Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer

Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC.

More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis.

On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals.

A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.