Preliminary results from RADICALS-RT, the largest and latest trial examining the timing of postoperative radiation therapy (RT) in men with prostate cancer, support the use of early salvage RT rather than adjuvant RT. But investigators not involved with the study caution that these results are not definitive and adjuvant RT should not be abandoned.
For the study, Christopher C. Parker, MD, of the Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, and colleagues randomly assigned 1396 patients with adverse pathology (pT3-4, Gleason score 7-10, positive margins, or preoperative PSA of 10 ng/mL or more) to receive adjuvant RT or salvage RT. Of the 697 patients in the adjuvant RT group, 649 (93%) received RT within 6 months of randomization and 228 (33%) of the 699 patients in the salvage RT group underwent RT for biochemical recurrence within 8 years.
Biochemical progression-free survival rates at 5 years did not differ significantly between the adjuvant and salvage RT groups (85% vs 88%, respectively), the investigators reported in the Lancet. Additionally, the groups had similar freedom from non-protocol hormone therapy at 5 years (93% vs 92%, respectively).
With respect to adverse effects, adjuvant RT significantly increased the risk for urinary incontinence at 1 year (mean score 4.8 vs 4.0) and grade 3-4 urethral stricture within 2 years (6% vs 4%) compared with salvage RT.
“These findings strengthen the case for a policy of observation after radical prostatectomy, with early salvage radiotherapy reserved for use only in patients with PSA biochemical progression,” Dr Parker and his collaborators wrote. “Most individuals following such a policy will avoid the need for radiotherapy.” The investigators recommended early salvage RT as standard of care.
In an accompanying editorial, Derya Tilki, MD, of Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, in Hamburg, Germany, and Anthony V. D’Amico, MD, PhD, of Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, disagreed with abandoning adjuvant therapy. RADICALS-RT included patients who would not have received adjuvant RT in typical clinical practice because of their low risk of recurrence, the editorialists noted, such as those with a Gleason score of 3+4, pT2 disease, low preoperative PSA, and negative surgical margins. They argued that the cohort included many patients with favorable-risk disease and could be underpowered to detect any benefit from adjuvant RT. Half of the patients had Gleason 3+4 disease, whereas just 18% had seminal vesicle invasion, 17% had a Gleason score of 8-10, and 5% had lymph node involvement. Only a subset of trial participants were at high risk for progression (eg, Gleason score 8–10 and pT3b or higher). Additionally, Drs Tilki and D’Amico pointed out that among patients at high-risk, monitoring for PSA progression in the salvage RT group occurred later than in the adjuvant RT group due to trial design, possibly missing an adjuvant RT benefit due to immortal time bias.
“Pending longer follow-up of the RADICALS-RT study to evaluate the metastasis-free survival endpoint in high-risk subgroups, we believe it is prudent to consider adjuvant radiotherapy in these patients,” Drs Tilki and D’Amico wrote.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Parker CC, Clarke NW, Cook AD, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. doi:10.1016/S0140-6736(20)31553-1
Tilki D, D’Amico AV. Timing of radiotherapy after radical prostatectomy. Lancet. doi:10.1016/S0140-6736(20)31957-7