Understanding variation in treatment intensification for de novo metastatic castration-sensitive prostate cancer (mCSPC): A population-based cohort study.
Authors: Wallis Christopher J.D. , Satkunasivam Raj , Nguyen David-Dan , Aminoltejari Khatereh J.D. , Hird Amanda Elizabeth , Roy Soumyajit , Morgan Scott C. , Malone Shawn , Shayegan Bobby , Breau Rodney H. 
Published: January 2024

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Background: Treatment intensification using androgen receptor signaling inhibitors (ARSIs) or chemotherapy is guideline-recommended for patients with mCSPC based on improved survival and preserved quality of life. However, numerous studies across jurisdictions have shown relatively limited uptake, with most patients receiving androgen deprivation therapy (ADT) monotherapy. Therefore, we sought to understand patient, physician, and tumor characteristics associated with treatment intensification. Methods: This population-based cohort study in Ontario, Canada included older men (age ≥66 years) diagnosed with de novo mCSPC between Jan 2014 and Nov 2021 for whom the ADT-prescribing physician could be identified (>99.5% of all mCSPC patients). We used hierarchical regression modelling to assess the association (presented as odds ratio, OR) between patient sociodemographic characteristics and comorbidities, tumor characteristics, and physician characteristics with receipt of intensified treatment for mCSPC, defined as receipt of an ARSI, docetaxel, or both within 6mo. We used Darlington’s method to assess the relative importance of these predictors (presented as standardized regression coefficients, SRC). Results: Among 4450 eligible older men newly diagnosed with de novo mCSPC, 18.8% received treatment intensification, with rates increasing from 6.3% in 2014 to 31.9% by 2021. In multivariable modeling, patient age was the most influential variable, with older patients significantly less likely to receive treatment intensification (SRC -43.8, OR 0.91, 95% CI 0.90-0.92). Socioeconomic status (SRC -12.2; OR 0.54, 95% CI 0.33-0.88 for quintile 1 vs 5) and a history of stroke (SRC -11.5, OR 0.28, 95% CI 0.09-0.86), but no other patient factors including comorbidity, were significantly associated with intensification. Patients prescribed ADT for mCSPC by radiation oncologists were less likely to receive intensification (SRC -16.5; OR 0.47, 95% CI 0.23-0.95) compared to other providers without significant differences between patients treated by urologists, medical oncologists, or other physicians. No other physician-level characteristic (age, sex, years in practice, or annual volume of prostate cancer patients) was associated with treatment intensification. More contemporary year of diagnosis was also strongly predictive (mean SRC 31.2) of intensification. We noted significant geographic variation (mean SRC 10.2; p<0.0001), that could not be explained by rurality (p=0.08) and persisted after adjustment for socioeconomic status and patient characteristics. Conclusions: Patient, disease, and physician characteristics contribute to variation in treatment intensification for mCSPC. These data may allow focused intervention to improve guideline-concordant care for patients with mCSPC.