Whether elective pelvic lymph nodes should be included in the radiation field for patients with clinically node-negative high-risk localized prostate cancer remains an open question. A new systematic review and meta-analysis brought together phase 3 randomized evidence comparing whole-pelvic radiotherapy (WPRT) with prostate-only radiotherapy (PORT), together with reconstructed individual-patient survival data, to assess whether extending the radiation field improves clinical outcomes.
The study, “Whole-pelvic Versus Prostate-only Radiotherapy in Clinically Node-negative High-Risk Localised Prostate Cancer: A Systematic Review and Meta-analysis with Reconstructed Individual-patient Data,” appears in Clinical Oncology, Volume 59, November 2026.
Authors: J.D. Subiela, E. Gomis Sellés, F. López Campos, J. Aumatell, D.A. González-Padilla, Á.G. Balbás, D. López-Curtis, V. Vera Barragán, J. Caño-Velasco, N. Picola Brau, P. de Pablos-Rodríguez, J. Gómez Rivas, L. San-José Manso, F.J. Burgos Revilla, F. Barletta, F. Alongi, C. Zamboglou, L. Nicosia, M. Shelan, A.-J. Conde-Moreno, P. Gajate, P. Guerrero, Ò. Buisan, and F. Couñago.
Bringing Together Five Phase 3 Trials
The investigators searched MEDLINE, Embase, ClinicalTrials.gov, and major oncology and radiation-oncology congress proceedings through May 2026. Eligible studies were phase 3 randomized trials comparing elective WPRT with PORT in patients with clinically node-negative localized high-risk, or unfavorable-intermediate-to-high-risk, prostate cancer treated with definitive external-beam radiotherapy and androgen-deprivation therapy (ADT).
Five trials met the inclusion criteria: RTOG 9413, GETUG-01, POP-RT, PEACE-2, and RTOG 0924, representing 5,172 randomized patients.
The studies spanned different treatment eras. RTOG 9413 and GETUG-01 were conducted using older 2D or 3D-conformal radiotherapy and conventional staging, while POP-RT, PEACE-2, and RTOG 0924 were conducted in the modern radiotherapy era. POP-RT was particularly distinct: it was a single-center trial enrolling patients with high or very-high-risk disease, used a nodal-risk eligibility threshold of at least 20%, and incorporated PSMA-PET/CT staging in approximately 80% of patients.
The primary outcomes of the meta-analysis were overall survival and metastasis-free survival. Biochemical/progression-free survival, prostate cancer-specific survival, and late genitourinary and gastrointestinal adverse events were also assessed. In addition to the aggregate-data analysis, the investigators reconstructed pseudo-individual-patient data from published Kaplan-Meier curves using the Guyot algorithm.
Survival Results
Across all five trials, WPRT did not improve overall survival compared with PORT. The pooled analysis showed an overall survival HR of 1.07 (95% CI, 0.94–1.21) among 5,172 patients, with no detectable between-trial heterogeneity (I²=0%). The reconstructed individual-patient-data analysis was consistent with the aggregate results, with an HR of 0.98 (95% CI, 0.80–1.20) across four reconstructable trials.
The overall survival finding also remained stable across the prespecified robustness and leave-one-out analyses. When the analysis was restricted to the three trials available as full-text publications, the HR was 1.08 (95% CI, 0.84–1.38).
POP-RT and Progression
For biochemical/progression-free survival, the pooled HR was 0.84 (95% CI, 0.54–1.29), with substantial heterogeneity across studies (I²=69%). The investigators found that this apparent benefit was strongly influenced by POP-RT. In the prespecified analysis excluding POP-RT, the pooled HR became 0.90 (95% CI, 0.77–1.06), while heterogeneity fell to 0%.
A similar pattern was observed for metastasis-free survival. Across four trials involving 4,728 patients, the pooled HR was 0.92 (95% CI, 0.54–1.57), with I²=55%. After POP-RT was excluded, the HR was 1.00 (95% CI, 0.70–1.43), again with no detectable heterogeneity. The reconstructed individual-patient-data analysis for metastasis-free survival included only POP-RT and PEACE-2 and produced a very wide confidence interval, reflecting the opposing results of the two trials and limiting meaningful interpretation of the pooled estimate.
These findings led the authors to conclude that the progression-related signal associated with WPRT was not consistently reproduced across the randomized trials and was largely driven by the single-center POP-RT study.
Safety With WPRT
Late grade 2 or higher genitourinary and gastrointestinal adverse events were modestly increased with WPRT in some trials. In POP-RT, late grade ≥2 genitourinary events occurred in 20% with WPRT versus 8.9% with PORT. In RTOG 0924, grade ≥2 gastrointestinal events occurred in 22% versus 18%, respectively. Severe toxicity remained uncommon in the modern IMRT-era trials. In POP-RT and RTOG 0924, grade ≥3 genitourinary and gastrointestinal events remained at or below 3.4% in both treatment groups, without significant between-group differences.
The more pronounced severe gastrointestinal toxicity signal came from the older RTOG 9413 trial, in which late grade ≥3 gastrointestinal events occurred in 5.1% with WPRT versus 1.9% with PORT.
What the Evidence Shows
Using the GRADE framework, the certainty of evidence was rated moderate for overall survival but very low for biochemical/progression-free survival and metastasis-free survival. The very low certainty of the progression-related outcomes reflected inconsistency between trials, differences in endpoint definitions, and imprecision; biochemical/progression-free survival was additionally downgraded for risk of bias. The trials also differed considerably in staging methods, radiotherapy techniques, ADT duration, and systemic treatment intensification.
Importantly, two of the five studies—PEACE-2 and RTOG 0924—were available only as congress presentations at the time of the analysis. Together, they accounted for 3,234 of the 5,172 randomized patients, or 63% of the evidence base. The reconstructed individual-patient data were also derived from published Kaplan-Meier curves rather than original patient-level datasets.
The authors additionally highlighted the considerable evolution in imaging and treatment across the more than two decades represented by the included trials, from conventional staging and 2D/3D-conformal radiotherapy to contemporary IMRT and molecular imaging.
POP-RT therefore remains an important but distinct signal within the evidence base. The trial enrolled a population enriched for very-high nodal risk and used PSMA-PET staging in most patients. However, the authors emphasized that whether this selected population truly derives a benefit from WPRT remains unproven and requires validation in contemporary prospective randomized trials.
Takeaway
In this meta-analysis of five phase 3 randomized trials involving 5,172 patients with clinically node-negative high-risk localized prostate cancer, elective whole-pelvic radiotherapy did not improve overall survival compared with prostate-only radiotherapy.
The apparent benefit in biochemical/progression-free and metastasis-free survival was not consistent across trials and was largely driven by POP-RT. Based on the available randomized evidence, the authors concluded that routine elective pelvic irradiation is not supported for unselected patients.
The findings instead highlight the need for better patient selection, with the authors proposing that future studies evaluate whether contemporary molecular imaging and genomic biomarkers can help identify patients with very-high-risk disease who may benefit from regional treatment intensification.
