The changing landscape of treatment and survival for men with castration-resistant prostate cancer in the era of novel treatments.

Abstract

67 Background: Several therapies for men with castration-resistant prostate cancer (CRPC) have become available since 2010 with the hope of prolonging survival for those at the end stages of their disease. Little is known about the survival of men who receive novel therapies in the real world and the disease burden of patients initiating treatment for CRPC between 2010 and 2017. Methods: Using the Veterans Health Affairs Corporate Data Warehouse, we identified Veterans with CRPC who received first-line therapy for castration-resistant disease between 2010-2017. Therapies included ketoconazole, docetaxel, abiraterone, and enzalutamide since > 99% of patients treated for CRPC received one of these therapies first-line for CRPC. We used a Cox model to calculate the overall survival of patients from time of first CRPC treatment for each year. We then adjusted for patient and disease characteristics, such as starting PSA level, and prognostic group at the start of treatment based on hemoglobin, alkaline phosphatase, and albumin levels. Results: In a cohort of 4,998 men started on treatment for CRPC between 2010-2017, survival from start of first-line treatment gradually increased between 2010-2017. In 2010, when 38% of men received docetaxel first-line and 62% ketoconazole, the probability of surviving at least one year from start of first-line therapy was 64%. In 2017, when the landscape of first-line treatment had changed (49% abiraterone, 9% docetaxel, 41% enzalutamide, 1% ketoconazole) one-year survival from start of first therapy improved to 72%. The unadjusted hazard ratio (HR) for an additional calendar year was 0.93 (95% confidence interval [CI], 0.91-0.95). Men started on first-line CRPC therapy in 2010 had worse prognostic labs at the start of therapy, suggesting worse disease, and had a higher PSA value at the start of therapy compared to those started on CRPC therapy in 2017 (median PSA 55.1 in 2010 vs 27.8 in 2017, p-value < 0.01). When adjusting for disease characteristics, the improvement in survival we saw between 2010 and 2017 was diminished with adjusted HR for an additional calendar year of 0.97 (95% CI, 0.94-1.00). Conclusions: With the development of novel therapies, the survival of patients with similar disease burden should gradually improve over time. Although we did see a modest improvement in survival between 2010-2017, this improvement was mitigated when adjusting for disease severity, suggesting that some of the improvement in survival may be affected by a lead-time bias—treating patients earlier in their CRPC.

OSCAR: Optimal subset cardinality regression using the L0-pseudonorm with applications to prognostic modelling of prostate cancer

“…Compromised intake of nutrients may be caused by cancer, cancer-related decrease in daily performance or cancer treatments, suggesting a potential link between ALB and cancer prognosis [ 48 , 49 ]. In addition, ALB is considered to reflect liver function and in metastasized, castration-resistant prostate cancer, and lowered levels of ALB is known to associate with increased tumor burden [ 50 , 51 ].…”

OSCAR: Optimal subset cardinality regression using the L0-pseudonorm with applications to prognostic modelling of prostate cancer

“…Compromised intake of nutrients may be caused by cancer, cancer-related decrease in daily performance or cancer treatments, suggesting a potential link between ALB and cancer prognosis [43, 44]. In addition, ALB is considered to reflect liver function and in metastasized, castration-resistant prostate cancer, and lowered levels of ALB is known to associate with increased tumor burden [45, 46].…”