Clinical role of pathological downgrading after radical prostatectomy in patients with biopsy confirmed Gleason score 3 + 4 prostate cancer

Objective To identify preoperative factors predicting Gleason score downgrading after radical prostatectomy in patients with biopsy Gleason score 3+4 prostate cancer. To determine if prediction of downgrading can identify potential candidates for active surveillance. Patients and Methods We identified 1317 patients with biopsy Gleason score 3+4 prostate cancer who underwent radical prostatectomy at Memorial Sloan-Kettering Cancer Center between 2005 and 2013. Several preoperative and biopsy characteristics were evaluated by forward selection regression, and selected predictors of downgrading were analyzed by multivariable logistic regression. Decision curve analysis was performed to evaluate the clinical utility of the multivariate model. Results Gleason score was downgraded after radical prostatectomy in 115 patients (9%). We developed a multivariable model using age, prostate specific antigen density, percent of positive cores with Gleason 4 cancer out of all cores taken, and maximum percent of cancer involvement within a positive core with Gleason 4 cancer. The area under the curve for this model was 0.75 after ten-fold cross validation. However, decision curve analysis revealed that the model was not clinically helpful in identifying patients who will downgrade at radical prostatectomy for the purpose of reassigning them to active surveillance. Conclusion While patients with pathology Gleason score 3+3 with tertiary Gleason pattern 4 or lower at radical prostatectomy in patients with biopsy Gleason score 3+4 prostate cancer may be potential candidates for active surveillance, decision curve analysis showed limited utility of our model to identify such men. Future study is needed to identify new predictors to help identify potential candidates for active surveillance among patients with biopsy-proven Gleason score 3+4 prostate cancer. Keywords: prostate, prostatic neoplasms, prostatectomy, downgrading, active surveillance, decision curve analysis Introduction The incidence of indolent prostate cancer has increased substantially over the past two decades due to the widespread use of prostate-specific antigen (PSA) testing for the early detection of prostate cancer. Many of the cases of prostate cancer identified by PSA testing benefit little, if any, from active treatment and thus represent overdiagnosis [1, 2]. Active surveillance evolved as a treatment strategy to prevent overtreatment. Early evidence shows that patients with low risk prostate cancer do not have significantly worse survival when treated with active surveillance compared to surgery or radiation [3, 4]. Recent studies suggest that eligibility for active surveillance might be extended to selected patients with biopsy Gleason score 3+4 prostate cancer. However, there is no concensus regarding how to select candidates for active surveillance among these patients [2, 5–7]. A certain subset of patients will have downgrading at radical prostatectomy [8–11] and these men have been shown to have more favorable outcomes after radical prostatectomy than would have been predicted by the biopsy Gleason score [9]. Furthermore, recent evidence suggests that men with Gleason score 6 prostate cancer in their radical prostatectomy specimen rarely develop distant metastasis or die from prostate cancer [12]. Taken together, these data suggest that most men with Gleason score 6 prostate cancer could be managed with active surveillance [2, 7]. Thus, we hypothesized that prediction of downgrading from Gleason score 3+4 at biopsy to Gleason score 3+3 after radical prostatectomy could help to select potential candidates for active surveillance in patients with biopsy-proven Gleason score 3+4 prostate cancer.