Favorable Intermediate-Risk Prostate Cancer Leads to Worse Survival Compared to Low-Risk Patients due to Adverse Pathology
Intermediate-risk (IR) prostate cancer is a heterogenous classification. While potential favorable criteria have been proposed to guide treatment decisions, recent evidence suggests rates of adverse pathology are not comparable to low-risk (LR) patients. Preoperative clinical stage and Grade Group (GG) on needle biopsy are often upstaged or upgraded on surgical pathology. Therefore, we aimed to quantify the rate of adverse surgical pathology and implications for survival for patients with favorable IR versus LR prostate cancer.
The National Cancer Database was queried to identify patients undergoing radical prostatectomy (RP) with data on biopsy and surgical pathology from 2009-2013. Baseline and pathologic outcomes were compared for patients meeting clinically LR (GG1(3+3), ≤cT2a, PSA<10) or GG2(3+4) IR (GG2, ≤cT2b, PSA<20) disease. Adverse pathology was defined as ≥GG3(4+3), seminal vesicle invasion (pT3b), or lymph node metastasis (pN1)). Various strata and definitions from the literature were explored including the Memorial Sloan Kettering definition (MSK; ≤GG2 with only one IR factor including GG2, cT2b, or PSA 10-20). Log-binomial regression compared rates of adverse pathologic findings while logistic regression assessed predictors. Kaplan-Meier survival curves and adjusted Cox proportional hazards regression models compared overall survival (OS) between GG2 IR and LR groups as well as the impact of adverse pathology for GG2 IR patients.</p>
A total of 3,519 (6.8%) of 51,688 LR and 8,888 (20.8%) of 42,720 GG2 IR patients included were found to have adverse pathologic findings (RR 3.06 (95%CI 2.95-3.17; p<0.001)), largely given by GG3 disease on surgical pathology. PSA and number of positive cores were significant predictors of adverse pathology but stratification minimally impacted the absolute rate. Results were similar for the MSK definition while restriction to GG1 IR patients led to a reduced increase in adverse pathology (RR 2.00 (1.86-2.16); p<0.001). GG2 IR patients had worse OS compared to LR patients in adjusted models (HR 1.25 (1.10-1.43; p=0.001)). Additionally, the presence of adverse pathology led to worse OS in the GG2 IR group (HR 1.26 (95% CI 1.03-1.54; p=0.023)).</p>
Adverse pathology is observed at a three-fold higher rate for patients classified as favorable IR compared to LR. The presence of adverse pathologic findings led to worse survival for men in the favorable IR risk group; favorable IR men as a whole experienced worse survival relative to LR men.