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Clinical Course of Stage IV Epithelial Ovarian Cancer

Massachusetts General Hospital, Boston, MA

To the Editor: We were curious that Bonnefoi et al¹ should report a similar survival for patients with cytologically positive pleural effusions as compared to patients with visceral metastases, two groups of patients who typically have very different prognoses. Their study prompted a retrospective review of patients presenting to the Massachusetts General Hospital with International Federation of Gynecology and Obstetrics stage IV ovarian cancer between 1980 and 1997. Patients were identified through the tumor registry and their charts were reviewed. After review, four patients were reclassified, and documentation of positive cytology could not be found for seven patients with large effusions that were clinically classified as stage IV. One hundred eight patients were identified, 52 with pleural disease and 56 with visceral metastases. Sixteen patients had liver metastases and 14 had lymphatic metastases with Sister Mary Joseph nodules or pathologically positive extra-abdominal lymph nodes. Other sites of metastases were the lung (seven patients), bone (four patients), spleen (three patients), CNS (three patients), and vulva-vagina (one patient), one patient had direct invasion of the abdominal wall, and one had a metastasis to the breast. Six patients had poorly defined metastases that apparently met the criteria for stage IV disease. Nineteen patients had multiple sites of metastases and 11 of those also had pleural effusions. Nine patients who presented with cytologically positive pleural effusions are still alive, and two of them are disease-free more than 5 years after diagnosis. In log-rank analysis, patients who had only cytologically positive pleural effusions had a statistically significantly better overall survival than patients with liver metastases (P = .0001), as illustrated in the Kaplan-Meier plot (Fig 1). There seemed to be a similar survival benefit for patients with lymphatic metastases. However, this did not reach statistical significance (P = .0528).

View larger version (21K): [in this window] [in a new window]   Fig 1. Stage IV ovarian cancer, 1980-1997.

Despite proven improvements in surgery and chemotherapy, there has not been a dramatic effect on overall survival.² However, improvements in treatment have led to a considerable increase in the median duration of survival.³ Bonnefoi et al¹ report a similar prognosis for patients with pleual effusions and visceral metastases, and failing to find a prognostically significant influence for size of postoperative residual disease, therefore question the role of cytoreductive surgery for all patients with stage IV disease. In view of the apparently better survival in patients with malignant pleural effusions and the large number of patients with small, untapped, poorly sampled or clinically irrelevant effusions that are typically classified as stage III, this would seem to be a potentially deleterious stage-based "treatment migration." Interpretation of subset data is prone to error. Although our sample of patients is more recent and all received platinum-based treatment, both data sets are small. Patients with liver metastases clearly have a terrible prognosis, and the role of surgery should be questioned. However, denying standard treatment to patients with cytologically positive pleural effusions, and possibly nodal metastases, may adversely effect their outcome.

Other disease-related prognostic factors in advanced ovarian cancer may be better predictors of a poorer outcome than cytologically positive pleural effusions, such as initial volume of disease⁴ and the presence of ascites.⁵ Although the molecular phenotype may eventually be the most powerful predictor of outcome,⁶ the present technology may still be insufficient to predict prognosis.⁷

Patients who have stage IV epithelial ovarian cancer by virtue of cytologically positive pleural effusions or nodal metastases should not be denied the potential benefit of surgical cytoreduction.

REFERENCES

1. Bonnefoi H, A'Hern RP, Fisher C, et al: Natural history of stage IV epithelial ovarian cancer. J Clin Oncol17:767-775, 1999[Abstract/Free Full Text]

2. Ozols RF, Vermorken JB: Chemotherapy of advanced ovarian cancer: Current status and future directions. Semin Oncol24:1-9, 1997 (suppl 2)[Medline]

3. Sharpless N, Seiden MV: Advanced ovarian cancer: Recent progress and current challenges. Intern Med18:46-55, 1997

4. Griffiths CT: Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma. Natl Cancer Inst Monogr42:101-104, 1975

5. Puls LE, Duniho T, Hunter JE, et al: The prognostic implication of ascites in advanced-stage ovarian cancer. Gynecol Oncol61:109-112, 1996[Medline]

6. Baekelandt M, Kristensen GB, Nesland JM, et al: Clinical significance of apoptosis-related factors p53, Mdm2, and Bcl-2 in advanced ovarian cancer. J Clin Oncol17:2061-2068, 1999[Abstract/Free Full Text]

7. van der Zee AG, Hollema H, Suurmeijer AJ, et al: Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. J Clin Oncol13:70-78, 1995[Abstract/Free Full Text]

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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 Similar articles in PubMed 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 Penson, R. T. Articles by Seiden, M. V. Search for Related Content PubMed PubMed Citation Articles by Penson, R. T. Articles by Seiden, M. V. Social Bookmarking                            What's this?