AUA 2018: Population-Based Outcomes of Men with a Single Negative Prostate Biopsy: Importance of Continued Follow Up Among Older Patients

San Francisco, CA ( In the PSA testing era, men are frequently being tested for elevated PSA levels and many subsequently undergo a prostate biopsy. Based on data from the PLCO trial, upwards of 13 men per 100 will have a biopsy for a positive prostate cancer screening test [1].Furthermore, prostate biopsies have false-negative rates of 20-30%. Men with a negative biopsy represent a unique cohort, and numerous ancillary testing (e.g. imaging modalities/biomarkers) have been proposed to risk-stratify this cohort.

Currently, the long-term health outcomes of North American men with a single negative TRUS-biopsy have yet to be defined at a population level. Men with negative biopsies may thus undergo repeat biopsies, get diagnosed with prostate cancer, receive treatment, and potentially die of prostate cancer. Dr. Rashid Sayyid from Augusta University at the prostate cancer epidemiology session at the 2018 AUA discussed results of their study determining the long-term health outcomes of North American men with a negative first transrectal ultrasound-guided prostate biopsy. 

For this study, the authors performed a population-based study, using data from linked health administrative databases, of all Ontario, Canada-based men with a negative first biopsy between January 1994 and October 2014 (n=95,675). Patients were followed from time of first biopsy till death, administrative censoring, or end of study period. Cumulative incidence functions were used to calculate the study outcomes’ cumulative incidences, which accounts for the competing risk of death from other causes in these patients. Covariates of interest included age at index biopsy, socioeconomic status, and area of residence (i.e. urban versus rural) were evaluated as potential predictors of both prostate diagnosis and prostate cancer mortality. These data were extracted from the Registered Persons Database, which contains demographic data of all Ontario residents with health coverage. Socioeconomic status, a categorical variable with five strata, was derived from the patient’s postal code and its associated neighborhood income quintile. 

Among patients included in the study, the median age was 63.0 years and median follow-up was 8.1 years. The 20-year prostate cancer diagnosis cumulative rate was 23.7%. Among patients subsequently diagnosed with prostate cancer, 71.3% were diagnosed after one biopsy, 19.4% after two, and 8.3% after three or more repeat biopsies. The 20-year cumulative rate of prostate cancer-specific mortality was 23.7%. Men ages 70-79 and 80-84 at initial biopsy had 20-year prostate cancer-specific mortality cumulative rates of 3.2% and 6.9%, respectively. The 20-year cumulative rates of receiving a radical prostatectomy was 7.6%, 6.1% for receiving definitive radiotherapy, and 7.2% for receiving androgen deprivation therapy, with men ages 70 and older significantly less likely to receive definitive therapy (p<0.001). A total of 5,783 patients underwent radical prostatectomies (5,401 as the primary treatment modality and 382 as salvage therapy following radiation), accounting for 6.0% of the cohort. The cumulative incidences of undergoing radical prostatectomy after 5, 10, 15, and 20 years of follow-up were 5.2%, 6.8%, 7.4%, and 7.6%, respectively. Higher socioeconomic status and urban residence were associated with higher diagnosis risks yet lower prostate cancer-specific mortality risks. 

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The strength of the current study is the granularity of the population-level analysis, with long term follow-up after a negative biopsy. Limitations to the study include the lack of pre-biopsy PSA levels and biopsy-derived Gleason score. Furthermore, there was a lack of data on other known predictors such as clinical stage, family history of prostate cancer, or patient ethnicity. Dr. Sayyid concluded with several take-home points, noting that this is the first population-based study assessing long-term cancer outcomes in North American men with a single negative transrectal ultrasound-guided prostate biopsy. Following a negative initial biopsy, 23.7% of men are still diagnosed with and 1.8% die of prostate cancer within 20 years. Cancer-specific mortality outcomes are significantly worse in older men, suggesting the need for more aggressive management approaches in appropriately selected elderly men. 

Presented By: Rashid Sayyid, Medical College of Georgia – Augusta University, Augusta, GA 
Co-Authors: Shabbir Alibhai, Rinku Sutradhar, Maria Eberg, Kinwah Fung, Zachary Klaassen, Hanan Goldberg, Nathan Perlis, David Urbach, Neil Fleshner, Toronto, Canada 

1. Pinsky PF, Parnes HL, Andriole G. Mortality and complications following prostate biopsy in the PLCO Cancer Screening Trial. BJU Int 2014;113(2):254-259. 

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre Twitter: @zklaassen_md at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA