Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology

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1 bs_bs_banner doi: /jog J. Obstet. Gynaecol. Res. Vol. 41, No. 2: , February 2015 Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology Wataru Yamagami and Daisuke Aoki Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan Abstract The Japan Society of Obstetrics and Gynecology collects and analyzes annual data on gynecologic cancers from member institutions. Here we present the Patient Annual Report for 2012 and the Treatment Annual Report for Data on 7028 patients with cervical cancer, 8217 with endometrial cancer, 5140 with ovarian cancer and 1725 with ovarian borderline tumor for whom treatment was initiated in 2012 were summarized in the Patient Annual Report. Data on the prognosis of 2699 patients with cervical cancer, 3243 with endometrial cancer and 1898 with ovarian cancer for whom treatment was initiated in 2006 were analyzed in the Treatment Annual Report. In the Patient Annual Report for 2012, stage I accounted for 55.4%, stage II for 23.0%, stage III for 11.0% and stage IV for 10.6% of all patients with cervical cancer. Stage I accounted for 72.2%, stage II for 7.0%, stage III for 13.4% and stage IV for 7.3% of all patients with endometrial cancer. Stage I accounted for 43.1%, stage II for 9.2%, stage III for 29.7% and stage IV for 7.2% of all patients with ovarian cancer. In the Treatment Annual Report for 2006, the 5-year overall survival rates for patients with cervical cancer were 92.9% for stage I, 74.6% for stage II, 55.3% for stage III and 24.3% for stage IV. The equivalent rates for patients with endometrial cancer were 96.3%, 92.7%, 80.6% and 35.8%, respectively; and those for patients with ovarian surface epithelial stromal tumors were 90.6%, 82.9%, 48.7% and 40.9%, respectively. Key words: annual report, cervical cancer, endometrial cancer, ovarian cancer, gynecologic cancer, Japan. Introduction The Japan Society of Obstetrics and Gynecology (JSOG) collects annual data on the clinicopathologic factors and prognosis of gynecologic cancers from member institutions every year and analyzes this information to investigate the trends in gynecologic cancers in Japan. Here we present the Patient Annual Report for 2012 and the Treatment Annual Report for The data presented in this paper are quoted and modified from previous reports. 1,2 Patients and Methods For patients whose treatment was initiated in 2012, data were collected, retrospectively analyzed and summarized in the Patient Annual Report for For patients whose treatment was initiated in 2006, data on prognosis were collected, analyzed and summarized in the Treatment Annual Report for 2006, assuming a 5-year follow-up period was necessary. This study was conducted with the approval of the ethics committee of JSOG. Patient Annual Report for 2012 The subjects included patients with cervical intraepithelial neoplasia 3 (CIN3), 7028 with stage I IV cervical cancer, 558 with atypical endometrial hyperplasia (AEH), 8217 with stage I IV endometrial cancer, 5140 with ovarian cancer and 1725 with borderline ovarian tumor. These patients were histopathologically diagnosed in one of the 346 member institutions of Received: August Accepted: August Reprint request to: Professor Daisuke Aoki, Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi Shinjuku-ku, Tokyo , Japan. aoki@z7.keio.jp 2014 The Authors 167

2 W. Yamagami and D. Aoki JSOG and were administered treatment between January and December The clinical stages of cervical cancer and surgical stages of endometrial cancer were based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 staging system. The surgical stages for ovarian cancer, including borderline ovarian tumor, were based on the FIGO 1988 staging system. Data on age, clinical stage, histologic type and treatment were collected for patients with cervical cancer; data on age, surgical stage, histologic type and treatment were collected for patients with endometrial cancer; and data on age, surgical stage, histologic type and treatment were collected for patients with ovarian cancer and borderline ovarian tumor. Patient information was anonymized in a linkable fashion and registered from each institution onto the website of JSOG. Statistical analyses were performed after two or more members of the Committee on Gynecologic Oncology checked the integrity of the collected data. Treatment Annual Report for 2006 In all, 199 institutions provided data on the 3-year and 5-year prognoses of patients registered in any of the member institutions of JSOG between January and December 2006 and those reported in the Patient Annual Report for These patients included 4750 with cervical cancer, 4631 with endometrial cancer and 3204 with ovarian cancer. The clinical stages of cervical cancer and surgical stages of endometrial cancer and ovarian cancer, including borderline ovarian tumor, were based on the FIGO 1988 staging system. Data from institutions in which 20% of registered patients were untraceable were not included in the analysis of treatment outcomes and prognoses because such data would decrease the reliability of treatment outcomes and prognoses. Accordingly, data of 2699 patients with cervical cancer, 3243 with endometrial cancer and 2002 with ovarian cancer were ultimately included in the outcome analysis. Personal information was anonymized in a linkable fashion and information on prognoses was then registered on the JSOG website. Thereafter, the data were statistically analyzed at the Biostatistics Center, Kurume University. Statistical analysis The overall survival rates were analyzed by the Kaplan Meier method and statistical significance was determined using the log rank test. Results Patient Annual Report for 2012 Cervical cancer Age distribution (Fig. 1). Patients aged 40 49, and years accounted for 25.5%, 19.4% and 18.5% of all registered patients, respectively; these findings demonstrated that the disease predominantly affected women in their 40s. Stages (Fig. 2). Stage I accounted for 55.4% (stage IA1, 14.2%; stage IA2, 1.7%; stage IB1, 29.6%; stage IB2, 7.6%; subclassification unknown, 2.4%), stage II accounted for 23.0% (stage IIA1, 3.1%; stage IIA2, 2.5%; stage IIB, 16.8%; subclassification unknown, 0.7%), stage III accounted for 11.0% (stage IIIA, 1.1%; stage IIIB, 9.8%; subclassification unknown, 0.1%) and stage IV accounted for 10.6% (stage IVA, 3.0%; stage IVB, 7.6%; subclassification unknown, 0.0%) of all patients. Histologic types (Table 1). Squamous cell carcinoma was the most commonly encountered histopathologic type, Figure 1 Age distribution by clinical stage for patients with stage I IV cervical cancer in 2012., Stage I;, Stage II;, Stage III;, Stage IV The Authors

3 Annual report of JSOG Figure 2 Distribution of clinical stages for patients with cervical cancer in *Subclassification unknown. Table 1 Histologic types of cervical cancer in 2012 Histologic type Number % Squamous cell carcinoma, classification unknown Squamous cell carcinoma, keratinizing type Squamous cell carcinoma, non-keratinizing type Basaloid carcinoma Verrucous carcinoma Condylomatous carcinoma Papillary squamous cell carcinoma Lymphoepithelioma-like squamous cell carcinoma Squamotransitional carcinoma Microinvasive squamous cell carcinoma Adenocarcinoma, classification unknown Mucinous adenocarcinoma, endocervical type Mucinous adenocarcinoma, intestinal type Endometrioid adenocarcinoma Clear cell adenocarcinoma Serous adenocarcinoma Mesonephric adenocarcinoma Mucinous adenocarcinoma, minimal-deviation type Mucinous adenocarcinoma, villoglandular type Microinvasive adenocarcinoma Adenosquamous carcinoma Glassy cell carcinoma Adenoid cystic carcinoma Adenoid basal carcinoma Carcinoid Atypical carcinoid Small cell carcinoma Large cell neuroendocrine carcinoma Undifferentiated carcinoma Carcinosarcoma Others Unknown Total The Authors 169

4 W. Yamagami and D. Aoki Figure 3 Distribution of treatment methods by clinical stage for patients with cervical cancer in 2012., Stage I;, Stage II;, Stage III;, Stage IV. Figure 4 Age distribution by surgical stage for patients with stage I IV endometrial cancer in 2012., Stage I;, Stage II;, Stage III;, Stage IV. accounting for 73.5% of all patients, while adenocarcinoma accounted for 23.4% of all patients. The other rare histologic types encountered are shown in Table 1. Treatment (Fig. 3). Of the patients, 38.1% underwent just surgery, 20.7% received chemotherapy and other therapies in addition to radiotherapy, 12.6% received chemotherapy and other therapies in addition to surgery, 12.1% received just radiotherapy and 4.8% received radiotherapy in addition to surgery. Other therapies shown in the figure include immunotherapy and hormone therapy. Endometrial cancer Age distribution (Fig. 4). Patients aged 50 59, and years accounted for 30.3%, 27.8% and 15.8%, respectively, of all patients; these findings showed that the disease predominantly affected women in their 50s. On the other hand, patients aged <40 years accounted for just 5.3% of all patients. Surgical stages (Fig. 5). Stage I accounted for 72.2% (stage IA, 54.3%; stage IB, 17.4%; subclassification unknown, 0.5%), stage II accounted for 7.0%, stage III accounted for 13.4% (stage IIIA, 4.3%; stage IIIB, 0.9%; stage IIIC1, 4.2%; stage IIIC2, 3.3%; subclassification unknown, 0.7%) and stage IV accounted for 7.3% (stage IVA, 0.3%; stage IVB, 6.9%; subclassification unknown, 0.1%) of all patients. Histologic types (Table 2). Endometrioid carcinoma was the most common, accounting for 82.3% of all tumors. Other histologic types included serous adenocarcinoma (5.0%), clear cell adenocarcinoma (2.1%) and mixed carcinoma (2.4%). Carcinosarcoma was observed in 4.9% of patients. Treatment (Fig. 6). Of the patients, 56.4% underwent just surgery, 37.9% received chemotherapy and other therapies, such as hormone therapy, after surgery and 0.9% received radiotherapy after surgery. Other therapies shown in the figure include immunotherapy. Ovarian cancer Age distribution (Fig. 7). Patients aged 60 69, and years accounted for 27.9%, 26.1% and 19.2%, The Authors

5 Annual report of JSOG Figure 5 Distribution of surgical stages for patients with endometrial cancer in *Subclassification unknown. Figure 6 Distribution of treatment methods by surgical stage for patients with endometrial cancer in 2012., Stage I;, Stage II;, Stage III;, Stage IV. Table 2 Histologic types of endometrial cancer in 2012 Histologic type No. of % patients Endometrioid adenocarcinoma Endometrioid adenocarcinoma with squamous differentiation Endometrioid adenocarcinoma, villoglandular variant 4 0 Endometrioid adenocarcinoma, secretory variant 2 0 Serous adenocarcinoma Clear cell adenocarcinoma Mucinous adenocarcinoma Squamous cell carcinoma Mixed carcinoma Transitional cell carcinoma 0 0 Small cell carcinoma Undifferentiated carcinoma Carcinofibroma 1 0 Carcinosarcoma Classification unknown Total The Authors 171

6 W. Yamagami and D. Aoki Figure 7 Age distribution by surgical stage for patients with ovarian cancer in 2012., Stage I;, Stage II;, Stage III;, Stage IV;, Unknown;, Neoadjuvant chemotherapy. Figure 8 Distribution of surgical stages in patients with ovarian cancer and borderline ovarian tumor in 2012., Ovarian cancer;, Ovarian borderline tumor. respectively, of all patients; this indicated that the disease predominantly affected women in their 50s and 60s. Surgical stages (Fig. 8). Stage I accounted for 43.1% (stage Ia, 16.4%; stage Ib, 1.0%; stage Ic, 25.7%), stage II accounted for 9.2% (stage IIa, 1.2%; stage IIb, 1.3%; stage IIc, 6.7%), stage III accounted for 29.7% (stage IIIa, 1.3%; stage IIIb, 4.2%; stage IIIc, 24.2%) and stage IV accounted for 7.2% of all patients. Neoadjuvant chemotherapy was administered to 10.7% of patients. Histologic types (Table 3). Surface epithelial stromal tumors accounted for 95.2%, serous adenocarcinoma for 35.4%, clear cell adenocarcinoma for 23.8%, endometrioid adenocarcinoma for 16.9% and mucinous adenocarcinoma for 10.9% of all tumors. Sex cord stromal and germ cell tumors were observed in 0.2% and 3.3% of patients, respectively. Treatment (Fig. 9). Of the patients, 79.7% received chemotherapy after surgery, 18.2% underwent just surgery and 1.4% received just chemotherapy. Borderline ovarian tumor Surgical stages (Fig. 8). Stage I accounted for 93.2% (stage Ia, 65.6%; stage Ib, 2.6%; stage Ic, 25.1%), stage II accounted for 1.9% (stage IIa, 0.2%; stage IIb, 0.6%; stage IIc, 1.0%), stage III accounted for 3.7% (stage IIIa, 0.5%; stage IIIb, 1.0%; stage IIIc, 2.1%) and stage IV accounted for 0.5% of patients. Neoadjuvant chemotherapy was administered to 0.6% of patients. Histologic types (Table 4). Mucinous tumors accounted for 55.7%, serous tumors for 21.2%, endometrioid tumors for 2.1% and mixed tumors for 3.0% of all tumors. In addition, granulosa cell tumors accounted for 8.3% and immature teratomas (G1, G2) for 4.0% of tumors The Authors

7 Annual report of JSOG Table 3 Histologic types of ovarian cancer in 2012 Histologic type No. of % patients Serous adenocarcinoma Mucinous adenocarcinoma Endometrioid adenocarcinoma Clear cell adenocarcinoma Undifferentiated carcinoma Mixed-type adenocarcinoma Others: adenosarcoma (homologous) Others: adenosarcoma (heterologous) Others: mesodermal mixed tumor (homologous) Others: mesodermal mixed tumor (heterologous) Others: stromal sarcoma Others: malignant Brenner tumor Others: transitional cell carcinoma Others: unclassifiable Others: others Sertoli-stromal cell tumor (poorly differentiated) Others: fibrosarcoma Others: others Immature teratoma G Dysgerminoma Yolk sac tumor Malignant mixed germ cell tumor Malignant mixed germ cell tumor: yolk sac tumor + dysgerminoma Malignant mixed germ cell tumor: yolk sac tumor + immature teratoma Malignant mixed germ cell tumor: others Mature cystic teratoma with malignant transformation Others: embryonal carcinoma Others: polyembryoma Others: choriocarcinoma Others: others Sarcoma Others: carcinoma of the rete ovarii Others: small cell carcinoma Others: hepatoid carcinoma Others: squamous cell carcinoma Others: gestational choriocarcinoma Others: malignant lymphoma (primary) Others: unclassifiable Others: tumor possibly originating from the Wolffian duct Others: others Total 5140 Treatment (Fig. 10). Of the patients, 92.8% underwent just surgery and 7.2% received chemotherapy after surgery. Treatment Annual Report for 2006 Cervical cancer Overall survival by clinical stage (Fig. 11). The overall survival (OS) rates by clinical stage are shown in Figure 11. The 5-year OS rates were 92.9% for stage I (stage Ia1, 99.0%; stage Ia2, 100%; stage Ib1, 93.3%; stage Ib2, 80.0%), 74.6% for stage II (stage IIa, 81.4%; stage IIb, 71.9%), 55.3% for stage III (stage IIIa, 53.4%; stage IIIb, 55.5%) and 24.3% for stage IV patients (stage IVa, 27.9%; stage IVb, 21.8%). There were significant differences in OS between stages I and II (P < ), stages II and III (P < ) and stages III and IV (P = ). OS by histologic type (Fig. 12). The OS rates by histologic type are shown in Figure 12. The 5-year OS rates were 78.1%, 76.9%, 78.9% and 53.9% in patients with squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and other cancers, respectively The Authors 173

8 W. Yamagami and D. Aoki Figure 9 Distribution of treatment methods by surgical stage for patients with ovarian cancer in 2012., Stage I;, Stage II;, Stage III;, Stage IV;, Unknown;, Neoadjuvant chemotherapy. Table 4 Histologic types of ovarian borderline tumor in 2012 Histologic type No. of % patients Serous tumor Mucinous tumor Others: endometrioid tumor Others: clear cell tumor Others: proliferating Brenner tumor Others: mixed tumor 52 3 Others: unclassifiable Others: others Granulosa cell tumor Sertoli-stromal cell tumor (moderately differentiated) Others: gynandroblastoma 0 0 Others: steroid cell tumor (unclassifiable) Others: others Immature teratoma (G1, G2) 69 4 Others: carcinoid Others: neuroectodermal tumor Others: others Tumor of borderline malignancy other than the above: 0 0 gonadoblastoma Tumor of borderline malignancy other than the above: mixed germ cell sex cord-stromal tumor Tumor of borderline malignancy other than the above: others 0 0 Total 1725 Patients with other cancers had a significantly worse prognosis compared with those with squamous cell carcinoma (P = ), adenocarcinoma (P = ) and adenosquamous carcinoma (P = ). Endometrial cancer OS by surgical stage (Fig. 13). The OS rates by surgical stage are shown in Figure 13. The 5-year OS rates were 96.3% for stage I patients (stage Ia, 98.8%; stage Ib, 96.6%; stage Ic, 92.3%), 92.7% for stage II patients (stage IIa, 92.9%; stage IIb, 93.2%), 80.6% for stage III patients (stage IIIa, 85.9%; stage IIIb, 54.5%; stage IIIc, 75.1%) and 35.8% for stage IV patients (stage IVa, 57.0%; stage IVb, 34.1%). There were significant differences between patients with stages I and II (P < ), stages II and III (P < ) and stages III and IV (P < ). OS by histologic type (Table 5). The 5-year OS rates were 96.8%, 89.9% and 80.0% for patients with G1, G2 and G3 endometrioid adenocarcinoma, respectively. Comparison of survival among stages revealed 5-year OS The Authors

9 Annual report of JSOG Figure 10 Distribution of treatment methods by surgical stage for patients with borderline ovarian tumor in 2012.,Stage I;, Stage II;, Stage III;, Stage IV;, Unknown;, Neoadjuvant chemotherapy. Figure 11 Overall survival in patients with stage I IV cervical cancer by clinical stage in Log rank P < , International Federation of Gynecology and Obstetrics (FIGO) stage I;, FIGO stage II;, FIGO stage III;, FIGO stage IV. Figure 13 Overall survival by surgical stage for patients with stage I IV endometrial cancer in Log rank P < , International Federation of Gynecology and Obstetrics (FIGO) stage I;, FIGO stage II;, FIGO stage III;, FIGO stage IV. Figure 12 Overall survival by histologic type for patients with stage I IV cervical cancer in Log rank P < , Squamous cell carcinoma;, Adenocarcinoma;, Adenosquamous carcinoma;, Others. rates of 96.9%, 90.1% and 93.6% for patients with stage I endometrioid carcinoma, serous/mucinous/clear adenocarcinoma and other histologic types, respectively, and 93.6%, 84.2% and 92.4% for patients with stage II endometrioid carcinoma, serous/mucinous/ clear adenocarcinoma and other histologic types, respectively. For patients with stage III endometrioid carcinoma, serous/mucinous/clear adenocarcinoma and other histologic types, the rates were 86.7%, 60.8% and 70.1%, respectively, while the 5-year OS rates were 45.6%, 14.2% and 25.7% for stage IV endometrioid carcinoma, serous/mucinous/clear adenocarcinoma and other histologic types, respectively. Ovarian cancer OS by surgical stage (Fig. 14). The OS rates by surgical stage are shown in Figure 14. When compared among 2014 The Authors 175

10 W. Yamagami and D. Aoki Table 5 Five-year survival rates of endometrial cancer patients by stage and histologic type FIGO stage Histology Patients treated 5-year survival No. % % I Endometrioid adenocarcinoma Serous, mucinous, clear cell adenocarcinoma Others II Endometrioid adenocarcinoma Serous, mucinous, clear cell adenocarcinoma Others III Endometrioid adenocarcinoma Serous, mucinous, clear cell adenocarcinoma Others IV Endometrioid adenocarcinoma Serous, mucinous, clear cell adenocarcinoma Others FIGO, International Federation of Gynecology and Obstetrics. Figure 14 Overall survival by surgical stage for patients with ovarian cancer in Log rank P < , International Federation of Gynecology and Obstetrics (FIGO) stage I;, FIGO stage II;, FIGO stage III;, FIGO stage IV. the stages of surface epithelial stromal tumors, the 5-year OS rates were 90.6% in stage I patients (stage Ia, 93.8%; stage Ib, 78.3%; stage Ic(b), 91.2%; stage Ic(1), 81.0%; stage Ic(2), 86.7%; stage Ic(a), 87.5%), 82.9% in stage II patients (stage IIa, 100%; stage IIb, 80.8%; stage IIc(b), 80.1%; stage IIc(1), 81.8%; stage IIc(2), 80.3%; stage IIc(a), 84.0%), 48.7% in stage III patients (stage IIIa, 65.2%; stage IIIb, 56.7%; stage IIIc, 47.0%) and 40.9% in stage IV patients. There were significant differences in OS between stages I and II (P < ), stages II and III (P < ) and stages III and IV (P < ). The above analysis did not include patients who received neoadjuvant chemotherapy; the 5-year OS rate of patients who received neoadjuvant chemotherapy was 40.3%. Figure 15 Overall survival by histologic type for patients with ovarian cancer in Log rank P < , Serous;, Mucinous;, Endometrioid;, Clear;, Other. OS by histologic type (Fig. 15). The OS rates by histologic type are shown in Figure 15. Patients with serous adenocarcinoma had a significantly poorer prognosis compared with those with mucinous adenocarcinoma (P < ), endometrioid adenocarcinoma (P < ) and clear cell adenocarcinoma (P < ). Discussion In this analysis, the number of patients with cervical cancer, endometrial cancer, ovarian cancer and borderline ovarian tumor had increased from the analysis of This increase was not only influenced by the increase in patients with gynecologic cancer in Japan but also by the increase in the number of member institutions in JSOG (305 institutions in institutions in 2012) The Authors

11 Annual report of JSOG For the Patient Annual Report in 2012, the FIGO 2008 staging classification was adopted for the statistical analysis of cervical and endometrial cancers, while the FIGO 1988 staging classification was adopted for the statistical analysis of ovarian cancer. Carcinoma in situ, which was previously defined as stage 0 cervical cancer, was excluded from this analysis. This classification was included with severe dysplasia as CIN3. Therefore, the population of CIN3 did increase from AEH that was previously defined as stage 0 endometrial cancer was also excluded from this analysis. The number of patients with stage I endometrial cancer had increased, while that of patients with stage III endometrial cancer had decreased. These findings were influenced by the modification that patients with positive peritoneal cytology were not classed as stage IIIA in the FIGO 2008 staging system. On the other hand, there were no significant differences from 2011 in the number of ovarian cancers and borderline ovarian tumors. For the treatment annual reports for 2006, the FIGO 1988 staging classification was adopted for this statistical analysis of cervical, endometrial and ovarian cancers. Prognosis was analyzed by the Kaplan Meier method. As in the previous report, 3 information from institutions where prognoses were untraceable for 20% of patients was excluded from the analysis in the present study. Among patients with a known prognosis, 56.8% with cervical cancer, 70.0% with endometrial cancer and 62.5% with ovarian cancer were included in the analysis of prognosis. However, it may be possible that this selection of cases was influenced by a selection bias and that prognoses appeared better than they actually were in this study. In particular, the prognosis of stage IV cervical cancer and stage IV endometrial cancer may be susceptible to some bias because the number of cases was limited. Therefore, a worse prognosis for stage IV cervical cancer and a better prognosis for stage IV endometrial cancer may have been observed in 2012 compared with those in Conclusions We thus presented the Patient Annual Report and Treatment Annual Report on gynecologic tumors (cervical, endometrial and ovarian cancers and borderline ovarian tumor) in Japan. Acknowledgment The authors thank the member institutions of the Japan Society of Obstetrics and Gynecology for their cooperation in providing data on patients with gynecologic tumors. The authors also thank all members of the Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology, Dr Hidetaka Katabuchi, Dr Hidenori Kato, Dr Toshiaki Saito, Dr Toru Sugiyama, Dr Nao Suzuki, Dr Toru Hachisuga and Dr Yoichi Aoki for their contribution in summarizing the data and Ms Miyuki Nakai for her secretarial help. The authors thank the Biostatistics Center, Kurume University for data analysis. Disclosure There are no conflicts of interest to declare. References 1. Aoki D. The patient annual report in Acta Obstet Gynaecol Jpn 2014; 66: Aoki D. The treatment annual report in Acta Obstet Gynaecol Jpn 2014; 66: Aoki D. Annual report of Gynecologic Oncology Committee, Japan Society of Obstetrics and Gynecology, J Obstet Gynaecol Res 2014; 40: The Authors 177