Outcome of Cytoreductive Surgery in Primary Ovarian Cancer: What is "Optimal"?
Abstract & Commentary
By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D., Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman is on the speaker's bureau for GlaxoSmithKline, Bristol-Myers Squibb, and Ortho Biotech.
Synopsis: Surgery to obtain complete resection of disease is feasible, associated with superior survival, and should be the goal of cytoreductive surgery.
Source: Chi DS, et al. What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol. 2006;103:559-564.
The resection of tumor nodules (or cytoreduction) before primary chemotherapy has been linked closely with survival in patients with advanced epithelial ovarian cancer. Chi and colleagues set out to evaluate the merits of cytoreduction completeness in a homogeneous cohort of ovarian cancer patients with bulky metastatic disease. The goal of this analysis was to determine if patients considered "optimally cytoreducted" (post-operative residual disease of 1 cm or less) had even further improved survival based on the quantification of residual disease 1 cm or less. They established three categories: no visible residual, less than 0.5 cm residual, and 0.5 to 1.0 cm residual. Patients were carefully screened to include only those with stage IIIC disease (2 cm or more upper abdominal disease) and epithelial, non-mucinous invasive histology. All patients had received platinum-based adjuvant chemotherapy following surgery and were followed a median 38 months.
Overall, the authors demonstrated that there was a clear distinction between no gross residual disease (median survival, 106 months), 0.5 cm or less residual (median survival, 66 months), and 0.6-1.0 cm residual (median survival, 48 months). Patients with 1-2 cm residual and greater than 2 cm residual had similar median survivorship (33 and 34 months, respectively). By multivariate analysis, age, ascites, and residual disease were independently associated with overall survival. Within this last category, no gross residual, 1 cm or less residual and more than 1 cm residual were significantly discriminating to overall survival (HR, 2.07 and 3.70, respectively). The authors conclude that surgery to obtain complete resection of disease is feasible, associated with superior survival, and should be the goal of cytoreductive surgery.
Commentary
The mantra of surgery as it relates to ovarian cancer debulking is predominately "more is better." Since the sentinel paper in 1975 by Griffiths demonstrating differential improved survival in patients with less volume of residual tumor following surgery, operative goals for newly diagnosed advanced-stage epithelial ovarian cancer patients has been to achieve the greatest degree of tumor reduction as possible.
Historically, few patients with grossly apparent and bulky upper abdominal disease were subjected to procedures that could render them disease-free. However, small volumes of residual disease (generally less than 1 cm) did allow a conventional distinction of "optimal," which has been used to triage patients into different clinical studies of adjuvant chemotherapy. However, in recent times, more aggressive upper abdominal and pelvic surgical procedures are being performed enabling more patients to be rendered disease-free, which may affect long-term survival even more. This is the focus of the report by Chi and colleagues, who have challenged the definition of what should be termed an "optimal" surgical outcome. Intuitively, that which makes cytoreduction of merit in ovarian cancer is likely amplified if no visible tumor is remaining after surgery. Cytoreduction and chemotherapy are inexorably linked — however, data to support the benefit of more extensive cytoreduction in the "optimal" patient are confusing and sparse.
This report helps to better define the potential virtues of aggressive surgery in patients with bulky intra-abdominal disease. Despite the obvious weaknesses of a retrospective report, the authors carefully selected only those patients with preoperative bulky upper abdominal disease. This helped to distinguish a potential bias of differential tumor biology based on disease extent at presentation. In addition, while complete resection may not be possible (in this series only 16% were "no visible residual") less than 1 cm and less than 0.5 cm residual were additionally beneficial, arguing for a continuous benefit in this category by residual volume. Clearly, a determination of what constitutes 0.4 mm or 0.5 mm residual is difficult and a source of inaccuracy in this kind of study. Additional considerations in understanding this surgical benefit but lacking in the report are the effects of taxane-based chemotherapy and the impact of intraperitoneal primary chemotherapy as well as second-look surgery. It could additionally be argued that progression-free survival may be a better indicator of the "one-two punch" of aggressive surgery and adjuvant chemotherapy. Prospective studies are truly needed.
References
- Goff BA, et al. Ovarian cancer: patterns of surgical care across the United States. Gynecol Oncol. 2006;103:383-390.
- Eisenhauer EL, et al. The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages IIIC-IV epithelial ovarian cancer. Gynecol Oncol. 2006;103:1083-1090.
- Bristow RE, et al. Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: A meta-analysis. Gynecol Oncol. 2006;103:1070-1076.
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