Total Gleason Pattern 4 Length Outperforms Grade Group and Clinical Models in Predicting Oncologic Outcomes in Grade Group 2-4 Prostate Cancer

Background and ObjectiveRisk stratification in localized prostate cancer relies primarily on Grade group (GG). In GG2-4 disease, risk assignment depends on the proportions of pattern 3 and pattern 4. We hypothesized that total pattern 4 length on biopsy would better predict oncologic outcome than GG, percent pattern 4, and multivariable models ("nomograms") based on clinical variables. MethodsWe identified 2499 patients with GG2-4 prostate cancer on biopsy who underwent radical prostatectomy. Discrimination for predictors was calculated for adverse pathologic stage (seminal vesicle invasion or lymph node invasion) and biochemical recurrence (BCR). Key Findings and LimitationsTotal pattern 4 length for the case demonstrated the highest discrimination for adverse pathologic stage in comparison with GG (AUC 0.779 vs 0.658; p<0.0001), percent pattern 4 (0.719), and a model including prostate-specific antigen level, clinical stage, GG, PI-RADS score, and number of positive cores (0.762). Results were similar for BCR, with total pattern 4 length outperforming GG (C-index 0.716 vs 0.662), percent pattern 4 (0.695), and the clinical model (0.699). Neither mm of pattern 3 nor the clinical model added discrimination to total mm of pattern 4. Conclusions and Clinical ImplicationsTotal length of Gleason pattern 4 on biopsy best predicts oncologic outcome in GG2-4 prostate cancer. Other common clinicopathologic variables do not further aid discrimination. Further research is warranted to determine the optimal method for quantifying pattern 4 before incorporation into risk stratification algorithms. O_LIWhat does the study add?: Patients with Grade group 2-4 prostate cancer constitute both the largest group and the one in which treatment decision-making is most difficult. For such patients, total length of Gleason pattern 4 on biopsy predicted oncologic outcomes better than Grade group or multivariable models including the standard predictors of stage, grade, PSA, PI-RADS and number of positive cores. Neither mm of pattern 3 nor the standard predictors add discrimination once total length of pattern 4 is known. C_LIO_LIPatient Summary: Treatment decisions in prostate cancer are often determined by the ratio of pattern 4 to pattern 3 disease. We showed that, in GG2-4 disease, using the total amount of pattern 4 for the case better predicts risk and therefore provides a better basis for treatment decisions. C_LI Take Home MessageIn Grade group 2-4 prostate cancer, total Gleason pattern 4 length for the case is a stronger predictor of adverse pathologic stage and biochemical recurrence than Grade group and other standard clinical variables. Further research is warranted to determine the optimal method for quantifying pattern 4 before incorporation into risk stratification algorithms.