Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score ≥ 8, or prostate-specific antigen [PSA] > 20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether sub-classification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk.
We identified 3,220 patients with NCCN unfavorable intermediate-risk (n=2,000) or high-risk (n=1,220) prostate cancer from a prospective multi-institutional registry cohort. We defined the following sub-classification of high-risk prostate cancer based on previously published data: favorable high-risk (cT1c, Gleason 6, and PSA > 20 ng/mL or cT1c, Gleason 4+4=8, PSA < 10 ng/mL); very high-risk (cT3b-T4 or primary Gleason pattern 5); and standard high-risk (all others with cT3a, Gleason score ≥ 8, or PSA > 20 ng/mL). We used a set of 33 previously developed genomic classifiers, including Decipher, to determine whether high-risk genomic features correlate with clinical sub-classes of high-risk prostate cancer.
Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 50.4%, 64.2%, 81.6% had a high-risk Decipher score, respectively (p<0.001). Among 32 other genomic signatures, 29 had a similar trend of increasing risk scores across the three sub-classes of high-risk disease (p<0.05 after correction for multiple hypothesis testing). Patients in the three sub-classes of high-risk disease had a median number of 4, 6, and 13 high-risk signatures, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.2% had a high-risk Decipher score and the median number of high-risk signatures was 3.
While NCCN guidelines currently used a two-tiered system for high-risk prostate cancer, genomic markers of risk correlate with the clinically validated sub-classification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, further confirming the prognostic utility of this three-tiered stratification.
International journal of radiation oncology, biology, physics. 2019 Jul 01 [Epub ahead of print]
Vinayak Muralidhar, Jingbin Zhang, Qiqi Wang, Brandon A Mahal, Santino S Butler, Daniel E Spratt, Elai Davicioni, Oliver Sartor, Felix Y Feng, Kent W Mouw, Paul L Nguyen
Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA 02114. Electronic address: ., GenomeDx Inc, San Diego, CA 92121., Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA 02114., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109., Departments of Medicine and Urology, Tulane School of Medicine, New Orleans, LA 70112., Department of Radiation Oncology, University of California, San Francisco, CA 94115.