Elsevier

The Lancet

Volume 357, Issue 9251, 20 January 2001, Pages 176-182
The Lancet

Articles
Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma

https://doi.org/10.1016/S0140-6736(00)03590-XGet rights and content

Summary

Background

Previous studies on prognostic factors in stage I invasive epithelial ovarian carcinoma have been too small for robust conclusions to be reached. We undertook a retrospective study in a large international database to identify the most important prognostic variables.

Methods

1545 patients with invasive epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stage I) were included. The records of these patients were examined and data extracted for univariate and multivariate analysis of disease-free survival in relation to various clinical and pathological variables.

Findings

The multivariate analyses identified degree of differentiation as the most powerful prognostic indicator of disease-free survival (moderately vs well differentiated hazard ratio 3·13 [95% CI 1·68–5·85], poorly vs well differentiated 8·89 [4·96–15·9]), followed by rupture before surgery (2·65 [1·53–4·56]), rupture during surgery (1·64 [1·07–2·51]), FIGO 1973 stage Ib vs Ia 1·70 [1·01–2·85]) and age (per year 1·02 [1·00–1·03]). When the effects of these factors were accounted for, none of the following were of prognostic value: histological type, dense adhesions, extracapsular growth, ascites, FIGO stage 1988, and size of tumour.

Interpretation

Degree of differentiation, the most powerful prognostic indicator in stage I ovarian cancer, should be used in decisions on therapy in clinical practice and in the FIGO classification of stage I ovarian cancer. Rupture should be avoided during primary surgery of malignant ovarian tumours confined to the ovaries.

Introduction

About 25% of patients with common invasive epithelial ovarian carcinoma are first seen with disease confined to the ovaries (International Federation of Gynaecology and Obstetrics [FIGO] stage I).1 5-year survival rates of 70–90% have been reported for invasive stage I ovarian carcinoma.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Classic clinical and pathological prognostic factors, such as degree of differentiation, FIGO substage, histological type, dense adhesions, large-volume ascites, rupture before surgery, extracapsular growth, and age of the patient, have been identified by multivariate analyses as independent prognostic characteristics2, 3, 4, 5, 6, 7, 8, 9, 10, and other factors, such as rupture during surgery, bilaterality, and positive peritoneal cytology, were of prognostic significance in some univariate analyses. Degree of differentiation is the only factor with independent prognostic value in all published multivariate analyses.

On the other hand, the latest FIGO subclassification of stage I distinguishes patients with unilateral tumours (stage Ia) from those with bilateral tumours (stage Ib) and separately identifies tumour spillage, extracapsular growth, and positive peritoneal cytology (stage Ic).11 This classification implies that the factors that assign a patient to substage Ib or Ic carry a worse prognosis than those associated with substage Ia. However, this classification does not take into account the degree of differentiation.

The main limitation of the conclusions derived from previous retrospective analyses is that the sample sizes of most were too small for some independent prognostic variables to be detectable with sufficient power. The aim of our study was to identify the significant prognostic clinical and pathological factors in stage I invasive epithelial ovarian carcinoma in a much larger database. In addition, because of the increasing trend to use laparoscopic surgery, in reviewing all patients' records, we paid special attention to the occurrence and timing of tumour rupture and to the presence of dense adhesions.

Section snippets

Patients

Patients with invasive epithelial FIGO stage I ovarian cancer were included. The records of six existing databases2, 3, 6, 7, 8, 9 were retrospectively reanalysed according to predefined criteria. The Norwegian cohort consisted of 380 patients referred to the Norwegian Radium Hospital between Jan 1, 1980, and July 1, 1998. The 277 Danish patients were treated between September, 1981, and September, 1986, and registered in the Danish Ovarian Cancer Study Group (DACOVA) register. Canadian

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