Early-Onset Colorectal Cancer: Contemporary Management, Immunotherapy, and Organ Preservation.

A 36-year-old man with no family history of colorectal cancer or inflammatory bowel disease presented with a 3-month history of bright red blood per rectum and constipation. Anoscopy demonstrated Grade II internal hemorrhoids, and he was initially treated conservatively with fiber and hydration. Despite compliance, bleeding persisted. Colonoscopy performed 6months later revealed a large, friable midrectal mass. Biopsies demonstrated poorly differentiated invasive adenocarcinoma with deficient mismatch repair (dMMR) protein expression on immunohistochemical staining. Staging CT of the chest, abdomen, and pelvis demonstrated no distant metastases, while pelvic MRI revealed a cT3N1 midrectal tumor. Given his young age and dMMR status, he was referred for genetic counseling and underwent germline multigene panel testing, which identified a pathogenic MLH1 variant consistent with Lynch syndrome. He received genetic counseling. Fertility preservation was discussed before treatment, and the patient elected to undergo sperm cryopreservation. After multidisciplinary review, neoadjuvant PD-1 blockade with dostarlimab was recommended. After 6 months of therapy, restaging with digital rectal examination, endoscopy, and pelvic MRI demonstrated a clinical complete response. After shared decision-making, the patient elected nonoperative management with intensive surveillance rather than total mesorectal excision. He remained without clinical evidence of disease at 12-month follow-up.