Standard adjuvant treatment to patients with stage III colon cancer is six months of adjuvant combination chemotherapy with a 5-fluorouracil derivate (5-FU) and oxaliplatin. In some cases, 5-FU monotherapy may be an option. The aim is to develop a different way of explaining the benefit of different treatment options by using the concept of “postponement of death”.
We identified pivotal phase III publications about adjuvant treatment for stage III colon cancer. Data regarding overall survival was extracted for observation versus 5-FU monotherapy and combination chemotherapy versus 5-FU. Data about the impact of N1 and N2 category was extracted if available. Data was used for restricted mean survival analysis. Postponement of death was defined as the mean difference in survival time between the two randomized treatment arms. Survival curves was plotted into the tool WebPlotDigitizer and the area under the curve (AUC) was calculated for each treatment.
AUC for patients receiving 5-FU was 69.1 months and for combination chemotherapy 71.9 months. The mean survival difference at 10 years was 2.8 months. For the subgroup of patients with N1 category, the postponement of death was 0.5 months if treated with combination chemotherapy instead of 5-FU. For patients with N2 category the difference was 11.6 months when treated with combination chemotherapy compared to monotherapy. In the trial comparing 5-FU with observation, the AUC was 73.7 months and 63.3 months, respectively, at 8.5 years. The overall postponement of death between 5-FU and observation was 10.4 months not adjusted for N status.
Postponement of death can be calculated using restricted mean survival analysis and published survival curves. Patients with colon cancer stage III can be advised that up to 6 months of 5-FU will postpone death on average 10 months compared to observation alone. Adding oxaliplatin will postpone death an additional 3 months with no adjustment for N status. Oxaliplatin has minor effect in N1 category (2 weeks) and major effect in N2 category (12 months). Future studies should investigate how the concept of postponement of death can be implemented in daily clinical practice.
Clinical trial identification
Legal entity responsible for the study
Natacha Dencker Trabjerg
Department of Oncology Vejle Hospital, Center of Clinical Excellence, Danish Colorectal Cancer Center South Denmark
All authors have declared no conflicts of interest.