ST. LOUIS — If detected and treated at an early stage, prostate cancer is often curable. That is not the case, however, with an advanced stage such as metastatic castration-resistant prostate cancer (mCRPC), which has a high risk of mortality.
“Multiple treatment options exist, the most common included docetaxel, abiraterone, and enzalutamide,” explained the researchers from the St. Louis VAMC, Saint Louis University and George Mason University in Fairfax, VA. “Docetaxel is a cytotoxic chemotherapy, whereas abiraterone and enzalutamide are androgen receptor pathway inhibitors (ARPI). ARPIs are preferred over docetaxel due to lower toxicity. No study has used machine learning with patients’ demographics, test results and comorbidities to identify heterogeneous treatment rules that might improve the survival duration of patients with mCRPC.”
The study in JMIR Medical Infomatics sought to measure patient-level heterogeneity in the association of medication prescribed with overall survival duration (in the form of follow-up days) and arrive at a set of medication prescription rules using patient demographics, test results and comorbidities.1
Excluded were patients with mCRPC who were on docetaxel, cabaxitaxel, mitoxantrone and sipuleucel-T either before or after the prescription of an ARPI. All 2,886 participants were African American or white and were prescribed either abiraterone or enzalutamide as the first line of treatment from 2014 to 2017, with follow-up until 2020. Considered the primary outcome of this study was follow-up days indicating survival duration while on the first-line medication. After estimating the treatment effect, the researchers constructed a prescription policy tree.
Results indicated that, for 2,886 veterans, enzalutamide is associated with an average of 59.94 (95% CI 35.60-84.28) more days of survival than abiraterone. The increase in overall survival duration for the two drugs varied across patient demographics, test results and comorbidities, the authors wrote, adding, that two data-driven subgroups of patients were identified by ranking them on their augmented inverse-propensity weighted (AIPW) scores.
The average AIPW scores for the two subgroups were 19.36 (95% CI -16.93 to 55.65) and 100.68 (95% CI 62.46-138.89). “Based on visualization and t test, the AIPW score for low and high subgroups was significant (P=.003), thereby supporting heterogeneity,” the researchers explained. “The analysis resulted in a set of prescription rules for the 2 ARPIs based on a few covariates available to the physicians at the time of prescription.”
The showed evidence of heterogeneity and that survival days might be improved for certain patients with mCRPC based on the medication prescribed, the authors concluded. “Findings suggest that prescription rules based on the patient characteristics, laboratory test results, and comorbidities available to the physician at the time of prescription could improve survival by providing personalized treatment decisions,” they advised.
- Gopukumar D, Menon N, Schoen MW. Medication Prescription Policy for US Veterans With Metastatic Castration-Resistant Prostate Cancer: Causal Machine Learning Approach. JMIR Med Inform. 2024 Nov 19;12:e59480. doi: 10.2196/59480. PMID: 39561358; PMCID: PMC11615563.
