KEY POINTS
- This systematic review and random-effects meta-analysis included all five phase III randomized trials comparing elective whole-pelvic with prostate-only radiotherapy in clinically node-negative high-risk localized prostate cancer: RTOG 9413, GETUG-01, POP-RT, RTOG 0924 and PEACE-2, totaling 5,172 patients.
- The trials spanned markedly different treatment eras: older studies used 2D/3D techniques and conventional staging, whereas modern studies used IMRT, longer androgen deprivation and, in POP-RT, prospective PSMA PET staging and enrichment for very-high nodal-risk disease. This clinical heterogeneity is central to interpreting the pooled results.
- Whole-pelvic RT produced no overall-survival benefit: pooled HR 1.07 (95% CI 0.94–1.21) across all five trials, with I²=0%. Reconstructed individual-patient data from four trials independently confirmed the null result, HR 0.98 (95% CI 0.80–1.20).
- The apparent metastasis-free-survival advantage was inconsistent: pooled HR 0.92 (95% CI 0.54–1.57; I²=55%). When the positive POP-RT trial was removed in a prespecified sensitivity analysis, the result became completely null: HR 1.00 (95% CI 0.70–1.43; I²=0%).
- Biochemical/progression-free survival showed the same pattern. The overall estimate was HR 0.84 (95% CI 0.54–1.29; I²=69%), but after excluding POP-RT it became HR 0.90 (95% CI 0.77–1.06; I²=0%). In other words, the apparent progression benefit was driven by one clinically distinctive single-center trial.
- Pelvic irradiation modestly increased late toxicity in several trials. In POP-RT, late grade ≥2 GU toxicity was 20% versus 8.9% (p=0.02) and GI toxicity 8.2% versus 4.5%; in RTOG 0924, corresponding rates were 27% versus 25% and 22% versus 18%, respectively. Severe grade ≥3 events generally remained uncommon.
- Evidence certainty was rated moderate for overall survival but very low for biochemical/progression-free and metastasis-free survival, reflecting inconsistency, indirectness and imprecision. The analysis therefore does not exclude a benefit in a contemporary, carefully selected very-high nodal-risk, PSMA-staged population, but current randomized evidence does not establish that subgroup benefit.
CLINICAL TAKEAWAY
For unselected clinically node-negative high-risk prostate cancer, these five randomized trials do not support routine elective whole-pelvic irradiation: survival is unchanged and the apparent progression advantage is not reproducible after excluding POP-RT. A benefit may still exist in very-high nodal-risk patients staged with modern molecular imaging, but that remains a prospective research question rather than established evidence.