(UroToday.com) The 2025 Western Section AUA annual meeting featured a prostate cancer session and a presentation by Dr. James Nie discussing genomic classifier scores and risk of histologic upgrading on confirmatory biopsy during active surveillance.
It remains unclear how best to tailor active surveillance to reduce the burden of serial testing and biopsy. Present guidelines recommend that patients undergo confirmatory testing such as repeat biopsy, molecular tumor analysis, or mpMRI within 6-12 months of initial biopsy. It has previously been shown that mpMRI alone is insufficient to detect grade re-classification; thus, confirmatory biopsy within 1-2 years remains the gold standard. Given their growing utilization, the question arises of whether genomic classifiers can supplant confirmatory biopsy.
Men at the University of California, San Francisco, on active surveillance (2000-2025) for Grade Group 1/Grade Group 2 prostate cancer with genomic classifier risk score (Oncotype Dx or Decipher) on diagnostic biopsy followed by confirmatory biopsy within 6 to 24 months, were included. Genomic classifier scores were classified as low, intermediate, and high risk per manufacturer cut points. Outcomes were upgraded to Grade Group 2 on confirmatory biopsy and a major upgrade to Grade Group 3+ on confirmatory biopsy. Multivariable logistic regression was used to determine the association between genomic classifier risk scores and the likelihood of upgrading. Models were adjusted for age, PSA, prostate volume, and percentage of positive cores at diagnosis.
Of 454 men diagnosed with Grade Group 1/Grade Group 2 disease, 269 (59%) were low risk, 173 (38%) were intermediate risk, and 12 (3%) were high risk by genomic classifier score. There were 144 (32%) men who experienced an upgrade to Grade Group 2 on confirmatory biopsy, and 48 (11%) experienced a major upgrade to Grade Group 3+:
The negative predictive value of intermediate/high genomic classifier score for upgrade to Grade 2+ was 71% (sensitivity 36%, specificity 71%) and to Grade Group 3+ disease was 92% (sensitivity 56%, specificity 61%):
On multivariate logistic regression, the intermediate genomic classifier was associated with upgrading to Grade Group 3+ (OR 1.96, 95% CI 1.07-3.61, p = 0.03):
Dr. Nie concluded his presentation discussing genomic classifier scores and risk of histologic upgrading on confirmatory biopsy during active surveillance with the following take-home points:
- Genomic classifier scores were significantly associated with upgrading to Gleason Group 2+ and Gleason Grade 3+ at confirmatory biopsy. However, the low negative predictive value for Gleason Grade 2+ upgrading indicates that genomic classifiers alone cannot reliably exclude higher risk disease
- Genomic classifiers may complement other tools (ie. MRI, PSA kinetics) to personalize surveillance intensity, but they should not replace confirmatory biopsy. Future work should explore whether an adjusted genomic classifier threshold improves prediction while minimizing biopsy burden
Presented by: James Nie, MD-MBA, UCSF, San Francisco, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Western Section American Urological Association (AUA) Annual Meeting, Napa Valley, CA, Sun, Nov 2 – Thurs, Nov 6, 2025.