Research in context
Evidence before this study
When this study was under development in 2007, the use of adjuvant radiotherapy to the prostate bed after radical prostatectomy had been shown to halve the risk of biochemical progression when compared with observation for men with prostate cancer with high-risk features. Results of three randomised trials initiated between 1988 and 1996 supported the use of adjuvant radiotherapy (ARO 96-02/AUO AP 09/95; EORTC trial 2291; SWOG8794), with one of these studies also showing improved metastasis-free survival and overall survival. Despite this evidence, adjuvant radiotherapy has not been widely adopted due to concerns over perceived toxicity. A potential limitation of these three randomised trials is that there was no standard management for patients on observation who developed relapse. Salvage radiotherapy was given intermittently and at varying lengths of time after relapse, with some patients having documented locoregional progression before treatment. The results of the three studies were used to generate American and European guidelines, which recommend that such men be referred for consideration of adjuvant radiotherapy. Due to this broad acknowledgment of the three studies in the field of post-prostatectomy prostate cancer management, a systematic review was not done before the development of the RAVES trial. The recommendation to routinely administer adjuvant radiotherapy comes at the potential cost of increased morbidity. There is the possibility that observing these patients and delivering salvage radiotherapy when prostate-specific antigen (PSA) first starts to rise could have similar efficacy.
Added value of this study
This study confirmed that men with high-risk features have a rising PSA in more than 50% of cases following surgery when observed. Our results have shown similar high rates of disease-free survival at 5 years for both the early salvage and adjuvant radiotherapy groups. This outcome has been achieved with relatively modest radiation doses in the salvage radiotherapy group by treating relapse very early as soon as the PSA reaches 0·20 ng/mL. The study also documented an increase in genitourinary morbidity when radiotherapy is given to all patients in an adjuvant setting.
Implications of all the available evidence
These results are being released concurrently with the RADICALS and GETUG-17 trials, along with a pre-planned meta-analysis of all three trials. These trials have concordant results suggesting that adjuvant radiotherapy does not improve event-free survival in men with high-risk features following radical prostatectomy. It now appears preferable to wait until the cancer recurs, heralded by a PSA rising to 0·20 ng/mL, before commencing radiotherapy, which would spare many men from potential radiotherapy-related side-effects.