questions remain whether a survival advantage exists and whether bowel-related toxicity increases with the expanded field of treatment. In this phase III randomized controlled study out of Mumbai, India, the authors report on the outcomes of prostate-only versus whole-pelvis radiotherapy in a very high–risk group of patients. Among a group of patients with a median PSA value of 28 and a calculated nodal risk of greater than 20% based upon the Roach formula, 222 men were randomized in a study opened in 2011 and completing enrollment in 2017. All were treated with concomitant androgen deprivation therapy for a minimum of 2 years. Interestingly, 80% were staged with PSMA-PET prior to initiation of treatment. The primary endpoint was biochemical failure–free survival at 5 years, with secondary endpoints of disease-free and overall survival. Overall, whole-pelvis treatment was associated with statistically improved survival for biochemical and disease-free outcomes at a median follow-up time of 68 months. No significant differences were seen in 5-year overall survival; however, improvements were noted in distant metastasis–free survival for whole-pelvis treatment. No statistically greater risk of grade 2 bowel toxicity was reported (8.2% vs 4.5%; P = .28). These data serve as a reasonable foundation to consider prophylactic radiotherapy in the very high–risk patients. Its role among unfavorable intermediate-risk and favorable/unfavorable high-risk patients remains to be seen.

To treat the pelvis or not to treat the pelvis remained controversial in the upfront management of men with high-risk prostate cancer in the aftermath of GETUG-01 and RTOG 9413. How refreshing it is to have the modern data from the randomized POP-RT trial. The two most important differences in terms of patients selected into this trial, compared with older trials, are the focus on high- and very high–risk disease and the use of advanced imaging (80% had PSMA-PET) for accurate staging. Over half (52%) of recurrences in the prostate-only radiotherapy (PORT) arm were in the pelvis versus just 12.5% with whole-pelvic radiotherapy (WPRT). That resulted in a significant improvement in 5-year biochemical failure–free survival from 82% to 95%. Pelvic RT also improved 5-year disease-free survival from 77.2% to 89.5%. With this trial nicely capturing and describing the relatively favorable toxicity profile, these results argue for adding back pelvic radiotherapy for these men.