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Immediate radiotherapy versus observation in patients with node-positive prostate cancer after radical prostatectomy

Prostate Cancer and Prostatic Diseases volume 27, pages 81–88 (2024)Cite this article

Subjects

Abstract

Background

The optimal management of node-positive (pN1) prostate cancer following radical prostatectomy (RP) remains uncertain. Despite randomized evidence, utilization of immediate, life-long androgen deprivation therapy (ADT) remains poor, and recent trials of early salvage radiotherapy included only a minority of pN1 patients. We therefore emulated a hypothetical pragmatic trial of adjuvant radiotherapy versus observation in men with pN1 prostate cancer.

Methods

Using the RADICALS-RT trial to inform the design of a hypothetical trial, we identified men aged 50-69 years with pT2-3 Rany pN1 M0, pre-treatment PSA < 50 ng/mL prostate cancer in the NCDB from 2006 to 2015 treated with 60–72 Gy of adjuvant RT (aRT) ± ADT within 26 weeks of RP or observation. After estimating a propensity score for receipt of aRT, we estimated absolute and relative treatment effects using stabilized inverse probability of treatment (sIPW) re-weighting.

Results

In total, 3510 patients were included in the study, of whom 587 (17%) received aRT (73% with concurrent ADT). Median follow-up was 40.0 -months, during which 333 deaths occurred. After sIPW re-weighting, baseline characteristics were well-balanced. Adjusted overall survival (OS) was 93% versus 89% at 5-years and 82% versus 79% at 7-years for aRT versus observation (p = 0.11). In IPW-reweighted Cox regression, aRT was associated with a lower risk of all-cause mortality (ACM) than observation, but this did not reach statistical significance (HR 0.70 p = 0.06). In analyses examining heterogeneity of treatment effects, aRT was associated with improved ACM only for men with Gleason 8–10 disease (HR 0.59, p = 0.01), ≥2 positive LNs (HR 0.49, p = 0.04 for 2 positive LNs; HR 0.42, p = 0.01 for ≥3 positive LNs), or negative surgical margins (HR 0.50, p = 0.02).

Conclusions

In observational analyses designed to emulate a hypothetical target trial of aRT versus observation in pN1 prostate cancer, aRT was associated with improved OS only for men with Gleason 8–10 disease, ≥2 positive LNs, or negative surgical margins.

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Fig. 1: Adjusted overall survival stratified by treatment group.
Fig. 2: Forest plot of treatment effects stratified by subgroup.

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Data availability

The data used herein (NCDB) is provided by the American College of Surgeons through a data request.

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Authors and Affiliations

  1. Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Christian Schaufler, Ruslan Korets, Peter Chang, Andrew Wagner, Aria F. Olumi & Boris Gershman

  2. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Sumedh Kaul & Aaron Fleishman

  3. Division of Urology, University of Colorado Anschutz Medical Center, Aurora, CO, USA

    Simon Kim

  4. Department of Medicine, Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Joaquim Bellmunt

  5. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Irving Kaplan

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Contributions

CS: study conception/design, interpretation of results, drafting manuscript, revision of manuscript. SK: study conception/design, interpretation of results, drafting manuscript, revision of manuscript. AF: study conception/design, interpretation of results, drafting manuscript, revision of manuscript. RK: study conception/design, interpretation of results, revision of manuscript. PC: study conception/design, interpretation of results, revision of manuscript. AW: study conception/design, interpretation of results, revision of manuscript. SK: study conception/design, interpretation of results, revision of manuscript. JB: study conception/design, interpretation of results, revision of manuscript. IK: study conception/design, interpretation of results, revision of manuscript. AO: study conception/design, interpretation of results, revision of manuscript. BG: study conception/design, interpretation of results, drafting manuscript, revision of manuscript; supervision.

Corresponding author

Correspondence to Boris Gershman.

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Competing interests

The authors have no conflicts of interest to disclose. The National Cancer Data Base (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC’s NCDB and the hospitals participating in the CoC NCDB are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.

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The study was exempt from ethics or Institutional Review Board approval. It was performed in accordance with the Declaration of Helsinki.

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Schaufler, C., Kaul, S., Fleishman, A. et al. Immediate radiotherapy versus observation in patients with node-positive prostate cancer after radical prostatectomy. Prostate Cancer Prostatic Dis 27, 81–88 (2024). https://doi.org/10.1038/s41391-022-00619-1

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