The Impact of Patient Characteristics and Tumor Biology on the Accuracy of Preoperative Staging of Colon Cancer in Denmark. A Nationwide Cohort Study

Abstract

Background: Colon cancer is a common disease in western populations. The aim of this study was to assess the impact of mismatch repair (MMR) deficiency and other patient and tumor characteristics on the accuracy of preoperative staging by comparing histopathological T- and N-categories of the resected specimen with the preoperative clinical stage in a nationwide cohort of patients treated for colon cancer by elective bowel resection with curative intent. Methods: A register study of a cohort extracted from the Danish Colorectal Cancer Group (DCCG) database, which holds prospective data on all new cases of colon and rectum cancer in Denmark. Patients diagnosed with colon cancer and treated with an elective bowel resection with curative intent in the years 2016–2019 were analyzed. Results: A total of 6102 patients were included (n = 3161 (52%) men and n = 2941 (48%) women) with a median age of 72 years (range 23–97 years). MMR was deficient in 24% of the patients and proficient in 76%. MMR deficiency, tumor sidedness and histopathological type were significant predictors of the accuracy of preoperative staging of colon cancer in univariate and multivariate analysis. MMR status in particular showed a strong impact on the risk of overstaging. Conclusions: MMR deficiency, but also tumor sidedness and to some degree histopathological type, impacted the accuracy of preoperative staging of colon cancer. MMR status should be taken into consideration in everyday clinical staging.

Neoadjuvant chemotherapy in patients undergoing colonic resection for locally advanced nonmetastatic colon cancer: A nationwide propensity score matched cohort study

“…The overrepresentation of MSI (and mucinous adenocarcinoma) tumours exemplifies that the preoperative CT scans might not assess the stage of disease, and thereby the indication for NCT, with sufficient accuracy. The clinical staging thus represents a challenge with respect to patient selection, with specificity and sensitivity for the assessment of locally advanced disease to be around 60% [25]. Future scientific effort should focus on enhancing the precision in selecting patients for NCT, and this selection process should also include histopathology subtypes and microsatellite stability.…”

The impact of mismatch repair status and systemic inflammatory markers on radiological staging in colon cancer

“…The overall sensitivity of CT for predicting “T status” in our cohort exceeded that reported in a recent Danish study (92% vs 68%). 17 Possible reasons for this include: the staging of patients in our study was performed exclusively by expert Gastrointestinal Radiologists and Pathologists, while in the previous study these details were unclear; a complete radiological staging data set from routine clinical practice was provided in our cohort, whereas staging details were missing in approximately 15% of patients in the prior study; and finally, patients were taken from two different geographical populations and healthcare systems.…”

“…Overall, we achieved a greater sensitivity (69% vs 55%) but lower specificity (52% vs 66%) for determining “N status” using CT than a recent study, which we believe is most likely a consequence of having a greater proportion of dMMR CC (44% vs 24%) and associated inflammatory lymphadenopathy in our study. 17 Furthermore, N staging may also have been performed in many of these patients using strict size criteria, which have been shown to be insufficient for reliably identifying lymph node metastases. 6,7 A recent study highlighted significant differences in the radiological appearance of the primary tumour and lymph nodes between dMMR and pMMR CC.…”

Intra- and Interobserver Variability in Magnetic Resonance Imaging Measurements in Rectal Cancer Patients

“…Colorectal cancers with deficient mismatch repair (dMMR) display a greater inflammatory response and local infiltration of lymphocytes in tumor and peritumoral tissue; dMMR can arise during DNA replication. The distinct clinicopathological features of dMMR colorectal cancer affect the accuracy of preoperative N staging [32,33]. Exactly how this affects the interobserver variation remains unclear.…”