Is the Easier Way Ever the Better Way?
Authors: Dennis S. Chi, Robert E. Bristow, Deborah K. Armstrong, Beth Y. Karlan
Journal: Journal of Clinical Oncology (2011)

For the past four decades, the standard management of patients with advanced ovarian cancer has been primary cytoreductive surgery followed by chemotherapy. Numerous studies have demonstrated that patientswhoareoptimallycytoreducedenjoyprolongedprogression-free and overall survival compared with those who are suboptimally debulked. Although the data in support of optimal cytoreduction are almost all retrospective, improved patient outcome with more extensive surgical debulking has been consistently observed, leading to the ideal goal of tumor cytoreduction to no macroscopic visible disease after initial diagnostic/therapeutic surgery. During the same four decades, the gynecologic oncology community has significantly improved the outcomes of patients with advanced ovarian cancer through the development of newer cytotoxic agents, improved schedules and routes of administration, and, more recently, advances in targeted therapies. Surgical improvements have paralleled the development of better medical therapies, with the evolution of the concept, principle, and proof of principle that patients left with no or minimal disease after cytoreduction have prolonged survival compared with those left with large-volume disease. Improved surgical instrumentation and supportive management (antibiotics, blood banking, and intensive care) have significantly reduced postoperative morbidity and mortality. The impact of debulking on patient survival has been shown to be equivalent whether complete debulking is attained with easily resectable disease involving the omentum and ovaries or whether it requires more extensive surgery involving the peritoneal diaphragm, rectosigmoid colon, or paraaortic lymph nodes. Furthermore, contemporary studies have demonstrated that the impact of potentially negative biologic factors such as grade and histology can be overcome by surgical debulking. Although initial tumor load and tumor biology will always have some influence on survival, the expansion of the surgical armamentarium available for cytoreductive procedures has led to an increase in the percentage of optimally debulked patients at many centers, with a commensurate improvement in chemotherapy response and progression-free and overall survival. Advocates of a less-is-more approach in this setting point to the potential of excessive morbidity associated with extensive surgery and conclude that anything more than hysterectomy, bilateral salpingooophorectomy, and omentectomy cannot be justified. It is true that surgeons not trained, capable, or willing to perform extensive surgical cytoreduction for advanced ovarian cancer should not attempt it. However, just as the gynecologic oncologist chides the general obstetrician/gynecologist for operating on a patient with a suspicious complex adnexal mass and elevated CA125 without gynecologic oncologic backup for surgical staging, gynecologic oncologists should be similarly chided for attempting advanced ovarian cancer debulking without the requisite tools for success. These procedures require the expertise of the gynecologic oncologist but may also necessitate the assistance of general surgeons, surgical oncologists, or hepatobiliary surgeons, particularly when there is extensive upper abdominal disease. It is sobering to consider that in these examples, the risk that the general obstetrician/gynecologist would encounter an ovarian cancer is less than 5%, whereas the likelihood that a gynecologic oncologist operating on a patient with advanced ovarian cancer would identify extensive upper abdominal disease is greater than 40%. Given the extended survival associated with achieving successful surgical resection to no gross residual disease in patients with advanced ovarian cancer, it is the duty of the treating clinician to give the patient the best opportunity to attain this result, irrespective of whether it falls within that surgeon’s current skill set. One must either obtain the necessary skills, through additional training or repeated multispecialty intraoperative consultation, or refer the patient to a surgeon capable of performing the necessary procedures. The question of the best timing for surgery, or what some have termed the less-is-more approach, regarding patients with advanced ovarian cancer was evaluated by the European Organization for Research and Treatment of Cancer–Gynecologic Cancer Group and the National Cancer Institute of Canada Clinical Trials Group and was recently reported by Vergote et al. In that trial, patients with stage IIIC or IV ovarian cancer were randomly assigned to primary debulking surgery (PDS) followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy (NACT) followed by interval debulking surgery. After debulking surgery, the largest residual tumor was 1 cm or smaller in diameter in 41.6% of patients in the PDS arm and in 80.6% of those in the NACT arm, with a trend toward more postoperative adverse events and mortality in the PDS arm. Progressionfree and overall survival were the same between the two arms. Complete resection of all macroscopic disease, at PDS or after NACT, was the strongest independent variable in predicting overall survival. These results were initially reported at the International Gynecologic Cancer Society meeting in Bangkok, Thailand, 2 years ago. Since JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 29 NUMBER 31 NOVEMBER 1 2011