Risk of prostate cancer diagnosis and mortality in men with a benign initial transrectal ultrasound-guided biopsy set: a population-based study

Background The risk of missing prostate cancer in the transrectal ultrasound-guided systematic biopsies of the prostate in men with suspected prostate cancer is a key problem in urological oncology. Repeat biopsy or MRI-guided biopsies have been suggested to increase sensitivity for diagnosis of prostate cancer, but the risk of disease-specifi c mortality in men who present with raised prostate-specifi c antigen (PSA) concentration and a benign initial biopsy result remains unknown. We investigated the risk of overall and prostate cancer-specifi c mortality in men with a benign initial biopsy set. Methods Data were extracted from the Danish Prostate Cancer Registry-a population-based registry including all men undergoing histopathological assessment of prostate tissue. All men who were referred for transrectal ultrasound-guided biopsy for assessment of suspected prostate cancer between Jan 1, 1995, and Dec 31, 2011, in Denmark were eligible for inclusion. Follow-up data were obtained on April 28, 2015. The primary endpoint was the cumulative incidence of prostate cancer-specifi c mortality, analysed in a competing risk setting, with death from other causes as the competing event. Findings Between Jan 1, 1995, and Dec 31, 2011, 64 430 men were referred for transrectal ultrasound-guided biopsy, of whom 63 454 were eligible for inclusion. Median follow-up was 5.9 years (IQR 3.8-8.5) and the total follow-up time, from the enrolment of the fi rst patient on Jan 1, 1995, until the extraction of causes of death on April 28, 2015, was 20 years. 10 407 (30%) of 35 159 men with malignant initial biopsy sets died from prostate cancer, compared with 541 (2%) of 27 181 men with benign initial biopsy sets. Estimated overall 20-year mortality was 761% (95% CI 730-79.2). In all men referred for transrectal ultrasound-guided biopsy, the cumulative incidence of prostate cancer-specifi c mortality after 20 years was 256% (247-26.5) versus 50.5% (475-535) for mortality from other causes. In men with benign initial biopsy sets, the cumulative incidence of prostate cancer-specifi c mortality was 52% (39-65) versus 599% (552-646) for mortality from other causes. In men with PSA concentrations 10 mu g/L or lower and benign initial biopsy sets (2779 men), the cumulative incidence of prostate cancer-specifi c mortality was 0.7% (02-1.3). Cumulative incidence of prostate cancer specifi c mortality in men with benign initial biopsy sets was 3.6% (95% CI 01-72) for men with a PSA higher than 10 ng/mL but 20 ng/mL or less (855 men) and 17.6% (12.7-22.4) and for men with a PSA higher than 20 ng/mL (454 men). Interpretation The fi rst systematic transrectal ultrasound-guided biopsy set holds important prognostic information. The 20-year risk of prostate cancer-specifi c mortality in men with benign initial results is low. Our fi ndings question whether men with low PSA concentration and a benign initial biopsy set should undergo further diagnostic assessment in view of the high risk of mortality from other causes. Funding Capital Region of Denmark's Fund for Health Research, Danish Cancer Society, Danish Association for Cancer Research, and Krista and Viggo Petersen's Foundation.