Making sense of adjuvant chemotherapy in colorectal cancer
Surgical resection is the only curative treatment for locoregional colon cancer. The goal of adjuvant chemotherapy is to eradicate micro-metastatic disease and improve survival. This has been most clearly demonstrated in stage III (node-positive) disease, whereas benefit of adjuvant chemotherapy in stage II disease remains controversial. In stage III colon cancer, 6 months of adjuvant chemotherapy with oxaliplatin-based chemotherapy have been accepted as the standard for the last 15 years. The recent IDEA collaboration has challenged this in 2018; while overall was a negative non-inferiority study, pre-planned subset analyses do support that for patients with low-risk stage III disease, 3 months of XELOX (capecitabine and oxaliplatin combination) is non-inferior to 6 months. In stage II colon cancer, where the potential benefit of adjuvant chemotherapy is small, the emergence of biomarkers has helped in decision-making. Tumors with deficient mismatch repair protein (dMMR) do not benefit from 5-fluorouracil-based chemotherapy. For patients with high clinicopathological risk stage II disease with proficient mismatch repair proteins and good performance status, six months of adjuvant chemotherapy is still recommended. In the management of rectal cancers, where the risk of local recurrence is higher, chemoradiation (CRT) is often included as neoadjuvant or adjuvant therapy in the management of stage II and III rectal cancer. The benefit of adjuvant chemotherapy in rectal cancer has been extrapolated from adjuvant colon cancer studies with updated results from adjuvant rectal cancer studies demonstrating similar benefits. This review summarizes the current landscape of adjuvant therapy for patients with resected stage II and III colorectal cancer.