Changes in Prostate Cancer Grade on Serial Biopsy in Men Undergoing Active Surveillance

Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time. Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates. Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy. A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.