Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy
Authors: Gögenur Mikail , Rosen Andreas Weinberger , Iveson Timothy , Kerr Rachel S. , Saunders Mark P. , Cassidy Jim , Tabernero Josep , Haydon Andrew , Glimelius Bengt , Harkin Andrea , Allan Karen , Pearson Sarah , Boyd Kathleen A. , Briggs Andrew H. , Waterston Ashita , Medley Louise , Ellis Richard , Dhadda Amandeep S. , Harrison Mark , Falk Stephen , Rees Charlotte , Olesen Rene K. , Propper David , Bridgewater John , Azzabi Ashraf , Cunningham David , Hickish Tamas , Gollins Simon , Wasan Harpreet S. , Kelly Caroline , Gögenur Ismail , Holländer Niels Henrik 
Published: June 2024

Importance

The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.

Objective

To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.

Design, Setting, and Participants

This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.

Intervention

In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.

Main Outcomes and Measures

The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.

Results

A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).

Conclusions and Relevance

In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.

Trial Registration

isrctn.org Identifier: ISRCTN59757862