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Background: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence. Objectives: To assess the impact of detecting methylated BCAT1/IKZF1 ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence. Design: A retrospective cohort study. Methods: The cohort included 180 patients (36 with recurrent CRC), who had undergone complete treatment and surveillance for a minimum of 3 years. Participant clinical details and ctDNA methylated BCAT1 / IKZF1 results were compared between those with and without recurrence, and cox regression analysis assessed each factor on disease-free survival. Results: Clinical factors independently associated with reduced disease-free survival included nodal involvement (HR = 3.83, 95% CI 1.56-9.43, P =.003), M1 stage (HR = 4.41, 95% CI 1.18-16.45, P =.027), a resection margin less than 2 mm (HR = 4.60, 95% CI 1.19-17.76, P =.027), perineural involvement (HR = 2.50, 95% CI 1.01-6.17, P =.047) and distal tumors (HR = 3.13, 95% CI 1.07-9.18, P =.037). Methylated BCAT1 / IKZF1 was detected in 51.7% (93/180) of pre-treatment plasma samples. When a positive ctDNA finding was considered in combination with these clinical prognostic factors, there was improved predictive power of recurrence for patients with perineural involvement (HR = 4.44, 95% CI 1.92-10.26, P <.001), and it marginally improved the predictive factor for M1 stage (HR = 7.59, 95% CI 2.30-25.07, P =.001) and distal tumors (HR = 5.04, 95% CI 1.88-13.49, P =.001). Conclusions: Nodal invasion, metastatic disease, distal tumor site, low resection margins and perineural invasion were associated with disease recurrence. Pre-treatment methylated ctDNA measurement can improve the predictive value for recurrence in a subset of patients, particularly those with perineural involvement. Registration: Australian and New Zealand Clinical Trials Registry #12611000318987. [ABSTRACT FROM AUTHOR]

Purpose: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC. Methods: This multicenter, prospective, randomized controlled trial will invite participants who are scheduled for surveillance colonoscopy (due to a personal history of adenomas or a family history of CRC) and who have returned a low fecal hemoglobin (< 2 μg Hb/g feces; F-Hb) using a two-sample FIT (OC Sensor, Eiken Chemical Company) in the prior 3 years. A total of 1344 individuals will be randomized to either surveillance colonoscopy as scheduled or delayed by 1 or 2 years for individuals originally recommended a 3- or 5-year surveillance interval, respectively. The primary endpoint is incidence of advanced neoplasia (advanced adenoma and/or CRC). Secondary endpoints include cost-effectiveness and consumer acceptability of extending surveillance intervals, determined using surveys and discrete choice experiments. Conclusion: This study will establish the safety, cost-effectiveness, and acceptability of utilizing a low FIT Hb result to extend colonoscopy surveillance intervals in a cohort at elevated risk for CRC. This personalized approach to CRC surveillance will lead to a reduction in unnecessary colonoscopies, increases in healthcare savings, and a better patient experience. Trial registration: Registration was approved on December 9, 2019 with the Australian New Zealand Clinical Trials Registry ANZCTR 12619001743156. [ABSTRACT FROM AUTHOR]

Background: Rectal Cancer is a common malignancy. The current treatment approach for patients with locally advanced rectal cancer involves neoadjuvant chemoradiotherapy followed by surgical resection of the rectum. The resection can lead to complications and long-term consequences. A clinical complete response is observed in some patients after chemoradiotherapy. A number of recent studies have shown that patients can be observed safely after completing chemoradiotherapy (without surgery), provided clinical complete response has been achieved. In this approach, resection is reserved for cases of regrowth. This is called the watch and wait approach. This approach potentially avoids unnecessary surgical resection of the rectum and the resulting complications. In this study, we will prospectively investigate this approach.Methods: Adult patients with a diagnosis of rectal cancer planned to receive neoadjuvant long course chemoradiotherapy (± subsequent combination chemotherapy) will be consented into the study prior to commencing treatment. After completing the chemoradiotherapy (± subsequent combination chemotherapy), based on the clinical response, subjects will be allocated to one of the following arms: subjects who achieved a clinical complete response will be allocated to the watch and wait arm and others to the standard management arm (which includes resection). The aim of the study is to determine the rate of local failure and other safety and efficacy outcomes in the watch and wait arm. Patient reported outcome measures and the use of biomarkers as part of the clinical monitoring will be studied in both arms of the study.Discussion: This study will prospectively investigate the safety of the watch and wait approach. We will investigate predictive biomarkers (molecular biomarkers and imaging biomarkers) and patient reported outcome measures in the study population and the cost effectiveness of the watch and wait approach. This study will also help evaluate a defined monitoring schedule for patients managed with the watch and wait approach. This protocol covers the first two years of follow up, we are planning a subsequent study which covers year 3-5 follow up for the study population.Trial Registration: Name of the registry: Australia and New Zealand Clinical Trials Registry (ANZCTR).Trial Registration Number: Trial ID: ACTRN12619000207112 Registered 13 February 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376810. [ABSTRACT FROM AUTHOR]