TY - JOUR
T1 - Quantifying treatment selection bias effect on survival in comparative effectiveness research
T2 - findings from low-risk prostate cancer patients
AU - Miccio, Joseph A.
AU - Talcott, Wesley J.
AU - Jairam, Vikram
AU - Park, Henry S.
AU - Yu, James B.
AU - Leapman, Michael S.
AU - Johnson, Skyler B.
AU - King, Martin T.
AU - Nguyen, Paul L.
AU - Kann, Benjamin H.
N1 - Funding Information:
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.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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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U2 - 10.1038/s41391-020-00291-3
DO - 10.1038/s41391-020-00291-3
M3 - Article
C2 - 32989262
AN - SCOPUS:85091605460
SN - 1365-7852
VL - 24
SP - 414
EP - 422
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 2
ER -