Risk stratification of prostate cancer with MRI and prostate-specific antigen density-based tool for personalized decision making

Objectives: MRI is now established for initial prostate cancer diagnosis; however, there is no standardized pathway to avoid unnecessary biopsy in low-risk patients. Our study aimed to test previously proposed MRI-focussed and risk-adapted biopsy decision models on a real-world dataset. Methods: Single-centre retrospective study performed on 2055 biopsy naive patients undergoing MRI. Diagnostic pathways included "biopsy all", "MRI-focussed" and two risk-based MRI-directed pathways. Risk thresholds were based on prostate-specific antigen (PSA) density as low (<0.10 ngmL(-2)), intermediate (0.10-0.15 ngmL(-2)), high (0.15-0.20 ngmL(-2)), or very high-risk (>0.20 ngmL(-2)). The outcome measures included rates of biopsy avoidance, detection of clinically significant prostate cancer (csPCa), missed csPCa, and overdiagnosis of insignificant prostate cancer (iPCa). Results: Overall cancer rate was 39.9% (819/2055), with csPCa (Grade-Group >= 2) detection of 30.3% (623/2055). In men with a negative MRI (Prostate Imaging-Reporting and Data System, PI-RADS 1-2), the risk of cancer was 1.2%, 2.6%, 9.0%, and 12.9% in the low, intermediate, high, and very high groups, respectively; for PI-RADS score 3 lesions, the rates were 10.5%, 14.3%, 25.0%, and 33.3%, respectively. MRI-guided pathway and risk-based pathway with a low threshold missed only 1.6% csPCa with a biopsy-avoidance rate of 54.4%, and the risk-based pathway with a higher threshold avoided 62.9% (1292/2055) of biopsies with 2.9% (61/2055) missed csPCa detection. Decision curve analysis found that the "risk-based low threshold" pathway has the highest net benefit for probability thresholds between 3.6% and 13.9%. Conclusion: Combined MRI and PSA-density risk-based pathways can be a helpful decision-making tool enabling high csPCa detection rates with the benefit of biopsy avoidance and reduced iPCa detection. Advances in knowledge: This real-world dataset from a large UK-based cohort confirms that combining MRI scoring with PSA density for risk stratification enables safe biopsy avoidance and limits the over-diagnosis of insignificant cancers.