Table S-2 displays cumulative risk of death from other causes (competing risk to CRC mortality estimates#), stratified by patient characteristics at index date.

BACKGROUND & AIMS:Longitudinal adherence with annual stool-based screening for colorectal cancer is guideline-recommended. This paper assessed patterns and predictors of repeat stool-based screening over time and associated outcomes. METHODS:This retrospective cohort study followed adults aged 50 to 65 years in 4 health systems eligible for repeat screening following a negative index fecal immunochemical test or guaiac fecal occult blood test in 2010 to 2011 for up to 10 years. Repeat stool-based testing patterns were categorized as: consistent (≥75% of rounds completed, inconsistent [<75%], and never repeaters. Multivariable predictors of consistent testing were analyzed, as well as associations between screening consistency and cancer stage at diagnosis. RESULTS:Among 492,812 individuals, 54% were consistent repeaters, 30% inconsistent repeaters, and 16% never-repeaters. The proportion of never-repeaters declined with more follow-up time, whereas inconsistent repeating increased. Consistent repeating remained fairly constant. Health system was the strongest predictor of consistent screening, with wide variation by site. Consistent repeating was also associated with older age, male sex, being non-Hispanic White, lower comorbidity, body mass index <25 kg/m2, public insurance, prior stool-based testing, and a primary care provider visit in the past year. Advanced stage colorectal cancer was more frequent among never-repeaters (19% vs 12% for inconsistent and 12% consistent repeaters). Early-stage cancer was more common among consistent repeaters (56% vs 49% inconsistent and 44% never-repeaters). CONCLUSIONS:Among patients initially screened with an annual stool-based test, about one-half (54%) consistently repeated it, and 16% never repeated during available follow-up. The health system where the patient was cared for was most strongly associated with consistent stool-based testing, and higher adherence was associated with earlier cancer stage at diagnosis.

BACKGROUND:Public health emergencies can substantially affect routine health care. Large cancer screening declines during the early months of the COVID-19 pandemic are well documented; however, COVID-19's impact on follow-up of abnormal screening exams and cancer diagnoses is less reported. We examined the impacts of COVID-19 on the cervical, colorectal, and lung cancer screening processes, within 10 health systems in the Population-based Research to Optimize the Screening Process (PROSPR) consortium. METHODS:PROSPR data were used to calculate: (i) monthly rates of cancer testing and, for pre-COVID and COVID time periods, (ii) proportions of individuals receiving recommended follow-up within 6 months of an abnormal test, and (iii) cancer incidence. Surveys were used to assess the healthcare systems' local context. RESULTS:During the first 2 months of the pandemic, cancer testing decreased across all health systems and cancer types (range, 18%-96%). Overall, decreases in monthly rates were followed by rapid recovery to prepandemic rates. The rates of 6-month follow-up of abnormal screening results trended down in the COVID versus pre-COVID periods, as did the diagnosis of new cancers. CONCLUSIONS:Declines in cancer testing in the early months of the COVID-19 pandemic were short term, with at least short-term impacts on diagnostic follow-up and cancer diagnosis. The systems with the smallest decreases were those that both utilized remote screening outreach (e.g., mailed fecal immunochemical test kits) and did not pause that outreach at the start of the pandemic. IMPACT:Strategies and policies implemented by healthcare systems during public health emergencies can help minimize disruptions in care. See related In the Spotlight, p. 1481.

631 Background: Adolescent and young adult (AYA) women with breast cancer who have not completed their desired childbearing pre-diagnosis may be more likely to decline adjuvant endocrine therapy (ET) and/or to temporarily or permanently stop ET to pursue pregnancy. Fertility counseling and use of fertility preservation strategies (e.g., oocyte/embryo cryopreservation) might impact these decisions. Methods: In the Valuing Opinions and Insights from Cancer Experiences (VOICE) Study, we investigated whether use of fertility preservation strategies were associated with ET initiation and early discontinuation amongst AYAs with fertility concerns. Eligible females were diagnosed with stage 1–3 estrogen-receptor positive breast cancer at age 15-39 during 2013-2022 and responded to a survey in 2023-2024. Those who reported that they had not completed their desired family size or had been unsure about having completed their desired family size at the time of their cancer diagnosis were categorized as having had fertility concerns. ET initiation was defined as 2+ ET prescription fills within 18 months after diagnosis. Among ET initiators, we assessed early discontinuation (defined as lack of ET prescription fill over any 180 day period until 5 years after their first ET fill date). Due to inadequate power, we did not model the relationship between oocyte/embryo cryopreservation and ET initiation. However, we did have power to assess the association between oocyte/embryo cryopreservation and ET discontinuation using multivariable Cox regression to calculate Hazard Ratios (HR) and 95% Confidence Intervals (CI). HRs for discontinuation were adjusted for age at diagnosis, stage, study site, diagnosis year, income, and children before diagnosis (yes/no). Results: Among 518 AYA breast cancer survivors, 56% (N = 290) had fertility concerns at diagnosis. Of these 290, 41% had 1+ child before diagnosis, 90% received fertility counseling, 27% froze eggs or embryos, and 10% had 1+ child after diagnosis. The majority (89%) initiated ET. Among the 32 who did not initiate ET, 7 (22%) reported that fertility concerns impacted that decision. Oocyte/embryo cryopreservation was used by 26% of ET initiators and 34% of ET non-initiators. Among the 258 ET initiators, 89 (35%) discontinued ET early. Compared to those who did not use fertility preservation strategies, patients who froze oocytes/embryos were more likely to discontinue ET (HR 1.89; 95% CI 1.18–3.05). Among those who discontinued ET, 19% had 1+ child after diagnosis (compared to 2% among those who did not discontinue ET). Conclusions: This study confirmed prior studies showing that many AYAs with breast cancer have fertility concerns, and these concerns may impact decisions about ET. In our analysis, those who cryopreserved oocytes/embryos were more likely to discontinue ET early, and a higher proportion who discontinued ET had 1+ live birth after breast cancer.

Supplemental Table 2. Data source for covariates assessed in the study.

Cancer screening guidelines specify ages at which routine screening should be discontinued and, except for cervical cancer screening, do not require specific screening history criteria be met for discontinuation. We estimated the prevalence of being up to date with average-risk screening guidelines for colorectal, cervical, and lung cancer as of the recommended ages for discontinuation of routine screening. We conducted a descriptive study among several U.S. healthcare systems during 2010-2019. Up-to-date screening prevalence, based on U.S. Preventive Services Task Force guidelines, was ascertained prior to 76th, 66th, and 81st birthdays among persons eligible for colorectal (N = 316,756 persons), cervical (N = 20,282 persons), and lung cancer (N = 1,151 persons) screening, respectively. Up-to-date screening prevalence was 84.4% for colorectal, 58.9% for cervical, and 6.3% for lung cancer screening. Up-to-date screening prevalence at the ages recommended for discontinuing routine colorectal, cervical, and lung cancer screening varied appreciably, and was particularly low for lung cancer screening.

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6

Supplemental Table 1. Classification of antibiotics in the study into broad-spectrum and narrow-spectrum antibiotics

Abstract Background: Diagnosing colorectal cancer in people below age 50 relies largely on the evaluation of symptoms despite recent recommendations to initiate screening at age 45. There is limited information on the positive predictive value (PPV) of symptoms as indicators of early-onset colorectal cancer. Methods: We identified patients aged 42 to 49 years in three community-based health systems between 2012 and 2020 whose first recorded colonoscopy had a diagnostic indication, with symptoms present in the two years before the colonoscopy. We computed the PPV for colorectal cancer by each individual symptom, combinations of the three most common symptoms, and combinations of the three symptoms with the highest PPVs and computed 95% confidence intervals (CI). We also evaluated the PPV of recent symptoms stratified according to the timing of onset and estimated the PPV of symptoms when followed by positive or negative fecal testing. Results: The study included 28,198 patients. The PPV for specific symptoms, with or without other symptoms, was 2.4% (95% CI, 2.2%–2.7%) for blood loss and 4.5% (95% CI, 3.3%–5.9%) for positive fecal testing. Pairwise and three-way combinations of blood loss, diarrhea, and abdominal mass had PPV point estimates for colorectal cancer above 3%. Conclusions: Our study suggests that specific symptoms and combinations may identify patients with a ≥3% prevalence of colorectal cancer in those aged 42 to 49 and that fecal testing results may further identify patients with a higher probability of colorectal cancer. Impact: Future research is needed to develop high PPV strategies for identifying early-onset colorectal cancer without compromising sensitivity. See related In the Spotlight, p. 1233

INTRODUCTION:Patient-reported measures are important tools in assessing cancer care quality, yet they may overlook the interpretive work patients do in making sense of provider and health system actions. Beyond practical aspects, patients read specific actions symbolically, as signals of respect, competence, and concern. This study explored how individuals diagnosed with cancer understand and define high- and low-quality care. METHODS:The authors have conducted semistructured interviews with 58 adults diagnosed with cancer within the previous year across 3 regions of an integrated health system. Interviews were analyzed using thematic coding. RESULTS:Participants consistently framed their experiences through interpretations of specific provider and system actions. Three primary domains emerged: timeliness and responsiveness, proactive coordination and advocacy, and clarity, with kindness identified as a meta theme. Actions including rapid callbacks, proactive scheduling, and clear explanations were understood as both operational efficiencies and evidence that providers were trustworthy and cared about patients. Conversely, delays, poor communication, and lack of coordination were interpreted as indifference or lack of urgency. DISCUSSION:The findings of the authors have underscored that patients interpret care actions through both practical and symbolic lenses. Even when clinical outcomes are favorable, perceived indifference or unclear communication can erode trust and heighten distress. These insights expand quality frameworks by highlighting relational and interpretive dimensions of care. CONCLUSION:Timeliness, coordination, clarity, and kindness are not merely operational goals but signals of empathy and respect that profoundly shape patient experience. Integrating these dimensions into quality improvement efforts can advance cancer care that is clinically effective and responsive to human needs.

Table S-1 shows characteristics of screen-eligible patients aged 76-85 years at index date, stratified by healthcare system.

Supplemental Table 4. Adjusted odds ratio for antibiotic exposures from 2 to 4.9 years prior to diagnosis/index date among those with ≥15 years of prior membership and those with ≥5 years of prior membership

Abstract Breast cancer (BC) is the most common cancer among female adolescents and young adults (AYAs; 15-39 years). While advances in treatment have improved survival, cardiovascular disease (CVD) can result from systemic therapies, and CVD is a leading cause of death in AYA cancer survivors. AYAs with BC face nearly a four-fold increased risk of CVD compared to their peers without cancer. However, data on the effects of systemic treatment on CVD in this population remains limited. We estimated risk of CVD in AYAs diagnosed with invasive BC (2006-2020), who survived ≥2 years, and were diagnosed and treated in the Kaiser Permanente (KP) Northern and Southern California. Patients were categorized by receipt of anthracycline-, alkylating-, HER2-, platinum-, and taxane-based therapies within 2 years of diagnosis. We examined the cumulative incidence of CVD starting 2 years post-diagnosis and used Cox proportional hazards regression to determine factors associated with CVD. Among 3,071 AYAs, 35.1% were non-Hispanic (NH) White, 31.6% were Hispanic, 18.3% were NH Asian, and 8.2% were NH Black. Most received systemic therapy (90.6%), including anthracycline- and alkylator without HER2-targeted therapy (41.9%) and HER2-targeted therapy without anthracycline (20.9%). Fewer AYAs received a taxane and alkylator (13.0%) or anthracycline with alkylator and taxane along with a HER2-targeting agent (6.4%). Mean follow-up after cancer diagnosis was 7.2 years (range: 2.0-17.5). The 10-year cumulative incidence of CVD was highest among AYAs who received anthracycline/alkylator/taxane/HER2-targeting therapy (19.6%), intermediate for those with anthracycline/alkylator without HER2-targeting therapy (13.0%) and those who received HER2-targeted therapy without anthracycline (14.6%), and lowest for those who received taxane/alkylator (7.3%). In the multivariable model adjusted for demographic factors and radiation, compared to taxane/alkylator, anthracycline/alkylator/taxane/HER2-targeting therapy (hazard ratio (HR)=2.63, 95% confidence interval (CI) 1.56-4.43); anthracycline/alkylator without HER2-targeting therapy (HR=1.75, CI 1.13-2.71); and HER2-targeting therapy without anthracycline (HR=2.13, CI 1.11-4.09) were associated with an increased risk of CVD. CVD risk was similar for taxane/alkylator and no systemic therapy. Other factors associated with higher risk of CVD included NH Black race/ethnicity (HR=1.90, CI 1.32-2.73 vs. NH White) and public health insurance (HR=1.67, CI 1.00-2.78 vs private). This study identifies AYA BC survivors at higher risk of CVD based on treatment regimens received, with highest risks found for those receiving anthracycline/alkylator/taxane/HER2 treatment combinations. In addition, AYAs of Black race/ethnicity and those with public health insurance experienced more CVD, underscoring the need for targeted interventions to mitigate these disparities. Citation Format: Theresa H. M. Keegan, Candice A. Sauder, Ann M. Brunson, Renata Abrahao, Anne C. Kirchhoff, Eric Haupt, Mallory Casperson, Ted Wun, Chun R. Chao, Andrew B. Smitherman, Hazel B. Nichols, Jessica Chubak, Erin E. Hahn, Lawrence H. Kushi, Kathryn J. Ruddy. Systemic therapy and cardiovascular disease in adolescent and young adult breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5219.

Figure S-1 illustrates selection of eligible study population from PRECISE cohort.

BACKGROUND:Exposure to broad-spectrum antibiotics may alter the risk of early-onset colorectal cancer (eoCRC) via gut dysbiosis. We evaluated the associations between oral broad-spectrum and narrow-spectrum antibiotic use and eoCRC. METHODS:We conducted a nested case-control study within Kaiser Permanente Southern California (KPSC). Cases were persons aged 15 to 49 years with in situ or invasive colorectal adenocarcinoma (2009-2021); controls were individually matched 10:1 on age, sex, and length of KPSC membership. Those with ≥15 years of membership were included to assess exposure 2 to 15 years earlier. Data were collected from electronic health records. Crude and multivariable conditional logistic regression was used to evaluate antibiotic use from 10 to 14.9, 5 to 9.9, and 2 to 4.9 years before diagnosis/index date with the risk of overall colorectal cancer, colon cancer, and rectal cancer. RESULTS:A total of 295 cases and 2,794 controls were included. In the 10 to 14.9 years before diagnosis/index date, the use of broad-spectrum antibiotics was not associated with eoCRC [adjusted odds ratio (aOR) for any use = 1.07 (95% confidence interval, 0.82-1.40); aOR for >90 days of cumulative use = 1.40 (0.82-2.38)]. An elevated risk of colon adenocarcinoma was suggested for >90 days of cumulative use of broad-spectrum antibiotics [aOR = 2.04 (1.09-3.85)]. No clear association was observed for broad-spectrum antibiotic use within 5 to 9.9 or 2 to 4.9 years prior to diagnosis or with rectal cancer during any period or for narrow-spectrum antibiotics in any exposure window. CONCLUSIONS:An association between long-term cumulative use of broad-spectrum antibiotics and early-onset colon cancer is suggested. IMPACT:Further investigation into antibiotics and eoCRC risk by the duration of use and the window of exposure is warranted.

Abstract Adolescents and young adult (AYA) cancer survivors face a higher risk of chronic medical conditions and are more likely to delay or forgo health care due to costs compared to same-age individuals without cancer. They also experience greater financial hardship than older adult survivors. However, gaps remain in our understanding of the financial hardships associated with cancer or the lasting health effects of treatment in AYA cancer survivors. In the Valuing Opinions and Insights from Cancer Experiences (VOICE) Study, participants diagnosed during 2016-2022 with 10 common AYA cancers between ages 15-39 years in California completed a survey in 2023-2024. Financial hardship was measured by financial debt due to cancer and 8 questions on the impact of medical expenses in the past year, categorized into trouble meeting needs (e.g., put off major purchases, unable to pay for basic necessities), asset depletion (e.g., took money from savings/retirement, credit card debt) and major financial changes (e.g., needed mortgage against home, thought about bankruptcy). In addition, we assessed whether AYAs were diagnosed after cancer diagnosis with 10 chronic medical conditions (asthma/lung problems, blood clots, bladder dysfunction, diabetes, heart conditions, hypertension, kidney dysfunction, liver problems, osteoporosis, thyroid problems). We examined the association of each financial hardship with 1 or ≥2 (vs 0) medical conditions using multinomial logistic regression, adjusting for age, sex, race/ethnicity, current health insurance and cancer type. Among 3,685 AYAs, most were age 30-39 years at diagnosis (70.6%), of non-Hispanic (NH) White (34.6%) or Hispanic (32.4%) race or ethnicity and had employer-sponsored insurance (66.6%). Breast (25.3%), thyroid (22.4%) melanoma (10.0%), and testicular (10.3%) were the most common cancers. Overall, 18.9% and 7.8% of AYAs developed 1 or ≥2 of the 10 chronic medical conditions, respectively. Nearly one-fifth (18.8%) of AYAs experienced financial debt since their cancer diagnosis. In the past year, approximately one-third of AYAs experienced trouble meeting needs (27.5%) and asset depletion (31.7%), while 6.1% experienced major financial changes. In multivariable models, AYAs with ≥2 conditions were more likely to have financial debt (odds ratio (OR)=1.99, 95% confidence interval (CI) 1.50-2.64 vs. no medical conditions), trouble meeting needs (OR=2.05, CI 1.58-2.67), asset depletion (OR=1.83, CI 1.42-2.37) and major financial changes (OR=2.24, CI 1.49-3.36). Financial hardship impacts one-third of AYA cancer survivors, and those with chronic medical conditions have a substantially greater likelihood of experiencing financial hardship. Our findings highlight the long-term economic impact of cancer in this population and the need to evaluate the effectiveness of targeted interventions, such as financial navigation, to address financial burden. Citation Format: Diego Del Toro Rivera, Qian Li, Anne Kirchhoff, Salene M. Jones, Candice A. Sauder, Ann M. Brunson, Charles P. Quensenberry, Lisa M. Moy, Renata Abrahao, Ted Wun, Hazel B. Nichols, Lawrence H. Kushi, Jessica Chubak, Erin E. Hahn, Theresa H. M. Keegan. Financial hardships and chronic medical conditions in adolescent and young adult cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7888.

Supplemental Table 3. Characteristics of the cases and controls with at least 5 years of prior membership in the sensitivity analysis

Purpose: This project examined test-retest reliability and survey mode administration across single-item and multi-item measures among adolescent and young adult (AYA) cancer survivors.Methods: Forty-six AYAs randomly assigned to survey mode (phone, online, and paper) completed the survey and were invited to complete the survey again 1 week later.Results: Mode effects were found on 6% of single-items and 25% of multi-item scores. Reliability was low for 52% of single-items and 8% of multi-item scores.Conclusion: Multi-item measures should generally be used over single-item measures due to better reliability, but single-item measures may be preferable when mode effects are large.

INTRODUCTION:Obesity is associated with a risk for several screen-detectable cancers, yet cancer screening rates are lower among adults with obesity. It is unclear whether associations between BMI and screening initiation differ by race, ethnicity, or sex. METHODS:A retrospective cohort study was conducted among adults initiating cervical, colorectal, or lung cancer screening using electronic health record data from 10 U.S. health systems (2010-2020 for the cervical/colorectal cohorts; 2014-2021 for lung). Associations between screening initiation (within 15 months of becoming age eligible) and BMI categories were analyzed using separate logistic regression models. Effect modification by race/ethnicity and sex was assessed. Data were analyzed from 2023 to 2025. RESULTS:Among 23,849 adults eligible for cervical cancer screening, patients with overweight (BMI of 25 to <30 kg/m2), Class 1 obesity (BMI of 30 to <35 kg/m2), Class 2 obesity (BMI of 35 to <40 kg/m2), and Class 3 obesity (BMI of ≥40 kg/m2) had lower odds of screening initiation than adults with a healthy weight (BMI of 18.5 to <25 kg/m2). Similarly, among 561,132 adults eligible for colorectal cancer screening, overweight and Classes 1-3 obesity were associated with lower odds of screening. Race and ethnicity moderated the associations between BMI and cervical (p=0.0013) and colorectal (p<0.0001) screening, and sex moderated the associations between BMI and colorectal screening (p<0.0001). Stratified analysis was not conducted for the lung cohort (49,199) owing to a smaller sample size. CONCLUSIONS:Adults with obesity have lower odds of timely screening initiation. Given the increased risk of cancers in adults with obesity, effective interventions to target suboptimal cancer screening are critically important.