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Quantifying treatment selection bias effect on survival in comparative effectiveness research: findings from low-risk prostate cancer patients

Prostate Cancer and Prostatic Diseases volume 24, pages 414–422 (2021)Cite this article

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Abstract

Background

Comparative effectiveness research (CER) using national registries influences cancer clinical trial design, treatment guidelines, and patient management. However, the extent to which treatment selection bias (TSB) affects overall survival (OS) in cancer CER remains poorly defined. We sought to quantify the TSB effect on OS in the setting of low-risk prostate cancer, where 10-year prostate cancer-specific survival (PCSS) approaches 100% regardless of treatment modality.

Methods

The Surveillance, Epidemiology, and End Results database was queried for patients with low-risk prostate cancer (cT1-T2a, PSA < 10, and Gleason 6) who received radical prostatectomy (RP), brachytherapy (BT), or external beam radiotherapy (EBRT) from 2005 to 2015. The TSB effect was defined as the unadjusted 10-year OS difference between modalities that was not due to differences in PCSS. Propensity score matching was used to estimate the TSB effect on OS due to measured confounders (variables present in the database and associated with OS) and unmeasured confounders.

Results

A total of 50,804 patients were included (8845 RP; 18,252 BT; 23,707 EBRT) with a median follow-up of 7.4 years. The 10-year PCSS for the entire cohort was 99%. The 10-year OS was 92.9% for RP, 83.6% for BT, and 76.9% for EBRT (p < 0.001). OS differences persisted after propensity score matching of RP vs. EBRT (7.4%), RP vs. BT (4.6%), and BT vs. EBRT (3.7%) (all p < 0.001). The TSB effect on 10-year OS was estimated to be 15.0% for RP vs. EBRT (8.6% measured, 6.4% unmeasured), 8.5% for RP vs. BT (4.8% measured, 3.7% unmeasured), and 6.5% for BT vs. EBRT (3.1% measured, 3.4% unmeasured).

Conclusions

Patients with low-risk prostate cancer selected for RP exhibited large OS differences despite similar PCSS compared to radiotherapy, suggesting OS differences are almost entirely driven by TSB. The quantities of these effects are important to consider when interpreting prostate cancer CER using national registries.

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Fig. 1: CONSORT diagram delineating cohort selection.
Fig. 2: Unadjusted overall and prostate cancer-specific survival for low-risk prostate cancer patients receiving definitive management with either radical prostatectomy, brachytherapy, or external beam radiotherapy.
Fig. 3: Propensity score-matched overall survival of radical prostatectomy vs. external beam radiotherapy, radical prostatectomy vs. brachytherapy, and brachytherapy vs. external beam radiotherapy.
Fig. 4: Composition of unadjusted 5- and 10-year overall survival differences between cohorts.

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Authors and Affiliations

  1. Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, USA

    Joseph A. Miccio, Wesley J. Talcott, Vikram Jairam, Henry S. Park & James B. Yu

  2. Department of Urology, Yale School of Medicine, New Haven, CT, USA

    Michael S. Leapman

  3. Huntsman Cancer institute, University of Utah, Salt Lake City, UT, USA

    Skyler B. Johnson

  4. Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Martin T. King, Paul L. Nguyen & Benjamin H. Kann

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  1. Joseph A. Miccio
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Correspondence to Benjamin H. Kann.

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Conflict of interest

HSP reports honoraria from RadOnc Questions, LLC. JBY reports personal fees from Boston Scientific and Galera Pharmaceuticals. PLN reports honoraria from Janssen, research grants from Janssen, Astellas, Bayer, consultation for Astellas, COTA, and Boston Scientific, and advisory board for Astellas. MTK has received research grants from Bayer and Palette Life Sciences. All of these conflicts of interest are outside of the submitted work and no other conflicts of interest were reported.

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Miccio, J.A., Talcott, W.J., Jairam, V. et al. Quantifying treatment selection bias effect on survival in comparative effectiveness research: findings from low-risk prostate cancer patients. Prostate Cancer Prostatic Dis 24, 414–422 (2021). https://doi.org/10.1038/s41391-020-00291-3

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