Immediate radiotherapy versus observation in patients with node-positive prostate cancer after radical prostatectomy | Prostate Cancer and Prostatic Diseases - Nature.com

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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.

Data availability

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

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Author information

Authors and Affiliations

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

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

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

    Sumedh Kaul&nbsp;&amp;&nbsp;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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  1. Christian Schaufler
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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.

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