Endoscopic resection of high-risk T1 colorectal carcinoma prior to surgical resection has no adverse effect on long-term outcomes.

OBJECTIVE: It is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients' outcomes compared with primary surgery. DESIGN: Patients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication. RESULTS: 602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome. CONCLUSIONS: Our data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients.

Narrow Band Imaging, Magnifying Chromoendoscopy, and Gross Morphological Features for the Optical Diagnosis of T1 Colorectal Cancer and Deep Submucosal Invasion: A Systematic Review and Meta-Analysis.

OBJECTIVES: Optical diagnosis of T1 colorectal cancer (CRC) and T1 CRC with deep submucosal invasion is important in guiding the treatment strategy. The use of advanced imaging is not standard clinical practice in Western countries. A systematic review and meta-analysis were conducted comparing the accuracy of narrow band imaging (NBI), magnifying chromoendoscopy (MCE), and gross morphological features (GMF) seen with conventional view for the optical diagnosis of T1 CRC and deep submucosal invasion. METHODS: A literature search identified studies on the optical diagnosis of T1 CRC and deep invasion using NBI, MCE, or GMF. Pooled estimates (PE) of sensitivity and specificity across studies reporting on NBI or MCE were compared using a random effects bivariate meta-regression approach, and a paired analysis focusing on studies that performed both techniques within the same patient was performed. RESULTS: Thirty-three studies with 31,568 polyps were included. For the optical diagnosis of T1 CRC, both NBI (4 studies; PE 0.85, 95% confidence interval (CI) 0.75-0.91) and MCE (5 studies; PE 0.90, 95% CI 0.83-0.94) yielded higher sensitivity as compared with GMF (3 studies; range 0.21-0.46). No significant preference for NBI or MCE was found (sensitivity relative risk (RR) 0.93, 95% CI 0.79-1.09, P=0.37; specificity RR 0.98, 95% CI 0.86-1.11, P=0.74). Similarly, for the optical diagnosis of deep invasion, both NBI (13 studies; PE 0.77, 95% CI 0.68-0.84) and MCE (17 studies; PE 0.81, 95% 0.75-0.87) yielded higher sensitivity as compared with GMF (6 studies; range 0.18-0.88), and no significant preference for either NBI or MCE was found (sensitivity RR 0.92, 95% CI 0.76-1.11, P=0.36; specificity RR 1.00, 95% CI 0.96-1.04, P=0.92). CONCLUSIONS: This review supports the use of advanced imaging techniques in preference to GMF to reduce the risk of performing piecemeal resection for T1 CRCs or unnecessary surgical referral for lesions amendable to endoscopic resection. A preference for either NBI or MCE could not be observed.

Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study.

OBJECTIVES: The decision to perform secondary surgery after endoscopic resection of T1 colorectal cancer (CRC) depends on the risk of lymph node metastasis and the risk of incomplete resection. We aimed to examine the incidence and risk factors for incomplete endoscopic resection of T1 CRC after a macroscopic radical endoscopic resection. METHODS: Data from patients treated between 2000 and 2014 with macroscopic complete endoscopic resection of T1 CRC were collected from 13 hospitals. Incomplete resection was defined as local recurrence at the polypectomy site during follow-up or malignant tissue in the surgically resected specimen in case secondary surgery was performed. Multivariate regression analysis was performed to analyze factors associated with incomplete resection. RESULTS: In total, 877 patients with a median follow-up time of 36.5 months (interquartile range 16.0-68.3) were included, in whom secondary surgery was performed in 358 patients (40.8%). Incomplete resection was observed in 30 patients (3.4%; 95% confidence interval (CI) 2.3-4.6%). Incomplete resection rate was 0.7% (95% CI 0-2.1%) in low-risk T1 CRC vs. 4.4% (95% CI 2.7-6.5%) in high-risk T1 CRC (P=0.04). Overall adverse outcome rate (incomplete resection or metastasis) was 2.1% (95% CI 0-5.0%) in low-risk T1 CRC vs. 11.7% (95% CI 8.8-14.6%) in high-risk T1 CRC (P=0.001). Piecemeal resection (adjusted odds ratio 2.60; 95% CI 1.20-5.61, P=0.02) and non-pedunculated morphology (adjusted odds ratio 2.18; 95% CI 1.01-4.70, P=0.05) were independent risk factors for incomplete resection. Among patients in whom no additional surgery was performed, who developed recurrent cancer, 41.7% (95% CI 20.8-62.5%) died as a result of recurrent cancer. CONCLUSIONS: In the absence of histological high-risk factors, a 'wait-and-see' policy with limited follow-up is justified. Piecemeal resection and non-pedunculated morphology are independent risk factors for incomplete endoscopic resection of T1 CRC.

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): rationale and design of a multicenter randomized clinical trial.

BACKGROUND: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. METHODS: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. DISCUSSION: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. TRIAL REGISTRATION: NCT02657044 (Clinicaltrials.gov), registered January 8, 2016.

National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer.

Background: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this observational study was to compare surgical outcomes for T1 colorectal cancer with those for more advanced colorectal cancer. Methods: This was a population-based cohort study of patients treated surgically for pT1-3 colorectal cancer between 2009 and 2016, using data from the Dutch ColoRectal Audit. Postoperative complications (overall, surgical, severe complications and mortality) were compared using multivariable logistic regression. A risk stratification table was developed based on factors independently associated with severe complications (reintervention and/or mortality) after elective surgery. Results: Of 39 813 patients, 5170 had pT1 colorectal cancer. No statistically significant differences were observed between patients with pT1 and pT2-3 disease in the rate of severe complications (8·3 versus 9·5 per cent respectively; odds ratio (OR) 0·89, 95 per cent c.i. 0·80 to 1·01, P = 0·061), surgical complications (12·6 versus 13·5 per cent; OR 0·93, 0·84 to 1·02, P = 0·119) or mortality (1·7 versus 2·5 per cent; OR 0·94, 0·74 to 1·19, P = 0·604). Male sex, higher ASA grade, previous abdominal surgery, open approach and type of procedure were associated with a higher severe complication rate in patients with pT1 colorectal cancer. Conclusion: Elective bowel resection was associated with similar morbidity and mortality rates in patients with pT1 and those with pT2-3 colorectal carcinoma.