Supplemental online content for : NCCN Guidelines ® Insights : Ovarian Cancer , Version 1 . 2019

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.

[1]  D. Kolin,et al.  Serous borderline tumor of the ovary with isolated cardiophrenic lymph node spread at diagnosis , 2020, Gynecologic oncology reports.

[2]  N. Ismaili COVID-19 and gynecological cancers: A Moroccan point-of-view☆ , 2020, Radiotherapy and Oncology.

[3]  Peng-Hui Wang,et al.  Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer , 2020, International journal of environmental research and public health.

[4]  Chong-xiang Chen,et al.  The role of the CDCA gene family in ovarian cancer , 2020, Annals of translational medicine.

[5]  Jia-xin Yang,et al.  Clinicopathological Characteristics and Treatment Outcomes of Pregnancy Complicated by Malignant Ovarian Germ Cell Tumors , 2020, Cancer management and research.

[6]  D. Alberts,et al.  Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy Plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Young Tae Kim,et al.  Incorporation of paclitaxel-based hyperthermic intraperitoneal chemotherapy in patients with advanced-stage ovarian cancer treated with neoadjuvant chemotherapy followed by interval debulking surgery: a protocol-based pilot study , 2018, Journal of gynecologic oncology.

[8]  M. Parmar,et al.  Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. , 2018, The Lancet. Oncology.

[9]  Gabe S. Sonke,et al.  Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer , 2018, The New England journal of medicine.

[10]  G. Scambia,et al.  Upfront HIPEC and bevacizumab-containing adjuvant chemotherapy in advanced epithelial ovarian cancer , 2018, International Journal of Hyperthermia.

[11]  D. Matei,et al.  Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy , 2018, British Journal of Cancer.

[12]  M. van der Aa,et al.  Interval between debulking surgery and adjuvant chemotherapy is associated with overall survival in patients with advanced ovarian cancer. , 2018, Gynecologic oncology.

[13]  L. Ansaloni,et al.  Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian and gastrointestinal peritoneal carcinomatosis: results from a 7-year experience. , 2018, Journal of gastrointestinal oncology.

[14]  P. Bossuyt,et al.  The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy , 2018, International Journal of Gynecologic Cancer.

[15]  H. Mackay,et al.  OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  B. Monk,et al.  Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters—patient-centered end points in trials of maintenance therapy , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  B. Afşar,et al.  Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. , 2018, The New England journal of medicine.

[18]  T. Walsh,et al.  Mutations in Homologous Recombination Genes and Outcomes in Ovarian Carcinoma Patients in GOG 218: An NRG Oncology/Gynecologic Oncology Group Study , 2017, Clinical Cancer Research.

[19]  Val Gebski,et al.  Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. , 2017, The Lancet. Oncology.

[20]  R. Burger,et al.  A phase III trial of maintenance therapy in women with advanced ovarian/fallopian tube/peritoneal cancer after a complete clinical response to first-line therapy: An NRG oncology study , 2017 .

[21]  R. Bristow,et al.  Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer. , 2017 .

[22]  Y. Zhang,et al.  Application of combined intraperitoneal and intravenous neoadjuvant chemotherapy in senile patients with advanced ovarian cancer and massive ascites. , 2017, European journal of gynaecological oncology.

[23]  J. Calzas,et al.  Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with primary or secondary cytoreductive surgery in the treatment of advanced epithelial ovarian cancer. , 2017, Minerva ginecologica.

[24]  I. Floriani,et al.  Feasibility and outcome of interval debulking surgery (IDS) after carboplatin-paclitaxel-bevacizumab (CPB): A subgroup analysis of the MITO-16A-MaNGO OV2A phase 4 trial. , 2017, Gynecologic oncology.

[25]  R. Rouzier,et al.  Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: Results from the ANTHALYA trial. , 2017, European journal of cancer.

[26]  Yun-Qiang Tang,et al.  Hyperthermic Intraperitoneal Perfusion Chemotherapy and Cytoreductive Surgery for Controlling Malignant Ascites From Ovarian Cancer , 2016, International Journal of Gynecologic Cancer.

[27]  I. Vergote,et al.  Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. , 2016, Gynecologic oncology.

[28]  T. Kasamatsu,et al.  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. , 2016, European journal of cancer.

[29]  C. Pomel,et al.  Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. , 2016, Gynecologic oncology.

[30]  G. Scambia,et al.  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. , 2016, European journal of cancer.

[31]  B. Monk,et al.  Early initiation of chemotherapy following complete resection of advanced ovarian cancer associated with improved survival: NRG Oncology/Gynecologic Oncology Group study. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  M. Gasparri,et al.  Primary chemotherapy versus primary surgery for ovarian cancer , 2015, The Lancet.

[33]  B. Monk,et al.  Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG Oncology/GOG study. , 2015, Gynecologic oncology.

[34]  Jacobus Pfisterer,et al.  Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial , 2015, The Lancet. Oncology.

[35]  I. Bover,et al.  Phase II randomized trial of neoadjuvant (NA) chemotherapy (CT) with or without bevacizumab (Bev) in advanced epithelial ovarian cancer (EOC) (GEICO 1205/NOVA TRIAL). , 2015 .

[36]  J. W. Kim,et al.  Major clinical research advances in gynecologic cancer in 2014 , 2015, Journal of gynecologic oncology.

[37]  L. Ansaloni,et al.  Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study , 2015, Journal of gynecologic oncology.

[38]  J. Spiliotis,et al.  Cytoreductive Surgery and HIPEC in Recurrent Epithelial Ovarian Cancer: A Prospective Randomized Phase III Study , 2015, Annals of Surgical Oncology.

[39]  B. Monk,et al.  Incorporation of pazopanib in maintenance therapy of ovarian cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  M. Barone,et al.  Peritonectomy and hyperthermic chemotherapy in patients with advanced or recurrent ephitelial ovarian cancer: a single center cohort study. , 2014, Minerva chirurgica.

[41]  W. Jiménez,et al.  Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: upfront therapy, at first recurrence, or later? , 2013, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[42]  P. Bossuyt,et al.  Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. , 2013, European journal of cancer.

[43]  H. Hirte,et al.  Palliative systemic therapy for women with recurrent epithelial ovarian cancer: current options , 2013, OncoTargets and therapy.

[44]  L. Landrum,et al.  Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: a Gynecologic Oncology Group study. , 2012, Gynecologic oncology.

[45]  P. Pattyn,et al.  Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion in Women with Heavily Pretreated Recurrent Ovarian Cancer , 2012, Annals of surgical oncology.

[46]  Jeffrey J H Low,et al.  Epithelial ovarian cancer , 2018, An Atlas of Gynecologic Oncology.

[47]  D. Matei,et al.  Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. , 2012, The New England journal of medicine.

[48]  S. Kakolyris,et al.  Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Intraoperative Chemotherapy in the Treatment of Advanced Epithelial Ovarian Cancer , 2012, Journal of oncology.

[49]  D. Chi,et al.  Current surgical management of ovarian cancer. , 2012, Hematology/oncology clinics of North America.

[50]  B. Kopf,et al.  Evaluation of Extensive Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Epithelial Ovarian Cancer , 2012, International Journal of Gynecologic Cancer.

[51]  D. Levine,et al.  An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT). , 2012, Gynecologic oncology.

[52]  B. Monk,et al.  Incorporation of bevacizumab in the primary treatment of ovarian cancer. , 2011, The New England journal of medicine.

[53]  B. Mosgaard,et al.  Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis. , 2011, Danish medical bulletin.

[54]  H. Mackay,et al.  Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. , 2011, The Lancet. Oncology.

[55]  G. Scambia,et al.  HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. , 2011, Gynecologic oncology.

[56]  M. Solazzo,et al.  Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial. , 2011, Gynecologic oncology.

[57]  J. Spiliotis,et al.  The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent advanced ovarian cancer: a prospective study. , 2011, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[58]  G. Kenter,et al.  Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. , 2010, The New England journal of medicine.

[59]  Mark Robson,et al.  Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial , 2010, The Lancet.

[60]  Jan Lubinski,et al.  Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  Ie-Ming Shih,et al.  The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory , 2010, The American journal of surgical pathology.

[62]  O. Nanni,et al.  Phase III trial of observation versus six courses of paclitaxel in patients with advanced epithelial ovarian cancer in complete response after six courses of paclitaxel/platinum-based chemotherapy: final results of the After-6 protocol 1. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[63]  C. Leutner,et al.  Neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian cancer--a prospective multicenter phase II trial (PRIMOVAR). , 2009, Oncology reports.

[64]  G. Scambia,et al.  Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study. , 2009, Gynecologic oncology.

[65]  D. Alberts,et al.  Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. , 2009, Gynecologic oncology.

[66]  N. Spirtos,et al.  Gynecologic Oncology Group Surgical Procedures Manual , 2009 .

[67]  Sohee Park,et al.  Hyperthermic Intraperitoneal Chemotherapy After Extensive Cytoreductive Surgery in Patients with Primary Advanced Epithelial Ovarian Cancer: Interim Analysis of a Phase II Study , 2009, Annals of Surgical Oncology.

[68]  M. Rocco,et al.  Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer , 2008, Cancer.

[69]  E. Cotte,et al.  Cytoreductive Surgery and Intraperitoneal Chemohyperthermia for Chemoresistant and Recurrent Advanced Epithelial Ovarian Cancer: Prospective Study of 81 Patients , 2007, World Journal of Surgery.

[70]  R. Burger,et al.  Intraperitoneal cisplatin and paclitaxel in ovarian cancer. , 2006, The New England journal of medicine.

[71]  J. Bull,et al.  Thermal enhancement of drug uptake and DNA adducts as a possible mechanism for the effect of sequencing hyperthermia on cisplatin-induced cytotoxicity in L1210 cells , 1994, Cancer Chemotherapy and Pharmacology.

[72]  B. Monk,et al.  Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  F. Bressolle,et al.  Population pharmacokinetics of cisplatin in patients with advanced ovarian cancer during intraperitoneal hyperthermia chemotherapy. , 2002, Anticancer research.

[74]  B N Bundy,et al.  Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Gr , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  H. Bartelink,et al.  Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. , 1998, European journal of cancer.

[76]  D. Alberts,et al.  Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. , 1996, The New England journal of medicine.

[77]  T. Wobbes,et al.  Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas. , 1992, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[78]  P. Buamah,et al.  Serum CA 12‐5 concentrations and CA 12‐5/CEA ratios in patients with epithelial ovarian cancer , 1990, Journal of surgical oncology.