Prediagnostic circulating 25-hydroxyvitamin D and prostate cancer-specific survival: a collaborative pooled analysis of 13 prospective studies

Background Previous research suggests higher risk of prostate cancer diagnosis in men with high vitamin D serology, but there are limited data related to prostate cancer survival. In this study, we examine the associations between prediagnostic circulating levels of 25-hydroxyvitamin D [25(OH)D] with risk of prostate cancer-specific mortality, as well as mortality from other causes, in participants diagnosed with prostate cancer. Methods We conducted a prospective multi-national collaborative analysis of pre-diagnostic circulating 25(OH)D, the major biochemical indicator of vitamin D status, with data for 12,635 incident prostate cancer cases from 13 cohorts. Multivariable-adjusted Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between study-specific/season-standardized categories as well as clinically defined 25(OH)D categories (<30, 30-<50, 50-<75, and ≥75 nmol/L) and mortality from prostate cancer and other causes. Results Analyses of circulating 25(OH)D and mortality were based on 3,445 deaths, of which 1,316 (38.2%) were due to prostate cancer. In fully adjusted models, men with high pre-diagnostic 25(OH)D concentrations experienced lower prostate cancer-specific mortality (HR for 80-percentile increase = 0.75, 95% CI: 0.64, 0.88; P trend < 0.001) and slightly lower risk of mortality from other causes (HR = 0.85, 95% CI: 0.75, 0.96, P trend = 0.009). In the subset of cases with complete stage and grade data (5,078 cases [40.2%] and 761 deaths from prostate cancer [57.8%]), the association between 25(OH)D and prostate cancer mortality was 0.81 (0.65, 0.99, P trend =0.04). Conclusions In this pooled analysis of 13 prospective cohorts, higher pre-diagnostic circulating vitamin D (25(OH)D) was associated with increased prostate cancer survival.