Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered a "Negative Core" in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis

OBJECTIVE: To assess the impact of excluding Gleason Grade Group 1 (GG1) prostate cancer (CaP) cores from current pre-radical prostatectomy (RP) nomograms.

METHODS: Multi-institutional retrospective chart review was performed on all RP patients with prostate biopsy between 2008 and 2018. Patients were individually assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti nomograms using the following iterations: (1) Original [ORIG] - all available core data and (2) Selective [SEL] - GG1 cores considered negative. Nomogram outcomes - lymph node invasion (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations and stratified based on biopsy GG. Clinically significant impact on management (CSIM) was defined as change in LNI risk above or below 2% or 5% (Δ2/Δ5). Nomogram outcomes were validated with RP pathology.

RESULTS: 7718 men met inclusion criteria. In men with GG2 who also had GG1 cores, SEL better predicted LNI (MSKCC - ORIG 4.97% vs SEL 3.50%; Briganti - ORIG 4.81% vs SEL 2.49%, RP outcome 2.46%), OCD (MSKCC - ORIG 40.91% vs SEL 48.44%, RP outcome: 68.46%) and ECE (MSKCC - ORIG 57.87% vs SEL 50.38%, RP outcome: 30.41%), but not SVI (MSKCC - ORIG 5.42% vs SEL 3.34%, RP outcome: 5.62%). This was also consistent in patients with GG3-5 disease. The greatest CSIM was on GG1-2 CaP; Δ2 and Δ5 in GG1 patients was 26.3%-31.0% and 1.5%-5.2%, respectively, and Δ2 and Δ5 in GG2 patients was 3.4%-22.2% and 12.3%-13.6%, respectively.

CONCLUSION: Excluding GG1 CaP cores from pre-RP nomograms better predicts final RP pathologic outcomes. More importantly, this may better reflect extent of true cancer burden.