Time to initiation of adjuvant chemotherapy and survival in patients with stage II and III rectal cancer not receiving total neoadjuvant therapy

While the delay in adjuvant chemotherapy (AC) is known to impact colon cancer outcomes, its effect on rectal cancer is less clear. This study aims to evaluate the influence of AC timing on survival in stage II and III rectal cancer. This retrospective multicenter study enrolled 1,144 patients receiving chemotherapy following resection of stage II–III rectal cancers. The effect of delayed AC on survival was assessed using multivariable Cox models with restricted cubic splines and logistic regression. Compared to patients initiating AC within four weeks postsurgery, those initiating within 5–8 weeks had a similar survival (HR=0.85, 95 % CI=0.66–1.11), whereas those initiating within 8–12 weeks (HR=1.62, 95 % CI=1.05–2.51) or beyond 12 weeks (HR=2.07, 95 % CI=1.21–3.56) had a significantly inferior survival. A delayed time to chemotherapy (>8 weeks) was associated with worse survival in patients aged ≥60 years but not in younger patients (<60 years: HR=1.36; 95 % CI=0.75–2.46, p=0.312; ≥60 years: HR=2.37; 95 % CI=1.56–3.60, p<0.001). Additionally, our exploratory analysis suggested that FOLFOX and FOLFIRI were more effective when starting within 5–8 weeks post-surgery, while CAPEOX and a single agent showed a slight advantage when starting within four weeks. Our findings advocate for initiating AC within eight weeks post-surgery in stage II–III rectal cancer, especially in older patients. Delayed treatment is linked to significantly worse survival outcomes.