Does the Sequence of Colorectal Cancer Diagnosis Matter for Patients with Multiple Primary Cancers? A Surveillance, Epidemiology, and End Results Database Cohort Study

BACKGROUND: We aimed to assess features and outcomes of isolated primary colorectal cancer (CRC) compared with CRC presenting in a sequence of multiple primary cancers. STUDY DESIGN: A retrospective cohort including patients with stage I to IV colorectal adenocarcinoma from the Surveillance, Epidemiology, and End Results database (from 2000 to 2020) was assessed. Patients were classified into 3 groups as follows: group A, CRC as the only malignancy; group B, CRC as the first of multiple primary malignancies; and group C, CRC as the second of multiple primary malignancies. Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). RESULTS: From our sample of 592,063 patients, 424,920 (71.8%), 70,432 (11.9%), and 96,711 (16.3%) were in groups A, B, and C, respectively. Group A patients were younger (65.7 vs 67.3 vs 72.6 years, p < 0.001), had elevated pretreatment CEA (49.7% vs 43.2% vs 46.9%, p < 0.001), had more frequent liver metastases (17.5% vs 7.4% vs 12.1%, p < 0.001), had more frequent lung metastases (6.3% vs 2.5% vs 4.2%, p < 0.001), and underwent systemic adjuvant treatments (10.4% vs 8.9% vs 5.8%, p < 0.001). Group A included more T4 tumors (14.5% vs 10.4% vs 12.4%, p < 0.001) and fewer surgical treatments than groups B and C (86.4% vs 94.8% vs 88.1%, p < 0.001). Group B included more men (57.1% vs 51.8% vs 53.1%, p < 0.001) and patients who had left-sided CRC (37.9% vs 37.1% vs 32.2%). Group C entailed more patients with right-sided CRC (38.6% vs 33.1% vs 35.3%). Group B had the longest OS and CSS (50.4 and 51.3 months, respectively). CONCLUSIONS: CRC presenting as the first of multiple primary malignancies less often presented at an advanced stage, more often underwent surgical treatment, and was associated with improved OS and CSS than CRC presenting as an isolated primary or second primary malignancy.