5069 Background: Owing to tumor heterogeneity, no standard selection criteria exist among prospective AS cohorts. Generally, men with low-stage, -volume, and -grade PC and low prostate-specific antigen (PSA) are eligible. In our prospective single-institution AS trial, men with early-stage PC were stratified: Gr I (favorable risk), II (pt’s choice), or III [competing comorbidities prevent local therapy (Tx)]. We report our experience with Gr I. Methods: Eligibility for Gr I: Gleason score (GS) ≤6, 1 positive (pos) core (<3 mm), and PSA <4 ng/mL or GS 7 (3+4), 1 pos core (<2 mm), and PSA <4 ng/mL. Monitoring q6mo included PSA, testosterone, and digital rectal exam. All pts had repeat biopsy (re-BX) at 1 y and then on predetermined BX scheme. Later, re-BX was required within 6 mo of study entry per an 11-core BX scheme (also used during AS). Definitive Tx was offered to pts who met reclassification based on clinical, BX (upgrading, ↑ in pos core BX, and/or ↑ tumor length), and/or radiographic progression. Imaging studies [bone/CT scans, endorectal MRI (eMRI)] were at physician’s discretion. Results: From 2/2006 to 2/2012, 585 pts enrolled; 191 met Gr I criteria (41 before, 150 after re-BX requirement). Median age was 64 y (range, 36–83); 82% were white, 8% African-American, 8% Hispanic, 2% Asian; 4% had cT1a/cT1b, 84% cT1c, and 12% cT2 disease. Most (189/191) had GS 6 [1 had GS 5, and 1, GS 7 (3+4)]. Median PSA was 3.3 (range, 0.2–10). With median follow-up of 36.2 mo (95% CI: 30.6–41.7), 32/191 (17%) were reclassified [20/41 (49%) before and 12/150 (8%) after re-BX requirement]. Of 32 reclassified, 17 were due to GS: 11 to GS 7 (3+4), 4 to GS 7 (4+3), and 2 to GS 8 (4+4). Ten of the 32 reclassified chose Tx [4 radical prostatectomy (RP); 4 radiation; 2 cryotherapy]. RP showed a pT2N0 GS9 (4+5) apical tumor in 1 at 5 y, a pT3aN0 GS7 (4+3) tumor in 1 at 3 y, a pT2N0 GS7 (4+3) tumor in 1 at 1 y, and a T2N0 GS 7 (3+4) tumor in 1 at 2 y. Conclusions: Restrictive selection criteria and re-BX at study entry improve clinical risk classification; however, other improvements, including imaging and markers of disease progression could enhance pt selection for AS.