Coexistence of Small-Cell Lung Cancer and Gastrointestinal Malignancies: A Narrative Systematic Review of Case Reports.

The coexistence of small-cell lung cancer (SCLC) and primary gastrointestinal (GI) malignancies is an exceptionally rare phenomenon that complicates diagnosis and treatment. We conducted a systematic review of published case reports to better understand the clinical characteristics, therapeutic approaches, and outcomes of these patients. A comprehensive search of major databases up to April 2025 identified six eligible reports describing patients diagnosed with both SCLC and distinct GI cancers, including gastric, duodenal, rectal, and jejunal tumors, as well as one patient with multiple primary malignancies involving rectosigmoid adenocarcinoma, renal cell carcinoma, and prostate adenocarcinoma in addition to SCLC. The patients were predominantly older males with heavy smoking histories, and most cases were extensive-stage SCLC at presentation. Treatment varied widely and included platinum-based chemotherapy, immune checkpoint inhibitors, EGFR-targeted therapy, surgery, and supportive care, with clinical outcomes ranging from a few months to more than one year of survival. Several patients showed partial or complete responses to systemic therapy, and in one case, the GI malignancy regressed following chemotherapy given for SCLC, suggesting overlapping chemosensitivity. However, other patients experienced delayed diagnosis of the second malignancy or limited survival due to disease progression or comorbidities. This synthesis demonstrates that distinguishing dual primaries from metastatic disease is a critical challenge in clinical practice and highlights the need for thorough evaluation in patients with atypical or persistent symptoms. Although data remain limited, awareness of this rare coexistence may help clinicians avoid misclassification and tailor multidisciplinary treatment strategies to improve outcomes.