Gastric-Type Adenocarcinoma of the Uterine Cervix Associated with Poor Response to Definitive Radiotherapy

SIMPLE SUMMARY: Cervical cancer is the most common frequent gynecological malignancy. The incidence has decreased owing to screening programs and human papillomavirus vaccination; however, the incidence of adenocarcinoma has recently increased in some countries, especially in the young population. Adenocarcinoma treated with definitive radiotherapy, the recommended approach for treating locally advanced cervical cancer, has a lower response and survival rate than squamous cell carcinoma. Our study aimed to assess the response to definitive radiotherapy by histological subtype and to investigate prognostic factors of adenocarcinoma according to the uniform staging system and histological classification. We confirmed that 52 patients with adenocarcinoma responded significantly less to definitive radiotherapy and had shorter survival times than 275 patients with squamous cell carcinoma. In the adenocarcinoma population, univariate and multivariate analyses showed that gastric-type adenocarcinoma was an independent poor prognostic factor associated with response to definitive radiotherapy. The pathogenesis of gastric-type adenocarcinoma must be investigated to overcome its poor response to treatment and establish novel therapeutic strategies for it. ABSTRACT: We aimed to evaluate the response to definitive radiotherapy (RT) for cervical cancer based on histological subtypes and investigate prognostic factors in adenocarcinoma (AC). Of the 396 patients treated with definitive RT between January, 2010 and July, 2020, 327 patients met the inclusion criteria, including 275 with squamous cell carcinoma (SCC) and 52 with AC restaged based on the 2018 International Federation of Gynecology and Obstetrics staging system. Patient characteristics, response to RT, and prognoses of SCC and AC were evaluated. The complete response (CR) rates were 92.4% and 53.8% for SCC and AC, respectively (p < 0.05). Three-year overall survival and progression-free survival (PFS) rates of SCC were significantly higher than those of AC (88.6% vs. 74.1%, p < 0.05 and 76.3% vs. 59.3%, p < 0.05, respectively). Among the AC population, univariate and multivariate analyses were performed to examine prognostic factors associated with non-complete response (CR). In the multivariate analysis, gastric-type adenocarcinoma (GAS) was associated with non-CR in AC (adjusted odds ratio, 12.2; 95% confidence interval 1.0–145.6; p < 0.05). The 3-year PFS rate in patients with GAS was significantly lower than that in patients with other histological types of AC (44.4% vs. 66.7%, p < 0.05). Definitive RT for cervical cancer was significantly less effective for AC than for SCC. GAS was the only independent prognostic factor associated with non-CR in AC.