Intraperitoneal Radioactive Phosphorus (32P) vs Observation After Negative Second-Look Laparotomy for Stage III Ovarian Carcinoma

Abstract & Commentary

Synopsis: Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative second-look surgery.

Source: Varia MA, et al. J Clin Oncol. 2003;21: 2849-2855.

In a gynecologic oncology group study, Varia and colleagues reported that 202 patients with negative second-look surgery were randomized to either intraperitoneal chromic phosphate or no further therapy. With a median follow-up of 63 months in living patients, 68 patients in the treatment group (65%) and 63 patients in the observation group (64%) developed tumor recurrence. The relative risk of recurrence was 0.90 (90% confidence interval [CI], 0.68-1.19). The 5-year relapse-free survival rate was 42% and 36% for the treatment and observation groups, respectively; the difference was not statistically significant. There was no statistically significant difference in overall survival. The relative risk of death was 0.85. Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with 8 in each group. Varia et al concluded that intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after negative second-look surgery. Despite complete pathologic remission at second-look after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative second-look surgery. They further concluded that these findings indicate a need for more effective initial therapy and further studies of consolidation therapy.

Comment by David M. Gershenson, MD

One of the greatest challenges facing oncologists is to improve the cure rate of patients with advanced epithelial ovarian cancer. Currently, only about 20% of patients with stage III disease and less than 5% of those with stage IV are cured. Although a very high percentage of patients (60-70%) are clinically disease-free following standard therapy consisting of primary cytoreductive surgery followed by combination chemotherapy with paclitaxel and carboplatin, most of these patients eventually relapse and die of their cancers. Even with negative findings on second-look surgery performed to assess disease status, up to 50% of patients will have false-negative findings and succumb to their disease. In other words, we are able to achieve minimal, microscopic, or surgically undetectable tumor burden in most patients but unable to completely eradicate the malignancy with our current approach. Several strategies have been considered or tested in this most favorable group of patients—those with negative second-look surgery findings—in an attempt to reduce the disappointing relapse rate. Whole abdominal radiotherapy has been investigated, and essentially all studies reveal no improvement in disease-free survival plus a disturbingly high rate of intestinal injury secondary to radiation. Consolidation chemotherapy has thus far been found to prolong progression-free survival but has not been demonstrated to improve overall survival. This randomized trial tests intraperitoneal chromic phosphate—a treatment used for decades in various settings for ovarian cancer—but without evidence of a favorable effect on either relapse-free survival or overall survival. Therefore, the search continues for effective consolidation therapy to achieve a superior outcome. Although second-look surgery has essentially disappeared from the scene, the surrogate group for future trials will be patients who are clinically disease-free at the conclusion of primary treatment.

Dr. Gershenson is Professor and Chairman Department of Gynecology M.D. Anderson Cancer Center, Houston.