Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence.

OBJECTIVE: We evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative. DESIGN: Study participants were patients aged 45-75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3-9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups. RESULTS: We randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001). CONCLUSION: Among adults who had declined prior CRC screening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care. Further research is needed on how to balance the favourable adherence with lower advanced adenoma detection compared with other available tests. TRIAL REGISTRATION NUMBER: NCT05987709.

Longitudinal adherence to breast cancer surveillance following cancer genetic testing in an integrated health care system.

PURPOSE: Screening with mammography and breast magnetic resonance imaging (MRI) is an important risk management strategy for individuals with inherited pathogenic variants (PVs) in genes associated with increased breast cancer risk. We describe longitudinal screening adherence in individuals who underwent cancer genetic testing as part of usual care in a vertically integrated health system. METHODS: We determined the proportion time covered (PTC) by annual mammography and breast MRI for individuals with PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, and ATM. We determined time covered by biennial mammography beginning at age 50 years for individuals who received negative results, uncertain results, or with PVs in genes without specific breast cancer screening recommendations. RESULTS: One hundred and forty individuals had PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, or ATM. Among these individuals, average PTC was 48% (range 0-99%) for annual screening mammography and 34% (range 0-100%) for annual breast MRI. Average PTC was highest for individuals with PVs in CHEK2 (N = 14) and lowest for individuals with PVs in TP53 (N = 3). Average PTC for biennial mammography (N = 1,027) was 49% (0-100%). CONCLUSION: Longitudinal screening adherence in individuals with PVs in breast cancer associated genes, as measured by the proportion of time covered, is low; adherence to annual breast MRI falls below that of annual mammography. Additional research should examine screening behavior in individuals with PVs in breast cancer associated genes with a goal of developing interventions to improve adherence to recommended risk management.

Risk-reducing surgery in unaffected individuals receiving cancer genetic testing in an integrated health care system.

BACKGROUND: Germline genetic testing enables primary cancer prevention, including through prophylactic surgery. We examined risk-reducing surgeries in unaffected individuals tested for hereditary cancer susceptibly between 2010 and 2018 in the Kaiser Permanente Northwest health system. METHODS: We used an internal genetic testing database to create a cohort of individuals who received tests including one or more high-penetrance hereditary cancer susceptibility gene. We then identified, after testing, bilateral mastectomy, bilateral salpingo-oophorectomy (BSO), and total hysterectomy procedures in electronic health record and claims data through 2019. We describe surgery utilization by genetic test results and National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: The cohort included 1020 individuals, 16% with pathogenic/likely pathogenic (P/LP) variants in one or more of the following genes: BRCA1, BRCA2, CHEK2, APC, MUTYH, ATM, MSH2, PALB2, BRIP1, MLH1, MSH6, EPCAM, FLCN, RAD51C, RAD51D, or TP53. Among individuals with P/LP variants making them candidates for mastectomy, BSO, or hysterectomy per NCCN guidelines, 34% (33/97), 24% (23/94), and 8% (1/12), respectively, underwent surgery during follow-up. Fifty-three percent (18/37) of hysterectomies were among APC, BRCA1, and BRCA2 P/LP variant heterozygotes, typically concurrent with BSO. Three individuals with variants of uncertain significance (only) and 22 with negative results had prophylactic surgery after genetic testing. CONCLUSIONS: Uptake of risk-reducing surgery following usual care genetic testing appears to be lower than in studies that actively recruit high-risk patients and provide testing and follow-up care in specialized settings. Factors in addition to genetic test results and NCCN guidelines motivate prophylactic surgery use and deserve further study.

Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system.

INTRODUCTION: Lynch syndrome (LS) is associated with an increased risk of colorectal (CRC) and endometrial (EC) cancers. Universal tumor screening (UTS) of all individuals diagnosed with CRC and EC is recommended to increase identification of LS. Kaiser Permanente Northwest (KPNW) implemented a UTS program for LS among individuals newly diagnosed with CRC in January 2016 and EC in November 2016. UTS at KPNW begins with immunohistochemistry (IHC) of tumor tissue to determine loss of mismatch repair proteins associated with LS (MLH1, MSH2, MSH6, and PMS2)., IHC showing loss of MLH1 is followed by reflex testing (automatic testing) to detect the presence of the BRAF V600E variant (in cases of CRC) and MLH1 promoter hypermethylation to rule out likely sporadic cases. MATERIALS AND METHODS: Individuals newly diagnosed with CRC and EC were identified between the initiation of the respective UTS programs and July 2018. Electronic medical records were reviewed to extract patient data related to UTS, including IHC and reflex testing results, date of referrals to the genetics department, and results of germline genetic testing for LS. RESULTS: 313 out of 362 individuals diagnosed with CRC and 61 out of 64 individuals diagnosed with EC who were eligible were screened by IHC for LS. Most (47/52 or 90%, including 46/49 CRC and 1/3 EC) individuals that were not screened by IHC only had a biopsy sample available. Fourteen individuals (3.7% overall, including 13/313 CRC and 1/61 EC) received an abnormal result after reflex testing and were referred for genetic counseling. Of these, 10 individuals (71% overall, including 9/13 CRC and 1/1 EC) underwent germline genetic testing for LS. Five individuals diagnosed with CRC were found to have pathogenic variants. in PMS2 (n = 3), MLH1 (n = 1), and MSH6 (n = 1). No pathogenic variants were identified in individuals diagnosed with EC. CONCLUSIONS: UTS identified individuals at risk for LS. Most individuals who screened positive for LS had follow-up germline genetic testing for LS. The consistent use of biopsy samples is an opportunity to improve UTS.

Retrospective assessment of barriers and access to genetic services for hereditary cancer syndromes in an integrated health care delivery system.

BACKGROUND: A critical step in access to genetic testing for hereditary cancer syndromes is referral for genetic counseling to assess personal and family risk. Individuals meeting testing guidelines have the greatest need to be evaluated. However, referrals to genetics are underutilized in US patients with hereditary cancer syndromes, especially within traditionally underserved populations, including racial and ethnic minorities, low-income, and non-English speaking patients. METHODS: We studied existing processes for referral to genetic evaluation and testing for hereditary cancer risk to identify areas of potential improvement in delivering these services, especially for traditionally underserved patients. We conducted a retrospective review of 820 referrals to the Kaiser Permanente Northwest (KPNW) genetics department containing diagnosis codes for hereditary cancer risk. We classified referrals as high- or low-quality based on whether sufficient information was provided to determine if patients met national practice guidelines for testing. Through chart abstraction, we also assessed consistency with practice guidelines, whether the referral resulted in a visit to the genetics department for evaluation, and clinical characteristics of patients receiving genetic testing. RESULTS: Most referrals (n = 514, 63%) contained sufficient information to assess the appropriateness of referral; of those, 92% met practice guidelines for genetic testing. Half of referred patients (50%) were not offered genetic evaluation; only 31% received genetic testing. We identified several barriers to receiving genetic evaluation and testing, the biggest barrier being completion of a family history form sent to patients following the referral. Those with a referral consistent with testing guidelines, were more likely to receive genetic testing than those without (39% vs. 29%, respectively; p = 0.0058). Traditionally underserved patients were underrepresented in those receiving genetic evaluation and testing relative to the overall adult KPNW population. CONCLUSIONS: Process improvements are needed to increase access to genetic services to diagnose hereditary cancer syndromes prior to development of cancer.

Cancer Health Assessments Reaching Many (CHARM): A clinical trial assessing a multimodal cancer genetics services delivery program and its impact on diverse populations.

Advances in the application of genomic technologies in clinical care have the potential to increase existing healthcare disparities. Studies have consistently shown that only a fraction of eligible patients with a family history of cancer receive recommended cancer genetic counseling and subsequent genetic testing. Care delivery models using pre-test and post-test counseling are not scalable, which contributes to barriers in accessing genetics services. These barriers are even more pronounced for patients in historically underserved populations. We have designed a multimodal intervention to improve subsequent cancer surveillance, by improving the identification of patients at risk for familial cancer syndromes, reducing barriers to genetic counseling/testing, and increasing patient understanding of complex genetic results. We are evaluating this intervention in two large, integrated healthcare systems that serve diverse patient populations (NCT03426878). The primary outcome is the number of diagnostic (hereditary cancer syndrome) findings. We are examining the clinical and personal utility of streamlined pathways to genetic testing using electronic medical record data, surveys, and qualitative interviews. We will assess downstream care utilization of individuals receiving usual clinical care vs. genetic testing through the study. We will evaluate the impacts of a literacy-focused genetic counseling approach versus usual care genetic counseling on care utilization and participant understanding, satisfaction, and family communication. By recruiting participants belonging to historically underserved populations, this study is uniquely positioned to evaluate the potential of a novel genetics care delivery program to reduce care disparities.