Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.

Autor:	Liss MA; Department of Urology, University of Texas Health San Antonio, San Antonio, Texas., Zeltser N; Department of Human Genetics, University of California Los Angeles, Los Angeles, California.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California., Zheng Y; Department of Biostatistics, Fred Hutchinson Cancer Center, Seattle, Washington., Lopez C; Department of Biostatistics, Fred Hutchinson Cancer Center, Seattle, Washington., Liu M; Department of Biostatistics, Fred Hutchinson Cancer Center, Seattle, Washington., Patel Y; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.; Institute of Precision Health, University of California Los Angeles, Los Angeles, California., Yamaguchi TN; Department of Human Genetics, University of California Los Angeles, Los Angeles, California.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.; Institute of Precision Health, University of California Los Angeles, Los Angeles, California., Eng SE; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California., Tian M; Department of Human Genetics, University of California Los Angeles, Los Angeles, California.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.; Institute of Precision Health, University of California Los Angeles, Los Angeles, California., Semmes OJ; Department of Microbiology and Molecular Cell Biology, Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia., Lin DW; Division of Public Health Sciences, Department of Urology, Fred Hutchinson Cancer Center, University of Washington, Seattle, Washington., Brooks JD; Department of Urology, Stanford University, Palo Alto, California., Wei JT; Department of Urology, University of Michigan, Ann Arbor, Michigan., Klein EA; Glickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio., Tewari AK; Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York., Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York., Khani F; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York., Robinson BD; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York., Aasad M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York., Troyer DA; Department of Microbiology and Molecular Cell Biology, Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia.; Department of Pathology, University of Texas Health San Antonio, San Antonio, Texas., Kagan J; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland., Sanda MG; Department of Urology, Emory University, Atlanta, Georgia., Thompson IM; The Children's Hospital of San Antonio Foundation and Christus Health, San Antonio, Texas., Boutros PC; Department of Human Genetics, University of California Los Angeles, Los Angeles, California.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.; Institute of Precision Health, University of California Los Angeles, Los Angeles, California.; Department of Urology, University of California Los Angeles, Los Angeles, California., Leach RJ; Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, Texas.; Department of Pediatrics, University of Texas Health San Antonio, San Antonio, Texas.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2024 Nov 01; Vol. 33 (11), pp. 1500-1511.
DOI:	10.1158/1055-9965.EPI-24-0326
Abstrakt:	Background: 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. Methods: 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. Results: 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. Conclusions: In a cohort of patients with low-grade prostate cancer, 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. Impact: Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu