"Older clinical trials had shown that for men with localized prostate cancer, immediate radiotherapy (after surgery) reduced the risk of cancer coming back. But they had not conclusively shown that it improved longer term outcomes; in addition, we now have more sensitive tests that can pick up the return of cancer earlier," coauthor Dr. Clare Vale of University College Hospital, London, UK, told Reuters Health by email.
"This meant up until now, clinicians were uncertain whether giving radiotherapy immediately following surgery offered patients better outcomes than delaying radiotherapy until there was an indication of the cancer progressing," she said.
In the past week, three teams have reported on randomized trials looking at the timing of radiotherapy after surgery (https://bit.ly/3l9xyts in The Lancet, and https://bit.ly/36zmPEx and https://bit.ly/30Cotl3 in The Lancet Oncology).
"We worked with the trial investigators to plan the ARTISTIC meta-analysis, and to bring the results of the trials together in the most efficient way to answer this question for clinicians and patients," Dr. Vale said. "Our results showed that there is no evidence that immediate radiotherapy delays the cancer coming back compared with delayed ('early salvage') radiotherapy. However, adopting the early salvage approach means that many men can be spared radiotherapy and its potential side effects."
"At the moment, clinical guidelines on treating men with localized prostate cancer vary in their guidance," she added. "But we think the evidence is now clear that early salvage radiotherapy should be recommended following surgery for prostate cancer in these men."
By collaborating with the trialists using the prospective framework for adaptive meta-analysis (FAME) approach, Dr. Vale and colleagues were able to anticipate when results would emerge and develop a protocol to analyze them.
The team obtained updated results for event-free survival for 2,153 patients recruited between 2007-2016. Median follow-up ranged from 60 months to 78 months, with a maximum of 132 months. A total of 1,075 patients were randomly assigned to receive adjuvant radiotherapy and 1,078 to early salvage radiotherapy, of whom 421 (39.1%) had started treatment at the time of analysis.
Patient characteristics were similar overall and within trials: median age was about 64-65 and most (77.6%) had a Gleason score of 7. The trials had a low risk of bias. The definition of event-free survival was from the time of randomization until either biochemical progression (prostate-specific antigen of at least 0.4 ng/mL and rising after completion of any postoperative radiation); clinical or radiological progression; initiation of a non-trial treatment; death from prostate cancer; or a PSA level of at least 2.0 ng/mL at any point after randomization.
Based on 270 events, the meta-analysis showed no evidence that adjuvant radiation improved five-year event-free survival compared with early salvage radiation (89% vs. 88%; hazard ratio, 0.95). Results were consistent across trials.
The authors state, "Results of the collaborative ARTISTIC meta-analysis provide greater evidence on the effects of radiotherapy timing than any of the individual trials alone...Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy as it offers the opportunity to spare many men radiotherapy and its associated side-effects."
Dr. Derya Tilki of University Hospital Hamburg-Eppendorf and Dr. Anthony D'Amico of Brigham and Women's Hospital and Dana Farber Cancer Institute in Boston, coauthors of an editorial published with the meta-analysis, commented by email. "While the studies support the use of early salvage as opposed to adjuvant radiotherapy for many patients after radical prostatectomy, they did not contain an adequate number of men to assess timing of radiotherapy in men with adverse pathology at radical prostatectomy."
Further, they told Reuters Health, "the PSA endpoint may not be a reliable measure of success, given that ADT (androgen deprivation therapy) use delays PSA failure. Also, PSA failure on the salvage arm could be delayed given that you can not assess for response during the delivery of salvage RT."
By Marilynn Larkin
SOURCE: https://bit.ly/36yZ6o1 and https://bit.ly/30wYvPW The Lancet, online September 28, 2020.
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