Three randomized trials and a meta-analysis of the trials failed to show a significant effect of adjuvant radiotherapy on biochemical progression or combined clinical events after radical prostatectomy for early, high-risk prostate cancer.
In the largest of the three trials, salvage radiotherapy was associated with a 3% absolute advantage for biochemical progression-free survival (bPFS) at 5 years, although the difference did not reach statistical significance. One of the smaller trials showed absolute difference in bPFS of 1% at 6 years in favor of salvage therapy, whereas the other showed a nonsignificant 2% higher event-free survival (EFS) with salvage radiotherapy.
The meta-analysis, which included 2,153 randomized patients, yielded a 5-year EFS of 89% with adjuvant radiotherapy and 88% with salvage therapy, also not significant.
The largest of the trials and the meta-analysis were published simultaneously in the Lancet, and the two smaller trials in the Lancet Oncology.
Collectively, the trials had some limitations and potential confounders that left the door open for a beneficial effect of adjuvant radiotherapy in selected patients, according to the authors of an accompanying commentary. For example, one of the randomized trials included patients who normally would skip radiotherapy because of low clinical risk, while another trial had a potential time bias for assessment of bPFS after salvage radiotherapy. Also, use of hormonal therapy varied.
“Nonetheless, the four studies represent an important step forward and support the use of early salvage as opposed to adjuvant radiotherapy for many patients after radical prostatectomy, with the possible exception of those at high risk for progression…which comprised less than 20% of men in the three randomized trials, and for whom shared patient and clinician decision making should be considered,” wrote Derya Tilki, MD, of University Hospital Hamburg-Eppendorf in Germany, and Anthony V. D’Amico, MD, PhD, of Dana Farber Cancer Institute in Boston.
Follow-up continues in the RADICALS-RT randomized trial, which has a primary endpoint of metastasis-free survival. However, as previously reported, the analysis of bPFS showed no significant benefit with adjuvant radiotherapy. The trial included 1,396 patients with localized prostate cancer associated with at least one high-risk characteristic (pathologic T-stage 3 or 4, Gleason score 7-10, positive surgical margins, or preoperative PSA ≥10 ng/mL).
All patients underwent radical prostatectomy and were randomized to early adjuvant radiotherapy or to a watch-and-wait strategy of salvage irradiation. In the adjuvant group, radiation therapy was delivered within 6 months in 93% of patients, whereas a third of patients in the salvage group received radiotherapy within 8 years of surgery.
The 5-year bPFS was 85% with adjuvant therapy and 88% with salvage therapy, representing a nonsignificant 10% increase in the risk of biochemical progression in the adjuvant group (95% CI 0.81-1.49, P=0.56). Additionally, adjuvant radiation therapy was associated with a higher incidence of urinary morbidity, reported Matthew R. Sydes, MD, of University College London, and colleagues.
Conducted in Australia and New Zealand, data analysis for the phase III RAVES trial included 333 patients with high-risk features. The trial had a