Questioning the status quo: Should Gleason 3+3=6 PCa be considered a “negative core” for pre-RP risk nomograms?

Abstract

31 Background: Current pre-radical prostatectomy (RP) nomograms predicting RP pathology do not differentiate between Gleason 6 prostate cancer (Gl6 PCa) and clinically significant Gleason 7-10 PCa. As such, use of these nomograms can be problematic. We assess the impact of excluding Gl6 PCa on nomogram and RP outcomes. Methods: Utilizing a prospectively maintained database, all men who underwent prostate biopsy (PBx) prior to RP were identified. Each patient was assessed using the MSKCC Kattan and Briganti nomogram using the following iterations: 1) “Original” [ORIG] (all available core data) and 2) "Selective” [SEL] (only cores Gleason score ≥7). Nomogram outcomes (risk of LNI, ECE, SVI, and OCD), were compared across iterations and stratified based on pre-RP risk classification (3+3 [low], 3+4, 4+3, 8-10 [high]). Clinically significant impact on management [CSIM] was defined as a change in risk of LNI above or below 2% (Δ2) or 5% (Δ5), based on current guidelines recommendations for PLND. Nomogram outcomes were validated using RP pathology. Results: 1118 men met inclusion criteria. Using the Kattan nomogram, when compared to actual RP pathology, the SEL iteration was a better predictor of LNI, ECE and OCD than the ORIG iteration, but not SVI. Using the Briganti nomogram, the SEL iteration was a better predictor of LNI. As for CSIM, the greatest impact was on men with Gl7 PCa. In the 359 Gl 3+4 patients, Δ2 was 3.9-28.13% and Δ5 was 12.81-17.27%. In the 184 Gl 4+3 patients, Δ2 was 0% and Δ5 was 7.61-11.41%. In all cases, the change favored decreased need for PLND. Conclusions: As Gleason 3+3=6 PCa is increasingly being considered an insignificant prostate cancer, its inclusion in established pre-RP nomograms becomes problematic. We find that excluding Gl6 PCa cores from these nomograms can reduce the need to complete a PLND at the time of RP, and more importantly, may better reflect the true extent of cancer. [Table: see text]