The nature of progression on long term active surveillance for confirmed Gleason grade group 1 prostate cancer in the modern era.
Authors: Shee Kevin , Cowan Janet E , Wang Lufan , Ding Chien-Kuang Cornelia , Washington Samuel L , Shinohara Katsuto , Nguyen Hao , Cooperberg Matthew R. , Carroll Peter 
Published: February 2025

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Background:
Gleason Grade Group 1 (GG1), or Gleason 3+3, prostate cancer (PCa), are considered low-risk, and unlikely to lead to major adverse outcomes such as metastasis or PCa-specific mortality. However, initial diagnoses of GG1 can upgrade over time, and balancing the need for monitoring with concerns about overtreatment of GG1 has led to the emergence of active surveillance (AS) as the standard of care for GG1 PCa. There has been a recent controversy regarding whether the label of cancer should be removed from GG1 tumors; proponents argue that such a change would dramatically reduce patient anxiety and overtreatment of GG1 PCa, while detractors argue that this could lead to failure to follow such patients and a missed opportunity for cure in those who might benefit. We sought to describe the nature of progression of GG1 disease in the modern era for confirmed GG1 patients after multiparametric prostate MRI-targeted biopsy in a large, well-annotated AS cohort.
Methods:
The Urologic Outcomes Database (UODB) at the University of California San Francisco (UCSF) was queried for men with cT1-2N0/xM0/x, PSA <20ng/ml, GG1 PCa with ≤33% biopsy core positivity with a minimum of 2 biopsies on AS with at least one multiparametric prostate MRI-targeted biopsy. Clinicodemographic factors and pathology data at diagnosis and at subsequent biopsies were obtained. Outcomes were any upgrade (≥GG2), major upgrade (≥GG3), increase in percentage of positive cores to >33%, and progression to active treatment. Life-table estimates and Kaplan-Meier analyses were used to describe major outcomes variables.
Results:
803 men met inclusion criteria. Median (IQR) follow-up for the cohort was 114 (75-157) months. CAPRA score at diagnosis was low risk and intermediate risk in 749 (93%) and 54 (7%) patients, respectively. Median (IQR) PSA at diagnosis, any upgrade, and major upgrade was 5.0 (3.8-6.7) ng/mL, 6.9 (4.5-9.9) ng/mL, and 7.8 (5.5-11.8) ng/mL, respectively. At 5 and 10 years, any upgrade rate was 28% and 61%, major upgrade rate was 5% and 17%, rate of increase in core positivity from ≤33% to >33% was 22% and 37%, and active treatment rate was 15% and 33%, respectively. Patients with both upgrade to GG2 and increased core positivity and major upgrade were more likely to progress to active treatment compared to patients with either upgrade to GG2 or increased core positivity alone (Log-rank p<0.01).
Conclusions:
Men with confirmed GG1 PCa on AS with at least one MRI-targeted biopsy have high rates of minor upgrade, moderate rates of increased core positivity and progression to active treatment, and low rates of major upgrade on subsequent biopsy, and are more likely to progress to treatment if they experience major upgrade or both upgrade to GG2 and increase in core positivity. These findings highlight heterogeneity of outcomes in patients with confirmed GG1 PCa in the modern era and highlights the critical need for continued monitoring with AS in such patients.