A Nationwide Analysis of Risk of Prostate Cancer Diagnosis and Mortality following an Initial Negative Transrectal Ultrasound Biopsy with Long-Term Followup

Abstract

Purpose: Magnetic resonance imaging (MRI) targeted prostate biopsy has been shown to find many high-grade prostate cancers in men with concurrent negative transrectal ultrasound (TRUS) systematic biopsy. The oncologic risk of such tumors can be explored by looking at long-term outcomes of men with negative TRUS biopsy followed without MRI. The aim was to analyze the mortality after initial and second negative TRUS biopsy.

Materials and methods: All men who underwent initial TRUS biopsies between January 1, 1995 and December 31, 2016 in Denmark were included. A total of 37,214 men had a negative initial TRUS biopsy and 6,389 underwent a re-biopsy. Risk of cause-specific mortality was analyzed with competing risks. Diagnosis of Gleason score ≥7 prostate cancer following negative biopsies was analyzed with multivariable logistic regression including time to re-biopsy, prostate specific antigen (PSA), age and digital rectal examination.

Results: The 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7-2.1). Prostate cancer-specific mortality was 1.3% (95% CI: 0.9-1.6) and 4.6% (95% CI: 3.4-5.8) for men with PSA <10 and >20 ng/ml, respectively. Of the TRUS re-biopsies 12% were Gleason score ≥7 and risk of Gleason score ≥7 increased with longer time to re-biopsy (p <0.001). Mortality after re-biopsy was similar to after initial biopsy.

Conclusions: Men with negative TRUS biopsies have a very low prostate cancer-specific mortality, especially with PSA <10 ng/ml. This raises serious questions about the routine use of MRI targeting for initial prostate biopsy and suggests that MRI targeting should only be recommended for men with PSA >10 ng/ml after negative biopsy.

Keywords: biopsy; epidemiology; magnetic resonance imaging; mortality; prostatic neoplasm.

Figure 1:

Flow chart for the cohort. Abbreviations: MRI: magnetic resonance imaging, PCa: prostate cancer, PIN: prostatic intraepithelial neoplasia, PSA: prostate specific-antigen, TRUS: transrectal ultrasound-guided.

Figure 2:

Cumulative incidence of prostate cancer-specific mortality after initial negative transrectal ultrasound-guided biopsies, stratified on prostate-specific antigen (PSA) values (N=19,094).

Figure 3:

Non-parametric regression model with locally estimated scatterplot smoothing (LOESS) for prostate-specific antigen (PSA) of men with cT1 at the time of initial biopsy for men with benign histopathological evaluation. Figures illustrate the risk of prostate cancer-specific death (Blue) and other cause death (Red) at 10 years (solid line) or 15 years (dashed line) following an initial negative transrectal ultrasound-guided biopsy (A) and a magnification for prostate cancer-specific death with 95% confidence interval of the fitted line (B). The density plot shows the distribution of the PSA-values for the cause of death (A). Note that there is a second y-axis in plot A on the right illustrating the scale of the density plot and that the y-axes between plot A and B are different.

Figure 4:

Risk of Gleason score 7 or above prostate cancer in transrectal ultrasound-guided (TRUS) re-biopsy depending on the time between initial biopsy and first re-biopsy modelled for mean age, median prostate-specific antigen (PSA) and a normal digital rectal examination. at time of initial TRUS-biopsies. The 95% confidence interval is depicted with dotted lines (N=6,389). The density plot shows the distribution of time between initial biopsy and first re-biopsy. Note that there is a second y-axis on the right illustrating the scale of the density plot.