Impact of the evolving United States Preventative Services Task Force policy statements on incidence and distribution of prostate cancer over 15 years in a statewide cancer registry.

BACKGROUND: The United States Preventative Services Task Force (USPSTF) guideline on Prostate Specific Antigen (PSA)-based prostate cancer screening evolved both in 2008 (Grade I for men < 75 years and Grade D for men > 75 years) and in 2012 (Grade D for all ages). MATERIALS AND METHODS: A statewide cancer registry operated by the Pennsylvania Department of Health was accessed to analyze over a 15-year period prostate cancer rates across different categories including age, stage, and geographic distribution. RESULTS: Local prostate cancer rates decreased significantly when comparing before and after USPSTF's guideline changes: 2002-2008 vs. 2009-2012 vs. 2013-2016 (p < 0.005). Conversely, the distant cancer rates increased significantly in Caucasian men (but not in African American men) (p = 0.0078). In age group analysis, distant cancer rates increased significantly in all age ranges, most notably in younger men (50-59 years). No observed difference in the trend of distant cancer rates when considering rural versus urban counties. CONCLUSIONS: Incident prostate cancer cases diagnosed in Pennsylvania have decreased over the past 15 years with a recent rise in distant carcinomas potentially attributable to the USPSTF recommendations against PSA-based screening. Although the USPSTF revised their PSA-based prostate cancer screening guideline in 2018 (Grade C for men 55-69 years and Grade D for men > 70 years), the implications of the aforementioned observations on mortality outcomes merit further follow-up.

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.