Small Cell Neuroendocrine Carcinoma of the Uterine Cervix: Prognostic Value of Clinicopathology, Survival Comparing to Adenocarcinoma and Squamous Cell Carcinoma, and Histological Type-Specific Determinants

Abstract

Cervical cancer is the third most common cancer in women worldwide. Annually, more than 529,800 new cases occur and the estimated deaths are over 275,000. Of these, over 85% of the cases and the deaths occur in developing countries, including Thailand. Although, cervical cancer is preventable and highly curable when diagnosed at its early stage, patients in developing countries have usually been found with an advanced cancer stage due to the lack of effective screening programs and/or an inability to access the programs. As a result, they have a poor prognosis. Prognostic factors for patients with cervical cancer vary in previous studies, including clinical factors such as age and treatment modality, and pathological factors such as FIGO stage, lymph node involvement, tumor size, lymphovascular space invasion, deep stromal invasion, parametrial involvement and histological type. However, prognostic factors for patients with cervical small cell neuroendocrine (SNEC), a very aggressive and rare histological type, are still controversial due to the rather small sample sizes. Previous studies on SNEC have been limited by the lack of central pathology review for diagnosis of SNEC and/or the variation of treatment modality among institutes of collected cases, which may influence the results. Moreover, conflicting data still exists on the prognostic impact of the histological type on survival in patients with cervical cancer. Additionally, any differences in histological type-specific prognostic factors among cervical SNEC, adenocarcinoma (ADC), and squamous cell carcinoma (SCC) have not yet been clearly identified. All cohort studies in this thesis were carried out at Chiang Mai University Hospital, Chiang Mai, Thailand. Our studies aimed to explore the prognostic factors for cervical SNEC, ADC, and SCC, and evaluate the prognostic value of histology in early and advanced cancer stages among the three histological types. Our findings revealed that the histological type is an independent prognostic factor for patients with cervical cancer. Patients with SNEC had the poorest survival regardless of stage compared with ADC, and SCC. Advanced ADC was associated with a poorer survival compared with SCC while survival between the two was comparable at an early cancer stage. For histological type-specific prognostic factors, age and deep stromal invasion were prognostic factors for cancer-specific survival (CSS) among early stage patients with SNEC, while age and lymph node involvement were prognostic factors for surgically-treated patients with SNEC. For advanced SNEC, age and FIGO stage were found to be prognostic factors. In patients with SCC, deep stromal invasion was a prognostic factor for patients with surgically-treated SCC, and FIGO stage were prognostic factors for advanced stage SCC. Since there were only a few cancer-related deaths in surgically-treated ADC, multivariable analysis could not be performed for this group. For advanced ADC, FIGO stage was the only prognostic factor. We also found the benefit of adjuvant chemotherapy over other types of adjuvant therapy among surgically-treated patients with SNEC, with a significantly higher 5-year CSS rate. However, this finding could have been confounded by confounding by indication, which we did not adjust for. In conclusion, histological type is an independent prognostic factor for patients with cervical cancer, and prognostic factors for patient with cervical cancer differ according to histological type. Adjuvant chemotherapy may provide some benefits for surgically-treated patients with SNEC. Knowledge of histological type-specific prognostic factors and the influence of the histological type on survival should be taken into consideration for tailored treatment and surveillance of treatment outcomes in patients with cervical cancer.