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Tailored Therapy and Long-Term Surveillance of Malignant Germ Cell Tumors in the Female Genital System: 10-Year Experience

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Tailored Therapy and Long-Term Surveillance of Malignant Germ Cell Tumors in the Female Genital System: 10-Year Experience J Gynecol Oncol. 2016 May;27(3):e26 http://doi.org/10.3802/jgo.2016.27.e26 pISSN 2005-0380 · eISSN 2005-0399 Original Article Tailored therapy and long-term surveillance of malignant germ cell tumors in the female genital system: 10-year experience Qianying Zhao,1 Jiaxin Yang,1 Dongyan Cao,1 Jiangna Han,2 Kaifeng Xu,2 Yongjian Liu,2 Keng Shen1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 2Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China Received: Aug 19, 2015 ABSTRACT Revised: Dec 21, 2015 Accepted: Dec 23, 2015 Objective: To explore the appropriate treatment of malignant germ cell tumor (MGCT) in the female genital system, and to analyze the factors influencing both therapeutic response and Correspondence to Keng Shen survival outcome. Department of Obstetrics and Gynecology, Methods: A cohort of 230-Chinese women diagnosed with MGCT of the genital system Peking Union Medical College Hospital, Chinese was retrospectively reviewed and prospectively followed. The demographic and pathological Academy of Medical Sciences & Peking Union features, extent of disease and surgery, treatment efficiency, recurrence and survival were Medical College, No. 1 Shuaifuyuan, Dongcheng, analyzed. Beijing, 100730, China. Results: MGCTs from different genital origins shared a similar therapeutic strategy and E-mail: [email protected] response, except that all eight vaginal cases were infantile yolk sac tumors. The patients’ cure Copyright © 2016. Asian Society of rate following the initial treatment, 5-year overall survival and disease-free survival (DFS) Gynecologic Oncology, Korean Society of were 85.02%, 95.00%, and 86.00%, respectively. Although more extensive excision could Gynecologic Oncology enhance the remission rate; it did not improve the patients’ survival. Instead, the level of the This is an Open Access article distributed under medical institution, extent of surgery and disease were independent prognostic factors for the terms of the Creative Commons Attribution Non-Commercial License (http:// relapse (p<0.05). Approximately 20% of patients had recurrent or refractory disease, more creativecommons.org/licenses/by-nc/4.0/) than half of whom were in remission following secondary cytoreductive surgery with salvage which permits unrestricted non-commercial chemotherapy. use, distribution, and reproduction in any Conclusion: Fertility-sparing surgery with or without standardized PEB/PVB (cisplatin, medium, provided the original work is properly etoposide/vincristine, and bleomycin) chemotherapy is applicable for female MGCTs cited. of different origins. Comprehensive staging is not required; nor is excessive debulking ORCID suggested. Appropriate cytoreduction by surgery and antineoplastic medicine at an Qianying Zhao experienced medical institution can bring about an excellent prognosis for these patients. http://orcid.org/0000-0003-3026-4827 Jiaxin Yang http://orcid.org/0000-0001-7566-3675 Keywords: Female Genital System; Malignant Germ Cell Tumor; Prognosis; Therapeutic Uses http://ejgo.org 1/12 MGCTs in female genital system Dongyan Cao INTRODUCTION http://orcid.org/0000-0002-7260-2495 Jiangna Han Malignant germ cell tumor (MGCT) is a rare entity in the female genital system. Ovarian http://orcid.org/0000-0002-7059-1999 Kaifeng Xu malignant germ cell tumors (MOGCTs) are highly malignant, rapidly growing, and have a http://orcid.org/0000-0003-0554-4915 peak incidence in women under the age of 20 years [1]. MOGCTs account for 5% of all ovarian Yongjian Liu malignancies in Western countries, but may represent approximately 15% of ovarian cancers http://orcid.org/0000-0002-2168-5315 in Asians and in blacks [2]. However, Surveillance, Epidemiology, and End Results (SEER) Keng Shen data (1973 to 2002) demonstrated lower rates of MOGCTs in blacks than whites and other http://orcid.org/0000-0003-3867-7407 nonwhites, and an increased incidence for Asian/Pacific Islanders and Hispanics [3]. The Conflict of Interest relatively low frequency of advanced-stage disease, together with their excellent sensitivity to No potential conflict of interest relevant to this contemporary platinum-based chemotherapy, has resulted in favorable cure rates for MOGCT article was reported. patients [4]. Additionally, the predominant unilaterality of these tumors allows for fertility- sparing surgery as initial treatment of choice, and the minimal recommended approach is unilateral oophorectomy [5]. Because this disease affects adolescent and young women of childbearing age and has much less aggressive surgical extent but better curability than epithelial ovarian cancer, the correct evaluation, treatment, and regular follow-ups are of the highest importance for these patients. Tumors arising primarily from the vagina comprise 3% to 8% of all MGCTs [6], and endodermal sinus tumor/ yolk sac tumor is the most common histological subtype at that site [7]. Although the cisplatin, etoposide and bleomycin (PEB) chemotherapy regimen without surgery has achieved complete remission (CR) in some early cases [8], the proper diagnosis and appropriate initial treatment remains unsolved challenges, and long-term surveillance information is limited due to the rarity of this malignancy in the pediatric population [9]. In addition, disorder of sex development (DSD) has been recognized as one of the main risk factors for the development of germ cell tumors [10]. Therefore, we retrospectively analyzed and prospectively followed a cohort of 230 Chinese women diagnosed with MGCT in the genital system, including 17 DSD females (social gender) with concomitant MGCTs. The objective was to summarize our 10-year experience towards the optimal management of MGCTs and to explore the key factors affecting the relapse and prognosis of these tumors. MATERIALS AND METHODS We herein collected a total of 230 female patients with MGCTs in the genital system, who were either initially admitted or subsequently transferred to Peking Union Medical College Hospital (PUMCH) between September 2004 and September 2014 (end date of the study). Paraffin-embedded tissue section specimens of the transferred patients were reviewed, and their diagnosis confirmed by experienced pathologists at PUMCH or other tertiary referral hospitals. The histological diagnosis followed the ICD-O-3 (International Classification of Disease for Oncology) criteria that recognize pure dysgerminoma (9060–9061 [n=44]) and non-dysgerminoma (9070–9071 [n=74], 9073 [n=4], 9080–9084 [n=68], 9091 [n=7], and 9100 [n=6]) (Table 1). Moreover, another 27 tumors had at least two malignant components, thus defined as mixed MGCTs. The clinical information was retrieved from the medical record database, including the patient’s age at diagnosis, ethnic group, primary tumor site, histological subtype, extent of disease and operation, International Federation of Gynecology and Obstetrics (FIGO) stage when a comprehensive staging procedure was performed, and chemotherapy regimen. Specifically, the extent of the disease was categorized into local (disease confined to the ovaries) and metastatic disease, the latter comprising regional http://ejgo.org http://doi.org/10.3802/jgo.2016.27.e26 2/12 MGCTs in female genital system Table 1. Patients’ characteristics of a 230-Chinese cohort diagnosed with malignant germ cell tumors Characteristic NO. (%) Age group (yr) < 1 7 (3.04) 1–9 16 (6.96) 10–19 84 (36.52) 20–29 79 (34.35) 30–39 32 (13.91) 40–49 6 (2.61) 50–59 1 (0.44) 60–69 2 (0.87) ≥ 70 3 (1.30) Ethnic group Han 214 (93.04) Minority 16 (6.96) Extent of disease Localized 164 (71.30) Metastatic 66 (28.70) Primary tumor site Ovary 201 (87.39) Pelvis 4 (1.74) Vagina 8 (3.48) Dysgenetic gonads 17 (7.39) Histological type (ICD-O-3) Dysgerminoma (9060) 40 (17.39) Seminoma (9061) 4 (1.74) Embryonal carcinoma (9070) 1 (0.43) Endodermal sinus tumor (9071) 73 (31.74) Gonadoblastoma (9073) 4 (1.74) Immature teratoma (9080) 62 (26.96) Teratoma, Malignant transformation (9084) 6 (2.61) Strumal carcinoid (9091) 7 (3.04) Choriocarcinoma (9100) 6 (2.61) Mixed germ cell tumor 27 (11.74) Total 230 (100.00) ICD-O, International Classification of Disease for Oncology. spread in the pelvis and distant metastases. Fertility-sparing surgery with unilateral salpingo- oophorectomy was the standard practice, and radical cytoreductive strategy was applied for advanced disease based upon the experience with epithelial ovarian cancer, especially for those without child-bearing requirement. The initial treatment, consisting of surgery with or without standardized platinum-based chemotherapy (≤6 courses), was considered to be effective if the neoplasm was excised satisfactorily and the surveillance indicators (tumor markers, imaging, and physical examinations) were all negative for at least 4 weeks after completion of therapy. Potential impact factors for the treatment efficiency were simultaneously analyzed. Long-term surveillance and survival outcomes were obtained through either the Outpatient Surveillance System of PUMCH or telephone interviews with patients and relatives. The overall survival (OS) and disease-free survival (DFS) of patients with germ cell cancer were evaluated, with an emphasis on recurrent cases, and clinical prognostic factors were reviewed. Categorical variables were described with proportions, and continuous variables with median
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