title: Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome.
abstract: To establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL).
  
  
  
  This is a single-Institution, superiority, randomised phase III trial enrolling supposed AEOC women. Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index (PI) of tumour load. All AEOC women with PI≥8 or≤12 (considered as HTL) were included. They were randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy (arm A, standard), or NACT followed by IDS (NACT/IDS) (arm B, experimental). Co-primary outcome measures were postoperative complications (graded according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system) and progression free survival (PFS); secondary outcomes were overall survival, and quality of life (QoL). QoL was assessed using the EORTC QoL questionnaires. A sample size of 110 patients was required for the analysis of the first co-primary end-point (major peri-operative morbidity) whereas recruitment is still on-going to achieve the statistical power on PFS.
  
  
  
  Between October 2011 and November 2014, we registered 280 AEOC. Of the 110 eligible women, 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery, rates of complete residual disease (residual tumour=0 cm) were superimposable between the groups (45.5% versus 57.7%; p=0.206). Twenty-nine patients (52.7%) in arm A experienced early grade III-IV complications versus three patients (5.7%) in IDS (p=0.0001). The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage (17/55 women (30.9%) in arm A versus 1/52 (1.9%) in arm B, p=0.0001). Three grade IV (5.4%) (i.e., two re-operations for postoperative haemorrhage and one septic multi-organ failure), and two grade V (3.6%) (two deaths for acute cardiopulmonary failure) early complications were observed in arm A only. Mean QoL scores of several scales/items were shown to ameliorate over time in both arms. Emotional functioning, cognitive functioning, nausea/vomiting, dyspnoea, insomnia and hair loss were statistically and clinically better in NACT/IDS compared to PDS arm.
  
  
  
  Perioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS arm than PDS in AEOC patients with very HTL. Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL.
authors.affiliation: Division of Minimally Invasive Gynecological Surgery, St. Maria Hospital, University of Perugia, Terni, Italy. Electronic address: anna.fagotti@rm.unicatt.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Fagotti
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vizzielli
authors.affiliation: Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fanfani
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Gallotta
authors.affiliation: Division of Gynecologic Oncology, Foundation for Research and Care "Giovanni Paolo II", Catholic University of the Sacred Heart and University of Molise, Campobasso, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Chiantera
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Costantini
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Pasquale Alessandro
authors.initials: PA
authors.lastname: Margariti
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gueli Alletti
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cosentino
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Tortorella
authors.affiliation: Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001828:Body Image; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D065426:Cytoreduction Surgical Procedures / Q000379:methods; D005260:Female; D006801:Humans; D007902:Length of Stay; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000601:surgery*; D061646:Operative Time; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D017239:Paclitaxel / Q000008:administration & dosage; D011183:Postoperative Complications / Q000209:etiology; D011788:Quality of Life; D055815:Young Adult
chemical_list: D016190:Carboplatin; D017239:Paclitaxel
keywords: Advanced ovarian cancer; Cytoreduction; Laparoscopy; Peri-operative complications; Quality of life; Randomised clinical trial