Variation in Colorectal Cancer Stage and Mortality across Large Community-Based Populations: PORTAL Colorectal Cancer Cohort.

INTRODUCTION: Colorectal cancer (CRC) incidence and mortality can be reduced by effective screening and/or treatment. However, the influence of health care systems on disparities among insured patients is largely unexplored. METHODS: To evaluate insured patients with CRC diagnosed between 2010 and 2014 across 6 diverse US health care systems in the Patient-Centered Outcomes Research Institute (PCORI) Patient Outcomes Research To Advance Learning (PORTAL) CRC cohort, we contrasted CRC stage; CRC mortality; all-cause mortality; and influences of demographics, stage, comorbidities, and treatment between health systems. RESULTS: Among 16,211 patients with CRC, there were significant differences between health care systems in CRC stage at diagnosis, CRC-specific mortality, and all-cause mortality. The unadjusted risk of CRC mortality varied from 27% lower to 21% higher than the reference system (hazard ratio [HR] = 0.73, 95% confidence interval = 0.66-0.80 to HR = 1.21, 95% confidence interval = 1.05-1.40; p < 0.01 across systems). Significant differences persisted after adjustment for demographics and comorbidities (p < 0.01); however, adjustment for stage eliminated significant differences (p = 0.24). All-cause mortality among patients with CRC differed approximately 30% between health care systems (HR = 0.89-1.17; p < 0.01). Adjustment for age eliminated significant differences (p = 0.48). DISCUSSION: Differences in CRC survival between health care systems were largely explained by stage at diagnosis, not demographics, comorbidity, or treatment. Given that stage is strongly related to early detection, these results suggest that variation in CRC screening systems represents a modifiable systems-level factor for reducing disparities in CRC survival.

Evaluating Screening Participation, Follow-up, and Outcomes for Breast, Cervical, and Colorectal Cancer in the PROSPR Consortium.

BACKGROUND: Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium. METHODS: We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40-74 years; cervical: ages 21-64 years; colorectal: ages 50-75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type. RESULTS: The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively. CONCLUSIONS: Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings.

Time to Follow-up After Colorectal Cancer Screening by Health Insurance Type.

INTRODUCTION: The purpose of this study was to test the hypothesis that patients with Medicaid insurance or Medicaid-like coverage would have longer times to follow-up and be less likely to complete colonoscopy compared with patients with commercial insurance within the same healthcare systems. METHODS: A total of 35,009 patients aged 50-64years with a positive fecal immunochemical test were evaluated in Northern and Southern California Kaiser Permanente systems and in a North Texas safety-net system between 2011 and 2012. Kaplan-Meier estimation was used between 2016 and 2017 to calculate the probability of having follow-up colonoscopy by coverage type. Among Kaiser Permanente patients, Cox regression was used to estimate hazard ratios and 95% CIs for the association between coverage type and receipt of follow-up, adjusting for sociodemographics and health status. RESULTS: Even within the same integrated system with organized follow-up, patients with Medicaid were 24% less likely to complete follow-up as those with commercial insurance. Percentage receiving colonoscopy within 3 months after a positive fecal immunochemical test was 74.6% for commercial insurance, 63.10% for Medicaid only, and 37.5% for patients served by the integrated safety-net system. CONCLUSIONS: This study found that patients with Medicaid were less likely than those with commercial insurance to complete follow-up colonoscopy after a positive fecal immunochemical test and had longer average times to follow-up. With the future of coverage mechanisms uncertain, it is important and timely to assess influences of health insurance coverage on likelihood of follow-up colonoscopy and identify potential disparities in screening completion.

The Be-Well Study: a prospective cohort study of lifestyle and genetic factors to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer.

PURPOSE: Bladder cancer is one of the top five cancers diagnosed in the U.S. with a high recurrence rate, and also one of the most expensive cancers to treat over the life-course. However, there are few observational, prospective studies of bladder cancer survivors. METHODS: The Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study) is a National Cancer Institute-funded, multi-center prospective cohort study of non-muscle-invasive bladder cancer (NMIBC) patients (Stage Ta, T1, Tis) enrolled from the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) health care systems, with genotyping and biomarker assays performed at Roswell Park Comprehensive Cancer Center. The goal is to investigate diet and lifestyle factors in recurrence and progression of NMIBC, with genetic profiles considered, and to build a resource for future NMIBC studies. RESULTS: Recruitment began in February 2015. As of 30 June 2018, 1,281 patients completed the baseline interview (774 KPNC, 511 KPSC) with a recruitment rate of 54%, of whom 77% were male and 23% female, and 80% White, 6% Black, 8% Hispanic, 5% Asian, and 2% other race/ethnicity. Most patients were diagnosed with Ta (69%) or T1 (27%) tumors. Urine and blood specimens were collected from 67% and 73% of consented patients at baseline, respectively. To date, 599 and 261 patients have completed the 12- and 24-month follow-up questionnaires, respectively, with additional urine and saliva collection. CONCLUSIONS: The Be-Well Study will be able to answer novel questions related to diet, other lifestyle, and genetic factors and their relationship to recurrence and progression among early-stage bladder cancer patients.

Index colonoscopy-related risk factors for postcolonoscopy colorectal cancers.

BACKGROUND AND AIMS: Postcolonoscopy colorectal cancers (PCCRCs) are defined as those detected ≤10 years after an index colonoscopy negative for cancer, but modifiable risk factors are not well established in large, community-based populations. METHODS: We evaluated risk factors from the index colonoscopy for PCCRCs diagnosed 1 to 10 years after an index colonoscopy using a case-control design. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for potential confounders. RESULTS: A proximal polyp ≥10 mm (OR, 8.18; 95% CI, 4.59-14.60), distal polyp ≥10 mm (OR, 3.30; 95% CI, 1.65-6.58), adenoma with (OR, 3.23; 95% CI, 1.83-5.68) and without advanced histology (OR, 1.87; 95% CI, 1.37-2.55), and an incomplete colonoscopy (OR, 5.52; 95% CI, 2.98-10.21) were associated with PCCRC. Risk factors for early versus late cancers (12-36 months vs >36 months to 10 years after examination) included incomplete polyp excision in the colonic segment of the subsequent cancer (OR, 4.76; 95% CI, 2.35-9.65); failure to examine the segment (OR, 2.42; 95% CI, 1.27-4.60); and a polyp ≥10 mm in the segment (OR, 2.38; 95% CI, 1.53-3.70). A total of 559 of 1206 patients with PCCRC (46.4%) had 1 or more risk factors that were significant for PCCRC (incomplete examination, large polyp, or any adenoma). CONCLUSIONS: In a large community-based study with comprehensive capture of PCCRCs, almost half of PCCRCs had potentially modifiable factors related to polyp surveillance or removal and examination completeness. These represent potential high-yield targets to further increase the effectiveness of colorectal cancer screening.

Modifiable Failures in the Colorectal Cancer Screening Process and Their Association With Risk of Death.

BACKGROUND & AIMS: Colorectal cancer (CRC) deaths occur when patients do not receive screening or have inadequate follow-up of abnormal results or when the screening test fails. We have few data on the contribution of each to CRC-associated deaths or factors associated with these events. METHODS: We performed a retrospective cohort study of patients in the Kaiser Permanente Northern and Southern California systems (55-90 years old) who died of CRC from 2006 through 2012 and had ≥5 years of enrollment before diagnosis. We compared data from patients with those from a matched cohort of cancer-free patients in the same system. Receipt, results, indications, and follow-up of CRC tests in the 10-year period before diagnosis were obtained from electronic databases and chart audits. RESULTS: Of 1750 CRC deaths, 75.9% (n = 1328) occurred in patients who were not up to date in screening and 24.1% (n = 422) occurred in patients who were up to date. Failure to screen was associated with fewer visits to primary care physicians. Of 3486 cancer-free patients, 44.6% were up to date in their screening. Patients who were up to date in their screening had a lower risk of CRC death (odds ratio, 0.38; 95% confidence interval, 0.33-0.44). Failure to screen, or failure to screen at appropriate intervals, occurred in a 67.8% of patients who died of CRC vs 53.2% of cancer-free patients; failure to follow-up on abnormal results occurred in 8.1% of patients who died of CRC vs 2.2% of cancer-free patients. CRC death was associated with higher odds of failure to screen or failure to screen at appropriate intervals (odds ratio, 2.40; 95% confidence interval, 2.07-2.77) and failure to follow-up on abnormal results (odds ratio, 7.26; 95% confidence interval, 5.26-10.03). CONCLUSIONS: Being up to date on screening substantially decreases the risk of CRC death. In 2 health care systems with high rates of screening, most people who died of CRC had failures in the screening process that could be rectified, such as failure to follow-up on abnormal findings; these significantly increased the risk for CRC death.

Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings.

Importance: Guidelines recommend a 10-year rescreening interval after a colonoscopy with normal findings (negative colonoscopy results), but evidence supporting this recommendation is limited. Objective: To examine the long-term risks of colorectal cancer and colorectal cancer deaths after a negative colonoscopy result, in comparison with individuals unscreened, in a large, community-based setting. Design, Setting, and Participants: A retrospective cohort study was conducted in an integrated health care delivery organization serving more than 4 million members across Northern California. A total of 1 251 318 average-risk screening-eligible patients (age 50-75 years) between January 1, 1998, and December 31, 2015, were included. The study was concluded on December 31, 2016. Exposures: Screening was examined as a time-varying exposure; all participants contributed person-time unscreened until they were either screened or censored. If the screening received was a negative colonoscopy result, the participants contributed person-time in the negative colonoscopy results group until they were censored. Main Outcomes and Measures: Using Cox proportional hazards regression models, the hazard ratios (HRs) for colorectal cancer and related deaths were calculated according to time since negative colonoscopy result (or since cohort entry for those unscreened). Hazard ratios were adjusted for age, sex, race/ethnicity, Charlson comorbidity score, and body mass index. Results: Of the 1 251 318 patients, 613 692 were men (49.0%); mean age was 55.6 (7.0) years. Compared with the unscreened participants, those with a negative colonoscopy result had a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, and although reductions in risk were attenuated with increasing years of follow-up, there was a 46% lower risk of colorectal cancer (hazard ratio, 0.54; 95% CI, 0.31-0.94) and 88% lower risk of related deaths (hazard ratio, 0.12; 95% CI, 0.02-0.82) at the current guideline-recommended 10-year rescreening interval. Conclusions and Relevance: A negative colonoscopy result in average-risk patients was associated with a lower risk of colorectal cancer and related deaths for more than 12 years after examination, compared with unscreened patients. Our study findings may be able to inform guidelines for rescreening after a negative colonoscopy result and future studies to evaluate the costs and benefits of earlier vs later rescreening intervals.

Agreement between medical records and self-reports: Implications for transgender health research.

A key priority of transgender health research is the evaluation of long-term effects of gender affirmation treatment. Thus, accurate assessment of treatment receipt is critical. The data for this analysis came from an electronic medical records (EMR) based cohort of transgender individuals. A subset of cohort members were also asked to complete a self-administered survey. Information from the EMR was compared with survey responses to assess the extent of agreement regarding transmasculine (TM)/transfeminine (TF) status, hormone therapy receipt, and type of surgery performed. Logistic regression models were used to assess whether participant characteristics were associated with disagreement between data sources. Agreement between EMR and survey-derived information was high regarding TM/TF status (99%) and hormone therapy receipt (97%). Lower agreement was observed for chest reconstruction surgery (72%) and genital reconstruction surgery (84%). Using survey responses as the "gold standard", both chest and genital reconstruction surgeries had high specificity (95 and 93%, respectively), but the corresponding sensitivities were low (49 and 68%, respectively). A lower proportion of TM had concordant results for chest reconstruction surgery (64% versus 79% for TF) while genital reconstruction surgery concordance was lower among TF (79% versus 89% for TM). For both surgery types, agreement was highest among the youngest participants. Our findings offer assurance that EMR-based data appropriately classify cohort participants with respect to their TM/TF status or hormone therapy receipt. However, current EMR data may not capture the complete history of gender affirmation surgeries. This information is useful in future studies of outcomes related to gender affirming therapy.

Colorectal Cancer Screening Participation Among Asian Americans Overall and Subgroups in an Integrated Health Care Setting with Organized Screening.

BACKGROUND: Screening reduces colorectal cancer deaths, but <50% of Asian Americans are screening up-to-date according to surveys, with variability across Asian subgroups. We examined colorectal cancer screening participation among Asian Americans overall and Asian subgroups in a large integrated health care system with organized screening. METHODS: Data were electronically accessed to characterize screening in 2016 for Asians overall and subgroups relative to the National Colorectal Cancer Roundtable target of ≥80% screening and compared with non-Hispanic whites. Screening up-to-date was defined as a colonoscopy with 10 years, a sigmoidoscopy within 5 years, or a fecal immunochemical test (FIT) completed in 2016. RESULTS: Among 436,398 patients, 69,826 (16.0%) were Asian, of whom 79.8% were screening up-to-date vs. 77.6% of non-Hispanic whites (p < 0.001). Almost all subgroups met the 80% target: Chinese (83.3%), Vietnamese (82.4%), Korean (82.1%), other Asian (80.3%), Filipino (78.7%), Asian Indian (79.6%), and Japanese (79.0%). Among Asians overall and non-Hispanic whites, 50.6% and 48.4% of members were up-to-date with screening by colonoscopy, and 28.0% and 28.2% were up-to-date by FIT, respectively. Across Asian subgroups, colonoscopy most frequently accounting for being screening up-to-date (range: 47.4-59.7%), followed by FIT (range: 21.6-31.5%). CONCLUSIONS: In an organized screening setting, there were minimal differences in screening participation among Asian subgroups and almost all met the 80% screening target, despite differences in language preference. Screening test type differences across subgroups suggest possible preferences in screening modality, which can inform future research into tailored education or outreach.

Effects of Organized Colorectal Cancer Screening on Cancer Incidence and Mortality in a Large Community-Based Population.

BACKGROUND & AIMS: Little information is available on the effectiveness of organized colorectal cancer (CRC) screening on screening uptake, incidence, and mortality in community-based populations. METHODS: We contrasted screening rates, age-adjusted annual CRC incidence, and incidence-based mortality rates before (baseline year 2000) and after (through 2015) implementation of organized screening outreach, from 2007 through 2008 (primarily annual fecal immunochemical testing and colonoscopy), in a large community-based population. Among screening-eligible individuals 51-75 years old, we calculated annual up-to-date status for cancer screening (by fecal test, sigmoidoscopy, or colonoscopy), CRC incidence, cancer stage distributions, and incidence-based mortality. RESULTS: Initiation of organized CRC screening significantly increased the up-to-date status of screening, from 38.9% in 2000 to 82.7% in 2015 (P < .01). Higher rates of screening were associated with a 25.5% reduction in annual CRC incidence between 2000 and 2015, from 95.8 to 71.4 cases/100,000 (P < .01), and a 52.4% reduction in cancer mortality, from 30.9 to 14.7 deaths/100,000 (P < .01). Increased screening was initially associated with increased CRC incidence, due largely to greater detection of early-stage cancers, followed by decreases in cancer incidence. Advanced-stage CRC incidence rates decreased 36.2%, from 45.9 to 29.3 cases/100,000 (P < .01), and early-stage CRC incidence rates decreased 14.5%, from 48.2 to 41.2 cases/100,000 (P < .04). CONCLUSIONS: Implementing an organized CRC screening program in a large community-based population rapidly increased screening participation to the ≥80% target set by national organizations. Screening rates were sustainable and associated with substantial decreases in CRC incidence and mortality within short time intervals, consistent with early detection and cancer prevention.

Patterns and predictors of repeat fecal immunochemical and occult blood test screening in four large health care systems in the United States.

OBJECTIVES: Effectiveness of fecal occult blood test (FOBT) for colorectal cancer (CRC) screening depends on annual testing, but little is known about patterns of repeat stool-based screening within different settings. Our study's objective was to characterize screening patterns and identify factors associated with repeat screening among patients who completed an index guaiac FOBT (gFOBT) or fecal immunochemical test (FIT). METHODS: We performed a multi-center retrospective cohort study among people who completed a FOBT between January 2010 and December 2011 to characterize repeat screening patterns over the subsequent 3 years. We studied at 4 large health care delivery systems in the United States. Logistic regression analyses were used to identify factors associated with repeat screening patterns. We included individuals aged 50-71 years who completed an index FOBT and had at least 3 years of follow-up. We excluded people with a history of CRC, colonoscopy within 10 years or flexible sigmoidoscopy within 5 years before the index test, or positive index stool test. Consistent screening was defined as repeat FOBT within every 15 months and inconsistent screening as repeat testing at least once during follow-up but less than consistent screening. RESULTS: Among 959,857 eligible patients who completed an index FIT or gFOBT, 344,103 had three years of follow-up and met inclusion criteria. Of these, 46.6% had consistent screening, 43.4% inconsistent screening, and 10% had no repeat screening during follow-up. Screening patterns varied substantially across healthcare systems, with consistent screening proportions ranging from 1 to 54.3% and no repeat screening proportions ranging from 6.9 to 42.8%. Higher consistent screening proportions were observed in health systems with screening outreach and in-reach programs, whereas the safety-net health system, which uses opportunistic clinic-based screening, had the lowest consistent screening. Consistent screening increased with older age but was less common among racial/ethnic minorities and patients with more comorbidities. CONCLUSIONS: Adherence with annual FOBT screening is highly variable across healthcare delivery systems. Settings with more organized screening programs performed better than those with opportunistic screening, but evidence-based interventions are needed to improve CRC screening adherence in all settings.

Association Between Gender Confirmation Treatments and Perceived Gender Congruence, Body Image Satisfaction, and Mental Health in a Cohort of Transgender Individuals.

BACKGROUND: Transgender individuals sometimes seek gender confirmation treatments (GCT), including hormone therapy (HT) and/or surgical change of the chest and genitalia ("top" and "bottom" gender confirmation surgeries). These treatments may ameliorate distress resulting from the incongruence between one's physical appearance and gender identity. AIM: The aim was to examine the degree to which individuals' body-gender congruence, body image satisfaction, depression, and anxiety differed by GCT groups in cohorts of transmasculine (TM) and transfeminine (TF) individuals. METHODS: The Study of Transition, Outcomes, and Gender is a cohort study of transgender individuals recruited from 3 health plans located in Georgia, Northern California, and Southern California; cohort members were recruited to complete a survey between 2015-2017. Participants were asked about: history of GCT; body-gender congruence; body image satisfaction; depression; and anxiety. Participants were categorized as having received: (1) no GCT to date; (2) HT only; (3) top surgery; (4) partial bottom surgery; and (5) definitive bottom surgery. OUTCOMES: Outcomes of interest included body-gender congruence, body image satisfaction, depression, and anxiety. RESULTS: Of the 2,136 individuals invited to participate, 697 subjects (33%) completed the survey, including 347 TM and 350 TF individuals. The proportion of participants with low body-gender congruence scores was significantly higher in the "no treatment" group (prevalence ratio [PR] = 3.96, 95% CI 2.72-5.75) compared to the definitive bottom surgery group. The PR for depression comparing participants who reported no treatment relative to those who had definitive surgery was 1.94 (95% CI 1.42-2.66); the corresponding PR for anxiety was 4.33 (95% CI 1.83-10.54). CLINICAL TRANSLATION: Withholding or delaying GCT until depression or anxiety have been treated may not be the optimal treatment course given the benefits of reduced levels of distress after undergoing these interventions. CONCLUSIONS: Strengths include the well-defined sampling frame, which allowed correcting for non-response, a sample with approximately equal numbers of TF and TM participants, and the ability to combine data on HT and gender confirmation surgeries. Limitations include the cross-sectional design and the fact that participants may not be representative of the transgender population in the United States. Body-gender congruence and body image satisfaction were higher, and depression and anxiety were lower among individuals who had more extensive GCT compared to those who received less treatment or no treatment at all. Owen-Smith AA, Gerth J, Sineath RC, et al. Association Between Gender Confirmation Treatments and Perceived Gender Congruence, Body Image Satisfaction and Mental Health in a Cohort Of Transgender Individuals. J Sex Med 2018;15:591-600.

Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study.

OBJECTIVE: Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers. DESIGN: We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures. RESULTS: We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53). CONCLUSIONS: Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population.

Cohort profile: Study of Transition, Outcomes and Gender (STRONG) to assess health status of transgender people.

PURPOSE: The Study of Transition, Outcomes and Gender (STRONG) was initiated to assess the health status of transgender people in general and following gender-affirming treatments at Kaiser Permanente health plans in Georgia, Northern California and Southern California. The objectives of this communication are to describe methods of cohort ascertainment and data collection and to characterise the study population. PARTICIPANTS: A stepwise methodology involving computerised searches of electronic medical records and free-text validation of eligibility and gender identity was used to identify a cohort of 6456 members with first evidence of transgender status (index date) between 2006 and 2014. The cohort included 3475 (54%) transfeminine (TF), 2892 (45%) transmasculine (TM) and 89 (1%) members whose natal sex and gender identity remained undetermined from the records. The cohort was matched to 127 608 enrollees with no transgender evidence (63 825 women and 63 783 men) on year of birth, race/ethnicity, study site and membership year of the index date. Cohort follow-up extends through the end of 2016. FINDINGS TO DATE: About 58% of TF and 52% of TM cohort members received hormonal therapy at Kaiser Permanente. Chest surgery was more common among TM participants (12% vs 0.3%). The proportions of transgender participants who underwent genital reconstruction surgeries were similar (4%-5%) in the two transgender groups. Results indicate that there are sufficient numbers of events in the TF and TM cohorts to further examine mental health status, cardiovascular events, diabetes, HIV and most common cancers. FUTURE PLANS: STRONG is well positioned to fill existing knowledge gaps through comparisons of transgender and reference populations and through analyses of health status before and after gender affirmation treatment. Analyses will include incidence of cardiovascular disease, mental health, HIV and diabetes, as well as changes in laboratory-based endpoints (eg, polycythemia and bone density), overall and in relation to gender affirmation therapy.

Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis.

IMPORTANCE: The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression. OBJECTIVE: To evaluate time to colonoscopy after a positive FIT result and its association with risk of colorectal cancer and advanced-stage disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study (January 1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern California. Participants were 70 124 patients aged 50 through 70 years eligible for colorectal cancer screening with a positive FIT result who had a follow-up colonoscopy. EXPOSURES: Time (days) to colonoscopy after a positive FIT result. MAIN OUTCOMES AND MEASURES: Risk of any colorectal cancer and advanced-stage disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were adjusted for patient demographics and baseline risk factors. RESULTS: Of the 70 124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years]; men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to 30 days (n = 27 176), there were no significant differences between follow-up at 2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9 months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8-30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3 months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000 patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per 1000 patients). CONCLUSIONS AND RELEVANCE: Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.

Optimizing patient-reported outcome and risk factor reporting from cancer survivors: a randomized trial of four different survey methods among colorectal cancer survivors.

PURPOSE: The goal of this study was to determine response rates and associated costs of different survey methods among colorectal cancer (CRC) survivors. METHODS: We assembled a cohort of 16,212 individuals diagnosed with CRC (2010-2014) from six health plans, and randomly selected 4000 survivors to test survey response rates across four mixed-mode survey administration protocols (in English and Spanish): arm 1, mailed survey with phone follow-up; arm 2, interactive voice response (IVR) followed by mail; arm 3; email linked to web-based survey with mail follow-up; and arm 4, email linked to web-based survey followed by IVR. RESULTS: Our overall response rate was 50.2%. Arm 1 had the highest response rate (59.9%), followed by arm 3 (51.9%), arm 2 (51.2%), and arm 4 (37.9%). Response rates were higher among non-Hispanic whites in all arms than other racial/ethnic groups (p < 0.001), among English (51.5%) than Spanish speakers (36.4%) (p < 0.001), and among higher (53.7%) than lower (41.4%) socioeconomic status (p < 0.001). Survey arms were roughly comparable in cost, with a difference of only 8% of total costs between the most (arm 2) and least (arm 3) expensive arms. CONCLUSIONS: Mailed surveys followed by phone calls achieved the highest response rate; email invitations and online surveys cost less per response. Electronic methods, even among those with email availability, may miss important populations including Hispanics, non-English speakers, and those of lower socioeconomic status. IMPLICATIONS FOR CANCER SURVIVORS: Our results demonstrate effective methods for capturing patient-reported outcomes, inform the relative benefits/disadvantages of the different methods, and identify future research directions.

Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue.

BACKGROUND: Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population. AIMS: To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening. METHODS: FIT-negative and FIT-positive colorectal cancer patients 50-77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889). RESULTS: One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p = 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups. CONCLUSIONS: The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.

Endoscopist fatigue estimates and colonoscopic adenoma detection in a large community-based setting.

BACKGROUND AND AIMS: Endoscopist fatigue may impact colonoscopy quality, but prior studies conflict, and minimal data exist from community-based practices where most colonoscopies are performed. METHODS: Within a large, community-based integrated healthcare system, we evaluated the associations among 4 measures of endoscopist fatigue and colonoscopic adenoma detection from 2010 to 2013. Fatigue measures included afternoon versus morning colonoscopy and the number of GI procedures performed before a given colonoscopy, including consideration of prior procedure complexity. Analyses were adjusted for potential confounders using multivariate logistic regression. RESULTS: We identified 126 gastroenterologists who performed 259,064 total GI procedures (median, 6 per day; range, 1-24), including 76,445 screening and surveillance colonoscopies. Compared with morning examinations, colonoscopies in the afternoon were not associated with lower adenoma detection for screening examinations, surveillance examinations, or their combination (OR for combination, .99; 95% CI, .96-1.03). The number of procedures performed before a given colonoscopy, with or without consideration of prior procedure complexity, was also not inversely associated with adenoma detection (OR for adenoma detection for colonoscopies in the fourth quartile of fatigue based on the number of prior procedures performed vs colonoscopies performed as the first procedure of the day, .99; 95% CI, .94-1.04). CONCLUSIONS: In a large community-based setting, adenoma detection for screening and surveillance colonoscopies were not associated with either time of day or the number of prior procedures performed by the endoscopist, within the range of procedure volumes evaluated. The lack of association persisted after accounting for prior procedure complexity.

Human papillomavirus vaccination and subsequent cervical cancer screening in a large integrated healthcare system.

BACKGROUND: Human papillomavirus vaccination may result in lowered intention to be screened for cervical cancer, potentially leading to gaps in screening coverage and avoidable cervical cancer diagnoses. OBJECTIVE: The purpose of this study was to examine the association between human papillomavirus vaccination and subsequent cervical cancer screening initiation and adherence to recommended screening intervals to detect gaps in screening coverage and inform future prevention efforts. STUDY DESIGN: A retrospective cohort study was conducted in 2 distinct cohorts of female members of Kaiser Permanente Southern California, which is a large integrated healthcare delivery system. Papanicolaou screening initiation was evaluated in women who reached 21 years from 2010-2013. Adherence to recommended screening intervals was evaluated in women who were 25-30 years old in 2010. All women were observed to the end of 2013 for the evaluation of their screening behaviors. History of human papillomavirus vaccination and Papanicolaou screening were obtained from electronic medical records. Adherence to recommended screening intervals was measured as ≥85% vs <85% of the observed "screening up-to-date" person-time. Multivariable Cox and logistic regression models were used to examine associations between vaccination history and screening initiation and interval adherence. Demographic characteristics, gynecologic health history, healthcare use, and characteristics of women's primary care providers were included as potential confounders in the analyses. RESULTS: There were 27,352 and 41,328 women included in the screening initiation and screening interval adherence analyses, respectively. In comparison with unvaccinated women, adjusted hazard ratios (95% confidence intervals [CIs]) for screening initiation among women who had been vaccinated against human papillomavirus were 1.19 (95% CI, 1.11-1.28), 1.44 (95% CI, 1.34-1.53), and 1.57 (95% CI, 1.50-1.65) for 1, 2, and ≥3 doses, respectively. Adjusted odds ratios for screening interval adherence were 0.93 (95% CI, 0.83-1.04), 1.73 (95% CI, 1.52-1.97), and 2.29 (95% CI, 2.05-2.56), for 1, 2, and ≥3 doses, respectively. CONCLUSION: Women who had been vaccinated against human papillomavirus in this community-based, integrated healthcare setting were more likely to be screened for cervical cancer than were unvaccinated women. Our findings underscore the need for targeted interventions among unvaccinated women who may be disproportionally affected by cervical cancer, despite the presence of population-based screening programs.