Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States.

BACKGROUND: New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among patients with CRPC in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We also estimated the proportion of men with CRPC with bone metastases and overall survival. METHODS: We conducted a retrospective cohort study of United States (US) men aged ≥ 65 years with CRPC. Cohort entry was from January 1, 2000, to December 31, 2011, with follow-up through December 31, 2013. Castration resistance was defined by treatment with second-line systemic therapy (after surgical or medical castration). SPM were diagnoses of primary cancers (other than prostate) in SEER or Medicare data. RESULTS: Altogether 2,234 patients met eligibility criteria. Most (1,887; 84.5%) had evidence of bone metastases in Medicare claims. SPM occurred in 172 patients (incidence rate 5.9 per 100 person-years; 95% confidence interval [CI], 5.0-6.8; standardized incidence ratio = 3.1, 95% CI, 2.8-3.6, based on SEER incidence rate of all malignancies except prostate cancer among men aged ≥ 65 years). The most common SPM were lung/bronchus (n = 29, 16.9%), urinary bladder (n = 22, 12.8%), and colon/rectum (n = 21, 12.2%). Median survival was 1.2 years (95% CI, 1.1-1.3); 5-year survival was 9% (95% CI, 7-11%). CONCLUSIONS: This study provides the first estimate of SPM risk in older men with CRPC in the US. The incidence rate is approximately threefold higher than the population-based cancer incidence among men without prostate cancer.