Quantification of Gleason Pattern 4 Metrics Identifies Pathologic Progression in Patients with Grade Group 2 Prostate Cancer on Active Surveillance

Pathological progression to Grade Group 3 (GG3) disease in active surveillance prompts intervention, but the optimal method for Gleason pattern 4 (GP4) quantification remains unclear. Significant increases in GP4 length do not always meet GG3 criteria, while upgrading to GG3 can happen with minimal changes in GP4 length. We present an alternative method for grading GP4 is presented, highlighting limitations in current assessment practices. Background: During active surveillance (AS) for Grade Group (GG) 2 prostate cancer, pathologic progression to GG3 on surveillance biopsy is a trigger for intervention. However, this ratio of GP3:GP4, may be obscured by increases of relatively indolent disease. We aimed to explore changes in GP4 quantity during AS and propose alternative definitions for progression based on GP4 changes.Design, Design, Setting, and Participants: We assessed patients enrolled on AS between November 2014 and March 2020 with GG2 disease on diagnostic biopsy and subsequent surveillance biopsy approximately 1 year later. Outcome measures included change in overall %GP4 and total length GP4 (mm). Results and Limitations: 61 patients met the inclusion cr iter ia, the median change in total length of GP4 and %GP4 was-0.12 mm (IQR -0.31, 0.09) and -2.5% (IQR -8.6, 0.0), respectively. Excluding the 35 patients with no evidence of GP4 on surveillance biopsy, median change in total GP4 length and %GP4 was 0.19 mm (IQR -0.04, 0.67) and 1.2% (IQR -1.6, 6.6), respectively. Three patients progressed to GG3 disease on surveillance biopsy, one of whom had only a small increase in %GP4. Conversely, an additional 2 patients who did not meet the cr iter ion for GG3 had a large increase (> > 1 mm) in total GP4 length. Conclusions: Presence of GG3 disease on surveillance biopsy as a trigger for treatment in men on AS is of questionable use alone; we suggest including other measures that do not depend on a ratio, such as an increase in total GP4 length.