Integrating primary care, shared decision making, and community engagement to facilitate equitable access to multi-cancer early detection clinical trials.

Effective implementation of cancer screening programs can reduce disease-specific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is sub-optimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many are underway. In the conduct of MCED test trials, it is crucial that participant recruitment efforts successfully engage participants from diverse populations experiencing cancer disparities. Strategic partnerships involving health systems, clinical practices, and communities can increase the reach of MCED trial recruitment efforts among populations experiencing disparities. This goal can be achieved by developing health system-based learning communities that build understanding of and trust in biomedical research; and by applying innovative methods for identifying eligible trial patients, educating potential participants about research trials, and engaging eligible individuals in shared decision making (SDM) about trial participation. This article describes how a developing consortium of health systems has used this approach to encourage the uptake of cancer screening in a wide range of populations and how such a strategy can facilitate the enrollment of persons from diverse patient and community populations in MCED trials.

How Would You Screen This Patient for Colorectal Cancer? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Colorectal cancer (CRC) is the third leading cause of cancer death for men and women in the United States, with an estimated 52 580 people expected to die in 2022. Most frequently, CRC is diagnosed among persons aged 65 to 74 years. However, among persons younger than 50 years, incidence rates have been increasing since the mid-1990s. In 2021, partially because of the rising incidence, the U.S. Preventive Services Task Force (USPSTF) recommended CRC screening for adults aged 45 to 49 years (Grade B recommendation). Options for CRC screening include stool-based and direct visualization tests. The USPSTF did not recommend a specific screening test; rather, its guidance was to select a test after a discussion with the patient. Here, a primary care physician and a gastroenterologist discuss the recommendation to begin CRC screening at age 45, review options for CRC screening, and discuss how to choose among the available options.

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer.

OBJECTIVES: The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful. METHODS: A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy. RESULTS: For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients. CONCLUSIONS: Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

Phase I double-blind, placebo-controlled trial of dolcanatide (SP-333) 27 mg to explore colorectal bioactivity in healthy volunteers.

Guanylyl cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of the luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Previous studies revealed that linaclotide, an oral GUCY2C agonist formulated for gastric release, did not persist to activate guanylyl cyclase signaling in the distal rectum. Dolcanatide is an investigational oral uroguanylin analog, substituted with select D amino acids, for enhanced stability and extended persistence to activate GUCY2C in small and large intestine. However, the ability of oral dolcanatide to induce a pharmacodynamic (PD) response by activating GUCY2C in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of oral dolcanatide 27 mg daily for 7 d to healthy volunteers did not activate GUCY2C, quantified as accumulation of its product cyclic GMP, in epithelial cells of the distal rectum. These data reveal that the enhanced stability of dolcanatide, with persistence along the rostral-caudal axis of the small and large intestine, is inadequate to regulate GUCY2C across the colorectum to prevent tumorigenesis. These results highlight the importance of developing a GUCY2C agonist for cancer prevention formulated for release and activity targeted to the colorectum.

Cost-effectiveness of surveillance with CT colonography after resection of colorectal cancer.

OBJECTIVE: Surveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test. DESIGN: We developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6 mm detected by CTC underwent OC. Detection of an adenoma 10 mm or larger was followed by OC at 1 year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effects at 3% per year. RESULTS: For persons with resected stage III CRC, the standard-of-care strategy was more costly (US$293) and effective (2.6 averted CRC cases and 1.1 averted cancer deaths per 1000) than the CTC-based strategy, with an incremental cost-effectiveness ratio of US$55 500 per quality-adjusted life-year gained. Our analysis was most sensitive to the sensitivity of CTC for detecting polyps 10 mm or larger and assumptions about disease progression. CONCLUSION: In a simulation model, we found that replacing the standard-of-care approach to postdiagnostic surveillance with a CTC-based strategy is not an efficient use of resources in most situations.

Comparing the clinical impact of pancreatic cyst surveillance programs: A trial of the ECOG-ACRIN cancer research group (EA2185).

BACKGROUND: The optimal surveillance strategy for pancreatic cysts, which occur in up to 20% of the adult population, is ill defined. The risk of malignant degeneration of these cysts is low, however the morbidity and mortality associated with pancreatic cancer are high. Two clinical surveillance guidelines are in regular use. Both the Fukuoka and American Gastroenterological Association (AGA) guidelines rely on radiographic and endoscopic imaging. They differ primarily in their recommended frequencies of interval surveillance imaging. While evidence driven clinical guidelines should promote higher quality care, competing guidelines on the same topic may provide discordant recommendations and potential reduction in the quality and/or value of care. OBJECTIVES: The primary objective is to compare the clinical effectiveness of the two surveillance guidelines to identify patients most likely to benefit from pancreatic resection. Secondary objectives include comparison of resource utilization, patient reported outcomes, incidental findings are other clinical outcomes. METHODS: 4606 asymptomatic patients with newly identified pancreatic cysts ≥1 cm in diameter will be randomized 1:1 to high intensity (Fukuoka) or low intensity (AGA) surveillance. All participants will be followed prospectively for 5 years. CONCLUSION: Differing guidelines confuse providers, patients and policymakers. This large, prospective, randomized trial will compare the clinical effectiveness and resource allocation requirements of two guidelines addressing a common clinical entity. CLINICALTRIALS. GOV IDENTIFIER: NCT04239573.

Post-operative colorectal cancer surveillance: preference for optical colonoscopy over computerized tomographic colonography.

PURPOSE: Post-operative surveillance strategies for colorectal cancer (CRC) include periodic optical colonoscopy (OC) and abdominal-pelvic CT scan. Adherence with these recommendations is limited. For CRC screening, CT colonography (CTC) identifies larger adenomas and cancers nearly as well as OC. Most screening studies demonstrate that patients prefer CTC. However, CTC has never been compared to OC in the post-operative surveillance setting. METHODS: We hypothesized that CTC might represent an attractive substitute for the standard OC/CT scan combination. Here, 223 patients underwent CTC followed by same day OC 1 year after curative CRC resection. RESULTS: Of the 144/223 (64.6%) participants with a preference, 65.9% (95/144) preferred OC. This preference was more pronounced in women and in patients with polyps detected. No additional patient level factors significantly altered this primary result. CONCLUSIONS: In contrast to CRC screening, this first study in CRC post-operative surveillance patients demonstrates a preference for OC. Assuming patient preference is an important determinant, introduction of CTC as a method to increase patient adherence with CRC surveillance is unlikely to be effective. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT02143115.

Adherence to postresection colorectal cancer surveillance at National Cancer Institute-designated Comprehensive Cancer Centers.

Guidelines recommend surveillance after resection of colorectal cancer (CRC), but rates of adherence to surveillance are variable and have not been studied at National Cancer Institute (NCI)-designated Comprehensive Cancer Centers. The aim of this study was to determine rates of adherence to standard postresection CRC surveillance recommendations including physician visits, carcinoembryonic antigen (CEA), computed tomography (CT), and colonoscopy after CRC resection at three NCI-designated centers. Data on patients with resected CRC from 2010 to 2017 were reviewed. Adherence to physician visits was defined as having at least two visits within 14 months after surgical resection. CEA adherence was defined as having at least four CEA levels drawn within 14 months. CT and colonoscopy adherence were defined as completing each between 10 and 14 months from surgical resection. Chi-square test and logistic regression analyses were performed for overall adherence and adherence to individual components. A total of 241 CRC patients were included. Overall adherence was 23%. While adherence to physician visits was over 98%, adherence to CEA levels, CT, and colonoscopy were each less than 50%. Center was an independent predictor of adherence to CEA, CT, and/or colonoscopy. Stage III disease predicted CT adherence, while distance traveled of 40 miles or less predicted colonoscopy adherence. Overall adherence to postresection CRC guideline-recommended care is low at NCI-designated centers. Adherence rates to surveillance vary by center, stage, and distance traveled for care. Understanding factors associated with adherence is critical to ensure CRC patients benefit from postresection surveillance.

Yield and Cost-effectiveness of Computed Tomography Colonography Versus Colonoscopy for Post Colorectal Cancer Surveillance.

Purpose. As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion. Methods. Using data from 231 patients who underwent same-day CTC followed by OC, we created a decision tree that outlined the choices and outcomes at 1-year clinical follow-up. Colorectal polyp prevalence, sensitivity, and specificity of CTC were compared with five exemplary studies and meta-analyses. Detection criteria were derived for ≥6 mm or ≥10 mm polyps. OC was the gold standard. Costs were gleaned from cataloging components of the cases at the principal investigator's institution. Analyses included marginal cost of the OC strategy to detect additional actionable polyps and number of polyps missed per 10,000 patients. Results. At our prevalence of 0.156 for ≥6 mm (0.043 ≥10 mm), CTC_S would miss 779 ≥6 mm actionable polyps per 10,000 patients (≥10 mm: 173 per 10,000). Cost to detect an additional ≥6 mm polyp in this cohort is $5,700 (≥10 mm: $28,000). Sensitivity analyses demonstrate that any improvement in performance characteristics would raise the cost of OC to detect more actionable polyps. Similar results were seen using Medicare costs, or when literature values were used for performance characteristics. Conclusion. At an action threshold of ≥6 mm, OC costs at least $5,700 per extra polyp detected relative to CTC_S in patients undergoing surveillance after colorectal cancer surgery, on the order of incremental cost-effectiveness ratios found for other clinical problems involving short-term events.

Computed Tomography Colonography vs Colonoscopy for Colorectal Cancer Surveillance After Surgery.

BACKGROUND & AIMS: Recommendations for surveillance after curative surgery for colorectal cancer (CRC) include a 1-year post-resection abdominal-pelvic computed tomography (CT) scan and optical colonoscopy (OC). CT colonography (CTC), when used in CRC screening, effectively identifies colorectal polyps ≥10 mm and cancers. We performed a prospective study to determine whether CTC, concurrent with CT, could substitute for OC in CRC surveillance. METHODS: Our study enrolled 231 patients with resected stage 0-III CRC, identified at 5 tertiary care academic centers. Approximately 1 year after surgery, participants underwent outpatient CTC plus CT, followed by same-day OC. CTC results were revealed after endoscopic visualization of sequential colonic segments, which were re-examined for discordant findings. The primary outcome was performance of CTC in the detection of colorectal adenomas and cancers using endoscopy as the reference standard. RESULTS: Of the 231 participants, 116 (50.2%) had polyps of any size or histology identified by OC, and 15.6% had conventional adenomas and/or serrated polyps ≥6 mm. No intra-luminal cancers were detected. CTC detected patients with polyps of ≥6 mm with 44.0% sensitivity (95% CI, 30.2-57.8) and 93.4% specificity (95% CI, 89.7-97.0). CTC detected polyps ≥10 mm with 76.9% sensitivity (95% CI, 54.0-99.8) and 89.0% specificity (95% CI, 84.8-93.1). Similar values were found when only adenomatous polyps were considered. The negative predictive value of CTC for adenomas ≥6 mm was 90.7% (95% CI, 86.7-94.5) and for adenomas ≥10 mm the negative predictive value was 98.6% (95% CI, 97.0-100). CONCLUSIONS: In a CRC surveillance population 1 year following resection, CTC was inferior to OC for detecting patients with polyps ≥6 mm. Clinical Trials.gov Registration Number: NCT02143115.