Association between a 22 feature genomic classifier (Decipher) and biopsy Gleason upgrade during active surveillance for prostate cancer.

Active surveillance (AS) is the recommended initial management strategy for most patients with low-grade prostate cancer and an option for selected patients with favorable intermediate-risk disease and is adopted by the majority of eligible patients.  Evidence supports the long-term safety of AS and its effectiveness as a strategy to avoid or defer definitive treatment.  Nonetheless, 20-60% of patients who are initially enrolled in AS ultimately experience reclassification of the aggressiveness of their disease based on changes in biopsy Gleason grade, PSA levels, or cancer volume.  Consequently, up to half of the patients convert to definitive treatment in the near term, most frequently due to Gleason upgrading.  A smaller number of patients with clinically low-risk features ultimately experience clinically significant progression over time, highlighting the need for close monitoring to detect early signs of reclassification.  Estimating the risk of disease reclassification during AS based on standard clinical parameters is currently imperfect, leading to patient anxiety, avoidable treatment, and over or under-use of surveillance testing.

Genomic classifiers measuring features associated with prostate cancer aggressiveness developed largely in patients with high-risk disease provide robust predictions of disease outcome, yet little is known about their role in estimating the trajectory of untreated favorable-risk prostate cancer.  The Decipher classifier (GenomeDx Biosciences, Vancouver, BC Canada) is a tissue-based platform evaluating the expression of 22 genes which has been widely validated. However, less information is available regarding its utility in predicting the outcome of patients being managed with AS.

This study aimed to evaluate the association between the Decipher genomic classifier and biopsy

outcomes among patients with favorable-risk prostate cancer. The primary study objective was to examine the association between a patient’s baseline Decipher score and Gleason upgrading during AS.

This study found that the Decipher genomic classifier was associated with subsequent biopsy upgrading among patients enrolled in AS for low-risk or favorable-intermediate-risk prostate cancer.

Among patients with prostate cancer electing AS, Decipher scores of those with GG1, but not GG2 were independently associated with Gleason upgrading on a subsequent biopsy. These findings suggest that the Decipher classifier may be useful in identifying patients whose initial biopsies may have been misclassified or will experience progression of their disease in the short term.

The results from this study indicate that among patients undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time and that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance.

Press, B. et al. medrxiv. 2022 Jan 12. doi: https://doi.org/10.1101/2021.11.22.21266727.