Introduction

Active surveillance (AS) is an established treatment modality for select men with prostate cancer (PC). Eligibility criteria are based on clinicopathologic features including PSA and Gleason grade. Prior studies have validated a combined cell-cycle progression risk (CCR) score, which combines cell-cycle progression (CCP) gene expression data with the Cancer of the Prostate Risk Assessment (CAPRA) score to add significant prognostic discrimination to newly diagnosed PCs. Our objective was to assess the value of the CCR score for identifying men with higher risk clinicopathologic characteristics who qualify for AS.

Methods

Prostate biopsy samples from 17,017 men were submitted by their physicians for CCP testing (Myriad Genetic Laboratories). The CCP score was calculated from RNA expression of 46 genes (31 CCP and 15 housekeeping genes), and combined with CAPRA to generate the CCR score. Clinicopathological data was obtained from physician-completed test request forms. A threshold CCR score of 0.8 was previously developed and validated in a cohort of conservatively managed men (survival data censored at 10 yrs). We evaluated the proportion of men eligible for AS based on their CCR score whose clinicopathologic criteria would traditionally disqualify them from AS: PSA>10ng/mL, Gleason grade group≥2 (Gleason Score ≥3+4), higher AUA risk.

Results

Overall, 66.6% of clinically tested men qualified for AS based on their CCR score. Table 1 shows that a proportion of tested men with higher risk clinicopatholic features qualified for AS based on their CCR score, including AUA intermediate (42.9%) and high (14.1%) risk as well as Gleason grade group 2 (48.8%) and Gleason grade group >2 (1-3%). In addition, 48% of men with Gleason score 6 and PSA >10 ng/mL qualified for AS.

Conclusions

Clinical characteristics and Gleason grade are often used as stand-alone indicators to offer men with localized PC immediate definitive treatment rather than AS. However, our study demonstrates that a significant proportion of men who qualify for AS based on their CCR score have a range of PSA and Gleason grade prostate cancer that may not traditionally be considered for AS. This supports using CCR score to improve risk stratification in PC and identify men for AS.

Funding

none