MyProstateScore in men considering repeat biopsy: validation of a simple testing approach

Abstract

Background Men with persistent risk of Grade Group (GG) ≥ 2 cancer after a negative biopsy present a unique clinical challenge. The validated MyProstateScore test is clinically-available for pre-biopsy risk stratification. In biopsy-naïve patients, we recently validated a straightforward testing approach to rule-out GG ≥ 2 cancer with 98% negative predictive value (NPV) and 97% sensitivity. In the current study, we established a practical MPS-based testing approach in men with a previous negative biopsy being considered for repeat biopsy. Methods Patients provided post-digital rectal examination urine prior to repeat biopsy. MyProstateScore was calculated using the validated, locked model including urinary PCA3 and TMPRSS2:ERG scores with serum PSA. In a clinically-appropriate primary (i.e., training) cohort, we identified a lower (rule-out) threshold approximating 90% sensitivity and an upper (rule-in) threshold approximating 80% specificity for GG ≥ 2 cancer. These thresholds were applied to an external validation cohort, and performance measures and clinical outcomes associated with their use were calculated. Results MyProstateScore thresholds of 15 and 40 met pre-defined performance criteria in the primary cohort (422 patients; median PSA 6.4, IQR 4.3–9.1). In the 268-patient validation cohort, 25 men (9.3%) had GG ≥ 2 cancer on repeat biopsy. The rule-out threshold of 15 provided 100% NPV and sensitivity for GG ≥ 2 cancer and would have prevented 23% of unnecessary biopsies. Use of MyProstateScore >40 to rule-in biopsy would have prevented 67% of biopsies while maintaining 95% NPV. In the validation cohort, the prevalence of GG ≥ 2 cancer was 0% for MyProstateScore 0–15, 6.5% for MyProstateScore 15–40, and 19% for MyProstateScore >40. Conclusions In patients who previously underwent a negative prostate biopsy, the MyProstateScore values of 15 and 40 yielded clinically-actionable rule-in and rule-out risk groups. Using this straightforward testing approach, MyProstateScore can meaningfully inform patients and physicians weighing the need for repeat biopsy.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer

“…In one prior study, among 229 patients undergoing repeat biopsies, the EPI test provided 82% sensitivity and 27% specificity for high-grade cancer . Among 268 patients undergoing repeat biopsies, MPS provided 100% sensitivity and 23% specificity . In the current analysis including 247 patients, at 94.4% sensitivity, MPS2+ provided 51% specificity, compared with 8.7% with PHI, 14% with the derived multiplex 2-gene model, 16% with the derived multiplex 3-gene model, and 15% with MPS.…”

Development and Validation of MyProstateScore 2.0 to Detect Clinically Significant Prostate Cancer

“…One example is the MyProstateScore test (MPS), which measures expression of prostate cancer antigen 3 (PCA3) and the TMPRSS2:ERG (T2:ERG) gene fusion in clinical urine specimens. 15 The multivariable MPS model has outperformed PSA-based tools in detecting clinically significant prostate cancer across multiple validation studies 16,17 and is currently proposed by the National Comprehensive Cancer Network (NCCN) for consideration prior to biopsy in men with elevated PSA. 10 Acknowledging the indolent nature of low-grade prostate cancer, contemporary guidelines emphasize a narrowed clinical focus on detection of higher-grade, clinically significant cancers.…”