Background
Phase III, open-label, multicenter RCT (part of the RADICALS program). 1,396 patients with prostate cancer post-radical prostatectomy who had biochemical features suggesting possible incomplete resection or early relapse (PSA 0.1–2.0 ng/mL or specific pathological criteria including pT3/T4, positive surgical margins). RADICALS-RT addressed the long-standing uncertainty of whether adjuvant RT (given immediately after RP) is superior to early salvage RT (deferred until PSA rises).
Interventions and follow up
Arm A: Adjuvant radiotherapy — 66 Gy in 33 fractions or 52.5 Gy in 20 fractions, started within 6 months of RP when PSA <0.1 ng/mL
Arm B: Early salvage radiotherapy — same dose/fractionation, started at PSA 0.1–2.0 ng/mL
Primary endpoint: Metastasis-free survival
mFollow up: ~10 year
Arm B: Early salvage radiotherapy — same dose/fractionation, started at PSA 0.1–2.0 ng/mL
Primary endpoint: Metastasis-free survival
mFollow up: ~10 year
Results
10-yr MFS: 95.8% vs 94.9%, HR 1.10 (95% CI 0.73–1.65), P=.634 — no significant difference
Freedom from biochemical failure (5-yr): HR 0.68 (95% CI 0.54–0.85), P=.001 — significantly better with adjuvant RT
Urinary incontinence at 2 yr: 51.7% vs 37.3% (significantly worse with adjuvant RT)
Freedom from biochemical failure (5-yr): HR 0.68 (95% CI 0.54–0.85), P=.001 — significantly better with adjuvant RT
Urinary incontinence at 2 yr: 51.7% vs 37.3% (significantly worse with adjuvant RT)
Adverse events
Main adverse events: Urinary incontinence at 2 years significantly worse with adjuvant RT (51.7% vs 37.3%). Late bowel and urinary toxicity: modestly higher with adjuvant RT. Approximately 50% of patients randomized to salvage RT never received RT (never experienced PSA recurrence), sparing them unnecessary radiation.
Conclusions
Adjuvant RT did not improve metastasis-free survival compared with early salvage RT in post-RP prostate cancer, while causing greater short-term urinary toxicity. These findings support a policy of surveillance after RP with early salvage RT at PSA rise, avoiding unnecessary radiation in the ~50% of patients who will not relapse.
Key Limitations
Key Limitations: RADICALS-RT was not designed for patients with very high PSA at randomization or macroscopic residual disease — findings may not apply to the highest-risk margin-positive cases. Concurrent hormonal therapy was not routinely used, which may limit applicability in current practice where ADT is commonly added to salvage RT (as shown by RTOG 9601). The trial predated modern staging (PSMA-PET), which may change patient selection for adjuvant vs salvage RT. Biochemical PFS favored adjuvant RT — clinical significance of this benefit without MFS difference remains debated.
Clinical Context
RADICALS-RT, combined with RAVES (Australia) and GETUG-AFU 17 (France) in the ARTISTIC meta-analysis (Lancet 2020), consistently showed no MFS benefit of adjuvant vs salvage RT. This has shifted practice toward a watchful waiting strategy with early salvage RT, endorsed by AUA/ASTRO/EAU guidelines. The shift avoids unnecessary radiation in ~50% of patients and reduces toxicity.