Image Guidance Improves Cytoreductive Surgery in Colorectal Cancer

Take-Away Points

• ■ Major Focus: Using a dual-labeled anti-carcinoembryonic antigen (CEA) antibody conjugate to identify peritoneal metastases from colorectal cancer and guide cytoreductive surgery.

• ■ Key Results: Pre- and intraoperative identification of peritoneal disease was safe and feasible in 15 patients undergoing cytoreductive surgery and changed the surgical plan in three patients.

• ■ Impact: Imaging with In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-CEA antibody conjugate, may improve identification of peritoneal metastases to achieve adequate cytoreduction in this cohort.

Colorectal cancer metastases to the peritoneum can be managed with curative intent in selected patients, such as those without extraperitoneal disease or high tumor burden. Cytoreductive surgery is typically performed, often in combination with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and can improve survival compared with systemic chemotherapy alone. Accurate preoperative and intraoperative staging is crucial to select patients, guide surgery, and achieve complete cytoreduction. Conventional imaging with CT or fluorodeoxyglucose PET frequently understages tumor burden, and accurate discrimination between tumor and adhesions or fibrosis can be challenging at the time of surgery, leading to inadequate cytoreduction.

CEA is overexpressed by colorectal cancer cells in 90% of patients. Labetuzumab is a humanized monoclonal antibody specifically targeting CEA. The authors labeled this antibody with a gamma-emitter (indium 111 [¹¹¹In]) and a near-infrared (NIR) fluorophore (IRDye800CW) for preoperative staging with SPECT/CT and intraoperative radio- and NIR-fluorescence–guided surgery. In a phase 1 study, de Gooyer et al found that [¹¹¹In]In-DOTA-labetuzumab-IRDye800CW revealed previously undetected sites of peritoneal disease and altered the surgical plan in three of 15 patients undergoing CRS-HIPEC for colorectal cancer peritoneal metastases. With the two highest doses of antibody, intraoperative NIR imaging detected 41 of 42 malignant lesions visible by standard operative inspection and detected four additional small metastases initially missed at cytoreductive surgery. CEA-targeted preoperative SPECT/CT alone did not detect small (<10 mm) peritoneal metastases or distinguish them from benign tissue. However, imaging identified extraperitoneal nodal disease in one patient, an important finding as extraperitoneal disease is a contraindication for CRS-HIPEC.

This phase 1 study demonstrates that a multimodal imaging strategy with a dual-labeled anti-CEA antibody conjugate is safe and allows for pre- and intraoperative identification of peritoneal metastases, potentially changing the surgical plan and achieving adequate cytoreduction.

Highlighted Article

• de Gooyer JM, Elekonawo FMK, Bremers AJA, et al. Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin. Nat Commun 13, 2621 (2022). https://doi.org/10.1038/s41467-022-29630-9