Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602.
We conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS.



Patients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523).



Between November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively).



Our findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017.
Department of Gynecology, Kitasato University School of Medicine, Japan. Electronic address: takashi-tky@umin.ac.jp.
Takashi
T
Onda
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Japan.
Toyomi
T
Satoh
Gynecology Service, National Kyushu Cancer Center, Japan.
Toshiaki
T
Saito
Department of Gynecologic Oncology, National Cancer Center Hospital, Japan.
Takahiro
T
Kasamatsu
Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Japan.
Toru
T
Nakanishi
JCOG Data Center/Operations Office, National Cancer Center, Japan.
Kenichi
K
Nakamura
JCOG Data Center/Operations Office, National Cancer Center, Japan.
Masashi
M
Wakabayashi
Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Japan.
Kazuhiro
K
Takehara
Department of Obstetrics and Gynecology, Jikei University Hospital, Japan.
Motoaki
M
Saito
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan.
Kimio
K
Ushijima
Department of Obstetrics and Gynecology, Kyushu University Hospital, Japan.
Hiroaki
H
Kobayashi
Department of Obstetrics and Gynecology, The University of Tokyo Hospital, Japan.
Kei
K
Kawana
Department of Gynecologic Oncology, Saitama Cancer Center, Japan.
Harushige
H
Yokota
Department of Obstetrics and Gynecology, National Defense Medical College, Japan.
Masashi
M
Takano
Department of Gynecologic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan.
Nobuhiro
N
Takeshima
Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Japan.
Yoh
Y
Watanabe
Department of Obstetrics and Gynecology, Tohoku University Hospital, Japan.
Nobuo
N
Yaegashi
Department of Obstetrics and Gynecology, Kyoto University Hospital, Japan.
Ikuo
I
Konishi
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan.
Toshiharu
T
Kamura
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Japan.
Hiroyuki
H
Yoshikawa
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D065426:Cytoreduction Surgical Procedures / Q000379:methods*; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D016019:Survival Analysis
D016190:Carboplatin; D017239:Paclitaxel
Interval debulking surgery; Neoadjuvant therapy; Ovarian neoplasms; Primary debulking surgery