Total Gleason Pattern 4 Length Outperforms Grade Group and Clinical Models in Predicting Oncologic Outcomes in Grade...

Risk 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.

We 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).

Total 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.

Total 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. What 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. Patient 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.

In 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.