Background
Phase III RCT (NRG Oncology/RTOG 0534 SPPORT). 2,203 patients after radical prostatectomy with rising or persistent PSA (0.1–2.0 ng/mL), pT2 or pT3, Gleason ≤9, pN0/Nx at 283 centers in the USA, Canada, and Israel. Three-arm design to assess incremental value of ADT and pelvic lymph node radiotherapy added to prostate bed RT. Median follow-up 11.1 years.
Interventions and follow up
Arm A: Prostate bed RT (PBRT) alone 64.8–70.2 Gy (n=734)
Arm B: PBRT + short-term ADT (4–6 months) (n=734)
Arm C: Pelvic lymph node RT (PLNRT, 45 Gy) + PBRT + short-term ADT (n=735)
Primary endpoint: Freedom from progression (biochemical failure, local/distant recurrence, or death)
mFollow up: 11.1 year
Arm B: PBRT + short-term ADT (4–6 months) (n=734)
Arm C: Pelvic lymph node RT (PLNRT, 45 Gy) + PBRT + short-term ADT (n=735)
Primary endpoint: Freedom from progression (biochemical failure, local/distant recurrence, or death)
mFollow up: 11.1 year
Results
Freedom from progression at 5 years: 70.9% (PBRT) vs 81.3% (PBRT + ADT) vs 87.4% (PLNRT + PBRT + ADT)
PLNRT + PBRT + ADT vs PBRT alone: HR 0.45 (95% CI 0.35–0.57), P<.0001
PBRT + ADT vs PBRT alone: HR 0.67 (95% CI 0.55–0.82), P<.0001
OS at 8 years: 95% (PLNRT + PBRT + ADT) vs 93% (PBRT + ADT) vs 91% (PBRT alone); PLNRT arm vs PBRT alone: HR 0.62 (95% CI 0.42–0.90), P=.011
PLNRT + PBRT + ADT vs PBRT alone: HR 0.45 (95% CI 0.35–0.57), P<.0001
PBRT + ADT vs PBRT alone: HR 0.67 (95% CI 0.55–0.82), P<.0001
OS at 8 years: 95% (PLNRT + PBRT + ADT) vs 93% (PBRT + ADT) vs 91% (PBRT alone); PLNRT arm vs PBRT alone: HR 0.62 (95% CI 0.42–0.90), P=.011
Adverse events
Main adverse events: Grade ≥2 GI toxicity higher in PLNRT arm vs PBRT alone (21% vs 14%). Grade ≥2 GU toxicity similar across arms (~25–27%). Late-grade ≥3 toxicity numerically higher in PLNRT arm but not statistically significant. ADT-related toxicities (hot flushes, sexual dysfunction) as expected.
Conclusions
Both the addition of short-term ADT to PBRT and further addition of pelvic lymph node irradiation to PBRT + ADT significantly improved freedom from progression and overall survival compared with PBRT alone. PLNRT + PBRT + ADT represented the superior salvage regimen in this broadly eligible post-prostatectomy population.
Key Limitations
Key Limitations: Freedom from progression (primarily biochemical) as the primary endpoint may not fully capture clinically meaningful benefit. Not all patients may require pelvic nodal coverage — risk stratification for PLNRT use remains an open question. ADT duration (4–6 months) was at physician discretion; longer ADT may confer additional benefit in higher-risk patients. Treatment with IMRT/IGRT not uniformly mandated early in the trial.
Clinical Context
SPPORT is the definitive trial establishing pelvic nodal irradiation as a component of optimal post-prostatectomy salvage therapy in selected patients. Results support a risk-stratified approach: low-risk biochemical recurrence may need PBRT alone, while higher-risk features support PLNRT + ADT addition. Current NRG/RTOG guidelines incorporate SPPORT findings into salvage RT recommendations.
References
References: Pollack A et al, Lancet 2022; PMID: 35569466