This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Crawford, S. C. Articles by Hay, A. Search for Related Content PubMed Articles by Crawford, S. C. Articles by Hay, A. Related Articles Related Correspondence Social Bookmarking                            What's this?

In Reply:

Department of Gynaecological Oncology, Southampton University Hospitals Trust, Southampton, United Kingdom

Jim Paul

Cancer Research UK Department of Medical Oncology, Glasgow, United Kingdom

Stan B. Kaye

Royal Marsden Hospital, London, United Kingdom

Paul A. Vasey

Division of Oncology, Royal Brisbane and Women’s Hospital, Brisbane, Australia

Jo A. Davis

Department of Gynaecological Oncology, North Glasgow University Hospitals Trust, Glasgow, United Kingdom

Andrea Hay

Cancer Research UK Department of Medical Oncology, Glasgow, United Kingdom

Drs Chi and Barakat make a number of general and specific points in their letter that reflect on our recent publication.¹ They state that they are concerned that the title will lead readers to draw a premature conclusion without reading the discussion within the article. We do not accept this. It is entirely reasonable to expect readers to read the article especially the discussion. Moreover the title is phrased as a question rather than a statement.

Four points are made regarding what Chi and Barakat consider faults of the study. We refute each of these points. Firstly, they raise the issue of inclusion of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage II disease. They suggest that the inclusion of these patients means that we are somehow confusing our observation on the change in surgical effect with extent of disease, with the effect of disease extent itself. We are not and figure 4 in our article illustrates very clearly how the effect of optimal debulking depends upon the extent of disease; this dependency is statistically significant as indicated by the test of interaction (P < .003). This observation has nothing to do with stage of disease; indeed, the whole point of our analysis is to remove the effect of the background biology as far as possible.

Secondly, a point is raised that the definition of aggressive surgery is never defined. We fully acknowledge that this is a relative term. However, it is a collective term for surgery whose aim is to achieve optimal debulking irrespective of its extent, removing not only the diseased ovaries, but also any other tissues and removable organs that might be involved. However, the lack of a precise definition does not affect the results discussed within the article because it is the effect of the completeness of debulking on survival that is important.

Thirdly, the multivariate model is criticized. Although 28% of the cancer antigen-125 (CA-125) values in the prognostic model were imputed, a model restricted to those patients where the actual CA-125 were available gave very similar hazard ratios and P values (in particular the P value for CA-125 remains P < .001). The publication the correspondents cite² refers to a number of other articles that have found CA-125 to be prognostic and we are sure many will not find its presence in such a model surprising.

As to the unvalidated nature of the model, we must emphasize again that the point of the study was not to build a prognostic model, but to disentangle the effects of surgery from the background biology. To this end we prospectively collected biologic information of the patients disease at surgery not usually available; our model was therefore bound to be novel. The key observation however is not the model itself, but the fact that effect of the surgery depends on the prognosis of the patient based on their biologic status at surgery.

The final specific point relates the definition of optimal cytoreduction. We note in the introduction that there is not a universal definition of optimal debulking; however, the less than 2 cm definition is still a widely accepted definition in clinical practice. If the graphs in Figure 4 are replotted, splitting the no residual disease group from the less than 2 cm residual disease group, the same pattern of decreasing effect with increasing extent is present. Thus even for those patients who achieve complete debulking, this has reduced benefit in those patients with extensive disease. This analysis is not affected by a varying proportion of patients with 1 to 2 cm residual disease.

Chi and Barakat conclude with two general comments: the surgical study was some sort of retrospective afterthought; and the implication that the evidence base for cytoreductive surgery is sufficiently robust that the universal role of surgery should not be questioned.

We would like to re-emphasize that the surgical study was an integral component of the Scottish Randomized Trial in Ovarian Cancer, whose methodology was conceived before any patient recruitment had occurred and whose data were collected prospectively. The conclusions of this study are not that initial cytoreductive surgery should be abandoned, indeed we are able to demonstrate a benefit for this; however, we would defend our position that this may not be the case in all patients.

Author’ Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Simon C. Crawford Chief Scientist's Office (B)

Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C) $100,000 (N/R) Not Required

REFERENCE

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Aggressive Surgery and Ovarian Cancer
  Dennis S. Chi and Richard R. Barakat
  JCO 2006 24: 2395-2396 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Crawford, S. C. Articles by Hay, A. Search for Related Content PubMed Articles by Crawford, S. C. Articles by Hay, A. Related Articles Related Correspondence Social Bookmarking                            What's this?