Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era
Abstract & Commentary
Synopsis: During the platinum era, maximal cytoreductive surgery was one of the most powerful determinants of cohort survival among patients with advanced ovarian cancer.
Source: Bristow R, et al. J Clin Oncol. 2002;20: 1248-1259.
Bristow and associates identified 28 cohorts of patients with stage III or IV ovarian cancer (6885 patients) from articles in MEDLINE (1989-1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival time. When actuarial survival was estimated, cohorts with < 25% maximal cytoreduction had a mean weighted median survival time of 22.7 months, whereas cohorts with more than 75% maximal cytoreduction had a mean weighted median survival time of 33.9 months—an increase of 50%. The relationship between platinum dose-intensity and log median survival time was not statistically significant. Bristow et al concluded that during the platinum era, maximal cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian cancer. Consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival.
Comment by David M. Gershenson, MD
Since the reports of seminal studies of primary cytoreductive surgery for advanced epithelial ovarian cancer appeared in the 1970s, this procedure has been the cornerstone of treatment for this condition. These studies revealed that patients with minimal residual disease (< 1-2 cm) at the completion of primary surgery had a better survival than those with bulky residual disease. However, because there are no randomized trials comparing primary surgery with no surgery, the precise value of such an intervention has remained in question. In other words, it has been difficult, if not impossible, to distinguish the effects of the biology of the ovarian cancer from the influence of the surgical intervention. Although the present meta-analysis does not resolve this issue, it does significantly strengthen the argument that primary cytoreduction does play a major role in the overall therapeutic approach to advanced ovarian cancer. In fact, in the multivariate analysis, the percent maximal cytoreductive surgery was the most powerful independent factor associated with survival. Of course, major limitations of any meta-analysis, as pointed out by Bristow et al, include the potential for selection bias and the imprecision of data measurement. The major implication for a study such as this is the importance of maximizing a woman’s opportunity for optimal cytoreduction. Several studies have detailed the fact that women with suspected ovarian cancer should seek consultation with a gynecologic oncologist. This recommendation is based on observations that such experts are more likely to accomplish optimal cytoreductive surgery with minimal residual disease than nonexperts, thereby improving the probability of survival.
Dr Gershenson is Professor and Chairman, Department of Gynecology, M.D. Anderson Cancer Center, Houston.
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