Clinicopathologic variables and outcomes in elderly colorectal cancer patients with microsatellite instability and multiple primary malignancies.
Authors: Goksu Suleyman Yasin , Zahid Mohammad Faizan , Ozer Muhammet , Sanford Nina Niu , Sanjeevaiah Aravind , Al Mutar Salwan , Verma Udit , Jones Amy Little , Kainthla Radhika , Hsieh David , Beg Muhammad Shaalan , Kazmi Syed Mohammad Ali 
Published: June 2021

e15516

Background: The biology of microsatellite instability-high (MSI-H) in elderly colorectal cancer (CRC) patients is attributed to hypermethylation of promoter region of genes coding for mismatch repair proteins. It is unknown if such patients are predisposed to other malignancies. It is also unknown if the presence or absence of multiple primary malignancies affects elderly MSI-H CRC patients' survival. We aimed to evaluate the clinicopathologic features and outcomes in elderly CRC patients with MSI-H and multiple primary malignancies. Methods: We analyzed the National Cancer Database and included elderly (≥ 65 years) patients with CRC diagnosed between 2010-2016. MSI status was determined using genetic and immunohistochemical testing and categorized as microsatellite stable (MSS) and MSI-H. We further categorized the population into single primary malignancy versus multiple primary malignancies. We compared the baseline characteristics using the Chi-square test. Kaplan-Meier and log-rank tests were performed to calculate the overall survival (OS). Results: Among 52,494 elderly CRC patients, 78.0% were MSS, and 22.0% were MSI-H. The probability of MSI-H disease increased with increasing age, female gender, and non-Hispanic White ethnicity (all p < .001). MSI-H patients were associated with elevated CEA, wild-type KRAS, multiple neoplasms, right-sided tumors, stage II disease, and grade III/IV histology. The proportion of patients with multiple primary malignancies was higher in the MSI-H population versus MSS (36% vs. 31%, p < 0.001). The rate of multiple primary malignancies increased with age in both groups. Among MSI-H CRC patients, the factors associated with multiple primary malignancies included female gender (61.6%), non-Hispanic White ethnicity (86.3%), comorbidity index ≥ 2 (14.8%), and right-sided tumors (77.2%). Multiple primary malignancies were more frequently associated with stage I-III CRC as compared to metastatic CRC. For stage III-IV elderly MSI-H patients, the utilization of chemotherapy was 57.8% overall, but it was not significantly different between single primary malignancy versus multiple primary malignancies groups. MSI-H patients with single primary malignancy had the highest OS, followed by MSS patients with single primary malignancy, MSI-H patients with multiple primary malignancies, and MSS patients with multiple primary malignancies (74.7, 66.7, 58.1, 54.8 mos, respectively) (log-rank p < 0.001). Conclusions: Elderly CRC patients with MSI-H had a higher rate of multiple primary malignancies than MSS. This was associated with female gender, non-Hispanic White ethnicity, and right-sided tumor. MSI-H patients with single primary malignancy had the highest survival while the presence of multiple primary malignancies adversely affected survival in both MSI-H and MSS populations.