O-018
Microsatellite instability and survival after adjuvant chemotherapy among stage II and III colon cancer patients: results from a population-based study
Introduction
Adjuvant chemotherapy treatment for stage II and III colon cancer patients is usually based on 5-FU as monotherapy or, more recently, in combination with other agents. Previous studies have found conflicting results regarding the benefit of administering 5-FU-based chemotherapy to colon cancer patients with microsatellite instable (MSI-high) tumors, and results from stage-specific analyses are scarce. The aim of this study was to determine the association between adjuvant chemotherapy and patient survival by stage of disease and MSI status of the tumor.
Adjuvant chemotherapy treatment for stage II and III colon cancer patients is usually based on 5-FU as monotherapy or, more recently, in combination with other agents. Previous studies have found conflicting results regarding the benefit of administering 5-FU-based chemotherapy to colon cancer patients with microsatellite instable (MSI-high) tumors, and results from stage-specific analyses are scarce. The aim of this study was to determine the association between adjuvant chemotherapy and patient survival by stage of disease and MSI status of the tumor.
Methods
Patients with stage II or III colon cancer were recruited between 2003 and 2015 as part of a population-based study conducted in more than 20 hospitals in the study region in the southwest of Germany. Propensity scores were calculated and used to correct for the covariate imbalance between the treated and untreated groups. Cox regression models including propensity score weighting were used to calculate hazard ratios and confidence intervals for the association between adjuvant chemotherapy (5-FU or oxaliplatin-based) and cancer-specific, relapse-free and overall survival for the entire study population and by stage of disease and MSI status of the tumor. Median follow-up was 6.2 years.
Patients with stage II or III colon cancer were recruited between 2003 and 2015 as part of a population-based study conducted in more than 20 hospitals in the study region in the southwest of Germany. Propensity scores were calculated and used to correct for the covariate imbalance between the treated and untreated groups. Cox regression models including propensity score weighting were used to calculate hazard ratios and confidence intervals for the association between adjuvant chemotherapy (5-FU or oxaliplatin-based) and cancer-specific, relapse-free and overall survival for the entire study population and by stage of disease and MSI status of the tumor. Median follow-up was 6.2 years.
Results
A total of 1010 colon cancer 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 cancer-specific survival (HR 0.65 [0.49-0.86]; P = .002) compared to those who received surgery alone. Among stage II patients, only 64 (12%) cancer-related deaths were observed, none of which were in MSI-high patients who received chemotherapy. Patients with MSI-high tumors who received adjuvant treatment showed better cancer-specific survival and a tendency towards better relapse-free survival compared to MSI-high patients who did not receive chemotherapy (HRCSS 0.36 [0.15-0.82]; P = .01 and HRRFS 0.49 [0.22-1.06]; P = .07, respectively). Patients with microsatellite stable (MSS) tumors receiving adjuvant chemotherapy also had significantly better survival (HRCSS 0.65 [0.48-0.87]; P = .003 and HRRFS 0.68 [0.52-0.88]; P = .003).
A total of 1010 colon cancer 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 cancer-specific survival (HR 0.65 [0.49-0.86]; P = .002) compared to those who received surgery alone. Among stage II patients, only 64 (12%) cancer-related deaths were observed, none of which were in MSI-high patients who received chemotherapy. Patients with MSI-high tumors who received adjuvant treatment showed better cancer-specific survival and a tendency towards better relapse-free survival compared to MSI-high patients who did not receive chemotherapy (HRCSS 0.36 [0.15-0.82]; P = .01 and HRRFS 0.49 [0.22-1.06]; P = .07, respectively). Patients with microsatellite stable (MSS) tumors receiving adjuvant chemotherapy also had significantly better survival (HRCSS 0.65 [0.48-0.87]; P = .003 and HRRFS 0.68 [0.52-0.88]; P = .003).
Conclusion
In this population-based study including stage II and III colon cancer 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. Our analyses reflect the real-world effectiveness based on observed treatment patterns in an unselected cohort of patients over time.
In this population-based study including stage II and III colon cancer 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. Our analyses reflect the real-world effectiveness based on observed treatment patterns in an unselected cohort of patients over time.
Publisher
Oxford University Press
Source Journal
Annals of Oncology
