Utilization of genetic testing in men with advanced prostate cancer

Abstract

Background: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution. Methods:We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network highrisk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05.Results: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression.Conclusions: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics

Genetic testing practices among specialist physicians who treat prostate cancer

“…This model was developed to facilitate testing patients with a strong family history of cancer, where the individual's medical and family history determine the probability of a cancer-predisposing germline mutation. 35 Given the volume of the mPCa population, mainstreaming germline genetic testing by clinicianinitiated ordering, guided by specific local criteria or international guidelines, 28 is recommended as a model that ensures timely access to testing while lessening the burden on genetics services. Germline testing using a multi-gene panel that includes a minimum of ATM, BRCA1, BRCA2, CHEK2, HOXB13, PALB2, MLH1, MSH2, MSH6, PMS2, and EPCAM (large deletions) is recommended.…”

Pilot Trial of Streamlined Genetic Education and Traceback Genetic Testing in Prostate Cancer Survivors

“…11,19 Despite these benefits, few individuals with PCa undergo genetic testing. 20,21 Limited data on men with PCa suggest that lack of awareness and physician referral drive low test uptake. 22,23 This aligns with studies documenting low test uptake among men from families with hereditary breast and/or ovarian cancer.…”

“…"Traceback testing" refers to genetic outreach in previously diagnosed but untested patients with cancer, 37,38 and is relevant in PCa for several reasons. First, in addition to low test uptake among patients with PCa, 20,21 many PCa survivors became retroactively eligible for testing with the 2018 expansion of NCCN's recommendations for PCa genetic testing. 39 Second, detecting a PV could have treatment implications for survivors who experience disease progression or recurrence.…”

Upregulation of the ZWINT expression correlates with prostate cancer progression and immune infiltration

“…According to the IMPACT study (ClinicalTrials.gov identifier NCT00261456), the incidence of PCa is higher in Breast cancer susceptibility gene 2 (BRCA2) carriers compared to BRCA2 non-carriers [6]. Also, genetic testing identifies whether DNA damage-repair-related genes are expressed abnormally, which in turn allows patients to benefit from targeted drugs [7]. Therefore, the identification of effective prognostic biomarkers for PCa is an important measure to improve the prognosis of PCa patients.…”