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Surgery in Advanced Epithelial Ovarian Cancer

Sisters of Charity HospitalBuffalo, NY

To the Editor:Twelve years ago (1988) we reported in the Journal of Clinical Oncology on "The Impact of Aggressive Debulking Surgery and Cisplatin-Based Chemotherapy on Progression Free Survival in Stage III and IV Ovarian Carcinoma".¹ In that prospective trial, we were able to achieve optimal results (less than 2 cm residual disease) in 87% of the women with advanced-stage epithelial ovarian cancer. Therefore, it was somewhat disquieting to read in the paper by Hoskins et al,² that of those women with the amount of residual disease stated, only 18% (six of 39) had their tumor optimally cytoreduced to less than 2 cm. I had hoped to find an explanation in the Patients and Methods as to why in this new millennium the vast majority of women in the authors’ study did not have the benefit of optimal surgery before receiving chemotherapy in what is essentially a limited phase II toxicity and efficacy trial.

Although for ethical and practical considerations, a randomized prospective clinical trial will most likely never be done to answer the question as to the survival benefit of optimal versus suboptimal cytoreductive surgery in epithelial ovarian cancer, the overwhelming preponderance of retrospective evidence supports that cytoreductive surgery to less than 2 cm residual disease is associated with an improved long-term survival.³ In trying to put this innovative chemotherapy trial into a 21st century perspective as to its possible future value, I believe the readers of the Journal of Clinical Oncology deserve a more detailed explanation as to the lack of optimal cytoreductive surgery in 82% of the enrollees, other than the statement, "these were not prognostically optimal patients".

REFERENCES

1. Piver MS, Lele SB, Marchetti DL, et al: The impact of aggressive debulking surgery in cisplatin-based chemotherapy on progression free survival in stage III and IV ovarian carcinoma. J Clin Oncol 6: 983-989, 1988[Abstract/Free Full Text]

2. Hoskins P, Eisenhauer E, Vergo TI, et al: Phase II feasibility study of sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin as primary treatment for advanced epithelial ovarian cancer: A national Cancer Institute of Canada clinical trial group study. J Clin Oncol 18: 4038-4044, 2000[Abstract/Free Full Text]

3. Hoskins WJ, McGuire WV, Brady MF, et al: The effective diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol, 17: 974-979, 1994

Response

National Cancer Institute of Canada Clinical Trials GroupKingston, Ontario, Canada

In Reply:Dr Piver is absolutely correct in that effective debulking surgery is central to the management of epithelial ovarian cancer. The randomized, interval-debulking surgery study carried out by the European Organization for Research and Treatment of Cancer demonstrated its therapeutic impact with its accompanying survival benefit.¹ What is not clear is when is the optimal time to carry out such surgery. Is delayed surgery as good as up front surgery? The ongoing European Organization for Research and Treatment of Cancer–led randomized study comparing initial surgery followed by platinum-taxane chemotherapy with initial platinum-taxane chemotherapy with the debulking surgery performed between cycles 3 and 4 should answer this question. Patterns of practice in Canada have changed because of this uncertainty. There is an increasing tendency to use delayed surgery in patients with either a poor performance status or in whom the surgeon believes optimal up-front debulking is unlikely, and to be less aggressive during initial surgery, based on the intraoperative assessment of the likelihood of optimal debulking, and then perform delayed debulking. This trend was present when the couplet study was designed, and allowance for this was built in such that interval debulking was allowed. Our belief is that as long as good surgery is performed, its timing is not crucial. In our study, the number of optimally debulked patients was 43% (six patients up-front and 13 at interval debulking). Dr Piver’s optimal debulking rates of 87% are very impressive. They do not reflect what is achievable in practice in Canada or Western Europe. The rate of optimal debulking is 40% to 50%.^2,3 This is the same rate as in this study; ie, we are consistent.

REFERENCES

1. van der Burg MEL, van Lent M, Buyse M, et al: The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. N Engl J Med 332: 629-634, 1995[Abstract/Free Full Text]

2. Swenerton K, Jeffrey J, Stuart G, et al: Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: A randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 10: 718-726, 1992[Abstract/Free Full Text]

3. Piccart MJ, Bertelsen K, James K, et al: Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: Three-year results. Natl Cancer Inst 92: 699-708, 2000[Abstract/Free Full Text]

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