Background
Phase III RCT (RAVES — Radiotherapy-Adjuvant Versus Early Salvage). 333 men with pT3 or R1 prostate cancer after radical prostatectomy randomized between 2009 and 2015 at 26 Australian and New Zealand centers. Compared adjuvant radiotherapy (given within 6 months of surgery regardless of PSA) vs early salvage RT (given at PSA rise ≥0.2 ng/mL). Median follow-up ~6.1 years.
Interventions and follow up
Arm A: Adjuvant radiotherapy 64 Gy in 32 fractions within 6 months of RP (n=166)
Arm B: Early salvage radiotherapy 66 Gy in 33 fractions at PSA ≥0.2 ng/mL (n=167)
Primary endpoint: Event-free survival (EFS: PSA ≥0.4 ng/mL rising, clinical recurrence, or death)
mFollow up: 6.1 year
Arm B: Early salvage radiotherapy 66 Gy in 33 fractions at PSA ≥0.2 ng/mL (n=167)
Primary endpoint: Event-free survival (EFS: PSA ≥0.4 ng/mL rising, clinical recurrence, or death)
mFollow up: 6.1 year
Results
EFS at 5 years: 86% (adjuvant RT) vs 87% (early salvage RT) — no significant difference
Late grade ≥2 GU toxicity: Significantly higher in adjuvant RT arm (58% vs 40%)
Late grade ≥2 GI toxicity: Numerically higher in adjuvant RT arm
Late grade ≥2 GU toxicity: Significantly higher in adjuvant RT arm (58% vs 40%)
Late grade ≥2 GI toxicity: Numerically higher in adjuvant RT arm
Adverse events
Main adverse events: Adjuvant RT arm had significantly more late urinary toxicity (grade ≥2 GU: 58% vs 40%, P=.003). Urinary incontinence and erectile dysfunction more common with adjuvant approach. Quality of life significantly worse in adjuvant RT arm.
Conclusions
Adjuvant radiotherapy and early salvage radiotherapy produced equivalent event-free survival outcomes in men with high-risk pathological features after radical prostatectomy. The early salvage approach was associated with significantly lower late urinary toxicity and better quality of life, supporting a policy of observation followed by salvage RT at PSA rise for most patients.
Key Limitations
Key Limitations: Non-inferiority design with relatively short median follow-up (6.1 years) — longer-term OS and metastasis data are pending. The PSA threshold for salvage RT in this trial (≥0.2 ng/mL) is higher than some current guidelines recommending initiation at 0.1 ng/mL. Neither arm included ADT, limiting generalizability to higher-risk patients. Study was underpowered for OS.
Clinical Context
RAVES, together with RADICALS-RT (Parker et al, Lancet 2020), shifted practice away from routine adjuvant RT and toward early salvage RT for pT3/R1 prostate cancer. Current AUA/ASTRO/EAU guidelines support observation with early salvage RT initiation at low PSA levels (<0.5 ng/mL) for most patients, reserving adjuvant RT for select highest-risk cases.
References
References: Kneebone A et al, IJROBP 2019 (ASTRO abstract)