LOS ANGELES – Surgically exploring the retroperitoneum for disease may benefit some patients undergoing primary debulking of advanced ovarian cancer, a study reported at the annual meeting of the Society of Gynecologic Oncology has shown.
Investigators analyzed data from Gynecologic Oncology Group (GOG) trial 182, focusing on the 1,876 women who had stage IIIc epithelial ovarian cancer on the basis of intraperitoneal tumor size and who underwent optimal debulking.
Overall, one-third had a retroperitoneal exploration, defined in the study as removal of at least one pelvic or para-aortic lymph node.
Patients who had this procedure were 15% less likely to experience progression or death and 15% less likely to die after other factors were considered, reported lead investigator Dr. Bunja Rungruang, a gynecologic oncologist with Georgia Regents University in Augusta.
In stratified analyses, benefit was seen in the subgroup with minimal gross residual disease but not in the subgroup with microscopic residual disease.
"In this large multi-institutional trial, there is evidence that retroperitoneal exploration at the time of primary debulking surgery of patients with intraperitoneal stage IIIc epithelial ovarian cancer may provide survival benefit," she commented.
"Surgical effort and tumor biology interact to affect patient outcomes," Dr. Rungruang noted. "Retroperitoneal exploration may be a proxy for more thorough surgical effort in these patients, rather than tumor biology alone driving outcomes. Surgeon discretion is a potential factor here as well; it is conceivable that the surgeon’s impression or information about prognosis influences the retroperitoneal exploration decision, based on unmeasured indicators of patient disease burden or vitality.
"Given the small but significant survival differences and the large sample size of this study, it is possible that these survival advantages are to some degree indicative of unmeasured factors or the accuracy of the surgeon’s impression, and not completely about the act of pathologic exploration," she said.
One attendee noted that analyses have suggested that patients who do not have a retroperitoneal exploration fare even more poorly than those who have the procedure and are found to have positive lymph nodes.
"I am concerned that that is because the surgeon thought the prognosis was so bad that they didn’t bother. I don’t know whether you have a sense of whether that conclusion looked appropriate for your analysis of all the tumor burden in that patient," Dr. Rungruang said.
"For some of the patients, it seemed to be a surgeon preference that they didn’t sample the nodes because they felt that the patient was already stage IIIc and called them microscopic optimally debulked, or microscopic optimally debulked without assessing the lymph nodes. Other patients had a much larger surgery, a higher complexity of procedures, and still had a lymph node assessment on top of it. What I can tell from reading the actual operative notes is a lot of [the approach] is based on surgeon preference."
In discussing the lack of additional benefit for exploration in women with microscopic residual disease, Dr. Rungruang explained that "if you have microscopic residual disease, that seems like the best you can do for those patients. I think in the macroscopic residual patients, you see the difference because it is perhaps a proxy for just a more thorough surgical assessment in these patients. Plus, macroscopic residual disease is such a wide spectrum, you can be anywhere from one site of residual disease to miliary disease spread throughout, and that heterogeneity within that residual disease group also accounts for that difference."
Patients enrolled in GOG 182 had advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and underwent primary debulking to optimal residual disease (less than 1 cm), followed by randomization to a variety of platinum- and paclitaxel-based adjuvant chemotherapy regimens.
The investigators restricted analyses to the subset whose disease was stage IIIc on the basis of an intraperitoneal tumor measuring at least 2 cm. Overall, 37% of this subset had a retroperitoneal exploration.
The patients undergoing this additional procedure had better median progression-free survival (18.5 vs. 16.0 months, P less than .0001) and overall survival (53.3 vs. 42.8 months, P less than .0001), reported Dr. Rungruang.
When patients were stratified, retroperitoneal exploration was beneficial in those with minimal gross residual disease in terms of both progression-free survival (16.8 vs. 15.1 months, P = .01) and overall survival (44.9 vs. 40.5 months, P = .008). But there was no such benefit in patients who had microscopic residual disease.
In a multivariate analysis, retroperitoneal exploration independently predicted better progression-free survival (hazard ratio, 0.85; P = .004) and overall survival (HR, 0.85; P = .009).