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

By: Sandra Miriam Kawa, MD, PhD; Hein Vincent Stroomberg, MSc, PhD; Signe Benzon Larsen, MSc,; John Thomas Helgstrand, MD, PhD; Birgitte Gronkaer Toft, MD; Andrew Julian Vickers, PhD; Klaus Brasso, MD, PhD; Martin Andreas Roder, MD, PhD | Posted on: 01 Jul 2022

Kawa SM, Stroomberg HV, Larsen SB et al: A nationwide analysis of risk of prostate cancer diagnosis and mortality following an initial negative transrectal ultrasound biopsy with long-term followup. J Urol 2022; 208: 100.

Study Need and Importance

Magnetic resonance imaging (MRI) and targeted biopsies of the prostate can find high-grade prostate cancers in 50% of men with previous negative systematic transrectal ultrasound (TRUS) biopsies. However, the risk of missing lethal prostate cancer in systematic TRUS biopsies remains at debate. Long-term population-based analysis of men with initial negative TRUS biopsies without MRI can elucidate the oncologic risk of these missed cancers.

Figure. Nonparametric regression model with locally estimated scatterplot smoothing for 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 TRUS-guided biopsy (A) and a magnification for prostate cancer-specific death with 95% CI 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.

What We Found

Among 37,214 men with negative TRUS biopsy and a median followup of 10 years, the 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7–2.1). In men with prostate specific antigen (PSA) <10 ng/ml at the time of biopsy, the risk was 1.3% (95% CI: 0.9–1.6), even lower in men with normal digital rectal examination (see Figure). The risk was 4.6% (95% CI: 3.4–5.8) for PSA above 20 ng/ml. Among men who underwent re-biopsy, 12% were found to have Gleason score ≥7. The risk of detecting a Gleason score ≥7 increased with longer time to re-biopsy. Prostate cancer mortality after re-biopsy was similar to mortality after initial biopsy.

“Among 37,214 men with negative TRUS biopsy and a median followup of 10 years, the 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7–2.1).”


Missing pre-biopsy PSA values and missing information on other variables such as prostate volume or PSA kinetics were the primary limitations. Clinical information was not available, and there were no stringent guidelines for followup programs or indication for re-biopsy as the data reflect clinical practice over a 20-year period.

Interpretation for Patient Care

Our findings document that mortality from prostate cancer in men with initial negative systematic TRUS biopsies is very low and raise questions about the routine use of MRI in this clinical setting. The data point to the fact that high-grade cancers found by MRI in this setting do not have the oncologic risk attributed to men with high-grade prostate cancer found in the initial biopsy set.