According to current guidelines of both the European Association of Urology and the American Urological Association, an individual risk stratification should precede prostate biopsy (PBx) in patients with suspected prostate cancer (PCa).^1,2 This aims at reducing overdiagnosis as well as PBx-related complications. Recent findings have shown that risk stratification using the Rotterdam Prostate Cancer Risk Calculator (RPCRC, issued by SWOP) can lead to a significant decrease in the detection of low-risk PCa while simultaneously increasing the detection rate of clinically significant PCa (csPCa). Additionally, the number of cores taken per patient can be reduced significantly.³ But there is still fear of missing csPCa. Retrospective analyses have shown that between 4% and 6.8% of men harbor csPCa despite having been stratified as low risk according to the RPCRC.^4,5 Therefore, a clear pathway is needed to followup this low-risk subgroup of men not undergoing PBx in the first place.

Table. Baseline characteristics of 110 patients

The combination of low PSA density and negative multiparametric MRI (mpMRI) is a reliable predictor of the absence of csPCa.⁶ Thus, a safety net based on PSA density was analyzed (Fig. 1).

The safety net consists of 3 steps. After initial low-risk stratification, men and their referring urologist are asked to perform PSA testing and digital rectal examinations (DREs) regularly (step 1). If PSA density exceeds 0.15 ng/ml/ml in PBx-naïve men or 0.2 ng/ml/ml in men with prior PBx, a new MRI is recommended (step 2). If risk stratification based on the new parameters reveals a progression from low-risk to intermediate- or high-risk csPCa, patients are advised to undergo PBx. If risk stratification remains low risk, the surveillance should be continued (step 3).

Figure 1. Safety net based on PSA density.

A total of 112 men who had been stratified as low risk at our institution between September 2019 and February 2020 were included in this study; 49 men (44.1%) were biopsy-naïve. The median age of all men was 63 years (interquartile range [IQR] 58–68 years). Median PSA was 6.6 ng/ml (IQR 4.6–9.4) at initial presentation with a slight decrease to a median PSA of 6.1 ng/ml (IQR 4.4–8.1) during followup. During a median followup of 12.5 months, 110 men (98.2%) adhered to the proposed safety net. Further patient characteristics are shown in the Table.

A relevant increase of the PSA density was detected in 15 men (13.6%), resulting in a new MRI. After repeated risk stratification, 11 men (10%) had biopsy performed due to an increased risk of csPCa. Figure 2 depicts the distribution of risk classifications after followup. All men with an increased risk underwent MRI-fusion PBx. On MRI no high-grade Prostate Imaging–Reporting and Data System^® (PI-RADS^®) lesions according to PI-RADS V. 2.1 (ie PI-RADS score ≥3) were detected.⁷

Figure 2. Distributions of risk classifications after followup of 12.5 months.

Histopathological results showed low-risk PCa in only 1 patient (Gleason pattern 3+3 in 1 out of 12 cores, infiltration <5%). Hence, no csPCa was detected.

Furthermore, it should be noted that in addition to the 110 men discussed in this article, 12 men underwent subvesical desobstruction after initial low risk stratification. Pathology did not find PCa in any of these men.

To our knowledge, this study is the first to prospectively follow men who were stratified as low risk by using the RPCRC. In conclusion, omitting PBx in patients stratified as low risk according to the RPCRC appears to be safe. The probability of missing csPCa seems marginal at best. However, men who are stratified as low risk should be monitored closely. Special attention should be paid to younger, PBx-naïve men. In general, parameters such as PSA velocity and family history of PCa should be considered when counseling men on whether to omit PBx after low risk stratification, as well. A safety net based on PSA density might provide additional security for both patients and urologists.