To determine whether PSA density (PSAD), can sub-stratify risk of biopsy upgrade among men on active surveillance (AS) with normal baseline MRI.

We identified a cohort of patients with low and favorable intermediate-risk prostate cancer on AS at two large academic centers from February 2013 - December 2017. Analysis was restricted to patients with GG1 cancer on initial biopsy and a negative baseline or surveillance mpMRI, defined by the absence of PI-RADS 2 or greater lesions. We assessed ability of PSA, prostate volume and PSAD to predict upgrading on confirmatory biopsy.

We identified 98 patients on AS with negative baseline or surveillance mpMRI. Median PSA at diagnosis was 5.8 ng/mL and median PSAD was 0.08 ng/mL/mL. Fourteen men (14.3%) experienced Gleason upgrade at confirmatory biopsy. Patients who were upgraded had higher PSA (7.9 vs 5.4 ng/mL, P = .04), PSAD (0.20 vs 0.07 ng/mL/mL, P < .001), and lower prostate volumes (42.5 vs 65.8 mL, P = .01). On multivariate analysis, PSAD was associated with pathologic upgrade (OR 2.23 per 0.1-increase, P = .007). A PSAD cutoff at 0.08 generated a NPV of 98% for detection of pathologic upgrade.

PSAD reliably discriminated the risk of Gleason upgrade at confirmatory biopsy among men with low-grade prostate cancer with negative MRI. PSAD could be clinically implemented to reduce the intensity of surveillance for a subset of patients.