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210 Background: Prostate cancer (PCa) risk is understood to be mostly unmodifiable and inherited, but there is evidence that environmental and behavioral factors may also contribute. A recent study of health professional cohorts suggests a healthy lifestyle can mitigate a high inherited risk of lethal PCa. It is unknown how modifiable factors affect PCa risk in more diverse populations. Our objective was to determine the effects of healthy lifestyle and Agent Orange exposure on PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population. Methods: The Million Veteran Program (MVP) is a national, population-based cohort study of United States military veterans conducted 2011-2021 with 590,750 male participants available for analysis. Healthy lifestyle was quantified as: A healthy lifestyle score (range 0-3) was calculated with a point assigned for each of the following at MVP enrollment: not a current smoker, body mass index (BMI) 30 and strenuous activity 2 days per week. Agent Orange exposure was obtained from VA records. Genetic risk was assessed via a polygenic hazard score using genotype data. Results: Healthy lifestyle was independently associated with reduced metastatic PCa (HR 0.82, 95% CI 0.77–0.87, p

72 Background: Identifying cancer cases within the electronic health record (EHR) or claims data can be challenging because diagnosis codes are often entered into patient records during routine screenings or as “rule out” diagnosis codes when the patient is referred to a procedure. To improve accuracy of prostate cancer (PCa) case ascertainment, we compared algorithms that used diagnoses codes to natural language processing (NLP) tools applied to clinical notes and pathology reports to identify Veterans with prostate cancer (PCa). Methods: This is a retrospective observational cohort study using VA EHR data to identify veterans diagnosed with PCa between 2000 and 2020. Using International Classification of Diseases (ICD-10 CM or ICD-9 CM) diagnosis and procedure codes, we identified veterans who may have PCa. We deployed validated NLP tools to identify the presence of Gleason score, metastatic PCa, and castration sensitivity to identify evidence of PCa within the notes. We conducted a descriptive analysis to compare the results of algorithms that relied exclusively on diagnosis codes compared to use of NLP tools. Results: From 2000 through 2020,1,031,296 veterans had one or more PCa diagnosis code. This number decreased by 11% for each additional PCa diagnosis code required. When we required 4 or more PCa diagnosis codes to be present, only 746,350 veterans had PCa. When we deployed NLP tools to identify mention of a Gleason score or an indicator of mPCa, only 685,847 Veterans had these indicators of PCa, a 35% decrease in the number of PCa cases with a single diagnosis code. Chart review of patients with their first PCa diagnosis codes in 2019 and 4 or more codes in their records illustrated no evidence of Gleason score or mPCa disease in their EHR. Analysis of their pathology reports revealed that these patients had prostatic intraepithelial neoplasia or atypical small acinar proliferation and had not yet developed prostate cancer. Conclusions: Accurate ascertainment of PCa using EHR and claims data requires using NLP tools and clinical notes combined with structured data sources such as diagnosis codes. Relying on ICD diagnosis codes alone will overestimate the burden of PCa up to 30%.

47 Background: Practice guidelines have been modified to recommend hereditary and tumor gene mutation testing in patients with metastatic castration-resistant prostate cancer (mCRPC) to identify patients for molecularly targeted therapies. Identifying appropriate candidates for testing can be challenging in electronic health records and claims data. In this study, we used natural language processing (NLP) algorithms to identify veterans with mCRPC, reported gene mutation testing rates and identified factors associated with testing. Methods: This is a retrospective observational cohort study using NLP to identify veterans diagnosed with mCRPC between 2016 and 2020. Patient and facility characteristics were reported descriptively. Chi-square and t-tests were used to determine whether differences were statistically significant at a significance level of 0.05 based on receipt of testing. Generalized linear mixed models with binomial error distributions and logit links accounting for clustering by facility were used to determine which factors were independently associated with testing. Results: 9,282 veterans were diagnosed with mCRPC between 2016 and 2020, as determined by NLP algorithms identifying diagnosis of metastatic disease and castration-resistant disease. Among these patients, 381 died within 45 days of their diagnosis, and were excluded from analysis. In the analytic cohort of 8,901 veterans, 1,282 (14%) patients received testing. Of these, 1,041 (81%) received tumor tissue testing and 292 (23%) received hereditary testing. In bivariate analyses, age, race, ethnicity, Commission on Cancer (COC) facility certification, and facility complexity rating differed between veterans who received the test versus who did not (mean age of 73 versus 77, p < 0.0001; 30% versus 24% Black, p < 0.0001; 93% versus 92% non-Hispanic, p = 0.04; 64% versus 63% COC-certified facility, p = 0.04; and 59% versus 52% most complex facility, p < 0.0001). In multivariate analyses, older age and lower facility complexity rating were associated with lower odds of testing (for every 10-year increase in age, adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.54, 0.50-0.58; Mid-high and low complexity facilities compared to highest complexity facilities: aOR, 95% CI: 0.52, 0.32-0.85 and 0.39, 0.22-0.71, respectively). Conclusions: Gene mutation testing in veterans with mCRPC is underutilized. Older age and being seen in a lower complexity facility are independently associated with a lower odds of testing. Patient and facility barriers to testing should be identified to improve guideline concordant care.

60 Background: Veterans may benefit from promising innovations in treatments for mPCa. The Veterans Affairs (VA) and Prostate Cancer Foundation (PCF) leadership issued a challenge to identify, in real time, the national census of Veterans receiving care for mPCa. Administrative diagnostic and procedural coding do not accurately identify the risk status or disease state of prostate cancer (PCa). This study reports the development and validation of NLP tools deployed on clinical notes to identify risk status or disease state. Methods: Using diagnosis and histology codes, we queried the VA Corporate Data Warehouse to identify Veterans with prostate cancer. We included structured laboratory tests, medications, procedures, and surgeries related to prostate cancer diagnosis or treatment in the analysis. Using structured data, we identified 1000 likely mPCa cases and controls. Medical records were reviewed to confirm status and to extract term dictionaries related to cancer, anatomy, metastasis, and other diagnostic concepts. We went through several iterations of testing to refine and validate the NLP tool on a limited set of known cases and controls. We deployed the tool on all cancer, urology, pathology, and radiation oncology notes. Results: The NLP system was able to identify the patients' history of metastatic disease with 0.975 precision and 0.828 recall. Among the 1,081,137 Veterans with prostate cancer, NLP identified 63,222 (5.8%) with mPCa. There are 16,282 Veterans alive with mPCa. Mean age of diagnosis was 67 and 8,847 (54.3%) were diagnosed in the VA. Demographics were: White 9,756 (60%), Black 4,466 (27%), and other 2,060 (13%). Conclusions: NLP is a reliable tool for identifying Veterans who may benefit from novel innovations in mPCa diagnosis and treatment.[Table: see text]

394 Background: It is essential to study real-world evidence of novel molecular diagnostic tests to measure their impact on clinical decision-making and health outcomes. Studying test utilization within the Department of Veterans Affairs (VA) informs about clinical validity in a racially diverse population. This study analyzed the impact of DNA promoter methylation (ConfirmDx), on the diagnostic workup of Veterans. Methods: The VA Corporate Data Warehouse (CDW) was used to identify all incident prostate biopsies and cancers from 1/2014-10/2019. We captured patient clinical characteristics, including number and date of biopsies, date of cancer diagnosis, dates and values of PSA tests, comorbidities, demographics, whether the patient underwent DNA promoter methylation testing, and the results of that test. Results: Each year an average of 25,299 biopsies are conducted in the VA. Between 2014 and 2019, 151,794 biopsies were performed. 98,155 (70%) Veterans underwent first-time biopsies and 54,447 (55%) were positive for carcinoma. 8,062 (8.2%) underwent multiple biopsies, among whom 3,589 (44%) were subsequently diagnosed with cancer. 34 Veterans underwent 5 or more biopsies before being diagnosed. 33,878 (35%) did not undergo another biopsy in the study period. 328 (0.3%) of the 98,155 Veterans underwent the DNA promoter methylation test. 55 (17%) of these Veterans were eligible for Medicare coverage of the test. Of the 328 tested for DNA methylation, 217 (66%) were minorities. 132/328 (40%) tested positive for carcinoma and 168/328 (51%) were negative. Conclusions: Most Veterans referred for prostate biopsy have detectable cancer, and a large number are minorities with potential increased prostate cancer risk. DNA promoter methylation may improve care by reducing the need for multiple biopsies, limiting exposure to infection, and reducing time to diagnosis and treatment.

e18814Background: Extended RAS testing in colorectal cancer predicts response to therapy with EGFR-directed therapies cetuximab and panitumumab (EGFR mab’s). In 2010 VA policy recommended testing o...

e18248 Background: Renal cell carcinoma (RCC) accounts for 3% of cancers diagnosed in the Department of Veterans Affairs (VA). Each year, 15% of the 1,600 veterans diagnosed with RCC have advanced disease. Until a decade ago, there were few non-surgical treatments for advanced RCC. Approval of multi-targeted tyrosine kinase inhibitors (TKIs), sorafenib, sunitinib, and pazopanib significantly improved outcomes for patients. However, several studies demonstrated increased risk of congestive heart failure, stroke, and thromboembolic events in patients treated with TKIs. We sought to understand whether veterans, who have a high prevalence of comorbidities, have increased risk of cardiac events following TKI treatment. Methods: This was a retrospective study of patients diagnosed with advanced RCC from 2006 to 2015. The outcome variable was whether the patient had congestive heart failure, cardiomyopathy, acute myocardial infarction, stroke, or cardiovascular related death after initiation of at least one TKI. Clinical, demographic, and pharmacy data came from the VA Central Cancer Registry and Corporate Data Warehouse. Patient characteristics across treatments were evaluated using chi square tests, t-tests and ANOVAs, as appropriate. We used multivariate logistic regression to determine the likelihood of cardiac event in patients treated with TKIs. Results: We identified 3,510 patients eligible for treatment who did not have a prior cardiac event. Overall, 1,840 patients were treated with at least one TKI prior to any cardiac event: 953 (27.1%) were treated with only sunitinib, 179 (5.1%) with sorafinib, 289 (8.2%) with pazopanib, and 419 (11.9%) treated with a combination. There were 909 who had a cardiac event (25.9% of all patients). Only 259 (28.49%) were treated with a TKI. On multivariate analysis, statistically significant predictors of a cardiac event were having diagnoses of dyslipidemia (Odds ratio [OR] 2.1, 95% confidence interval [CI] 1.7-2.5) or diabetes (OR 1.5, 95% CI 1.3-1.8). Patients treated with TKIs had a lower likelihood of a cardiac event (OR 0.3, CI 0.2-0.3). Conclusions: Among veterans, treatment with TKIs do not pose as great a risk for cardiac events as underlying comorbid diagnoses.

e18051 Background: Tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes of advanced renal cell carcinoma (RCC) patients, although complete remission is uncommon. Disease-specific survival in RCC varies by race/ethnicity, but race is not an independent predictor of survival within single-payer healthcare systems, pointing to the importance of access to treatment. We analyzed patient-level utilization of three TKIs (sunitinib, sorafenib, and pazopanib) among veterans with RCC. Methods: In this retrospective cohort study, we used data from Department of Veterans Affairs (VA) Corporate Data Warehouse to identify veterans diagnosed with RCC from 2006 to 2015 and exposed to TKIs, and to obtain their demographic and clinical information. The distribution of patients’ characteristics across treatments was evaluated using chi square and t-tests. Results: Of 2,410 patients exposed to TKIs, 956 (40%) received more than one TKI. Sunitinib was prescribed to 1,761 (73%) patients, pazopanib to 766 (32%), and sorafenib to 600 (25%) patients. The use of sorafenib declined steadily over time, from 37% of patients diagnosed in 2006 to 2% of those diagnosed in 2015, while the use of pazopanib grew from 8% to 38%, respectively. The comparison group were unexposed patients in Stage IV RCC (N = 1,144). Patients exposed to targeted treatments were significantly younger at diagnosis than those with no exposure (mean [M] age 65 years, SD 9 vs. m = 70 years, SD 10; p < 001). There were no statistically significant racial/ethnic or gender differences between patients exposed and unexposed to TKIs. Exposed patients had significantly higher body mass index (BMI) than unexposed (M = 29.6, SD 6 vs m = 27.9, SD 6, respectively; p < 0.01). Receipt of TKI was positively correlated with both surgery and chemotherapy, and negatively correlated with Charlson comorbidity index (p < 0.01). Conclusions: We documented equal access to TKIs treatment within the VA among RCC patients of different ethnic backgrounds and gender. Treatment with TKIs was correlated with younger age and fewer comorbidities, but higher BMI. We observed trends in use of individual TKIs, with more recently approved pazopanib gradually replacing sorafenib and sunitinib.

e18244 Background: Extended RAS testing in colorectal cancer predicts response to therapy with EGFR-directed therapies cetuximab and panitumumab. In 2010 VA policy recommended testing of all potentially treatable metastatic colon cancer patients for KRAS mutations. We explored the uptake of RAS testing within the VA system and characterized mutation frequency and cetuximab use. Methods: We extracted records of VA patients with first primary colorectal cancers diagnosed between 2011 and 2015 from the VA Central Cancer Registry (VACCR). We included patients who had RAS testing from 4 commercial laboratories contracted with the VA . We gathered genomic testing results from the commercial vendors. We calculated descriptive statistics of mutation sites and used multivariable logistic regression to evaluate predictors of mutations and cetuximab use. Results: Colon cancer diagnoses decreased in the VA from 4285 cases in 2011 to 3275 cases in 2015 and we observed a concurrent increase in KRAS testing from 4.7% in 2011 (202 cases) to 10.3% in 2015 (336 cases) (p < 0.001). KRAS tested patients were 65.7% white, 26.1% black, 3.1% Hispanic, and 2.8% female. Among 1717 patients tested, 588 had mutations (34.2%), with 441(75%) in codon 2, 117 (19.9%) in codon 13, 23 (3.9%) in codon 61. There were no differences in mutation rates by age, race, ethnicity, or gender categories. A total of 189 patients received cetuximab; 11 of 558 (1.9%) KRAS mutants and 178 of 1095 (16.2%) KRAS wildtype received cetuximab. Across all patients, increasing age in years predicts for cetuximab non-use (OR 0.983, 95% CI 0.97-0.99); gender, race, and ethnicity did not. Conclusions: We found a significant increase in KRAS testing between 2011 and 2015, with mutation patterns reflective of the US population. We found a low rate of inappropriate cetuximab use among patients with KRAS mutations, as well as an also low rate of cetuximab use among KRAS wild type patients among which it may be indicated. Further study is warranted to understand patterns of appropriate and inappropriate use of targeted agents.

e15014Background: Surgical resection of Colorectal Liver Metastases offers the greatest chance of long-term survival. We aimed to study survival in patients presenting with hepatic metastasis at th...

694 Background: Multidisciplinary management including surgical resection of Colorectal Liver Metastases (CLM) offers the greatest chance of long-term survival. We aimed to study surgical intervention types, rates and factors affecting the decision making in the Veterans Health Administration. Methods: The Veterans Affairs Central Cancer Registry (VACCR) and VA Informatics & Computing Infrastructure (VINCI) were queried and linked to retrospectively analyze stage IV CLM from 10/01/2004-12/31/2012. Cohort construction and statistical analyses were performed utilizing SQL Server, SAS software, version 9.4 (SAS Institute Inc., Cary, NC) and Microsoft Excel. Results: We identified 118 VA stations and 1245 subjects meeting the inclusion criteria. Hemicolectomy was identified in 79%, (637) and 21 % (168) liver metastatectomy. Open versus laparoscopic hemicolectomy was 87.96% and 12.04% respectively. Follow-up imaging post metastatic disease diagnosis was carried in 88.9% (1,108) subjects. Immense variation in the percentage of surgeries conducted and the sites of surgery when stratified by geographic location. The percentage of patients receiving surgery at the colon remained high across almost all the stations. In 53 stations, hemicolectomy and hepatectomy were attempted in at least 15% of subjects with stage IV colorectal cancer and isolated liver metastases. Of the high volume stations, only 52% had a 15% or higher percentage of hemicolectomy and hepatectomy. Subjects receiving hepatectomy only were the least frequent and occurred in only three stations. Age at diagnosis, gender, Charlson comorbidity scores and the performance status at diagnosis did not differ significantly among surgery versus no-surgery groups. Conclusions: Geographic disparity emerged as a factor affecting metastatectomy decisions. Ongoing analysis to identify and analyze the differences amongst various stations is underway. Additional characterization of the liver metastases including size, number, and specific hepatic lobe and the surgical expertise is underway.

e17582 Background: Molecular profiling has resulted in new, targeted therapies that may improve survival for non-small cell lung cancer patients (NSCLC). Erlotinib is used in stage-IV patients and ...

e17510 Background: About 10% of Veterans seen in VA facilities are female, some of whom are diagnosed with breast cancer. In 2012, NCCN guidelines for BRCA1/BRCA2 testing criteria included offering...

e17511 Background: The number of Veterans diagnosed and treated for breast cancer within the Veterans Health Administration is increasing. The VA Central Cancer Registry (VACCR) reported 504 and 62...

e20625 Background: Metastatic basal cell carcinoma (mBCC) is a poorly characterized condition. Because it is rare, there are limited studies available on patient and disease characteristics. Recent...