Seminar in Medicine - Dr. Şahin Laçin

Surgical resection is a curative treatment option for locoregional colon cancer. After potentially curative resection, disease recurrence is accepted to arise from clinically occult micrometastases that are present at the diagnosis. Adjuvant therapy (postoperative) is used to eradicate these micrometastases, thereby increasing the cure rate. The benefits of adjuvant chemotherapy for colon cancer have been most clearly demonstrated especially in stage III disease. In stage II disease, the benefit of adjuvant chemotherapy is less certain and the use of chemotherapy in this group is variable. And therapy decision is influenced by tumoral deficiency of DNA mismatch repair (MMR) enzyme status/high levels of microsatellite instability (dMMR/MSI-H), which is associated with a better prognosis overall. Patients with dMMR have a better prognosis after surgery alone, MMR status is an important predictor of lack of benefit from fluoropyrimidine-based adjuvant chemotherapy. Some high-risk subgroups of stage II colon cancer are more likely to benefit from adjuvant therapy. Definition of high-risk clinicopathologic features includes a pT4 primary, poorly differentiated/undifferentiated histology (unless dMMR), fewer than 12 nodes in the surgical specimen, lymphovascular or perineural invasion, high levels of tumor budding, and clinical obstruction or perforation. For stage II patients with these risk factors (T4 primary or multiple high-risk factors), we consider the potential benefits and risks of an oxaliplatin-containing regimen, as was used in the MOSAIC trial. The optimal duration of combined adjuvant chemotherapy is unclear. Both three and six months of chemotherapy are reasonable options, although neurotoxicity rates are clearly higher with longer treatment. The treatment that includes capecitabine plus oxaliplatin (CAPOX) can be used for 3 months, however, FOLFOX is suggested for six months. For patients without high-risk features who have tumors with dMMR, observation is recommended. Patients with stage II dMMR tumors that have high-risk features are uncertain given a better prognosis compared with pMMR tumors. The decision for adjuvant chemotherapy must be individualized, the number of high-risk features, the patient's overall medical condition, and age are the most important factors for it. An oxaliplatin-based regimen rather than fluoropyrimidines alone is recommended for this patient subgroup. Adjuvant systemic therapy is the standard approach after resection of stage III colon cancer. Generally, adjuvant chemotherapy is initiated within six to eight weeks of surgery. For patients with high-risk colon cancer (T4N2), six months of adjuvant therapy is recommended. However, for patients with lower-risk disease, (T1-3, N1), limiting adjuvant therapy to three months is recommended. Oncologists should closely monitor neuropathy, if six months of therapy is chosen. Adjuvant chemotherapy can be stopped if neuropathy persists (especially T3N1), or the oxaliplatin can be eliminated with continuation of the FU/LV or capecitabine alone to complete six months of treatment.

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