Treatment Patterns and Prognosis of Clear Cell Adenocarcinoma of the Cervix: A Research Study

Academic Background

Cervical cancer ranks as the fourth most common gynecological malignancy globally and the third leading cause of cancer-related mortality in women. Among its subtypes, clear cell adenocarcinoma of the cervix (CCAC) is an extremely rare form, accounting for 4%-9% of cervical adenocarcinomas. CCAC is associated with a history of exposure to diethylstilbestrol (DES), a synthetic estrogen derivative widely used in pregnant women during the 1940s to 1970s. Since the ban on DES, the incidence of CCAC has significantly declined, but its unique biological behavior and clinical characteristics have made it a focal point of research.

Currently, there are no specific treatment guidelines for CCAC, and its management is primarily based on protocols for common cervical cancer types, such as squamous cell carcinoma, usual-type adenocarcinoma, and adenosquamous carcinoma. However, CCAC exhibits lower sensitivity to radiotherapy and chemotherapy, and its molecular biological features differ significantly from those of common cervical cancer types. Therefore, dedicated research on CCAC is crucial. This study aims to analyze the treatment patterns and prognosis of CCAC using the Surveillance, Epidemiology, and End Results (SEER) database, providing evidence-based insights for clinical practice.

Source of the Paper

This paper was co-authored by Jing Li, Huimin Qiao, Yang Yang, Lan Wu, Dongdong Xu, Zhongqiu Lin, and Huaiwu Lu, affiliated with the Department of Gynecological Oncology at Sun Yat-sen Memorial Hospital, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Bao’an Central Hospital of Shenzhen, Jiangmen Traditional Chinese Medicine Hospital, and Shenzhen Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. The paper was published online on August 2, 2024, in the International Journal of Surgery, with the DOI: 10.1097/js9.0000000000001997.

Research Process and Results

1. Data Source and Study Population

The study utilized the SEER database to identify female patients diagnosed with cervical cancer between 2000 and 2019. A total of 52,153 patients were included, of whom 528 had CCAC. Patients without histologic confirmation, incomplete tumor staging information, or unknown surgical status were excluded. Key variables included age at diagnosis, year of diagnosis, race, FIGO 2018 stage, NCCN stage, tumor size, lymph node metastasis, surgery, radiotherapy, and chemotherapy.

2. Research Methods

The study employed Kaplan-Meier analysis, propensity score matching (PSM), Cox regression analysis, and subgroup analysis to evaluate treatment patterns and prognosis in CCAC patients. The specific steps were as follows: - Kaplan-Meier Analysis: Used to assess the impact of different treatments on overall survival (OS). - Propensity Score Matching: Performed 1:1 matching between surgical and non-surgical groups to minimize baseline differences. - Cox Regression Analysis: Used to identify independent prognostic factors affecting OS. - Subgroup Analysis: Stratified by factors such as disease stage, age, and race.

3. Key Findings

• Clinical Characteristics of CCAC Patients: CCAC patients were significantly older at diagnosis compared to other cervical cancer types, with a median age of 58.5 years. The majority of CCAC patients were over 65 years old (36.0%). The lymph node metastasis rate in CCAC patients (14.6%) was higher than in squamous cell carcinoma (8.5%) and usual-type adenocarcinoma (6.8%) but lower than in adenosquamous carcinoma (17.2%).
• Treatment Patterns: Surgery was the preferred treatment for locally advanced CCAC patients (58.5%), while non-surgical treatments were more common in squamous cell carcinoma and usual-type adenocarcinoma patients. Radiotherapy combined with chemotherapy was the most common adjuvant therapy for locally advanced and metastatic CCAC patients.
• Impact of Surgery on Prognosis: Kaplan-Meier analysis showed that surgery significantly improved OS in CCAC patients (65.6% vs. 25.3%, p=0.000), particularly in locally advanced patients (57.9% vs. 26.7%, p=0.000). Multivariate Cox regression analysis further confirmed that surgery was significantly associated with better prognosis in locally advanced CCAC patients (HR 0.299, 95% CI: 0.153–0.585, p=0.000).
• Subgroup Analysis: Surgery significantly improved OS in IB3-IIA2 stage and locally resectable IIIC stage CCAC patients (HR 0.207, 95% CI: 0.043–0.991, p=0.049), but no similar trend was observed in IIB-IVA stage patients (excluding locally resectable IIIC stage).

4. Conclusions

The study suggests that surgery should be the preferred treatment for locally advanced CCAC patients, particularly those at IB3-IIA2 stage and locally resectable IIIC stage. Surgery not only significantly improves survival rates but also reduces tumor burden, enhancing the efficacy of subsequent radiotherapy and chemotherapy.

Research Highlights

• First Large-Scale Retrospective Study: This is the largest retrospective study to date on treatment patterns in CCAC, providing critical insights for managing this rare tumor.
• Significant Advantage of Surgery: The study is the first to demonstrate the significant survival benefit of surgery in locally advanced CCAC patients, particularly those at IB3-IIA2 and locally resectable IIIC stages.
• Clinical Implications: The findings challenge the NCCN guidelines’ recommendation of chemoradiotherapy as the first-line treatment for locally advanced cervical cancer, offering new perspectives for individualized treatment in CCAC patients.

Research Value and Significance

By analyzing the SEER database, this study systematically evaluates the treatment patterns and prognosis of CCAC, addressing a significant gap in the field. The findings provide a scientific basis for CCAC treatment and lay the groundwork for future multicenter prospective studies. Additionally, the study underscores the importance of surgery in managing locally advanced CCAC, offering valuable guidance for clinicians.

Additional Valuable Information

• Study Limitations: As a retrospective study, potential selection bias and uncontrolled confounding factors may exist. Furthermore, the SEER database lacks detailed information on radiotherapy and chemotherapy doses, necessitating further research to validate the impact of these treatments on CCAC prognosis.
• Future Research Directions: Multicenter retrospective studies are recommended to compare the efficacy of radiotherapy and chemotherapy versus radical surgery in locally advanced CCAC patients and to explore the prognostic impact of adjuvant radiotherapy and chemotherapy in different disease stages.

This study provides critical scientific evidence for CCAC treatment, demonstrating significant clinical value and application potential.