New Guidelines for Treating Ovarian Cancer
Epithelial ovarian cancer is the seventh most common cancer in women worldwide (based on data from 2012).1 Despite advances in diagnosis and treatment, ovarian cancer is usually diagnosed at an advanced stage: 60–70% of women with ovarian cancer are diagnosed at stage III and IV.2 The standard of care for these women has been primary cytoreductive surgery (PCS) with the goal of achieving a maximum residual tumour size of 3 However, treatment is associated with adverse effects and optimal debulking is only achieved in 30–60% of stage III/IV ovarian cancers.4 Neoadjuvant chemotherapy (NACT) has emerged as an alternative to primary cytoreduction, and employs chemotherapy prior to interval cytoreductive surgery (ICS) with the aim of reducing perioperative morbidity and mortality and increasing the likelihood of a complete surgical cytoreduction.5 However, the optimum strategy for treatment of ovarian cancer remains the subject of debate.
In August 2016, the American Society of Clinical Oncology (ASCO) and the Society of Gynaecologic Oncology (SGO) jointly issued new clinical practice guidelines for the treatment of patients with ovarian cancer.6 These are based on the findings of four randomized clinical trials that investigated the use of NACT followed by ICS. In the European Organisation for Research and Treatment of Cancer (EORTC) trial (EORTC55971)7 and the Chemotherapy or Upfront Surgery (CHORUS)8 trial, NACT/ICS was found to be non-inferior to standard of care in terms of progression-free and overall survival, and resulted in a lower incidence of postoperative infections, venous complications, fistula, hemorrhage and postoperative mortality in women with advanced ovarian cancer. CHORUS also included an analysis of no residual disease and found that 39% of patients in the NACT/ICS arm had no residual disease, compared with 17% in the primary surgery arm.8 The Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm (SCORPION) trial randomized patients with advanced ovarian cancer and high tumor load to PCS or NACT/ICS, and found that perioperative moderate/severe morbidity and quality of life scores were superior in the NACT/ICS arm.9 In a Japan Clinical Oncology Group (JCOG) trial (JCOG0602), patients with a clinical diagnosis of stage III/IV ovarian, tubal or peritoneal cancer were randomized to either PCS followed by 8 cycles of carboplatin + paclitaxel or to NACT with 4 cycles of carboplatin + paclitaxel followed by ICS, then 4 more cycles of paclitaxel + carboplatin. Operative time was longer in the NACT arm than in the PCS arm, but patients in the NACT arm experienced less blood loss and ascites during or after surgery, and reported fewer grade 3 or grade 4 adverse events after surgery.10
On the basis of these data, the following recommendations have been made:
- All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy to determine whether they are candidates for PCS.
- A primary clinical evaluation should include a computed tomography (CT) scan of the abdomen and pelvis to evaluate the extent of disease and the feasibility of surgical resection.
- Women with a high perioperative risk profile or low likelihood of achieving cytoreduction to
- For women who are fit for PCS, with potentially resectable disease, either NACT or PCS may be offered.
- For women with a high likelihood of achieving cytoreduction to
- For women who are fit for PCS but considered unlikely to have cytoreduction to
- Before NACT is administered, patients should have histologic confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer.
- For NACT, a platinum/taxane doublet is recommended. Alternate regimens, containing a platinum agent, may be selected based on individual patient factors.
- ICS should be performed after ≤ 4 cycles of NACT for women with a response to chemotherapy or stable disease.
- Patients with progressive disease on NACT have a poor prognosis. Options include alternative chemotherapy regimens, clinical trials, and/or discontinuation of active cancer therapy and initiation of end-of-life care. Surgery is not advised unless for palliation (e.g., relief of a bowel obstruction).
These recommendations have established a role for NACT in the treatment of patients with advanced ovarian cancer. The use of NACT has been associated with significant cost savings compared with PCS.11 It is expected that new strategies involving NACT will contribute to further improvements in the outcomes of patients with advanced ovarian, tubal, or peritoneal cancer.
1. Ferlay J, Soerjomataram, I., Ervik, M., et al, GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014, http://globocan.iarc.fr Accessed 10 August 2016, .
2. Maringe C, Walters S, Butler J, et al., Stage at diagnosis and ovarian cancer survival: evidence from the International Cancer Benchmarking Partnership, Gynecol Oncol, 2012;127:75-82.
3. du Bois A, Quinn M, Thigpen T, et al., 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004), Ann Oncol, 2005;16 Suppl 8:viii7-viii12.
4. Covens AL, A critique of surgical cytoreduction in advanced ovarian cancer, Gynecol Oncol, 2000;78:269-74.
5. Armstrong DK, Bundy B, Wenzel L, et al., Intraperitoneal cisplatin and paclitaxel in ovarian cancer, N Engl J Med, 2006;354:34-43.
6. Wright AA, Bohlke, K., Armstrong, D.K. et al, Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline, J Clin Oncol, 2016;e-pub ahead of print, doi: 10.1200/JCO.2016.68.6907 .
7. Vergote I, Trope CG, Amant F, et al., Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer, N Engl J Med, 2010;363:943-53.
8. Kehoe S, Hook J, Nankivell M, et al., Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial, Lancet, 2015;386:249-57.
9. Fagotti A, Ferrandina G, Vizzielli G, 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, Eur J Cancer, 2016;59:22-33.
10. Onda T, Yoshikawa, H., Shibata, T. 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 phase III randomized trial: JCOG0602., J Clin Oncol, 2014;32:suppl; abstr 5508.
11. Rowland MR, Lesnock JL, Farris C, et al., Cost-utility comparison of neoadjuvant chemotherapy versus primary debulking surgery for treatment of advanced-stage ovarian cancer in patients 65 years old or older, Am J Obstet Gynecol, 2015;212:763 e1-8.