What Is the Ideal Initial Treatment for Advanced Ovarian Cancer?

Among women with ovarian, fallopian tube or peritoneal cancers, more than % 70 receive, at advanced stages (3 and 4), a cancer diagnosis , and as in many cancers, prognosis (disease course) is poorer at an advanced stage (hereafter these cancers will be called tubo-ovarian cancer). First, Dr. Thomas Griffiths, in 1975, reported that even in advanced ovarian cancer, surgically removing all possible tumor sitesincreased survival rates, after which debulking became an essential and fundamental surgical treatment strategy in clinical practice.

However, to date, prospective randomized controlled clinical trialshave not shown that starting treatment with debulking surgery improves disease outcomes in advanced tubo-ovarian cancer.

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Note: Debulking surgery, meaning removing all visible tumors when the abdomen is surgically opened, is also called cytoreductive surgery.

An alternative to starting with debulking surgery is preoperative neoadjuvant (tumor-shrinking) chemotherapy. In 2010, the European Organisation for Research and Treatment of Cancer (EORTC) published the first findings of EORTC 55971, comparing neoadjuvant chemotherapy with immediate surgery. In women with stage IIIC or 4 tubo-ovarian cancer, both approaches produced similar overall and progression-free survival. However, adverse effects during and after surgery were lower with neoadjuvant chemotherapy. These findings were later confirmed in the randomized Medical Research Council (MRC) Chemotherapy or Upfront Surgery (CHORUS) study, leading to acceptance of neoadjuvant chemotherapy. Subsequently, in women with stage IIIC and 4 tubo-ovarian cancer, initial tumor-shrinking chemotherapy followed by debulking surgery became widespread as an alternative to starting directly with debulking surgery. However, whether women with advanced ovarian cancer should start with neoadjuvant chemotherapy or immediate surgery remains debated. To identify subgroups who may benefit from neoadjuvant chemotherapy, Ignace Vergote and colleagues analyzed long-term results of EORTC 55971 and CHORUS; on 6 November 2018, The LANCET Oncologypublished the analysis. It used "individual patient data", meaning direct patient data rather than study-level results.

Details of the Study

• The analysis included, from EORTC, 670 women and, from CHORUS, 550, totaling 1220.
• Among patients, 612 underwent immediate debulking surgery followed by at least 6 cycles of platinum -based adjuvant (protective) chemotherapy.
• The other 608 first received 3 cycles of neoadjuvant platinum-based chemotherapy, then underwent debulking surgery, followed by another 3 cycles of platinum-based chemotherapy.
• EORTC enrolled only patients with stages IIIC and 4, while CHORUS also included stages IIIA and IIIB.
• The median diameter of the largest metastatic tumor was 8 cm.
• Of patients, 55 (%5) had stage II - IIIB tubo-ovarian cancer, 831 (% 68) had stage IIIC disease, and 230 (% 19) had stage 4 cancer. Stage information was unavailable for 104 (% 9) patients.

Survival Results

• For all patients, median follow-up was 7.6 years (9.2 years in EORTC, 5.9 years in CHORUS).
• For all patients, median overall survival was 27.6 in the neoadjuvant chemotherapy group and 26.9 months in the debulking surgery group (not a statistically significant difference).
• Median progression-free survival was 11.6 months versus 11.1 months.
• Median overall survival was 30.2 months in EORTC and 23.6 months in CHORUS.
• In patients with stage 4 tubo-ovarian cancer, neoadjuvant chemotherapy produced significantly better median overall survival (24.3 versus 21.2 months) and progression-free survival (10.6 versus 9.7 months).

Conclusion

Although starting treatment with neoadjuvant chemotherapy or immediate surgery produces similar outcomes in advanced ovarian, fallopian tube or peritoneal cancers, patients with stage 4 cancer appear to benefit more from starting with neoadjuvant chemotherapy. This analysis of long-term follow-up clearly demonstrated the importance of neoadjuvant chemotherapy, particularly in stage IIIC and 4 ovarian cancer patients with poor general condition or a high tumor burden at diagnosis.

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