The Natural History of Confirmed Grade Group 1 Prostate Cancer Managed with Active Surveillance in the Modern Era

Grade group 1 (GG1, Gleason 3 + 3) prostate cancer (PCa) is considered low risk but can upgrade, and is managed with active surveillance (AS). Amidst recent controversy of whether GG1 PCa should be called cancer, we determined the nature of progression of GG1 disease in a modern AS cohort with multiparametric magnetic resonance imaging (mpMRI) and genomic testing.

The Urologic Outcomes Database at the University of California San Francisco was queried for men with confirmed GG1 PCa. The primary outcome was biopsy upgrade (≥GG2, Gleason ≥3 + 4). The secondary outcomes included major upgrade (≥GG3, Gleason ≥4 + 3), metastasis, mortality, PCa-specific mortality, and active treatment after upgrade. Life table estimates, Kaplan-Meier analyses, and multivariable Cox proportional hazards regression models were performed.

A total of 1429 men met the inclusion criteria. The 10-yr rates of upgrade and major upgrade were 62% and 19%, respectively. The 10-yr rates of metastasis, mortality, and PCa-specific mortality were 1.9%, 3.4%, and 0.1%, respectively. The 5-yr rate of active treatment after upgrade was 73%. On multivariable regression analyses, increasing age, percentage of positive cores, and prostate-specific antigen density, but not positive mpMRI, change in mpMRI, or high-risk genomics, were significantly associated with the risk of upgrade. Upgrade to ≥GG3 was the only factor associated with advancement to active treatment.

Men with confirmed GG1 PCa on AS have high rates of upgrade, and low rates of metastasis and mortality at 10 yr, confirming the appropriateness of AS. A high-risk genomic score, and initial positive mpMRI or change in mpMRI were not associated with upgrade outcomes, requiring further optimization.