Prognostic factors in neuroendocrine cervical carcinoma

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Original Article Obstet Gynecol Sci 2016;59(2):116-122 http://dx.doi.org/10.5468/ogs.2016.59.2.116 pISSN 2287-8572 · eISSN 2287-8580

Prognostic factors in neuroendocrine cervical carcinoma Da Yong Lee1, Chul Chong1, Maria Lee1,2, Jae Weon Kim1,2, Noh Hyun Park1,2, Yong Sang Song1,2, Sang Yoon Park3 Department of Obstetrics and Gynecology, 1Seoul National University Hospital, Seoul, 2Seoul National University College of Medicine, Seoul; 3Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea

Objective To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). Methods The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. Results Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. Conclusion Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed. Keywords: Cervical carcinoma; Neoplasm recurrence; Neuroendocrine carcinoma; Retrospective studies; Small cell carcinoma

Introduction Neuroendocrine cervical carcinoma (NECC) is a rare form of cervical cancer representing 0.5% to 5% of all cervical cancer cases. NECC is classified into four histologic subtypes (small cell, large, classical carcinoid and atypical carcinoid, with small cell carcinoma of cervix (SCCC) being the most frequent type [1]. Neuroendocrine carcinomas can be identified by characteristic light and electron microscopic criteria, such as small cells with hyperchromatic nuclei and scanty cytoplasm. NECC can be present with other histologic findings, such as squamous cell and adenocarcinoma, and the presence of the NECC component defines the clinical behavior [2]. The clinical course of SCCC is aggressive, and metastasis to the bone, brain, liver, and bone marrow is common [3]. The relapse and metastasis pattern infers the nature of hematog-

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enous dissemination [4]. Despite its known clinical behavior, there is no consistent method of treatment. The treatment regimen is based on small cell lung cancer, where the micro-

Received: 2015.5.17. Revised: 2015.9.30. Accepted: 2015.10.21. Corresponding author: Maria Lee Department of Obstetrics and Gynecology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-2842 Fax: +82-2-762-3599 E-mail: [email protected] http://orcid.org/0000-0002-8017-3176 Articles published in Obstet Gynecol Sci are open-access, distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Copyright © 2016 Korean Society of Obstetrics and Gynecology

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Da Yong Lee, et al. Prognostic factors in NECC

scopic characteristics are similar. This regimen is also applied to other types of NECC. Interestingly, Hoskins et al. [5] reported a three-year failure-free survival rate of 80% in early stages (I to II) patients who received primary radiation therapy and platinum-based combination chemotherapy. A recent study showed that primary radiation therapy with at least 5 cycles of platinum-based chemotherapy resulted in a five-year overall survival rate of 78%, better than that of 46% achieved through primary surgery alone in early stage SCCC [6]. However, some studies have reported primary radical surgery followed by adjuvant chemotherapy as the preferred treatment modality with relatively favorable survival outcomes [7]. Due to the low incidence of NECC, it is very difficult to undertake prospective studies to elucidate the impact of treatment modality on survival outcome. Moreover according to our review, there are not enough studies with sufficient cases in the Korean population. Thus, to understand the prognosis in our population and improve the treatment strategy, we evaluated the clinical and pathologic factors associated with survival in patients with NECC in two of the cancer institutes in Korea.

of survival were evaluated using Cox regression methods. Pvalues