Microsatellite instability and survival after adjuvant chemotherapy among stage II and III colon cancer patients: results from a population-based study

Mol Oncol. 2020 Feb;14(2):363-372. doi: 10.1002/1878-0261.12611. Epub 2020 Jan 7.

Abstract

Previous studies have reported conflicting results regarding the benefit of administering 5-FU-based chemotherapy to colon cancer (CC) patients with microsatellite-instable (MSI-high) tumors, and results from stage-specific analyses are scarce. Patients with stage II or III CC were recruited as part of a population-based study between 2003 and 2015. The Cox regression models including propensity score weighting were used to calculate hazard ratios and confidence intervals for the association between chemotherapy and cancer-specific (CSS), relapse-free (RFS), and overall survival (OS) by stage of disease and MSI status of the tumor. Median follow-up was 6.2 years. A total of 1010 CC patients were included in the analysis (54% stage II, 46% stage III, 20% MSI-high). Adjuvant chemotherapy was administered to 48 (8.7%) stage II and 366 (79%) stage III patients. Overall, patients who received adjuvant chemotherapy had better CSS [HR = 0.65 (0.49-0.86)] than those who received surgery alone. Among stage II patients, only 64 (12%) cancer-related deaths occurred, none of which in MSI-high patients who received chemotherapy. Patients with MSI-high tumors who received adjuvant treatment showed better CSS and a tendency toward better RFS compared to MSI-high patients who did not receive chemotherapy [HRCSS = 0.36 (0.15-0.82), HRRFS = 0.49 (0.22-1.06)]. Patients with microsatellite-stable (MSS) tumors receiving adjuvant chemotherapy also had significantly better survival [HRCSS = 0.65 (0.48-0.87) and HRRFS = 0.68 (0.52-0.88)]. In this population-based study including stage II and III CC patients, we observed a survival benefit of adjuvant chemotherapy for both MSS and MSI-high tumors. Adjuvant chemotherapy seemed to be beneficial among high-risk stage II patients with MSI-high tumors.

Keywords: adjuvant chemotherapy; colon cancer; microsatellite instability; survival.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant / mortality*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality
  • Female
  • Fluorouracil / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Male
  • Microsatellite Instability / drug effects*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models

Substances

  • Fluorouracil