Primary Colorectal Signet Ring Cell Carcinoma and the Risk of Multiple Primary Gastrointestinal Malignancies: A Retrospective Cohort Based on SEER Database from 2000-2021

Abstract

Background: Signet-ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer, constituting 0.5– 2.5% of all adenocarcinomas. It is characterized by signet ring cells as the dominant malignant cell type. Developing gastrointestinal (GI) second primary malignancies (SPMs) after SRCC is a rare event reported in the literature and insufficiently addressed. This study aimed to explore this gap and provide updated evidence about this rare cancer. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio (SIR) analyses with multiple outcome assessment were performed, applying a two-month latency exclusion period to evaluate the risk of GI SPMs in patients diagnosed with primary colorectal SRCC. The SIR was calculated as observed/expected (O/E), with excess absolute risk (EAR) per 10,000. Significance was achieved at 0.05 with a 95% confidence interval (CI). Results: There was an increased risk for GI SPMs after SRCC in the 2– 11 months interval (O/E=2.49, P< 0.05, EAR=37.31), and over 10 years of follow-up (O/E=3.08, P< 0.05, EAR=59.20). Small intestine SPMs in the 2– 11 months interval had an O/E of 4.17 (P< 0.05, 95% CI: 0.11– 23.26, EAR=1.97), with an overall O/E of 9.62 (P< 0.05, EAR=6.32). No events of GI SPMs were observed among young patients during follow-up (O/E=1.05, P> 0.05, EAR=0.12). Young patients had lack of observed events for GI SPMs (O/E=0.00, EAR=− 0.15), compared to middle-aged (O/E=7.66, P< 0.05) and elderly patients (O/E=2.36, P< 0.05). Patients received chemotherapy showed a slightly higher observed incidence of SPMs (O/E=2.39, P< 0.05, EAR=49.29); however, this finding should be interpreted cautiously given known limitations of chemotherapy data within the SEER database. Conclusion: Patients diagnosed with colorectal SRCC are at a significantly increased risk of developing GI SPMs. Given the poor overall prognosis of colorectal SRCC, early surveillance protocols must be carefully contextualized at short intervals (6– 12 months) for early detection of GI SPMs. However, a reduced intensity surveillance is recommended beyond 3– 5 years to integrate prevention with long-term follow-up. Recommendations should be tailored according to patients’ risk profiles with individualized patient focused programs. Keywords: signet-ring cell carcinoma, colorectal cancer, second primary malignancies, gastrointestinal malignancies, SEER database, surveillance