Association between chemotherapy for surgically treated rectal cancer and second primary endometrial cancer
Authors: Gao Tianyu , Liu Wenlu , Ma Dongjiang , Huang WeiPeng , Zhang Dongyan , Wei Qiuya , Yu Congcong , Chen Minxue , Fan Yong , Wang Chen , Du Peng 
Published: November 2023

Background:
The conventional approach to managing postoperative rectal cancer (RC) entails the administration of chemotherapy (CT) or radiotherapy, both of which carry the potential for adverse effects and the onset of various ailments. However, the potential association between CT treatment for rectal cancer in females and the incidence of second primary endometrial cancer (SEC), as well as its impact on survival rates within this demographic, remains unexplored. Consequently, our study endeavors to examine the potential correlation between CT for RC in females and the likelihood of developing SEC, as well as its implications for overall survival and cancer-specific survival in this particular cohort.
Methods:
This study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, encompassing a substantial cohort of patients diagnosed with RC between 1975 and 2018. To ascertain the cumulative incidence of SEC and the relative risk (RR) associated with CT compared to no CT (NCT), Fine-Gray competing risk regressions and standardized incidence ratios (SIR) were utilized. Furthermore, the survival outcomes were assessed, encompassing the estimation of overall survival (OS) and cancer-specific survival (CSS) at 10 years.
Results:
This study involved a total of 30,847 individuals who were diagnosed with RC. Among them, 168 individuals (5.45‰) experienced SEC. Furthermore, 107 patients (3.47‰) received CT treatment, while 61 patients (1.98‰) received NCT. The analysis of the overall occurrence of SEC revealed a significant association between SEC and CT treatment (hazard ratio: 1.80; 95% confidence interval (CI): 1.39–2.34; P-value < 0.001). Both univariate and multivariate analyses confirmed a significant association between CT treatment and an increased risk of developing SEC in RC patients (univariate analyses hazard ratio, 2.06; 95% CI, 1.51–2.81; P-value < 0.001; multivariate analyses hazard ratio, 1.99; 95% CI, 1.44–2.75; P-value < 0.001). Through the implementation of a dynamic analysis on the variables of RR and SIR, it was discerned that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC received to CT and those who developed SEC did not revealed no substantial disparities in the 10-year overall survival rate and cancer-specific survival rate (10-year OS, 10.81‰ vs 5.18‰; P-value = 0.083; 10-year CSS, 8.29‰% vs 7.29‰; P-value = 0.270), and the result was the same situation after propensity score matching (PSM) (10-year OS, 5.18‰ vs 5.18‰; P = 0.082; 10-year CSS, 6.58‰ vs 6.58‰; P-value = 0.240). Nevertheless, a notable discrepancy emerged when comparing the overall survival rate and cancer-specific survival rate at 10 years between patients afflicted with secondary endometrial cancer (SEC) subsequent to CT and those afflicted with primary endometrial cancer (PEC). (10-year OS, 25.58‰ vs 5.59‰; P-value < 0.001; 10-year CSS, 25.28‰ vs 5.14‰; P-value < 0.001), and the result was the same situation in the NCT group (10-year OS, 8.20‰ vs 1.66‰; P-value < 0.001; 10-year CSS, 6.00‰ vs 1.20‰; P-value = 0.009).
Conclusion:
The utilization of CT in patients diagnosed with RC has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing CT-related SEC occurrences and improving the prognosis of affected individuals.