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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.

Objectives: Seventy percent of ovarian cancer is diagnosed at advanced stages. Having a method for early diagnosis is a very attractive concept. Several attempts have been made, using monoclonal antibody-based immunoassays, ultrasound, or combinations of both, to identify methods that might prove to be sufficiently sensitive and specific as a screening test. Despite promising results, a mortality study of a large population has yet to be completed due in part to the high cost involved., Methods: One of the first studies aimed at devising a screening strategy for ovarian cancer used the CA 125 immunoassay followed by ultrasound. The study was performed in Stockholm from 1986 through 1988. Ten years now having passed, an analysis has been performed to further evaluate the results of that study., Results: Screening led to the diagnosis of ovarian cancer in six patients, five of whom have since died of the disease. By searching the Cancer Registry, we were able to identify 20 ovarian cancer patients who developed the disease after the screening period. Of these, 12 died of the disease, 2 are alive with disease, and 6 have no evidence of disease following treatment. The median survival for patients diagnosed by screening was 100 months. Median survival for ovarian cancer patients identified subsequent to screening was 20 months. Although there was no difference in survival between these two groups, median survival was better for women diagnosed by screening (borderline significance, P = 0.059)., Conclusion: These results indicate that a study of a large number of women with a sufficiently long observation time will be required to establish whether or not screening can reduce ovarian cancer mortality. Such a study may also provide insight into the natural history of ovarian cancer., (Copyright 2000 Academic Press.)

Background and Purpose: Irradiation of advanced ovarian cancer has been performed during the years 1976-1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated., Material and Methods: Seventy-five patients with stage IIb-IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991-1992 with surgery and chemotherapy only., Results: After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy., Conclusion: The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.

We tested 20 human carcinoma samples for the production of transforming growth factor beta (TGFbeta) in vitro. Tumour cell suspensions without obvious contamination with non-malignant cells were kept in culture conditions for 16 h and their supernatants were added to CCL-64 cells. The proliferation of these cells is inhibited by TGFbeta. According to this assay, the supernatants contained both active and latent TGFbeta. In addition, the supernatants were found to suppress the spontaneous cytotoxic function and activation of T-cell-enriched lymphocyte populations. A specific monoclonal antibody (mAb) counteracted these effects and therefore we concluded that they were mediated to a large extent by TGFbeta. In line with the results obtained with the supernatants, activation of lymphocytes could also be inhibited by tumour cells and their inhibitory effect was weaker in the presence of the TGFbeta-specific mAb. It is important to note that, when TGFbeta-specific mAb was added to autologous mixed lymphocyte/tumour cell cultures, lymphocyte activation occurred more often. These results thus substantiate the assumption that production of TGFbeta may help the survival of potentially immunogenic tumour cells in immunocompetent patients.

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.

Stored samples from women in the Stockholm screening study were reassayed for CA125II (Centocor, Malvern, PA) and OVX1. The postmenopausal women older than age 50 without ovarian cancer were randomly split into a training set to develop a screening test based on longitudinal marker levels and a second set to validate the test. The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CA125II) on time since first sample. The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot. A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women; it delineated a screening test. The specificity of this test was examined on the validation set with a specificity of 99.8%. Bayes' theorem was used to calculate the risk of ovarian cancer (ROC) based on the intercept, slope, and assay variability. It is important to account for assay variability because it can produce large slopes over short periods of time. The maximum risk, which identified 83% (5 of 6) of the ovarian cancers detected within a year of last assay, was applied as a test to the training set and confirmed a high specificity of 99.7%. With this specificity and sensitivity, the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16%, substantially greater than the positive predictive value based on a single assay. Further study is planned to confirm the sensitivity of this approach.

Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer.

To achieve better understanding of the factors influencing local control of ovarian cancer, an analysis of failure in early stages of ovarian carcinoma has been carried out. The material consisted of 185 patients diagnosed in early stages; 40 of them failed in their disease, 17 with local recurrence, 23 with distant metastases. The material was analyzed with respect to age, histology, grade, size and surface of the tumor, the surgical procedure and treatment modalities, and the time between treatment and recurrence, and recurrence and death. In the analysis, both the behavior of the ovarian cancer tumor and the pattern of failure was shown to be different for each histological group.

The symptomatology of ovarian cancer was retrospectively reviewed in 362 patients. According to the stage at diagnosis, the disease was classified as early (stages IA-IIA) or advanced (stages IIB-IV). The most common initial symptoms were abdominal swelling and/or palpable tumour, pain and gastro-intestinal symptoms. The initial symptoms, however, were not necessarily those that prompted the patients to seek medical advice. Most were first seen by a gynecologist, which possibly explains the shortness of doctor's delay in the urbanized catchment region.

Prognostic factors were studied in 770 cases of carcinoma of the ovary treated at Radiumhemmet during 1974 to 1979. Centralization of the treatment in a well-defined population with complete follow-up permits a nonselective study of the disease. The analysis was made separately for early and late stages. For the early cases, histology and grading were the most dominant prognostic factors. For the most advanced cases successful surgical treatment, either primary or secondary, showed significant relation to survival. Successful secondary surgery could be achieved in twice as many cases where radiotherapy was included in the treatment. Even for the advanced cases, the stage but not the histology was of prognostic significance. The major difficulties in evaluating treatment of ovarian cancer, especially in advanced cases, are associated with the multiplicity of sites of the disease and the prognostic factors that may contribute independently to the outcome.

Preoperative radiotherapy in advanced ovarian carcinoma was evaluated. The overall 5-year survival rate in the irradiated group was 27%. When tumour mass remaining after operation was less than 2 cm in diameter, this figure rose to 52%. Comparison was made between those in whom operation became feasible only after preoperative irradiation and patients in advanced stages who were primarily successfully operated to less than 2 cm and with a 5-year survival rate of 44%. Selection of the cases for preoperative radiotherapy is obviously necessary. Fixed, bulky tumours in the pelvis, with or without metastases, may be suitable for preoperative radiotherapy.