Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance

Abstract

Purpose: Latent grade group 2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group 2 cancers. Materials and Methods: Low-and intermediate-risk prostate cancer patients were assigned to training (n[333) and validation (n[202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with crossvalidation, we evaluated methods for training classifiers of pathological grade group 2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort.

Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance. Letter.

“…To the Editor: We read the article by Berman et al with great interest, which presents a classifier consisting of multimodal biomarkers for predicting Gleason pattern 4. 1 The study examined multiple molecular and clinical variables from 535 men who underwent prostatectomy between 1999 and 2013. The personalized risk stratification for patients with early prostate cancer (PRONTO) program generated 2 classifiers: PRONTO-e and PRONTO-m.…”

“…Additionally, it would be interesting to emphasize the cases with GG ≥3 in Figure 3, C in the article. 1 Due to a higher proportion of Gleason pattern 4 in the specimens, including Gleason pattern 5, the prediction scores may be higher. However, due to the limited sample size in this study, statistical significance may not be achieved.…”