Quantifying the hidden burden of metastatic prostate cancer.

96 Background: Preventing metastatic disease is the key goal of prostate cancer screening and local treatment. However, most evaluations of metastasis burden focus only on de novo metastatic disease at diagnosis and do not capture metastatic recurrences after local therapy, such as those based on cancer registries in the United States (U.S.). Methods: We inferred the full burden of metastatic prostate cancer in the Health Professionals Follow-up Study, a prospective cohort of U.S. male health professionals aged 40–75 years at enrollment in 1986 with follow-up in this analysis through January 2018. We captured three ways how metastatic prostate cancer manifested: (1) de novo metastases at initial diagnosis, (2) metastatic recurrences reported by participants during active follow-up, and (3) metastases were inferred from deaths attributed to prostate cancer, under the assumption that such deaths are almost invariably preceded by distant metastases. Cause-of-death adjudication assumed 90% specificity of coding, with a conservative 70% applied in sensitivity analyses. Absolute risk (cumulative incidence) of metastatic prostate cancer was estimated using the Aalen–Johansen method, accounting for death from other causes as a competing risk. Results: Our study population of 50,420 men had a median age of 54 years at enrollment (interquartile range, 46 to 63 years) when they were free from prostate cancer. The study population was predominantly of European descent (95%), with 2% Asian and 1% African American participants. Over up to 30 years of follow-up, we documented 8,305 prostate cancer diagnoses. Of these, 1,504 cases were adjudicated to be metastatic at diagnosis or to have metastasized after initial diagnosis. De novo metastatic disease accounted for only 249 (17%) of all metastatic cases. Conservative causes-of-death adjudication estimated 1,314 metastatic cases, with 19% being de novo metastases. The risk of metastatic prostate cancer among men was 0.8% (95% confidence interval CI 0.8, 0.9) by age 70, 2.4% by age 80 (95% CI 2.3, 2.6), and 4.0% (95% CI 3.8, 4.2) by age 90 years. Four in ten metastatic prostate cancers occurred after age 80 years. De novo metastatic disease risk represented about one-quarter of metastases by age 70, with lower relative contributions with advancing age. The risk of metastatic disease was particularly high in African-American men (3.6% by age 80, 95% CI 2.2, 5.8), while the risk among Asian men (2.3% by age 80, 95% CI 1.4, 3.7) was comparable to that among European men (2.5% by age 80, 95% CI 2.3, 2.6). Conclusions: One in 25 men in a widely PSA-screened population developed metastatic prostate cancer over the lifetime. Much of this substantial disease burden would remain hidden if using de novo disease as the only measure. Clinical and registry-based evaluations of early detection and local treatment need to capture the full burden of metastatic disease, which disproportionally impacts the oldest age groups.