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Influence of Adverse Pathologic Features on Potential Benefit of Hormone Therapy Use with Postoperative Radiotherapy in Recurrent Prostate Cancer: An Individual Patient Data Meta-analysis

In brief

Hormone therapy improves survival after postoperative prostate radiotherapy regardless of adverse pathology count

In an individual-patient meta-analysis of 4,781 men with low pre-radiotherapy PSA, adding hormonal therapy to postoperative radiotherapy enhanced overall and metastasis-free survival, and this benefit was not reduced in patients with more adverse pathological features. The adverse feature count remained a strong prognostic factor but did not predict who would gain less from hormonal therapy, supporting its use across risk groups.

Journal
European urology (Q1)
Published
28 July 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Amar U Kishan, Yilun Sun, Christopher C Parker, Paul Sargos, Matthew Sydes, Sylvie Chabaud, et al.
PMID
42521517
DOI
10.1016/j.eururo.2026.07.013

Why clinicians should know about it

  • Picked for Urology (top studies of the week, 2 August 2026): Adverse pathology does not modify hormone therapy benefit after radiotherapy
  • Picked for Pathology and Forensic Medicine (top studies of the week, 2 August 2026).

Abstract

BACKGROUND AND OBJECTIVE: A recent individual patient data (IPD) meta-analysis of randomized trials found a limited overall survival (OS) and metastasis-free survival (MFS) benefit to the addition of hormonal therapy (HT) to postoperative radiotherapy for prostate cancer in patients with pre-radiotherapy prostate-specific antigen (PSA) ≤0.5 ng/ml. We evaluated whether the OS and MFS benefits of adding HT might be significantly modified by an increasing count of adverse pathological features (adverse feature count [AFC]). METHODS: We obtained IPD from five randomized phase 3 trials of postoperative radiotherapy ± HT. AFC was prospectively defined as the sum (0-4) of grade group 4-5 disease, seminal vesicle invasion, positive surgical margins, and extracapsular extension. Intention-to-treat one-stage meta-analytical models were used. We also evaluated the interaction of the benefit of HT with a restricted score comprising only GG4-5 and seminal vesicle invasion (range 0-2), as a pre-specified sensitivity analysis. KEY FINDINGS AND LIMITATIONS: We included IPD from 4781 patients with a median follow-up of 9.1 yr. AFC was independently prognostic for OS and MFS. However, AFC did not significantly modify the OS benefit of HT (interaction hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.79-1.10; p = 0.4) or MFS benefit (interaction HR, 0.88; 95% CI, 0.77-1.01; p = 0.08). Results were similar when AFC was analyzed categorically and in high-risk subsets, and when the restricted AFC score was used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Overall, the data suggest that although adverse pathological features are prognostic, they do not appear predictive of HT benefit after postoperative radiotherapy, which is relevant for patients with a PSA ≤0.5 ng/ml before radiation.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.