Background: Active Surveillance (AS) of prostate cancers lowers morbidity and mortality with conservative management but requires vigilance to prevent disease progression. Understanding of disease aggression through genomic analysis has enhanced AS. About one third of prostatectomies reveal a Gleason upgrade to stage T3 or node positivity, and increased risk on a single genomic analysis increases the risk of progression and Gleason upgrade. More information is needed to compare these tests and determine their roles in academic and private practice settings. Methods: The Pennsylvania Urologic Regional Collaborative (PURC), funded by participating urology practices and the Partnership for Patient Care, a quality improvement initiative supported by the Health Care Improvement Foundation, Independence Blue Cross, and southeastern PA hospitals and health systems, database was analyzed with permission to find patients who received both AS and prostatectomy for treatment of prostate cancer. Patients were then selected who had genomic analysis performed on biopsy samples using analysis from Decipher Biopsy, Oncotype Dx, or Prolaris. Patients were sorted into genomic risk categories and biopsy pathology, prostatectomy pathology, and time to surgery was compared. Results: Thirty-nine patients met criteria for the study. Nineteen were considered to be very low risk based on genomic analysis, 11 were low risk, and nine were intermediate risk. Average time of progression from AS to prostatectomy was shorter with increased genomic risk: from 1.7 years for very low genomic risk individuals, to 1.3 for low risk, to 0.8 years for intermediate risk. All three groups had a significant decrease in Gleason Grade Group from biopsy to final pathology (p < 0.05). Five of the 19 patients (26%) in the very low risk group were upgraded to pT3 after prostatectomy, one (9%) of the low risk group was upgraded, and four of the 9 (44%) in the intermediate risk group were upgraded. Regardless of genomic risk, 14% of patients who had analysis performed with Oncotype Dx received a Gleason upgrade, compared to 67% of patients with Decipher Biopsy analysis and 43% of patients with Prolaris genomic analysis. Conclusions: Our pilot study indicates that while higher genomic risk categorization led to a more rapid progression to treatment, Gleason Grade Group decreased from biopsy to final pathology in each risk group, suggesting more time before progression to treatment may be warranted. Very low and low risk patients had less risk of Gleason upgrade compared to intermediate risk patients. While our numbers are low, the difference in Gleason upgrade based on genomic analysis provides an interesting exploratory analysis that requires further investigation. More analysis comparing the intricacies of the reporting methods is needed to elucidate the benefits and drawbacks for each genomic test available.