Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial -- Trimbos et al., 10.1093/jnci/djq149 -- JNCI Journal of the National Cancer Institute

Brief Communication

Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial

Baptist Trimbos, Petra Timmers, Sergio Pecorelli, Corneel Coens, Koen Ven, Maria van der Burg, Antonio Casado

Affiliations of authors: Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands (BT); Medisch Centrum Rijnmond Zuid, Rotterdam, the Netherlands (PT); EORTC Data Centre, Brussels, Belgium (PT, CC, KV, AC); Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy (SP); Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands (MvdB); Department of Medical Oncology, Hospital Universitario San Carlos, Madrid, Spain (AC)

Correspondence to: Baptist Trimbos, MD, PhD, Department of Gynecology, Leiden University Medical Center, POB 9600, 2300RC Leiden, the Netherlands (e-mail: j.b.m.z.trimbos@lumc.nl).

A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer follow-up with more events. In the ACTION trial, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation (no further treatment). The original analysis found that adjuvant chemotherapy improved recurrence-free survival but not overall survival and found in a subgroup analysis that completeness of surgical staging was an independent prognostic factor, with better recurrence-free and overall survival among those with complete (optimal) surgical staging. After a median follow-up of 10.1 years, we analyzed the more mature data from the ACTION trial and found support for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P = .05). More cancer-specific deaths were observed among nonoptimally staged patients (40 [27%] of the 147 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) than among optimally staged patients (seven [9%] of the 75 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) (two-sided ² test for heterogeneity, P = .06). Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging.

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CONTEXT AND CAVEATS Prior knowledge In the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation. After a median follow-up of 5.5 years, adjuvant chemotherapy was associated with improved recurrence-free survival but not overall survival. In a subgroup analysis, better recurrence-free and overall survival were observed among those with nonoptimal surgical staging than those with optimal staging. Study design Long-term analysis of data from this trial after a median of 10.1 years of follow-up. Contribution The long-term analysis supported most conclusions from the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy. More cancer-specific deaths were observed among nonoptimally staged patients than among optimally staged patients. Implications Completeness of surgical staging among patients with early ovarian cancer was statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy was restricted to patients with nonoptimal surgical staging. Limitations The trial was not designed to compare different surgical staging procedures. Patients could not be prospectively stratified by surgical staging category. The study had a limited sample size. Quality of life was not studied. From the Editors