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Importance of Surgical Aggressiveness in Advanced Ovarian Cancer

Department of Obstetrics and Gynecology, Mayo Clinic and Foundation, Rochester, MN

To the Editor:

Drs Crawford et al recently reported a subanalysis of the Scottish Randomized Trial in Ovarian Cancer ¹ to examine surgical effort and progression-free survival (PFS).² We applaud the attempt to quantify surgical outcomes in ovarian cancer and raise awareness for the surgical management of ovarian cancer. However, we were surprised by some of the decisions made in analyzing the data and have several questions for the Crawford et al.

Detailed surgical data were available from only 889 of the total 1,077 patients randomly assigned (17% not available). Were these patients uniformly distributed between the United Kingdom versus non-United Kingdom and equally across stage?

Patients with stage IC, II, and IIIA/B were included. Conclusions on more advanced ovarian cancer are not justified if patients with earlier stages were included. It is well established that PFS and overall survival for patients with stage IC, II, and IIIA and IIIB is markedly improved relative to IIIC/IV patients. In addition, the former group is the most likely have no residual disease (RD) with moderate surgical effort. This likely explains the divergence in outcomes for less advanced disease. A more homogeneous population for analysis would have been only including stage IIIC and IV patients. Was this analysis done?

Why was 2 cm chosen to define optimal RD? Patients with RD between 1 cm and 2 cm have a worse prognosis compared with patients with RD between 0 cm and 1 cm. To determine optimal debulking by this more rigorous standard, what percentage of patients had RD < 1 cm? Similarly, considering that patients with stage IC and II were included in the study, the overall rate of optimal debulking (< 2 cm) appears to be low. What was the actual rate of optimal debulking, and no gross residual confined to just stage IIIC and IV patients in the two countries of origin?

Patients were stratified according to presurgical clinical and biologic prognostic factors and the following were used in Cox models: stage, histology, omental cake present, and presurgery cancer antigen-125 (Table 4 reported). Why were variables such as presence of carcinomatosis, diaphragm involvement, and mesentery involvement not used since these data were collected and most accurately define extent of initial volume of disease? These variables more likely affect PFS, and can be more easily used as surrogates of biologically aggressive disease.

RD is not a surrogate of aggressive surgery. Surgical procedures employed and operative times are more accurate surrogates. For example, patients with a large omental cake and also other nodules < 2 cm spread throughout the abdomen can be reduced to < 2 cm with simple omentectomy. However, these would incorrectly be considered as aggressive surgery in the Crawford et al's analysis. How many patients underwent aggressive procedures (peritoneal stripping, removal of diaphragm disease, bowel resections, or splenectomy)? Patients with similar presurgical extent of disease could then be compared between aggressive and nonaggressive procedures to truly determine the value of surgery versus intrinsic tumor biology. Absent this type of analysis, we disagree that the conclusion that aggressive surgery is less helpful in advanced cases. In contrast, we and others have reported that use of radical procedures in advanced stage disease can negate the impact of extent of initial volume of disease in ovarian cancer patients stratified by RD.^3-4

We do not feel the conclusion that lymphadenectomy in patients with no gross RD was the reason for improved survival. To examine this, in addition to confining the analysis to those patients with no RD, Crawford et al needs to stratify by stage and further specifically eliminate those patients assigned to stage IIIC solely by virtue of having positive lymph nodes as this group of patients has a favorable prognosis and likely would skew the data.

We are grateful to Crawford et al for raising issues about improvement and standardization in surgical practice, especially regarding gynecologic oncology subspecialization. However, we believe that studies attempting to examine the impact of surgery on outcome need to carefully stratify for initial volume of disease, patient comorbidities, and RD. In addition, any models developed to predict the ability to achieve effective cytoreduction must account for the tendency of the operating surgeon to employ radical and lengthy procedures. Recognizing that, the results of the Scottish Randomized Trial in Ovarian Cancer must be interpreted with caution.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Vasey PA, Jayson GC, Gordon A, et al: Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96:1682-1691, 2004[Abstract/Free Full Text]

2. Crawford SC, Vasey PA, Paul J, et al: Does aggressive surgery only benefit patients with less advanced ovarian cancer? Results from an international comparison within the SCOTROC-1 Trial. J Clin Oncol 23:8802-8811, 2005[Abstract/Free Full Text]

3. Aletti GD, Dowdy SC, Gostout BS, et al: Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Obstet Gynecol 107:77-85, 2006[Medline]

4. Eisenkop SM, Spirtos NM: Procedures required to accomplish complete cytoreduction of ovarian cancer: Is there a correlation with "biological aggressiveness" and survival? Gynecol Oncol 82:435-441, 2001[CrossRef][Medline]

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Related Reply

• In Reply:
  Simon C. Crawford, Jim Paul, Stan B. Kaye, Paul A. Vasey, Jo A. Davis, and Andrea Hay
  JCO 2006 24: 2398-2399 [Full Text]

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