Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy

The 18-gene MyProstateScore 2.0 (MPS2) test was previously validated for detection of grade group (GG) ≥ 2 prostate cancer using post-digital rectal examination (DRE) urine. To improve ease of testing, we validated MPS2 using first-catch, non-DRE urine. Patients provided first-catch urine before biopsy. MPS2 values were calculated using previously validated models differing only by extent of clinical data included biomarkers alone (BA; no clinical data), biomarkers and clinical factors (BA + CF), and biomarkers, clinical factors, and prostate volume (BA + CF + PV). The primary outcome was GG ≥ 2 cancer on biopsy. MPS2 performance and clinical consequences of testing were compared with PSA and the Prostate Cancer Prevention Trial risk calculator (PCPTrc). The cohort included 266 men with median PSA 6.6 ng/mL (IQR, 4.9-9.1) of whom 103 (39%) had GG ≥ 2 cancer on biopsy. The AUC for GG ≥ 2 cancer was 57% for PSA, 62% for PCPTrc, and 71%, 74%, and 77% for MPS2 models. Under a testing approach detecting > 90% of GG ≥ 2 cancers, MPS2 testing would have avoided 36% to 42% of unnecessary biopsies, as compared with 13% using the PCPTrc. In patients with a prior negative biopsy, MPS2 testing would have avoided 44% to 53% of repeat biopsies, as compared with only 2.6% using PCPTrc. Using first-catch urine, MPS2 meaningfully improved the proportion of biopsies avoided relative to PCPTrc while maintaining highly sensitive detection of GG ≥ 2 cancer. Non-DRE testing provides a convenient, objective, and highly accurate testing option to reduce the need for imaging and biopsy in men with elevated PSA.