Evaluating the outcomes of active surveillance in Gleason Grade Group 2 Prostate cancer: Prospective results from the Canary-PASS Cohort
Adrian J. Waisman Malaret, MD1, Peter Chang, MD, MPH1, Kehao Zhu, MD4, Yingye Zheng, PhD2, Lisa Newcomb, PhD2, James D. Brooks, MD3, Atreya Dash, MD4, Peter Carroll, MD, MPH5, Cristopher P. Filson, MD6, Martin E. Gleave, MD7, Michael Liss, MD8, Frances M. Martin, MD9, Todd M. Morgan, MD10, Peter S. Nelson, MD2, Daniel W. Lin, MD4, Andrew A. Wagner, MD1.
1Beth Israel Deaconess Medical Center, Boston, MA, 2Fred Hutchinson Cancer Research Center, Seattle, WA, 3Stanford University, Standford, CA, 4University of Washington, Seattle, WA, 5University of California, San Francisco, CA, 6Emory University, Atlanta, GA, 7University of British Columbia, Voncouver, BC, Canada, 8University of Texas Health Sciences Center, San Antonio, TX, 9Urology of Virginia, Virginia Beach, VA, 10University of Michigan, Ann Arbor, MI.
BACKGROUND: The safety of Active Surveillance (AS) for grade group 2 (GG2) patients is debated. We sought to compare clinical outcomes of men with GG1 and GG2 prostate cancer undergoing AS in the Canary Prostate Cancer Active Surveillance Study (PASS) cohort.
METHODS: Participants were prospectively enrolled in an AS study on protocol-directed follow-up at 10 centers nationwide. We included those who had GG1 or GG2 at diagnosis and at least one confirmatory biopsy. Patients were stratified according to GG at diagnosis and whether they were reclassified from initial biopsy. Time from diagnosis to treatment and time from definitive treatment to biochemical recurrence (BCR) were evaluated using Kaplan-Meier method; adverse pathology (AP) at Radical Prostatectomy (RP), defined as GG ≥3, ≥pT3a, or pN1, was analyzed as interval censored data using Weibull regression.
RESULTS: Between August 2008 and February 2019, 1574 patients met the eligibility criteria. At diagnosis, 1440 (91%) patients had GG1 and 134 (9%) had GG2, out of which 102 (76%) presented with single core of GG2. Patients with GG2 were older (66 vs 62 years) and had shorter median follow-up (5.4 vs 6.9 years) compared to GG1 patients. Reclassification rate at 5 years occurred in 36% of GG2 and 38% of GG1 patients. Overall, patients with GG2 had shorter time to treatment compared to patients with GG1 (median: 4.3 vs. 10.3 years p<0.0001). Among those who were not reclassified, patients with GG2 had shorter time to treatment compared to GG1 (median: 4.55 vs not reached), but had longer time to treatment compared to GG1 and GG2 who got reclassified (Figure). The risk of AP at RP was slightly higher for GG2 than for GG1 (hazard ratio: 1.37; 95% CI: 0.73 - 2.54). BCR within 3 years of treatment among those treated with surgery or radiation for GG2 was 10% and for GG1 was 13% (p=0.50).
CONCLUSIONS: Most GG2 patients enrolled in this AS protocol had low volume GG2 disease. Adverse pathology after RP and BCR after definitive treatment are similar in low volume GG2 patients compared to GG1 patients. Our results show that AS patients with low volume GG2 will have a shorter time to treatment, and limited follow-up post-treatment suggest equal oncologic outcomes. 
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