[A Case of MSI‒Stable Rectal Cancer with Para‒Aortic Lymph Node Metastasis Treated by Sequential Therapy with...

Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in various malignancies, but their effectiveness in colorectal cancer is generally limited to MSI‒high tumors. We report a case of complete response in an MSI‒stable rectal cancer patient with para‒aortic lymph node metastasis treated with a sequential strategy involving targeted therapy and ICI. A 52‒year‒old woman underwent laparoscopic intersphincteric resection with bilateral lateral lymph node dissection for advanced lower rectal cancer, followed by adjuvant CAPOX. Two years postoperatively, para‒aortic lymph node metastasis was confirmed histologically. FOLFIRI plus cetuximab was initiated, resulting in marked regression of the nodes but without CEA normalization. Switching to FOLFIRI plus bevacizumab led to further CEA reduction. After 2 courses, nivolumab was added and CEA normalized. CEA levels rose again after completion of ICI, but continued FOLFIRI plus bevacizumab led to re‒normalization without radiologic progression. This case suggests that sequential treatment using cetuximab and bevacizumab may modulate the tumor microenvironment and enhance ICI response even in MSI‒stable colorectal cancer. Strategic immunomodulation could provide a promising option for ICI‒resistant tumors.