Diagnostic Open Laparoscopy in the Management of Advanced Ovarian Cancer
Abstract & Commentary
By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D. Anderson Cancer Center, Houston. Dr. Coleman is on the speaker's bureau for GlaxoSmithKline, Bristol-Myers Squibb, and Ortho Biotech.
Synopsis: Diagnostic open laparoscopy (DOL) could be considered a valid diagnostic tool in evaluating the extent of disease in advanced ovarian cancer (AOC). These data suggest that the use of DOL leads to a decrease in the rate of primary cytoreductive surgery for AOC; on the other hand, a higher optimal debulking rate (no residual tumor) at primary surgery is achieved.
Source: Angioli R, et al. Diagnostic open laparoscopy in the management of advanced ovarian cancer. Gynecol Oncol. 2006;100:455-461.
Optimal surgical cytoreduction is a recognized staple of initial advanced ovarian cancer care. However, within the spectrum of patients who undergo this surgery are those in whom complete resection is either impossible or unwarranted in the face of certain unacceptable morbidity. Identifying these patients before laparotomy is generally relegated to preoperative imaging and biomarkers—with limited success. Angioli and colleagues report their experience with laparoscopic evaluation of intraperitoneal disease to make this decision. Over the 50-month accrual period, 87 patients were consecutively evaluated. All were to have suspected metastatic disease (stage IIIC-IV) and were evaluated for the outcome of no post-operative tumor residual.
Those deemed unresectable were treated with neoadjuvant standard combination chemotherapy. Those in this latter group who did not progress during 3 cycles of chemotherapy were taken to cytoreduction. The primary end point of this observational study was to quantify their success in predicting cytoreduction in these patients. Overall, 53 (61%) were deemed appropriate surgical candidates at laparoscopy, in whom 51 (96%) were cytoreduced to no visible residual. Among the 34 in whom surgery was deferred, 25 (74%) were ultimately operated upon; 20 (80%) were similarly optimal at interval cytoreduction. Overall survival was best in those in whom surgery could be done initially; those undergoing surgery after chemotherapy had a significantly worse survival but was substantially better than those in whom chemoresistance was documented. Similar survival outcomes were observed for those patients who completed both surgery and chemotherapy, regardless of the sequence. Complication rates were also low in both surgical cohorts. The authors concluded that the open laparoscopy is a valuable tool to evaluate the extent of disease at presentation and may select patients in whom complete cytoreduction can be achieved at initial surgery.
Commentary
The standard clinical approach to newly diagnosed ovarian cancer is primary surgical cytoreduction followed by combination chemotherapy for patients with high-risk or advanced-stage disease. Several studies have suggested that better cytoreduction is important to response to chemotherapy and overall survival.1 However, approximately 50% of patients who undergo attempt at cytoreduction are left with macroscopic disease—in some cases bulky macroscopic disease, in whom poorer response to treatment (and overall survival) is observed. Since previously unexposed ovarian cancer is largely sensitive to chemotherapy, an alternative treatment approach for patients with bulky intraperitoneal disease is to administer chemotherapy ahead of surgery. This not only identifies patients with chemoresistant disease (by progression on therapy) but also can substantially reduce the volume of tumor to be resected, thereby increasing the rate of optimal cytoreduction and reducing the morbidity of surgery. To date, there have been 3 randomized trials that have been performed to evaluate the benefit of interval cytoreduction in this manner.2-4 The 3 studies span the decades of platinum and, most recently taxane use in the primary management of ovarian cancer. Each of these trials identified patients largely through a failed (suboptimal) cytoreduction attempt and randomized their care to either standard chemotherapy or interval surgery after an abbreviated treatment course. Two of the trials, including one utilizing a regimen considered a current standard of care combination did not identify a benefit by interval (or in this case, secondary) surgical attempt. One trial, using a non-taxane combination, did suggest improved progression-free and overall survival for those undergoing an interval surgery. However, a significant fraction of women enrolled in this trial did not have an aggressive first attempt and essentially underwent a neoadjuvant program. A randomized trial of each surgical approach (neoadjuvant, interval cytoreduction and standard cytoreduction) is underway.
The current trial is unique in that the bar set for cytoreduction is high (no visible disease). Althoughvarious definitions of "optimal" have been used over the years, none have specifically used this degree of resection as a primary goal. As listed in the authors procedures, the extent of radical resection in order to achieve this outcome is greater than that generally reported in studies conducted in the multi-institutional setting. Nonetheless, it is a desired result if one accepts the relationship between tumor volume residual and survival. The current study demonstrates that laparoscopy (better than clinical or radiographic measures) may be helpful in selecting patients in whom a radical approach is warranted. There are several unknowns that still require elucidation: what percent of patients deemed as poor candidates for cytoreduction could indeed by cytoreduced? What are the implications on survival for purposefully waiting to cytoreduce in these patients? What is the impact on survival for port site metastases seen in the delayed surgical cohort? Can a lower cytoreduction bar achieve the same result? Finally, is this strategy reproducible in the multi-institutional setting? These questions will need to be formally addressed before such an approach can be globally recommended. However, the bar for complete resection should be embraced as we approach primary surgical management.
References
1. Bristow RE, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20(5):1248-59.
2. Redman CW, et al. Intervention debulking surgery in advanced epithelial ovarian cancer. Br J Obstet Gynaecol. 1994;101:142-146.
3. van der Burg ME, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. 1995;332:629-634.
4. Rose PG, et al. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004;351:2489-2497.
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