Research in context
Evidence before this study
When this study was conceived in 2003, there was no evidence to guide clinical decision making for the timing of intervention with androgen-deprivation therapy for men with prostate cancer who have a rising prostate-specific antigen (PSA) after unsuccessful curative therapy. For asymptomatic men with overt disease who are not considered for curative treatment, three randomised phase 3 trials were either completed or closed to accrual with data maturing, which were identified through the programmes of recognised collaborative trial groups. We surmised that there was insufficient published evidence available to support a systematic literature review. The MRC-UK trial of men with established locally advanced or metastatic disease suggested a benefit from early rather than delayed intervention, but the men given delayed intervention were perhaps not optimally managed. The two studies subsequently reported from the European Organisation for Research and Treatment of Cancer (EORTC 30891 and 30846) for men with loco-regional disease showed an inconclusive result for 30846, but 30891 suggested a benefit to early intervention.
Added value of this study
To our knowledge this is the first randomised trial to provide evidence of the impact of the timing of androgen-deprivation therapy in men with prostate cancer with a PSA relapse. It provides a benchmark for the survival rates of men diagnosed with this disease stage, which was not previously available, and indicates the effects on survival, disease progression, development of complications, toxicity of treatment, and quality of life. We plan to combine these data for men with PSA-relapse with the parallel Canadian ELAAT study to increase the strength of the evidence. The small number of men in the overt disease group of our trial precluded useful analysis of treatment-timing to add evidence to the three previous studies.
Implications of all the available evidence
Results from our randomised trial, combined with the evidence from other studies, add weight to the concept that early intervention in incurable disease, whether occult or overt, improves survival. We provide evidence to guide discussions with men with a PSA relapse as to their preferred treatment approach, with benchmarks for survival rates, morbidity rates, and quality of life for both immediate and delayed strategies.