MRI-Diagnosed Tumor Deposits and EMVI Status Have Superior Prognostic Accuracy to Current Clinical TNM Staging in Rectal Cancer.

SUMMARY BACKGROUND DATA: MRI assessment of rectal cancer not only assesses tumor depth and surgical resectability but also extramural disease which affects prognosis. We have observed that nonnodal tumor nodules (tumor deposits; mrTDs) have a distinct MRI appearance compared to lymph node metastases (mrLNMs). OBJECTIVE: We aimed to assess whether mrTDs and mrLNMs have different prognostic implications and compare these to other known prognostic markers. METHODS: This was a retrospective cohort study of 233 patients undergoing resection for rectal cancer from January 2007 to October 2015. Data were obtained from electronic records and MRIs blindly rereported. Survival was determined using Kaplan-Meier method. Prognostic markers were evaluated using Cox regression and competing risks analysis. Inter-observer agreement for mrTD was measured using Cohen Kappa. RESULTS: On multivariable analysis, baseline mrTD/mrEMVI (extramural venous invasion) status was the only significant MRI factor for adverse survival [hazard ratio (HR) 2.36 (1.54-3.61] for overall survival, 2.37 (1.47-3.80) for disease-free survival (both P < 0.001), superseding T and N categories. mrLNMs were associated with good prognosis (HR 0.50 (0.31-0.80) P = 0.004 for overall survival, 0.60 (0.40-0.90) P = 0.014 for disease-free survival). On multivariable analysis, mrTDs/mrEMVI were strongly associated with distant recurrence (HR 6.53 (2.52-16.91) P ≤ 0.001) whereas T and N category were not. In a subgroup analysis of posttreatment MRIs in postchemoradiotherapy patients, mrTD/mrEMVI status was again the only significant prognostic factor; furthermore those who showed a good treatment response had a prognosis similar to patients who were negative at baseline. Inter-observer agreement for detection of mrTDs was k0.77 and k0.83. CONCLUSIONS: Current MRI staging predicting T and N status does not adequately predict prognosis. Positive mrTD/mrEMVI status has greater prognostic accuracy and would be superior in determining treatment and follow-up protocols. Chemoradiotherapy may be a highly effective treatment strategy in mrTD/mrEMVI positive patients.

Oncological outcomes of local excision versus radical surgery for early rectal cancer in the context of staging and surveillance: A systematic review and meta-analysis.

BACKGROUND: Local resection (LR) methods for rectal cancer are generally considered in the palliative setting or for patients deemed a high anaesthetic risk. This systematic review and meta-analysis aimed to compare oncological outcomes of LR and radical resection (RR) for early rectal cancer in the context of staging and surveillance assessment. METHODS: A literature search of MEDLINE, Embase and Emcare databases was performed for studies that reported data on clinical outcomes for both LR and RR for early rectal cancer from January 1995 to April 2023. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. The quality of assessment was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2.0 tool for randomised controlled trials. RESULTS: Twenty studies with 12,022 patients were included: 6,476 patients had LR and 5,546 patients underwent RR. RR led to an improvement in 5-year overall survival (OR 1.84; 95 % CI 1.54-2.20; p < 0.0001; I2 20 %) and local recurrence (OR 3.06; 95 % CI 2.02-4.64; p < 0.0001; I2 39 %) when compared to LR. However, when staging and surveillance methods were clearly adopted in LR cases, there was an improvement in R0 rates (96.7 % vs 85.6 %), 5-year disease-free survival (93.0 % vs 77.9 %) and overall survival (81.6 % vs 79.0 %) compared to when staging and surveillance was not reported/performed. CONCLUSIONS: LR may be appropriate for selected patients without poor prognostic factors in early rectal cancer. This study also highlights that there is currently no single standardised staging or surveillance approach being adopted in the management of early rectal cancer. A more specified and standardised preoperative staging for patient selection as well as clinical and image-based surveillance protocols is needed.

The Two-Week Referral System for colorectal cancer--not fit for purpose.

PURPOSE: The UK government target expects all suspected colorectal cancer (CRC) patients to be seen within the Two-Week Referral (TWR) system made by general practitioners. These guidelines originally derived from only level 5 evidence. However, this has significant impact on the workload for colorectal surgeons. The aim of the study is to investigate the effectiveness of this colorectal service and whether the referral criteria are predictive of CRC. METHODS: A retrospective study of all patients referred under the TWR guidance in 2010 was assessed. The first 573 TWRs were piloted for analysis. Clinical information from each patient was collected regarding TWR criteria and additional colorectal symptoms or risk factors. Multiple regression analysis was performed to determine which symptoms independently correlated with CRC. RESULTS: One hundred twenty-six CRCs were diagnosed via all methods of referral in 2010. There were 940 patients referred under the TWR guidelines in that year, when 50 CRC patients were identified. Amongst the 573 patients, 32 CRCs were diagnosed. Multiple regression analysis revealed tenesmus to be independently associated with CRC (p = 0.003, Pearson's r = 0.09185). None of the individual TWR criteria confidently predicted CRC. CONCLUSION: Our preliminary results suggest that the current TWR guidelines cannot effectively predict CRC. There is an urgent need for an evidence-based approach to referral criteria for suspected CRC.

Local recurrence in sigmoid cancer is a hidden problem, could CT prognostic factors be of value in their prevention? A multi-centre study of 414 patients.

INTRODUCTION: The incidence and patterns of local recurrence of colon cancer are not well reported. The aim of this study was to investigate the contemporary rates and patterns of local recurrence after sigmoid cancer resection, comparing pre and post-operative biomarkers in predicting local disease recurrence. MATERIALS AND METHODS: A multi-centre, retrospective analysis of 414 patients undergoing resectional surgery for sigmoid colon cancer was conducted. Multivariable Cox Proportional Hazard models were created to identify variables associated with local disease recurrence. Patterns of recurrence and prognostic significance of pre and post-operative variables were identified. RESULTS: In 414 patients, the local recurrence rate was 12.6%. The R1/R2 rate was 2.4%. Local recurrence occurred most commonly within the peri-anastomotic region (50%), followed by the peritoneum (33%). On multivariate analysis, local recurrence was predicted by pathological T stage (HR 1.15) and R1 resection (HR 2.95), but also computerised tomography (CT) identified tumour deposits (HR 2.40) and local peritoneal infiltration (2.70). CONCLUSIONS: Contemporary local recurrence rates for sigmoid cancer are high at 12.6%. Outcomes may be improved if local recurrence is reduced at the most common sites such as the peri-anastomotic area or peritoneum. Extra-nodal CT-imaging biomarkers of local peritoneal infiltration and tumour deposits were prognostically significant on multivariate analysis in addition to pathology staging variables.

The sigmoid take-off: An anatomical imaging definition of the rectum validated on specimen analysis.

BACKGROUND: A pre-operative imaging landmark to define the rectum would optimise clinical care of rectal cancer patients and research efforts to improve outcomes. The sigmoid take-off has been suggested as an imaging landmark for the rectosigmoid junction (RSJ). This study aimed to investigate whether this imaging definition of the rectum was validated by surgical specimen analysis. METHODS: This prospective study recruited 20 patients undergoing surgery and undertook radiological and pathological analysis of their rectal specimens. The radiological landmark of the sigmoid take-off was identified on pre-operative magnetic resonance imaging (MRI), and the distance to the anterior peritoneal reflection was measured by two readers. After surgery, the distance from the beginning of the sigmoid mesocolon to the anterior peritoneal reflection to the beginning of the sigmoid mesocolon on the specimen was measured, and compared to the distance on MRI using Pearson's Correlation Coefficient and Bland-Altman plots. RESULTS: In 17 patients, the mean distance from the anterior peritoneal reflection to the RSJ on MRI was 20.3 mm and 23.1 mm for two readers, and on pathology was 20.6 mm. The mean differences between MRI and specimen measurements were -0.31 mm (-2.83 to 2.20 mm), and 2.51 mm (95% confidence interval -0.31 to 5.33 mm) for each reader, with correlation coefficients of 0.77 and 0.81. CONCLUSION: The sigmoid take-off has been validated on specimen analysis to be an imaging landmark that defines the termination of the rectum. This anatomical landmark can be used to classify tumours and guide treatment and research of sigmoid colon and rectal cancer.

Assessment of a Staging System for Sigmoid Colon Cancer Based on Tumor Deposits and Extramural Venous Invasion on Computed Tomography.

Importance: Preoperative TNM stratification of colon cancer on computed tomography (CT) does not identify patients who are at high risk of recurrence that could be selected for preoperative treatment. Objective: To evaluate the utility of CT findings for prognosis of sigmoid colon cancer. Design, Setting, and Participants: This prognostic study used retrospective data from patients who underwent bowel resection for sigmoid colon cancer between January 1, 2006, and January 1, 2015, at a tertiary care center receiving international and national referrals for colorectal cancer. Statistical analysis was performed in April 2019. Main Outcomes and Measures: Cox proportional hazards regression analysis was performed to investigate CT findings associated with disease recurrence. Kaplan-Meier survival plots were calculated for disease-free survival using CT staging systems. Results: Of the 414 patients who had sigmoid colon cancer (248 [60.0%] men; mean [SD] age, 66.1 [12.7] years), with median follow-up of 61 months (interquartile range, 40-87 months), 122 patients (29.5%) developed disease recurrence. On multivariate analysis, nodal disease was not associated with disease recurrence; only tumor deposits (hazard ratio [HR], 1.90; 95% CI, 1.21-2.98; P = .006) and extramural venous invasion (HR, 1.97; 95% CI, 1.26-3.06; P = .003) on CT were associated with disease recurrence. Significant differences in disease-free survival were found using CT-T3 substage classification (HR, 1.88; 95% CI, 1.32-2.68) but not CT-TNM (HR, 1.55; 95% CI, 0.94-2.55). The presence of tumor deposits or extramural venous invasion on CT (HR, 2.45; 95% CI, 1.68-3.56) had the strongest association with poor outcome. Conclusions and Relevance: In this study, T3 substaging and detection of tumor deposits or extramural venous invasion on preoperative CT scans of sigmoid colon cancer were prognostic factors for disease-free survival, whereas TNM and nodal staging on CT had no prognostic value. T3 substaging and detection of tumor deposits or extramural venous invasion of sigmoid colon cancer was superior to TNM on CT and could be used to preoperatively identify patients at high risk of recurrence.

Meta-analysis of oncological outcomes of sigmoid cancers: A hidden epidemic of R1 "palliative" resections.

BACKGROUND: Colon cancer outcomes are now inferior to rectal cancer outcomes. The sigmoid colon is the most common site of colonic cancer. The aim of this review was to investigate the oncological outcomes for sigmoid cancer. METHODS: A systematic review and meta-analysis was performed. We included any study of the oncological outcomes for sigmoid cancer such as local recurrence, distant recurrence and disease free survival. A systematic search was conducted in Medline from inception to November 2016. Study quality was evaluated with the Newcastle-Ottawa Scale. The study was registered on PROSPERO (CRD42017069326). RESULTS: The search terms returned 1323 results. We identified a total of 17 eligible studies including 5953 patients. The pooled local recurrence rate was 10.5% in 15 studies with 5148 patients (95% CI 0.07-0.14) and heterogeneity measured by I2 was 94%. The pooled distant recurrence rate was 19.5% (7 studies, 2040 patients, 95% CI (0.14-0.25), I2 90%). The pooled disease free survival at 5 years was 80.4% (5 studies, 2336 patients, 95% CI 78.6%-82.1%, I2 11.5%.). The median Newcastle-Ottawa score was 4 out of 9. R1 and R2 resections were excluded or not described in 16/17 studies. Two studies described R1 and R2 rates of 15-20%. CONCLUSION: The pooled local recurrence rate of sigmoid cancer of 10.5% is higher than contemporary rates of local recurrence of rectal cancer. A large number of papers fail to describe or include R1 resections of sigmoid cancer, which are frequently described as palliative.

The rectosigmoid problem.

The lack of consensus over the transition point for the end of the sigmoid and beginning of the rectum is a problem for the colorectal multidisciplinary team. In this review, we survey the wide number of landmarks for the rectosigmoid junction, and describe the theoretical and evidence-based strengths and weaknesses of each one. Without a reliable definition of the rectum, sigmoid and rectal cancers will be classified inconsistently. As the treatment strategies for sigmoid and rectal cancers are radically different, incorrect tumour localisation has a substantial impact on patient management, leading to under or over treatment. Inconsistent classification will confound investigation of metastatic patterns and treatment outcomes. Now that the rectosigmoid junction has been recognised as a distinct segment of colon by the International Classification of Diseases, further heterogeneity in management and outcomes could result to the detriment of patients and research. We describe a bespoke, anatomical and reliable landmark for the rectosigmoid junction; the sigmoid take-off.