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IMPORTANCE Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.OBJECTIVE To validate the GC in the context of a randomized phase 3 trial. DESIGN, SETTING, AND PARTICIPANTSThis ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019.INTERVENTION Salvage radiotherapy (sRT) with or without 2 years of bicalutamide. MAIN OUTCOMES AND MEASURESThe preplanned primary end point of this study was the independent association of the GC with the development of DM. RESULTSIn this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (−7.8% vs 4.6%). CONCLUSIONS AND RELEVANCEThis ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT.

The aim of this study was to determine the correlation of ultrasonographic estimates of testicular volume with true testicular volume and to compare the accuracy and precision of the three most commonly utilized formulas. A total of 15 patients underwent high-resolution ultrasonography (US) analysis for testicular volume before orchiectomy. Testicular volume was calculated using three common formulas: (1) All three US formula measurements significantly underestimated the true testicular volume. The largest mean biases were observed with US formula 1, which underestimated the true volume by 3.3 mL (31%). US formula 2 had a smaller mean difference from the true volume, with an underestimation of only 0.6 mL (6%). Regression analysis showed that formulas 1 and 2 had better R 2 values than formula 3. However, all three US formulas displayed a strong linear relationship with the true volume (R 2 = 0.872−0.977; P < 0.001). Among the commonly used US formulas, the empirical formula of Lambert (L × W × H × 0.71) provided better accuracy than the other two formulas evaluated, and better precision than formula 3. Therefore, the formula of Lambert is the optimal choice in clinical practice.

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PurposeNeoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) in patients with non-metastatic muscle-invasive bladder cancer (MIBC) confers an absolute survival benefit of 5-10%. There is evidence that molecular differences between tumors may impact response to therapy, highlighting a need for clinically validated biomarkers to predict response to NAC. Materials and MethodsFour bladder cancer cohorts were included. Inverse probability weighting was used to make baseline characteristics (age, sex, and clinical tumor stage) between NAC-treated and untreated groups more comparable. Molecular subtypes were determined using a commercial genomic subtyping classifier. Survival rates were estimated using weighted Kaplan Meier (KM) curves. Cox proportional hazards (PH) models were used to evaluate the primary and secondary study endpoints of overall survival (OS) and cancer-specific survival (CSS), respectively. ResultsA total of 601 patients with MIBC were included, where 247 had been treated with NAC and RC and 354 underwent RC without NAC. With NAC, the overall net benefit to OS and CSS at three years was 7% and 5%, respectively. After controlling for clinicopathologic variables, non-luminal tumors had greatest benefit from NAC with 10% greater OS at 3 years (71% vs 61%) while luminal tumors had minimal benefit (63% vs 65%) for NAC vs. non-NAC, respectively. ConclusionsIn patients with MIBC, a commercially available molecular subtyping assay revealed non-luminal tumors received the greatest benefit from NAC, while patients with luminal tumors experienced a minimal survival benefit. A genomic classifier may help identify patients with MIBC who would benefit most from NAC.