Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower-grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.
We established a prospective, multi-institutional cohort of men with Grade Group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes and polygenic risk.
Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis.
In a cohort of low-grade prostate cancer patients, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance.
Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2024 Aug 19 [Epub ahead of print]
Michael A Liss, Nicole Zeltser, Yingye Zheng, Camden Lopez, Menghan Liu, Yash Patel, Takafumi N Yamaguchi, Stefan E Eng, Mao Tian, Oliver John Semmes, Daniel W Lin, James D Brooks, John T Wei, Eric A Klein, Ashutosh K Tewari, Juan Miguel Mosquera, Francesca Khani, Brian D Robinson, Muhammad Asad, Dean A Troyer, Jacob Kagan, Martin G Sanda, Ian M Thompson, Paul C Boutros, Robin J Leach
The University of Texas Health Science Center at San Antonio, San Antonio, Tex, United States., University of California, Los Angeles, Los Angeles, California, United States., Fred Hutchinson Cancer Center, Seattle, WA, United States., University of California, Los Angeles, Los Angeles, United States., University of Michigan-Ann Arbor, Ann Arbor, Michigan, United States., University of California, Los Angeles, United States., Eastern Virginia Medical School, Norfolk, VA, United States., University of Washington, Seattle, United States., Stanford University, Stanford, CA, United States., University of Michigan-Ann Arbor, Ann Arbor, MI, United States., Cleveland Clinic, Cleveland, Ohio, United States., Icahn School of Medicine at Mount Sinai, New York, NY, United States., Weill Cornell Medicine, New York, NY, United States., National Cancer Institute, United States., Emory University, Atlanta, United States., Christus Santa Rosa Health System, San Antonio, United States., The University of Texas Health Science Center at San Antonio, san antonio, tx, United States.