Whole-Pelvis Radiotherapy for High-Risk Prostate Cancer

Susan London

January 11, 2021

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

"A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, 'Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?' " said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

"A lot of effort has gone into trying to answer this question," he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study's final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).

Efficacy and Toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial's primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.

Explaining the Results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Murthy.

"We had a much higher-risk group," he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, "we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction," Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

"Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation," Murthy summarized. "There is no overall survival difference as of yet, but that remains to be seen."

"Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer," he concluded.

Practice-Changing Findings

"Overall, I'm very impressed with this study," commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. "The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also."

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

"I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT," Lawton said. "The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes."

"I agree with the authors' conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT," she concluded. "The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment."

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Murthy disclosed no conflicts of interest. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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