The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report

Abstract

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors.

SEMA6B Overexpression Predicts Poor Prognosis and Correlates With the Tumor Immunosuppressive Microenvironment in Colorectal Cancer

“…However, clinical immunotherapeutic trials have revealed that anti-CTLA-4 monoclonal antibodies (mAbs) yield unsatisfactory clinical efficacies in unselective CRC patients ( Chung et al, 2010 ), and anti-PD-L1 mAbs and anti-PD-1 have shown little or no response rates in metastatic CRC (mCRC) ( Le, Uram and Wang 2015 ; Overman and McDermott 2017 ). Although there is clear clinical evidence for a therapeutic role of immune checkpoint inhibitors in deficient mismatch repair (dMMR) or MSI-H mCRC, the majority of mCRC patients with proficient MMR (pMMR) or microsatellite stable (MSS) phenotypes do not benefit from this type of immunotherapy ( Koi and Carethers 2017 ; Ciardiello and Vitiello 2019 ; Ganesh et al, 2019 ; Judge et al, 2020 ; Morse et al, 2020 ). Furthermore, previously described molecular features, such as immunoscore, PD-1, PD-L1, MSI, mutational load, and consensus molecular subtypes have not been identified in predicting responses to immune checkpoint inhibitors based on immunotherapy.…”