How a Young Patient Overcame Multiple Treatment Challenges to Achieve Long-Term Remission

A 33-year-old Caucasian man with asthma, a history of active smoking, and a strong family history of colon cancer first presented in 2012 with severe abdominal pain, constipation, and significant weight loss. Several close relatives, including his mother, aunts, and uncle, had been affected by colon cancer—many at an early age. Workup uncovered a nearly obstructing descending colon mass, subsequently resected in January 2013 along with most of his colon. Pathology revealed stage IIIC (pT4bN1bMX) adenocarcinoma featuring microsatellite instability (MSI) from loss of MSH2/MSH6 expression, later confirmed as Lynch syndrome with an MSH2 Y656X mutation.

Adjuvant therapy with capecitabine-based chemoradiation was cut short by severe toxicities, including diarrhea, dehydration, and fungal endophthalmitis. Another capecitabine trial led to similar adverse events, necessitating a switch to weekly 5-FU plus leucovorin from August to November 2013. Imaging in late 2013 indicated lymph node involvement, and by mid-2015, further metastases to the liver and lungs were confirmed, rendering the disease unresectable. Various chemotherapy adjustments, including irinotecan plus bevacizumab, did not produce durable tolerance or control.

In October 2015, immunotherapy emerged as a viable option given the tumor’s MSI-High status. The patient began pembrolizumab 2 mg/kg every 21 days and quickly showed improvements: his carcinoembryonic antigen (CEA) levels normalized, his weight increased, and he reported better overall well-being. Aside from mild hypothyroidism—a manageable side effect—he tolerated pembrolizumab well through a total of 48 cycles.

By July 2018, with no FDG-avid lesions on PET scans and stable calcified lymph nodes, the decision was made to pause treatment. As of early 2019, surveillance imaging remained free of metastases, and his CEA stayed within normal limits. The patient continues close oncologic follow-up, including flexible sigmoidoscopy, upper endoscopy, and regular clinic visits with CEA checks.

This case highlights the transformative power of immunotherapy in microsatellite instability-high (MSI-H) metastatic colorectal cancer. Even after multiple chemotherapy regimens proved intolerable or ineffective, pembrolizumab provided durable disease control and significantly improved quality of life.