What do recent randomized trials and meta-analyses (2020–2025) conclude about timing of salvage radiotherapy and long-term outcomes?

1. The 2020 randomized trials and the pooled verdict: a shift from routine adjuvant RT to early salvage

Three large randomized trials—RADICALS‑RT, RAVES and GETUG‑AFU‑17—were pooled in a prospectively planned meta‑analysis that included 2,153 patients and found no evidence that immediate ART improved event‑free survival compared with an observation strategy with early SRT; the pooled HR for event‑free survival was 0.95 and 5‑year event‑free survival was essentially identical (89% vs 88%) ^{[1] [2]}. Trial investigators and editorials interpreted these results as supporting an observation policy with early SRT to spare many men radiotherapy and its morbidity ^{[5] [6]}.

2. What “early salvage” meant in the trials — and why the PSA threshold matters

Across the trials included in the meta‑analysis, early SRT was typically triggered at low PSA values (commonly 0.1–0.2 ng/mL or rising), with harmonised definitions of event‑free survival tied to biochemical and clinical progression ^{[7] [1]}. Guideline panels and the AUA/ASTRO/SUO materials explicitly advise clinicians to tell patients that salvage radiation is more effective when given at lower PSA levels, reflecting trial practice ^{[4] [8]}.

3. Patient‑reported harms and functional tradeoffs: SRT is not benign

Prospective PROMs studies document that combining surgery with salvage radiotherapy worsens urinary incontinence, bowel, sexual and hormonal function; clinical trials and cohort studies therefore weigh oncologic non‑inferiority against clear quality‑of‑life costs of irradiation ^{[3] [9]}. This functional toxicity was a central rationale for preferring a selective early salvage policy rather than routine adjuvant RT ^{[5] [1]}.

4. The evolving questions since 2020: ADT duration, pelvic nodal fields, and imaging

Post‑2020 randomized and pooled analyses have continued to probe adjuncts: randomized data and pooled meta‑analyses indicate that adding short‑course ADT to SRT can improve some outcomes, and longer ADT durations may improve metastasis‑free survival in some comparisons (reports cite e.g. 24 vs 6 months and study‑level meta‑analysis DADSPORT showing an MFS advantage for 6 months ADT) ^[10]. Trials such as OLIGOPELVIS and other phase II studies explore elective pelvic nodal radiotherapy plus ADT in nodal relapses, reporting prolonged control with limited toxicity in selected populations ^[11]. Meanwhile, the uptake of PSMA‑PET and other advanced imaging has complicated timing decisions, because physicians sometimes wait for PET staging before delivering SRT—guidelines note imaging has begun to shape care though its routine effect on long‑term outcomes is under study ^{[12] [8]}.

5. Recent randomized trials refining technique and fractionation, but not overturning timing guidance

From 2020–2025, randomized and phase‑2 trials have tested hypofractionation and SBRT schedules for salvage settings (SHORTER trial randomised 5 vs 20 fractions for SRT and found no significant short‑term worsening of patient‑reported GU/GI toxicity at 3–6 months, with longer follow‑up needed for late effects) ^[13]. Such trials address convenience and toxicity but do not contradict the timing conclusion that early SRT at low PSA remains appropriate when salvage is needed ^{[13] [14]}.

6. Where evidence is limited or still emerging — and how to interpret it

Long‑term survival differences (overall survival, very long‑term metastasis‑free survival) between ART and early SRT remain underpowered in the earlier meta‑analysis follow‑up; the pooled result covers median follow‑ups of ~5–7 years and relies on event‑free survival as the primary harmonised endpoint ^[1]. Later 2024–2025 follow‑ups, guidelines and subgroup analyses continue to investigate whether higher‑risk subgroups (e.g., multiple adverse features) might benefit from different approaches, but available sources do not yet provide a definitive long‑term survival advantage for routine ART ^{[15] [4]}.

7. Practical takeaways for clinicians and patients

The trials support close PSA surveillance after prostatectomy and initiating SRT at low PSA rather than delivering ART to all high‑risk surgical patients—this spares many men radiation and its functional harms without clear short‑to‑midterm loss in event‑free survival ^{[1] [5]}. Individual decisions should factor tumour‑grade, margin status, PSA kinetics, patient preference about quality‑of‑life tradeoffs, plans for PSMA‑PET staging, and whether ADT or pelvic fields are being considered ^{[4] [12] [10]}.

Limitations: this summary uses the trials and reviews available in the provided search set; questions about very long‑term survival differences, optimal ADT duration in every subgroup, and outcomes when PSMA‑PET guides delay to higher PSA are still matters of active research in the cited literature ^{[1] [10] [12]}.