Pd56-08 Molecular Classifier Testing for Newly Diagnosed Localized Prostate Cancer in the State of Michigan
Year: 2018
Type: article
Study design: Observational Study
Abstract: INTRODUCTION AND OBJECTIVES: Several factors such as age of diagnosis and family history may impact the likelihood of an underlying hereditary predisposition to prostate cancer.Gleason score (GS) and metastatic disease (Mþ) are prognostic factors in men with prostate cancer.It has been previously reported that men with BRCA1/2 germline mutations have higher GS and typically more aggressive disease than non-BRCA carriers.This study aims to assess if men with mutations in non-BRCA genes have more aggressive disease and/or higher GS, as has been previously described for BRCA1/2, since this may impact treatment planning for these patients.METHODS: Clinical histories and molecular results for 157 patients tested with a prostate-specific multigene panel test from September 2016-March 2017 were retrospectively reviewed.Patients without a diagnosis of prostate cancer were excluded.The average Gleason score was calculated for all genes that had 2 or more scores available.RESULTS: Germline mutations were detected in 13.4% (22/ 157) of patients tested.Mutations were identified in BRCA2 (38%), HOXB13 (19%), ATM (14%), CHEK2 (14%), PALB2 (5%), BRCA1 (5%), and NBN (5%).The median and average age of diagnosis is 55 years old (range: 38-70).Overall, a mean GS of 8 (N¼18) and Mþ in 38% (N¼8) were reported.The average GS was highest for BRCA1/2 (8.86), followed by ATM (7.67), CHEK2 (6.50), and HOXB13 (6.50).Metastatic status was confirmed in 1 ATM, 1 BRCA1, and 6 BRCA2 mutation carriers.No metastatic disease was confirmed in 1 ATM, 1 BRCA2, 1 CHEK2, 2 HOXB13 mutation carriers.CONCLUSIONS: Detection rates of hereditary cancer usually range from 5-10%; however the detection rate in this study was greater than 13% which highlights the importance of multigene panel testing for men with prostate cancer.The average GS was found to be highest and Mþ was seen in the majority of BRCA1/2 mutation carriers, consistent with previous studies.Interestingly, ATM, CHEK2, and HOXB13 were found to have lower average GS and no Mþ was seen in a portion of these mutation carriers as well, compared to BRCA1/2 mutation carriers.The current NCCNâ guidelines only account for higher GS seen with BRCA1/2 carriers, therefore other gene mutation carriers may be missed if a multigene panel approach isn't considered.This is the first time average GS and Mþ have been assessed for germline mutation carriers, therefore further studies are needed to examine these factors in larger populations to draw more concrete conclusions.
Source: The Journal of Urology
Authors: Jonathan Hu, Daniel Spratt, Jeffrey Tosoian, Ji Qi, Deborah Kaye, Anna Johnson, Susan Linsell, James Montie, Khurshid Ghani, David Miller, Kirk Wojno, Frank Burks, Todd Morgan, for the Michigan Urological Surgery Improvement Collaborative
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2795455490