Prognostic Significance of Sites of Metastatic Disease in Prostate Cancer: A Population-Based Study of 12,180 Patients

Abstract

Metastatic prostate cancer has a variable prognosis based on many patient and disease specific factors. To date, few population-based studies have examined the impact of metastatic disease sites on the survival of prostate cancer patients. We aimed to investigate this using the Surveillance, Epidemiology, and End Results (SEER) database. We included 12,180 patients from the SEER 18 registries diagnosed with metastatic prostate cancer from 2010-2014. From this population we identified those with metastatic disease in bone, brain, liver, and lung. Kaplan-Meier analyses and both univariate and multivariate Cox proportional hazards models were used to assess the impact of metastatic disease sites on overall survival (OS). The majority of patients were coded as having metastatic disease in bone without disease in the brain, liver or lung at the time of diagnosis (“bone-group,” n=10,620, 87% of the study population). With Cox regression accounting for age at diagnosis, race, prostate cancer histology, grade, T stage, N stage, PSA, and Gleason score, patients with disease coded as in the liver without bone, brain or lung metastases (“liver-group”) had poorer OS relative to patients in the bone-group (HR = 1.63, 95% CI 1.24-2.13, p<0.001). Patients with disease coded as metastases in the lung without bone, brain or liver metastases, or metastases in bone and lung without brain or liver metastases, did not differ significantly from patients in the bone-group with respect to OS (HR = 0.82, 95% CI, 0.63-1.06, p = 0.13; and HR = 1.12, 95% CI 0.98-1.28, p=0.10, respectively). Patients with other combinations of multiple metastatic disease sites at diagnosis had poorer OS than patients in the bone-group (p<0.001). This population-based hypothesis-generating analysis suggests that patients with prostate cancer confined to bone and/or lung may have improved OS relative to those with metastatic disease in the liver or affecting multiple sites. While it was anticipated that patients with bone metastases would represent a favorable subgroup, the favorable outcomes in patents with lung metastases (with or without bone metastases) was unexpected. These findings may inform future therapeutic investigations to improve the prognosis of prostate cancer patients harboring hepatic metastases and/or multiple sites of metastatic disease at presentation.