Population-based study of ovarian cancer in Côte d'Or: prognostic factors and trends in relative survival rates over the last 20 years

Ovarian cancer is the sixth most common cancer in women. Incidence rates are highest in developed countries [1]. In France, ovarian cancer accounted for 4375 new cases and 3180 deaths in 2005 [2].

Despite improved knowledge of prognostic factors and advances in treatments for ovarian cancer, the outcome in terms of long-term survival remains unknown. In fact, while some studies [3, 4] showed a significant increase in the survival rate over time, others showed similar survival rates over time [5]. Moreover, many previous studies on prognostic factors and survival in ovarian cancer were based on selected patients, and did not use relative survival (RS) as the primary end-point [4, 6‐8].

To our knowledge, no population-based study has used RS as the primary end-point to determine independent prognostic factors in ovarian cancer. Relative survival is an estimator of the excess mortality ratio. The use of RS could make it possible to correct indirectly for deaths not attributable to ovarian cancer [9].

The Côte d'Or gynaecologic cancer registry is the only cancer registry in France that focuses on gynaecologic cancers. It has been collecting comprehensive population-based data since 1982.

Our purpose was to study relative survival according to the main patient and tumour characteristics.

Our study included all cases of invasive ovarian cancer diagnosed between 1982 and 2005 in a well-defined population using a cancer registry specialized in ovarian cancer.

The results of our study showed a progressive decline in the survival rate with 3-year and 5-year RS rates of 55% and 44%, respectively. These results are in agreement with those reported in western Sweden [11] where the 5-year RS rate for patients diagnosed with ovarian cancer from 1993 to 1998 was 46%. In the same way, a population-based study in Germany [12] showed a 5-year RS rate of 45% among patients with ovarian cancer, diagnosed from 1999 to 2003.

In line with the present study, many studies on ovarian cancer found age to be an independent prognostic factor [7, 11, 13‐16]. It is important to emphasize that our analysis was based on a population-based cohort and that it is, to our knowledge, the only one to assess independent prognostic factors in ovarian cancer using RS as the primary end-point. In our study, women aged younger than 50 years had the best prognosis of all age groups. Multivariate relative analyses showed that only patients aged older than 70 years had significantly worse survival as compared to those younger than 50 years. This can be due to the particular management of ovarian cancer in elderly patients who are less likely to receive standard combination therapy [17, 18], and thus benefit less from advances in treatment.

As in other studies [11, 13‐16, 19], the results of the present study showed clearly that survival is stage-dependent. In fact, multivariate analyses showed that the FIGO stage was the most powerful prognostic factor, with a hazard ratio of 13 in stage IV in the multivariate analysis. In our study, we found 5-year RS rates of 85%, 48%, 29% and 14% for stages I, II, III and IV, respectively. This could be compared with the findings obtained from the SEER program which showed 5-year RS rates of 88.3%, 65.0%, 34.1% and 19.7%, respectively for patients with stage I, II, III and IV ovarian cancer diagnosed between 1988 and 2001[16]. The results were closer for stage I, III and IV, but a considerably lower survival rate was recorded in our sample for stage II disease. This difference concerning stage II may be explained by disparities in the proportion of patients who did not receive optimal debulking and were thereby understaged. It is worth noting that recent studies [20, 21] showed that a large number of ovarian cancer patients with clinically localized disease still underwent incomplete surgical staging.

Unlike some studies [11, 13] the result of the present study found histological subtype to be an independent prognostic factor in ovarian cancer. Our results showed that patients with non-epithelial or endometrioid-mucinous tumours had better survival as compared to those with serous tumours in univariate analyses of RS but not in the multivariate analyses. Moreover, patients with other epithelial subtypes, mainly clear cell and unspecified adenocarcinoma tumours, were found to have worse survival as compared to those with serous tumours. Clear cell histology is generally accepted as an unfavourable histology, but the results concerning other histology subtypes are contradictory. In a recent study [14] comparing the survival of women with clear cell versus other epithelial ovarian cancers, clear cell had poorer overall survival. In a recent review [7], clear cell histology and mucinous cancers were associated with worse survival. In contrast, an Australian study [15] found that endometrioid and non-epithelial tumours were associated with better survival as compared with serous tumours, while non-specified adenocarcinoma correlated with worse survival.

In multivariate analyses, the place of residence was an independent prognostic factor for relative survival in ovarian cancer. Women who lived in rural areas had a greater excess risk of death due to ovarian cancer than did those who lived in urban areas. This may be due to more restricted access to high performance treatment facilities in these regions. The results of the multivariate model suggest that differences in stage distribution (that women in rural areas may be diagnosed at a later stage) do not explain the poorer survival in rural areas, as the hazard ratio remained unchanged in the multivariate model.

In our study, we found the period of diagnosis to be an important independent prognostic factor. Patients diagnosed during the period 1998-2005 had significantly better survival as compared to those diagnosed during the period 1982-1989, whereas no difference in survival was found for women diagnosed in the period 1990-1997. Similar results were found by Engel et al in a population-based cohort of ovarian cancer patients during 1978-1997. This study [5] found that survival rates before and after 1988 were similar.

During the study period, we found an improvement in RS in women with early stage as well as in those with advanced stage ovarian cancer, but the improvement was more pronounced for women with advanced stages (Table 5). This may be explained by the importance of maximal cytoreduction in the recent period and by the fact that the workup and staging are more comprehensive. In fact, in our study, the proportion of FIGO stage III was higher in the most recent period compared to the first period of diagnosis (Table 2). In the same way, in their study [22], Chan et al showed a significant improvement across time in the survival of women with surgically stage III and IV diseases.

The survival improvement appearing after 1998 may be attributed to advances in treatment. Several studies have explored the role of surgery in advanced ovarian cancer [23]. Most of these studies supported the role of tumour debulking as the best first-line treatment in women with advanced ovarian cancer. It is also likely that advances in chemotherapy as well as in general medical support have contributed to this improvement.

The strength of the present study is that it includes all patients with ovarian cancer diagnosed from 1982 to 2005 in a well-defined geographical area. Furthermore, the follow up for vital status was nearly complete with a low lost-to-follow-up rate (7%). With this large panel, the results of our study could be considered representative of survival in French patients during this period. Unlike clinical trials, in which patients are highly selected, population-based survival studies are based on heterogeneous groups and can be used to determine prognostic factors in cancer, with little potential for selection bias [24].

The results of this population-based study showed that advanced age at diagnosis, advanced FIGO stage, period of diagnosis, histological type and place of residence are independent prognostic factors in ovarian cancer and that long-term survival has improved over the last 10 years. Despite the overall improvement in ovarian cancer survival, novel treatment strategies are still warranted.