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Aggressive Surgery and Ovarian Cancer

Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY

To the Editor:

We read with great interest the study by Crawford et al published in the December 1, 2005, issue of the Journal of Clinical Oncology.¹ The authors reported on the available surgical data of 889 patients who were enrolled on the Scottish Randomized Trial in Ovarian Cancer comparing docetaxel/carboplatin with paclitaxel/carboplatin.² Since the results of the Scottish Randomized Trial in Ovarian Cancer (SCOTROC) chemotherapy trial showed no difference in progression-free survival (PFS) between the docetaxel and paclitaxel arms, this means that all patients effectively had similar chemotherapy. One of the three main observations in the surgical study of Crawford et al was that optimal debulking was associated with increased PFS mainly for patients with less extensive disease at the outset. Therefore, Crawford et al concluded that increased PFS is associated with optimal surgery limited to patients with less-advanced disease, arguing for case selection rather than aggressive debulking.

Although Crawford et al¹ state in their discussion that "the primary aim of the study was not to develop a prognostic model for clinical use," we are quite concerned that many of the subscribers to this journal will only read the title, abstract, and conclusion, then cite this article to justify their reluctance to consider, offer, and/or perform maximal effort surgery in their patients with ovarian cancer.

There are four main problems with this study, beginning with the inclusion criteria. Approximately one in five patients had International Federation of Gynecology and Obstetrics stage I or II disease. The title and purpose of the article state that the study was analyzing patients with advanced ovarian cancer. Why were the approximately 20% of patients with early stage disease not excluded? Furthermore, in this analysis of aggressive surgery, more than half of the patients (356 of 675; 53%) did not have an omental cake. This implies that perhaps up to half of the patients in this study had stage IIIB disease or less. Therefore, it is not surprising that "optimal debulking was associated with increased PFS mainly for patients with less extensive disease at the outset" since the suboptimal group was presumably composed primarily of patients with stage IIIC and IV disease, while those with "less extensive disease at the outset," by definition, would be patients with stage IC to IIIB disease.¹ This observation is merely conveying that patients with stage I to IIIB disease do better than those with suboptimally cytoreduced stage IIIC and IV disease, rather than truly analyzing the specific benefit of aggressive surgery in patients with advanced disease.

The second problem is that the definition of aggressive surgery is never adequately established and, therefore, not appropriately analyzed in the study. What kind of procedure was considered aggressive? Given that as many as half of the patients did not have macroscopic upper abdominal disease, one would assume that a significant proportion of patients underwent lymphadenectomy and omentectomy as part of standard surgical staging as defined by the International Federation of Gynecology and Obstetrics. Did performance of a lymphadenectomy and/or omentectomy for staging constitute aggressive procedures or were they categorized as aggressive only if these structures were macroscopically involved with tumor? Were all bowel resections and colostomies considered aggressive, or only those that were performed in conjunction with an optimal debulking?

The third flaw is the multivariate prognostic model that was "used to stratify the patients into four equally sized presurgery prognostic groups."¹ This presurgery prognostic model was the basis for the observations regarding less and more extensive disease. The model relied heavily on preoperative serum cancer antigen-125 values, which were not available in 28% of patients and have not reliably been shown to be a prognostic factor in advanced ovarian cancer.³ Another factor, the presence or absence of omental cake, is more an indicator of stage IIIC or IV disease than insurmountable, innate poor tumor biology as suggested by Crawford et al.

The fourth and perhaps most important problem with this study is the simple definition of optimal cytoreduction. Numerous studies have demonstrated in advanced ovarian cancer patients that cytoreduction to 1 cm to 2 cm residual does not offer a significant survival advantage compared with those with > 2 cm residual, and the current Gynecologic Oncology Group definition of optimal residual is 1 cm.^3-5 By using a 2 cm cutoff to define optimal, it is very likely that a significant proportion of patients recorded as being optimally cytoreduced actually had 1 cm to 2 cm residual disease, which would therefore blunt the beneficial effects of cytoreduction and account for the finding that "in the most advanced group of ovarian cancers, the benefit of optimal debulking is much smaller."¹

The SCOTROC trial was an excellent trial, which added important information to our knowledge regarding chemotherapy for ovarian cancer. However, this attempt to analyze the benefit of aggressive surgery, which was not an end point of the trial by retrospectively using unclear and faulty definitions and an unvalidated preoperative prognostic model is significantly flawed. The notion that a bowel resection and/or pelvic/para-aortic node dissection to achieve optimal (1 cm residual) cytoreduction is too aggressive is not supported at all by the data in this study or any other. It is the concept itself—that the need to perform such procedures is an indication of poor tumor biology—which should be abandoned and not the cytoreductive procedures themselves.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. 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]

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

3. Chi DS, Liao JB, Venkatraman ES, et al: Identification of prognostic factors in advanced epithelial ovarian carcinoma. Gynecol Oncol 82:532-537, 2001[CrossRef][Medline]

4. Ozols RF, Bundy BN, Greer BE, et al: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 21:3194-3200, 2003[Abstract/Free Full Text]

5. Chi DS, Huh J, Haddad L, et al: What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma. Gynecol Oncol 96:934-935 (abstr 56)

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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
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