Advanced Stage Epithelial Ovarian Cancer Principles of Surgical Cytoreduction

Advanced epithelial ovarian cancer typically presents with widely disseminated intraabdominal disease. The standard treatment of advanced epithelial ovarian cancer (EOC) includes primary cytoreductive or debulking surgery followed by adjuvant systemic chemotherapy. The goal of primary surgery for advanced epithelial ovarian cancer is to accurately establish a diagnosis and leave little or no residual disease. There are several potential benefits to the surgical removal of bulky tumor masses1,2:

■ Removal of resistant clones of tumor cells decreases the likelihood of drug resistance according to the Goldie-Coldman hypothesis.

■ Removal of large poorly vascularized and hypoxic tumors enhances chemotherapy delivery.

■ The higher growth fraction in smaller, better-vascularized lesions increases cytotoxicity of chemotherapy.

Figure 7-1. Simple linear regression analysis: de-logged median survival time plotted against percent maximal cytoreductive surgery. Light shaded area, maximal cytoreductive surgery less than 25% and more than 75%; dark shaded area, corresponding range of median survival times. (From Bristow RE, Tomacruz RS, Armstrong DK, et al: Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248-1259, 2002, Figure 2.)

■ Smaller lesions require fewer cycles of chemotherapy, reducing development of drug resistance.

■ Removal of bulk disease rapidly improves symptoms of advanced EOC resulting in improved quality of life, appetite, and immune status.

With regard to surgical debulking, there are no randomized controlled trials supporting its initial use. Nearly every retrospective and prospective study since Griffiths' seminal study in 1975 has demonstrated an inverse relationship between residual tumor diameter and patient survival,3 including a recent meta-analysis by Bristow and colleagues,4 which identified 6885 patients from previous publications. They found that each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival (Fig. 7-1).

The definition of "optimal cytoreduction" continues to evolve. Since 1986, the Gynecologic Oncology Group (GOG) has defined optimal cytoreduction as leaving residual disease less than 1 cm in maximum tumor diameter based on their retrospective analysis and long-term follow-up of 726 patients with advanced epithelial ovarian cancer enrolled in two of their early adjuvant therapy trials.5 Thus, defined optimal cytoreduction can be achieved in 75% or more of women explored by gynecologic oncologists.6 The GOG has since performed two retrospective analyses of large chemotherapy trials, which again asserted the survival advantage of optimal debulking with residual tumor nodules less than 1 cm. They also suggested that cytoreduction that did not achieve optimal status or at least nodules less than 2 cm appears to have little benefit on survival7,8 (Fig. 7-2).

Several studies have also shown that patients deriving the most survival benefit are those in whom tumors are primarily reduced to microscopic levels. For 348 patients from GOG 52 with stage III ovarian cancer cytoreduced to less than 1 cm of residual disease, Hoskins and colleagues7 reported on the effect of diameter of the largest residual disease on survival. Five-year survival rates were greater for patients with microscopic residual disease (60%) even when compared with macroscopic disease less than 1 cm (35%). Chi and associates9 recently analyzed survival rates at

Months from entry into study

Size of residual




<2.0 cm




















Figure 7-2. Survival of women with suboptimal ovarian cancer entered on GOG protocol 97, according to maximal diameter of residual disease after debulking surgery. (From Hoskins WJ, McGuire WP, Brady MF, et al: The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol 170:974-979, 1994; discussion 979-980, Figure 3.)

specific residual disease diameters to determine the optimal goal of primary cytore-duction for bulky stage IIIC disease. In this retrospective analysis of 465 patients, patients with no gross disease had longer overall median survival compared with patients with macroscopic residual disease of 1 to 5 mm (106 months versus 66 months)9 (Fig. 7-3). Finally, the results of the two latest chemotherapy trials conducted by GOG seem to suggest a survival advantage for patients with microscopic residual disease when compared with those with macroscopic optimal disease.10,11 The number of residual nodules may also influence prognosis. In their retrospective analysis of 78 patients left with residual disease less than 5 mm in maximum diameter, Farias-Eisner and colleagues12 demonstrated a significant survival disadvantage for patients with extensive carcinomatosis. These studies provide compelling data supporting the benefit of macroscopic disease elimination when possible (Fig. 7-4).

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