Summer 2008

Society for Gynecologic Oncologists “Fight Night”

Peter Schwartz, MD

Conventional Radical Surgery vs. Neoadjuvant Chemotherapy as the First Step in the Management of Epithelial Ovarian Cancer

The conventional treatment of advanced stage epithelial ovarian cancer is to remove virtually all visible cancer at the initial surgery and follow that treatment with platinum–based combination chemotherapy. On March 10, 2008, Dr. Peter Schwartz debated Dr. Dennis Chi at the first–ever Society of Gynecologic Oncologists “Fight Night” at the Annual Meeting of the Society of Gynecologic Oncologists in Tampa, Florida. Dr. Chi, a gynecologic oncologist practicing at Memorial–Sloan Kettering Cancer Center (MSKCC), took the position that aggressive cytoreduction should be the first step in treatment. Dr. Schwartz advocated neoadjuvant chemotherapy for advanced stage disease, an approach that has been used at Yale in selected patients since 1979.

The debaters stood in a boxing ring and were introduced by a Don King look–alike. Two “ringside commentators” sat behind the debaters. Each “round” included the debater’s response to a question (90 seconds) and a rebuttal (30 seconds). Following each round, the “ringside commentators” used colorful language and slides to describe their interpretations of each debater’s performance. Both debaters were strongly supported—or scorned—by their “entourages” with cheers and jeers!

Photo credit: Nationwide Photographers, Martin Allred

Dr. Chi cited reports from MSKCC showing that the first step in the management of ovarian cancer should be aggressive cytoreductive surgery. He emphasized that he was able to “optimally cytoreduce” 70% of the patients cared for at his institution to ≤1 cm residual disease. Dr. Chi, who is a strong advocate for thoracoscopy as the first step in the evaluation of ovarian cancer patients with malignant pleural effusions, pointed out that for 12 of 21 patients who underwent thoracoscopy, 11 of the 12 were then able to undergo optimal cytoreductive surgery to ≤1 cm residual disease.

Dr. Schwartz took the position that the current treatment of ovarian cancer is no different than it was in 1974 when Griffiths reported that those patients who had no residual disease following surgery had a mean survival of 39 months. The mean survival for those with ‹0.5 cm was 28 months; those with ‹1.5 cm survived for 18 months, and those with ›1.5 cm residual had an 11–month mean survival. Dr. Schwartz cited a recent GOG study of 1895 Stage III patients, the largest Stage III study ever published, in which all the patients received cisplatin and paclitaxel for their initial treatment. The maximum survival benefit accrued to the 23% who had no visible residual disease. There was a dramatic difference in survival between no residual disease and residual disease of ≤1 cm or ›1 cm. However, the progression–free survival for patients who had ≤1 cm, so–called “optimal cytoreduction,” was only 2.7 months better and the overall survival for patients with residual disease ‹1 cm was a modest 7 months better than for patients with residual disease ›1 cm.

Dr. Schwartz then cited a second GOG study published this year reporting the largest number of Stage IV patients, all treated in a consistent fashion using cisplatin and paclitaxel following cytoreductive surgery. The major beneficiaries of aggressive surgical cytoreduction were the 8% who had no visible residual disease. Their progression–free and overall survival was 20.1 and 64.1 months, respectively. The progression–free and overall survival for those with ≤1 cm visible residual disease was no different than for those who had 1.1–5.0 cm of residual disease. Only patients who had >5 cm residual did worse. The progression–free and overall survival for 0.1–1.0 cm and for 1.1–5 cm residual disease was 13.0 and 28.7 months and 13.0 and 31 months, respectively.

Dr. Schwartz then challenged Dr. Chi on his data as only 22% of the patients on whom Dr. Chi operated for advanced stage ovarian cancer had no visible residual disease. The same data, 22% no visible residual disease, has recently been published by others who claim a 92% “optimum” surgical cytoreduction. In a recent study from the Mayo Clinic, only 6% of Stage IV disease patients were left with no visible residual disease. Further, Dr. Schwartz challenged Dr. Chi regarding Dr. Chi’s data on thoracoscopy. Dr. Schwartz acknowledged that 11 of 12 Stage IV ovarian cancer patients based on malignant pleural effusions who underwent thoracoscopy were optimally cytoreduced to ≤1 cm following thoracoscopic surgery. However, Dr. Schwartz pointed out that 6 of the 9 remaining patients, who were placed on neoadjuvant chemotherapy by Dr. Chi because their disease was too extensive in the chest and abdomen to undergo primary cytoreductive surgery, had no residual disease. The remaining 3 had ≤1 cm residual disease at surgery following neoadjuvant chemotherapy. Thus, for Stage IV patients in Dr. Chi’s series in terms of no residual disease, he was significantly more likely to accomplish that goal surgically if he administered neoadjuvant chemotherapy first.

Dr. Schwartz then presented Yale data in which patients with advanced stage ovarian cancer who appeared on their CT scans to be non–surgically cytoreducible or had Stage IV disease received neoadjuvant chemotherapy followed by aggressive cytoreductive surgery. Their survival for Stage III disease was exactly the same as the survival of patients who underwent aggressive cytoreductive surgery first. Approximately 75% of the patients who undergo surgical cytoreduction first at Yale are optimally cytoreduced to 1 cm or less; 33% of all patients are cytoreduced to no gross disease. However, when we looked at the survival for women treated with neoadjuvant chemotherapy, while they were exactly the same for Stage IIIC disease treated conventionally, they were statistically better for Stage IV disease, a finding that has now been reported by others. Patients at Yale who underwent surgical cytoreduction following neoadjuvant chemotherapy were subjectively better prepared for the surgery and the surgery was statistically shorter, associated with significantly less blood loss, shorter SICU stays and shorter hospitalizations compared to conventionally treated patients at Yale.

Using an electronic voting system, the audience of approximately 1000 people voted the debate in favor of Dr. Schwartz. Dr. Schwartz has been given a championship belt for winning the “fight” and is now referred to by colleagues as “champ.”