Neoadjuvant Chemotherapy or Upfront Surgery in Advanced Ovarian Cancer?

A pooled analysis of two randomized trials found that neoadjuvant chemotherapy and upfront debulking surgery yield similar outcomes in patients with advanced tubo-ovarian cancer, though patients with stage IV disease fare better with neoadjuvant therapy.

For several decades, upfront debulking surgery has been considered standard for women presenting with advanced cancer of the ovary, fallopian tube, or peritoneum. More recently, neoadjuvant chemotherapy followed by cytoreductive surgery has gained momentum. “However, the selection of women with advanced ovarian cancer for neoadjuvant chemotherapy or upfront debulking surgery remains controversial,” wrote study authors led by Ignace Vergote, MD, of University Hospitals Leuven in Belgium.

The new study examining these two treatment options was a pooled analysis of the randomized European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial and the CHORUS trial. It included a total of 1,220 women with tubo-ovarian cancer; of those, 612 were randomized to undergo upfront debulking surgery, and 608 received neoadjuvant chemotherapy. The results were published in Lancet Oncology.

In the full cohort, the median age was 63 years, and the median size of the largest metastatic tumor at diagnosis was 8 cm. A total of 55 women (5%) had stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 patients (19%) had stage IV disease; staging information was missing in 9% of the cohort.

The survival outcomes were similar with the two treatment approaches. The median overall survival (OS) was 27.6 months with neoadjuvant chemotherapy, compared with 26.9 months with upfront debulking surgery, for a hazard ratio (HR) of 0.97 (95% CI, 0.86–1.09; P = .586). The progression-free survival for the two therapies was 11.6 months and 11.1 months, respectively, for an HR of 0.98 (95% CI, 0.87–1.10; P = .688).

The results differed by disease stage, however. In patients with stage IIIC disease, the median OS was 30.8 months with neoadjuvant chemotherapy and 28.4 months with upfront surgery, for an HR of 1.04 (95% CI, 0.90–1.21; P = .569). In stage IV disease, though, the median OS with neoadjuvant chemotherapy was 24.3 months, compared with 21.2 months with upfront surgery, for an HR of 0.76 (95% CI, 0.58–1.00; P = .048). Progression-free survival was also better, with a median of 10.6 months compared with 9.7 months, for an HR of 0.77 (95% CI, 0.59–1.00; P = .049).

“Our data suggest that neoadjuvant chemotherapy should be the standard of care for most patients with FIGO stage IV tubo-ovarian cancer, and primary surgery should only be undertaken in these stage IV patients in exceptional circumstances with easily resectable disease,” the authors wrote.

In an accompanying editorial, Anna Fagotti, MD, of the Fondazione Policlinico Universitario Agostino Gemelli, and Giovanni Scambia, MD, of the Catholic University of the Sacred Heart, both in Rome, wrote that these results are “the most convincing findings to date showing that two different strategies have the same efficacy” in this setting.

They did note the study’s limitations, including a low proportion of patients with no macroscopic residual disease with upfront debulking surgery, as well as inclusion of women with earlier-stage disease. “Nevertheless, in the context of current clinical practice-where the balance between the extent of surgery and patient’s performance status is delicate, and the choice of one treatment over another can be questionable-data from this pooled analysis become more relevant.” Fagotti and Scambia wrote that new and ongoing trials may soon shed more light on the situation, including in combinations of novel agents and in timing of surgery.