ISUP Group 4 - a Homogenous Group of Prostate Cancers?

The International Society of Urological Pathology (ISUP) and the World Health Organisation have adopted a five-tiered prognostic grade group for prostate cancer in 2014. Grade group 4 is comprised of Gleason patterns 4 + 4, 3 + 5 and 5 + 3. Recent articles have suggested heterogeneity in their prognostic outcomes. We aimed to determine whether there was a difference in mortality outcomes within the ISUP 4 grouping, as identified on needle biopsy. A total of 4080 men who were diagnosed with non-metastatic (N0 M0) prostate cancer on biopsy with Gleason scores of 7, 8 and 9 were included. Multi-variable Cox Regression and Fine and Grey competing risk analysis were used to determine the All-Cause Mortality (ACM) and the Prostate Cancer Specific Mortality (PCSM) as a function of Gleason Scores (Gleason 3 + 4, 4 + 3, 4 + 4, 3 + 5/5 + 3, 9). Gleason score 4 + 4 was utilized as the referent. The 60 months' prostate cancer specific mortality with Gleason patterns 4 + 4 and 3 + 5/5 + 3 were 17% and 20% respectively (P < 0.01). Patients with 3 + 5/5 + 3 disease, had no statistically significant difference in the ACM (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [Cl] 0.68-1.4, p = 0.99) and PCSM risk (aHR 0.77, 95% Cl 0.47-1.2, p = 0.31) when compare with the referent group of patients. Patients with Gleason patterns 4 + 3 and 9 had statistically significant difference in their PCSM risk (aHR 0.70, 95% CI 0.54-0.91, P < 0.001 and aHR 1.5, 95% Cl 1.2-1.9, P < 0.001) when compared to the referent group. Our analysis suggest that ISUP group 4 is homogenous in terms of the all-cause mortality and the prostate cancer specific morality risk as differentiated by the presence of Gleason 5 score.