A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high‐risk features: background and rationale of the Radiotherapy – Adjuvant Versus Early Salvage (RAVES) trial

Abstract

Objectives To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to ‘standard’ treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient‐reported outcomes, adverse events, biochemical failure‐free survival, overall survival, disease‐specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation. Patients and Methods The Radiotherapy – Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at ≤4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of >0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs ± extraprostatic extension ± seminal vesicle involvement. The postoperative PSA level must be ≤0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients. Results Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta‐analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho‐oncology sub‐study to investigate a patient decision aid resource. Conclusion On the current evidence available, it remains unclear if ART is equivalent or superior to observation with early SRT.

Management of Biochemical Recurrence after Primary Curative Treatment for Prostate Cancer: A Review

“…Two ongoing trials may help to guide practice in future: RADICALS aims to recruit approximately 3,000 men with PCa and will study the best way to use RT after RP, as well as the potential merits of additional ADT in this context; and RAVES will compare early sRT with aRT in men with pT3 disease and/or positive margins after RP [65]. …”

Knowledge, attitudes and beliefs towards management of men with locally advanced prostate cancer following radical prostatectomy: an Australian survey of urologists

“…The result is a perceived lack of evidence to support the benefit of adjuvant radiotherapy over selective early salvage radiotherapy. This direct comparison is the focus of two ongoing clinical trials (RAVES [40] and RADICALs [41]). Urologists also expressed concern about possible overtreatment for a significant proportion of patients whose cancer may never recur.…”

AUA/ASTRO 2013 Guidelines for Adjuvant and Salvage Radiation Therapy After Prostatectomy: What are the Yields and the Changes?

“…'nın çok merkezli eşleştirilmiş kontrollü olgu analizinde adjuvan RT uygulanan veya izlenip PSA düzeyi ≤0,5 ng/ml olduğunda salvaj RT uygulanan pT3N0 olgularda 60 aylık biyokimyasal nüks oranları arasında fark ortaya konamamıştır (adjuvan RT %78,4-salvaj RT %81,8; p=0,9) (27). Bu önemli soruyu cevaplamaya yönelik planlanan Radiotherapy and Combined Androgen Deprivation after Local Surgery (RADICALS), Radiotherapy Adjuvant vs Early Salvage following Radical Prostatectomy (RAVES) ve Groupe d'Etude des Tumeurs Uro-Genitalés (GETUG-17) çalışmalarının sonuçları merakla beklenmektedir (28,29). RADICALS çalışmasında doğrudan adjuvan ve salvaj RT ve ± androjen supresyon tedavisi (6 ay ve 24 ay) karşılaştırılmaktadır.…”