Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

Objective Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. Study Design We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. Results The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). Conclusion ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters.

[1]  E. Partridge,et al.  Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer , 1996, New England Journal of Medicine.

[2]  R. Kimmig,et al.  Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationau , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  V. Gebski,et al.  Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Jacobus Pfisterer,et al.  Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials , 2009, Cancer.

[5]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[6]  J. Malek,et al.  Mesenchymal Cell Interaction with Ovarian Cancer Cells Triggers Pro-Metastatic Properties , 2012, PloS one.

[7]  E. Trimble,et al.  Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era: A Meta-Analysis. , 2023, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[9]  T. Bauknecht,et al.  A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. , 2003, Journal of the National Cancer Institute.

[10]  J. Huober,et al.  Surgery in Recurrent Ovarian Cancer: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR Trial , 2006, Annals of Surgical Oncology.

[11]  J. Dungan,et al.  Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer , 2011 .

[12]  E. Darai,et al.  Maximal Cytoreduction in Patients With FIGO Stage IIIC to Stage IV Ovarian, Fallopian, and Peritoneal Cancer in Day-to-Day Practice: A Retrospective French Multicentric Study , 2012, International Journal of Gynecologic Cancer.

[13]  M. Gnant,et al.  Incomplete surgical resection of ductal carcinomas in situ results in activation of ERBB2 in residual breast cancer cells. , 2008, Endocrine-related cancer.

[14]  Michael R Hamblin,et al.  CA : A Cancer Journal for Clinicians , 2011 .

[15]  X. Zhang,et al.  Autocrine production of interleukin-8 confers cisplatin and paclitaxel resistance in ovarian cancer cells. , 2011, Cytokine.

[16]  B. Weber,et al.  Mucinous advanced epithelial ovarian carcinoma: clinical presentation and sensitivity to platinum-paclitaxel-based chemotherapy, the GINECO experience. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  R. Coleman,et al.  Management Strategies for Recurrent Platinum-Resistant Ovarian Cancer , 2011, Drugs.

[18]  P. Sugarbaker,et al.  [Elective surgery in recurrent colon cancer with peritoneal seeding: when to and when not to proceed]. , 1999, Il Giornale di chirurgia.

[19]  D. Alberts,et al.  Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). , 2007, Gynecologic oncology.

[20]  S. Rubin,et al.  Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[22]  A. Rafii,et al.  Mesenchymal stem cells enhance ovarian cancer cell infiltration through IL6 secretion in an amniochorionic membrane based 3D model , 2013, Journal of Translational Medicine.

[23]  A. Reuss,et al.  Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. , 2006, Journal of the National Cancer Institute.

[24]  T. Burke,et al.  Secondary cytoreductive surgery for ovarian cancer. , 1994, Obstetrics and gynecology clinics of North America.

[25]  Jian Wu,et al.  Autocrine production of interleukin-8 confers cisplatin and paclitaxel resistance in ovarian cancer cells. , 2011, Cytokine.

[26]  M. Campiglio,et al.  Role of HER2 in wound-induced breast carcinoma proliferation , 2003, The Lancet.

[27]  C. Salpietro,et al.  Surgical Stress after Open and Transumbilical Laparoscopic-Assisted Appendectomy in Children , 2013, European Journal of Pediatric Surgery.