Journal Article

Survival by first‐line therapy and prognostic group among men with metastatic castration‐resistant prostate cancer

Shahinian, Vahakn, Reichert, Zachery R., Tsodikov, Alexander, Caram, Megan E. V., Stensland, Kristian D., Alumkal, Joshi J., Skolarus, Ted A., Kumbier, Kyle, Sparks, Jordan B., Hollenbeck, Brent K., Burns, Jennifer, Tsao, Phoebe A.

2024

Overview

Introduction Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration‐resistant diagnosis. Optimal first‐line therapy for those with different prognoses is unknown. Methods We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first‐line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow‐up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan–Meier methods to examine prostate specific antigen (PSA) progression‐free and overall survival (OS) according to prognostic group and first‐line therapy, and multivariable cox regression to determine variables associated with survival outcomes. Results Among 4135 patients, median PSA progression‐free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6–7.3), and median OS 18.8 months (95% CI 18.0–19.6), ranging from 5.7 months (95% CI 4.8–7.0) in the poor prognosis group to 31.3 months (95% CI 29.7–32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2–3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34–2.31; intermediate HR 1.78, 95% CI 1.41–2.25; poor HR 8.01, 95% CI 2.93–21.9). Conclusion Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First‐line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start. Hemoglobin, albumin, and alkaline phosphatase, used to categorize patients with metastatic castration resistant prostate cancer at start of new treatment into prognostic groups, was strongly predictive of survival, but survival did not vary substantially based on which treatment patients received within prognostic groups.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Aged / Aged, 80 and over / Alkaline phosphatase / Androgens / Androstenes - therapeutic use / Antifungal agents / Antigens / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Benzamides - therapeutic use / Cancer therapies / Castration / Clinical trials / Comorbidity / Disease / Disease progression / Docetaxel - administration & dosage / Docetaxel - therapeutic use / Hemoglobin / Humans / Kaplan-Meier Estimate / Ketoconazole / Ketoconazole - therapeutic use / Laboratories / Male / Medical prognosis / Metastases / Metastasis / Middle Aged / Nitriles - therapeutic use / novel therapies / Patients / Pharmacy / Phenylthiohydantoin - analogs & derivatives / Phenylthiohydantoin - therapeutic use / Phosphatase / Prognosis / Progression-Free Survival / Prostate cancer / Prostate-Specific Antigen - blood / Prostatic Neoplasms, Castration-Resistant - blood / Prostatic Neoplasms, Castration-Resistant - drug therapy / Prostatic Neoplasms, Castration-Resistant - mortality / Prostatic Neoplasms, Castration-Resistant - pathology / Retrospective Studies / Sociodemographics / Standard of care / Survival / Variables