Patterns of metastatic spread and survival outcomes for stage IV left-sided colon vs. rectal cancers: A real-world analysis.
Authors: Bhutiani Neal , Chiang Yi-Ju , Uppal Abhineet , Konishi Tsuyoshi , White Michael , Vauthey Jean-Nicolas , Kopetz Scott , Overman Michael J. , Chang George J. , Tran Cao Hop Sanderson 
Published: January 2025

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Background:
A growing body of literature has reported differences in biology, metastatic potential, and outcomes among patients with colorectal cancer based on the sidedness of their primary tumor (right vs. left). Left-sided primary tumors have comprised both colon and rectal tumors, despite differences in venous and lymphatic drainage patterns and treatment paradigms. The present work sought to investigate patterns of metastases and survival outcomes among patients with left sided colon primary tumors and rectal primary tumors. We hypothesized that these two disease sites metastasize differently and exhibit different survival patterns based on metastatic site.
Methods:
The National Cancer Database (NCDB) was queried for all patients with a diagnosis of metastatic left-sided colon (splenic flexure, descending colon, rectosigmoid) or rectal adenocarcinoma with known primary site and known metastatic site(s) between 2010 and 2021 using parameters outlined in the NCDB Data Dictionary. Patients with left-sided colon primaries (LP) were compared to patients with rectal primaries (RP) along clinicodemographic parameters. Incidence of metastases to the liver, lungs, bone, brain, and non-regional lymph nodes were also compared. Multivariable survival analyses were performed to analyze differences in overall survival (OS).
Results:
Among 84,958 patients, 51,931 (61.1%) had LP while 33,027 (38.9%) had RP. Patients with RP were less likely to have liver metastases than those with LP (79.4% vs. 90.3%), but more likely to have lung (40.7% vs. 29.2%), bone (8.3% vs. 6.0%), and distant lymph node metastases (11.3% vs. 8.6%) (all p<0.001). Compared to patients with LPs, patients with RP were less likely to undergo surgery to the primary tumor (25.1% vs. 46.3%) or any metastatic site (15.3% vs. 18.8%), more likely to receive chemotherapy for metastatic disease (80.8% vs. 75.2%), and more likely to receive radiation to the primary site (17.7% vs. 4.3%) (all p<0.001). Additionally, patients with RP had longer median OS than those with LP (27.3 months vs. 26.4 months, p<0.001). On multivariable analysis controlling for age, gender, tumor grade, RAS mutation status, MSI status, CEA level, clinical T and N category, and treatment details, patients with RP with liver metastases (HR 0.91, 95% CI 0.89-0.92), lung metastases (HR 0.85, 95% CI 0.82-0.87), and bone metastases (HR 0.89, 95% CI 0.84-0.95) (all p<0.001) demonstrated improved OS compared to those with LP.
Conclusions:
Patterns of metastases, treatment regimens, and, in certain instances, survival outcomes, differ among patients with stage IV left-sided colon cancer and rectal cancer. Future work evaluating the implications of sidedness in colorectal cancer as well as future staging efforts should consider assessing left-sided colon cancer separately from rectal cancer, as these demonstrate distinct clinical behavior and outcomes.