Aspects of locally advanced colon cancer

Abstract

In Sweden, nearly 5000 patients are diagnosed with colon cancer annually and about 20% of these patients have a locally advanced tumor at the time of diagnosis. These tumors are challenging for both surgeons and oncologists and a multimodal treatment strategy is necessary to offer cure. To accomplish a radical resection, the tumor has to be resected en bloc with surrounding invaded tissues. Many of the patients with locally advanced colon cancer present with an emergent obstruction, which is associated with higher morbidity and mortality compared to the elective setting. Our overall aim with this thesis was to identify important cornerstones in the multimodal treatment of locally advanced colon cancer to improve outcome in these patients.

In paper I, management and outcomes after multivisceral resection in patients with locally advanced colon cancer were described and evaluated. All patients operated for locally advanced colon cancer with en bloc multivisceral resections at Karolinska University Hospital between 2007 and 2014 were included (n=121). Malignant invasion in resected tissues were found in 77 patients and inflammatory adhesions were found in 44 patients. The proportion of radical (R0) resections was 91% in patients with tumor infiltration and 96% in patients with inflammation. Five-year overall survival was 61% and 87%, respectively. Female sex, low tumor stage, adjuvant chemotherapy and radical resection were independently associated with improved overall survival in the regression analysis. Age, ASA score, and tumor infiltration had no influence on survival in the model.

In paper II, the effect of preoperative MDT assessment on survival was assessed in a national register-based study. All patients diagnosed with non-metastatic locally advanced colon cancer who underwent elective tumor resection between 2010 and 2017 in Sweden were included in the study. Preoperative MDT assessment was performed in 2663 patients (84%) of 3157 included patients. Three-year colon cancer-specific survival was 80% in the MDT-group and 68% in the non-MDT group. Preoperative MDT assessment was independently associated with reduced colon cancer-specific mortality after adjustments for sex, age, ASA grade, CCI, year of diagnosis, pN stage and region.

In paper III, diverting stoma followed by elective resection was assessed as an alternative to emergency resection in patients with obstructive locally advanced colon cancer. In this national register-based study, all patients with obstructive locally advanced colon cancer treated with diverting stoma followed by elective resection or emergency resection between 2007 and 2017 in Sweden were included. A total of 751 patients with a right-sided tumor and 700 patients with a left-sided tumor were assessed. Diverting stoma followed by elective resection was more common in left-sided tumors (31%) than in right-sided tumors (9%). Emergency resection was independently associated with increased all-cause mortality in patients with a left-sided tumor (1.63, 95% CI 1.21-2.19). No such association could be found in patients with a right-sided tumor.

In paper IV, the effect of hospital volume on mortality in patients with locally advanced colon cancer was studied. All 5421 patients included in this national register-based study had been diagnosed with a non-metastatic locally advanced colon cancer between 2007 and 2017. Hospital volume of locally advanced colon cancer resections were presented as tertiles (1-10, 11-19 and >19 resections per year). An association was shown between high hospital volume and reduced all-cause mortality (HR 0.76, 95% CI 0.68-9.84) and colon cancer-specific mortality (HR 0.73, 95% CI 0.64-0.84) after adjustments for potential confounders (age, sex, year of diagnosis, comorbidity, emergency resection and university hospital) and mediators (preoperative MDT assessment, neoadjuvant chemotherapy and radical resection).

In conclusion, patients with a locally advanced colon cancer can be cured with a radical multivisceral resection. Preoperative MDT assessment and high hospital volume is associated with improved survival in these patients and centralization to high volume units with mandatory preoperative MDT assessment should be recommended. Diverting stoma followed by elective resection in