Medico

J Oncol. 2010;2010:852028. Epub 2009 Oct 25.
When Should Surgical Cytoreduction in Advanced Ovarian Cancer Take Place?
Igor E. Martinek* and Sean Kehoe
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Abstract
Initial surgical management is commonly accepted to date as paramount in the treatment of women presenting with epithelial ovarian cancer and permitsthe assessment of the disease (staging), the histological confirmation of disease type and grade, and the practice of maximal debulking preceding platinum-based chemotherapy. Many studies have shown that the volume of residual disease after initial surgical cytoreduction inversely correlates with survival. Thus, women with optimal debulking performed by a trained specialist have improved mediansurvival. In this review, we will focus on the answers gleaned from clinical trials on primary and interval surgery, which prompts the question on the timing of surgery in respect to chemotherapy. Interval debulking surgery (IDS) is secondary cytoreduction following primary debulking and is carried out in between the courses of chemotherapy. The major clinical trials and the latest systematicreviews seem unable to give any definitive guidance or recommendation for clinical practice. The choice of aggressive primary cytoreduction or upfront chemotherapy followed by second line surgical cytoreduction seems among others to have to be individualized according to tumour load, prediction of its resectability, and response to chemotherapy. The role of tumour biology must also be kept in mind.Finally, concrete answers are awaited on the timing of surgery from the ongoing prospective randomized control trials (CHORUS and EORTC 55971) though preliminary data from the latter have already been presented at major meetings (IGCS 2008; SGO 2009) and ignited strong debate.
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1. Introduction
Ovarian cancer represents the sixth most commonly diagnosed cancer among women in the world andcauses more deaths per year than any other cancer of the female reproductive system [1]. In advanced disease which constitutes about 75% of women at presentation, the accepted management is a combination of surgery and platinum based chemotherapy. This has been the approach for some decades, though the 5-year survival remains poor at about 40%. Epithelial ovarian cancer constitutes the majority ofdisease types, and this review will focus on reports relating to advanced epithelial ovarian carcinoma.
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2. Materials and Methods
A Medline database search (January 1966 to April 2009) was undertaken using key words: epithelial ovarian cancer, debulking surgery, and interval debulking surgery resulting in 80 articles with 14 relevant papers. The articles in full were obtained for each of thepapers and reviewed by the authors. Results in terms of overall survival (OS) and progression free survival (PFS) were evaluated in each study.
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3. Results
The 80 resulting articles were screened and 14 relevant papers were retained: 3 meta-analysis [2–4], 3 randomized control trials (RTC) [5–7] (Table 1) 2 Cochrane Reviews (CRs) [8, 9], and 6 case/control (CC) reports enrolling morethan 50 patients [10–15] (Table 2).

Table 1RCTs investigating the role of IDS. |

| Table 2Nonrandomized case control studies evaluating delayed primary debulking surgery. |
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4. Discussion
4.1. Primary Debulking Surgery
The initial studies supporting the concept of debulking surgery were published in the 1970s by Griffiths et al. [16]. The premise for considering the potentialimpact of reducing intra-abdominal tumour burden was based on the findings of work by Magrath et al. [17], which reported enhanced survival outcome by reducing intra-abdominal disease, in patients with Hodgkin's disease. Griffiths undertook a retrospective analysis of just over 100 women and noted that those with residual disease masses <1.6 cms in largest diameter had an improved survival outcome...