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6057 Background: Cardiovascular disease and stroke are important causes of long-term morbidity and mortality in patients with oropharyngeal squamous cell carcinoma (OPSCC). Cancer treatments including radiotherapy to the neck and chemotherapy have been associated with increased risk of stroke. In the era of treatment de-intensification for OPSCC, up-front surgical treatment has been proposed as one strategy that allows for de-escalation or avoidance of (chemo)radiotherapy. We sought to quantify the cumulative incidence of stroke in patients treated for non-metastatic OPSCC, and then evaluate whether patients receiving up-front surgery for OPSCC have decreased risk of stroke compared to those undergoing non-surgical treatment. Methods: We identified a cohort of 10,436 United States veterans diagnosed with non-metastatic OPSCC from 2000-2020, of whom 2,717 received up-front surgery (with or without perioperative radiotherapy or chemoradiotherapy) and 7,719 received non-surgical therapy (definitive radiotherapy or chemoradiotherapy). We estimated the cumulative incidence of stroke in this population, accounting for death as a competing risk. To assess the association between up-front surgery and risk of stroke, we generated a propensity score for the probability of receiving surgical treatment and used inverse probability weighting to construct pseudo-populations balanced on all potential confounders. Cox regression models of the inverse probability weighted population were used to estimate the cause-specific hazard ratio of stroke associated with surgical vs non-surgical treatment. Results: The 10-year cumulative incidence of stroke was 12.5% (95% CI 11.8-13.23) and death was 57.3% (95% CI 56.2-58.4). Up-front surgical patients who underwent perioperative (chemo)radiotherapy had shorter radiation and chemotherapy courses compared to non-surgical patients, suggestive of lower treatment intensity. Propensity score generation and inverse probability weighting yielded good overlap and covariate balance between surgical and non-surgical treatment groups. The inverse probability weighted cause-specific hazard ratio of stroke associated with up-front surgical treatment was 0.77 (95% CI 0.66-0.91, p = 0.002). This association was consistent across subgroups defined by age ( > /≤65 years) and baseline cardiovascular risk factors (hypertension, hyperlipidemia, diabetes). Conclusions: In over 10,000 US veterans with OPSCC, cumulative incidence of stroke was 12.5% at 10 years. Up-front surgical treatment was associated with a 23% reduced risk of stroke compared to definitive (chemo)radiotherapy. These findings present an important additional risk-benefit consideration to factor into treatment decisions and patient counseling, and should motivate future studies to examine cardiovascular events in this high-risk population.

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.

29 Background: Early-stage prostate cancer (PCa) is typically detected on prostate-specific antigen (PSA) screening and subsequent prostate biopsy, healthcare interventions that are considered routine elective procedures. The COVID-19 pandemic disrupted routine healthcare screenings and interventions. We sought to determine whether delayed screening and diagnostic workup of PCa was associated with increased rates of incident PCa, high-grade Gleason, and metastatic disease at diagnosis. Methods: We used the Corporate Data Warehouse of the Veterans Health Administration to collect PSA, prostate biopsy, PCa diagnosis, Gleason score, and metastasis information of White and Black Veterans aged 40 years or older newly diagnosed with PCa from January 2019 through June 2021. For each month, we calculated rates of PSA, prostate biopsy, and incident PCa per 100,000 men and plotted monthly rates by race. We performed descriptive analyses to compare age at first PSA, age at diagnosis, baseline PSA, Gleason scores, and metastasis pre- and post-January 2020, the month in which the U.S. declared COVID-19 a public health emergency. Results: The decrease in the rate of PSA screening immediately after January 2020 was similar in both White and Black Veterans (7% vs. 6%). However, the magnitude of reduction in the rate of prostate biopsy and the rate diagnosis of incident PCa were five times larger among Black Veterans compared to White Veterans (11% vs. 2% for both biopsy and diagnosis rates). Among the 17,771 White and 9,610 Black Veterans with incident PCa, the rate of Gleason of 4+3 or greater and the rate of metastatic disease at diagnosis increased three months after the pandemic in both race groups with comparable magnitude (2-3% increase in high-grade Gleason, 1% increase in metastatic disease). Conclusions: Utilization patterns indicated that while the decrease in PSA screening after the pandemic was similar in White and Black Veterans, reductions in prostate biopsy and diagnosis of incident PCa were five times greater in Blacks than Whites. Further research including risk-adjusted modeling is needed to determine whether Black Veterans were disproportionately affected by the pandemic-related disruptions in PSA screening and diagnostic workup of prostate cancer.[Table: see text]

178 Background: Prostate cancer comprises one third of male Veteran cancers and is their second leading cause of cancer death. Metastatic prostate cancer is lethal. Next Generation Sequencing (NGS) of somatic tumors is recommended for metastatic prostate to identify actionable alterations targeted with approved therapies. Veterans with prostate cancers harboring alterations in genes involved in the DNA damage response (e.g. BRCA1/2) or high microsatellite instability (MSI-High) may be eligible for PARP inhibitors or checkpoint blockade immunotherapy, respectively. Potential candidates may be identified for ongoing clinical trials of novel precision oncology approaches. Methods: This is a retrospective analysis of clinical, genomic, demographic data from Veterans with metastatic prostate cancer who underwent somatic NGS using the Foundation Medicine NGS platform from 2019-February 2021. To be included, prostate cancer was submitted diagnosis for the NGS testing and metastatic disease determined by the VINCI natural language processing tool. Variables included demographic, clinical, and pathological characteristics (self-identified race/ethnicity, age, rurality of residence, Gleason score, specimen site, other cancer diagnosis, mutation frequency). Primary outcome was mutation rates in homologous recombination (HR) genes under current FDA approval for olaparib (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L) or MSI-High. Raw variant data, submitted diagnosis, and clinical data were extracted from the NGS reports and harmonized for further variant annotation. Variant data included chromosome, position, reference and alternate allele, total depth, variant allele depth, and quality scores. Variants were annotated using ANNOVAR. Likely oncogenic and oncogenic mutations were identified using OncoKB. Results: 1,597 Veterans with metastatic prostate cancer underwent FMI NGS testing (63% White, 33% African American, 4% other). Median age was 66 years, 78.6% of cases from >60 years. Of the 1,597 who underwent blood or tumor testing, at least one likely oncogenic mutation in an HR gene under FDA approval for olaparib was found in 369 (23.1%) of Veterans (19% of tissue-based tests, 32.9% of blood-based tests). Of 651 liquid biopsy tests with at least one HR gene mutation, 125 of 214 (52%) had mutations at a variant allele frequency (VAF)

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]