Differential response to immunotherapy in different lesions of MSI-H double primary colorectal cancer: a case report and literature review.

Background: Mucinous adenocarcinoma is a rare type of colorectal cancer (CRC) associated with poor prognosis, particularly when it includes signet ring cell components. Furthermore, its rate of microsatellite instability-high (MSI-H) is significantly higher compared to non-mucinous adenocarcinoma. Immunotherapy has emerged as the standard treatment for MSI-H metastatic CRC (mCRC). In the KEYNOTE-177 trial, for individuals with advanced CRC exhibiting MSI-H or mismatch repair deficiency (dMMR), treatment with pembrolizumab as a single agent demonstrated a superior outcome compared to standard systemic chemotherapy. The study revealed a notably higher objective response rate (43.8% versus 33.1%) and an extended progression-free survival duration (16.5 versus 8.2 months). These findings imply that pembrolizumab may be regarded as a front-line treatment option for patients with advanced CRC who have MSI-H/dMMR status. Case Description: The patient with double primary CRC, both of which were identified as MSI-H through next generation sequencing (NGS). Following a regimen of immunotherapy-based combination therapy, the rectal lesion achieved a complete clinical response (cCR), while the colon lesion displayed continued progression, indicating primary resistance to treatment. Conclusions: Specific histological subtypes of CRC, such as mucinous adenocarcinoma, might adversely affect the efficacy of immunotherapy, resulting in primary treatment resistance. Consequently, in the case of this particular cancer subtype, local surgical resection may be a more appropriate treatment strategy.