Prostate cancer mortality in the United States has declined in recent years, but this cancer remains the most common nonskin epithelial malignancy in US men, with 186 320 new cases and 28 660 deaths (the second leading cause of cancer death) estimated for 2008.¹ An effective prevention strategy for prostate cancer would have substantial public health benefits, including the potential to reduce the incidence of biologically indolent prostate cancer, which is significantly overdetected by widespread screening with prostate-specific antigen (PSA) and for which most newly diagnosed men still undergo curative-intent therapy involving substantial morbidity despite surgical and other advances.^2-6

Lifetime risk of prostate cancer in the United States is currently estimated to be 16%.¹ Although most cases are found at an early, curable stage, treatment is costly and urinary, sexual, and bowel-related adverse effects are common.² Even men who choose active surveillance as an initial management strategy face anxiety, uncertain prognosis, and a measurable risk of sepsis with follow-up biopsies,³ and more than one-third of those who initially defer therapy are ultimately treated.^4,5 With such a high prevalence, risk of morbidity from treatment, and treatment-related costs, primary prevention of prostate cancer is an attractive option.

A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. NCT02889978.

Delays in time to treatment initiation (TTI) for new cancer diagnoses cause patient distress and may adversely affect outcomes. We investigated trends in TTI for common solid tumors treated with curative intent, determinants of increased TTI and association with overall survival. We utilized prospective data from the National Cancer Database for newly diagnosed United States patients with early-stage breast, prostate, lung, colorectal, renal and pancreas cancers from 2004–13. TTI was defined as days from diagnosis to first treatment (surgery, systemic or radiation therapy). Negative binomial regression and Cox proportional hazard models were used for analysis. The study population of 3,672,561 patients included breast (N = 1,368,024), prostate (N = 944,246), colorectal (N = 662,094), non-small cell lung (N = 363,863), renal (N = 262,915) and pancreas (N = 71,419) cancers. Median TTI increased from 21 to 29 days (P<0.001). Aside from year of diagnosis, determinants of increased TTI included care at academic center, race, education, prior history of cancer, transfer of facility, comorbidities and age. Increased TTI was associated with worsened survival for stages I and II breast, lung, renal and pancreas cancers, and stage I colorectal cancers, with hazard ratios ranging from 1.005 (95% confidence intervals [CI] 1.002–1.008) to 1.030 (95% CI 1.025–1.035) per week of increased TTI. TTI has lengthened significantly and is associated with absolute increased risk of mortality ranging from 1.2–3.2% per week in curative settings such as early-stage breast, lung, renal and pancreas cancers. Studies of interventions to ease navigation and reduce barriers are warranted to diminish potential harm to patients.