Abstract
Objective. This study assesses the role of preoperative serum CA125 levels in the planning treatment options for women diagnosed with uterine cancer. Material and Method. Ninety five consecutive patients diagnosed with uterine cancer during a four-year period were identified. Age ranged from 35 to 89 years with a mean age of 69 years. The preoperative CA125 levels were dichotomised at 28 U/mL (using ROC analysis to identify the best discriminating threshold for 5-year survival). This level was then correlated with preoperative prognostic indicators: patient age, tumour grade, and histopathological tumour cell type. Survival data was plotted using Kaplan-Meier curves and analysed using the log-rank test. Univariate and multivariate analysis were performed to identify the predictors of overall survival. Results. The mean age of patients was 69 years (range: 35–89). On univariate analysis, the use of preoperative CA125 levels of greater or less than 28 U/mL correlated significantly with age (P = 0.01), the grade of disease (P = 0.02) and unfavourable tissue type (P = 0.03). This threshold CA125 level had a sensitivity of 75%, specificity of 76%, positive predictive value of 35% and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for predicting nodal disease. Using a threshold of preoperative CA125 level of 28 U/mL (area under curve: 0.60) was also a significant predictor of 5-year survival (log-rank test, P = 0.01). Using Cox multivariate survival analysis to identify predictive preoperative factors overall, unfavourable cell type was the strongest predictor of survival (Chi square = 36.5, df = 4, and P = 0.001), followed by preoperative CA125 level (CA125 > 28 U/mL, P = 0.011) and unfavourable preoperative grade (P = 0.017). Amongst patients with a favourable histological tissue type (endometrioid), preoperative CA125 levels predicted overall survival (Chi square = 6.039, df = 2, P = 0.02); however unfavourable preoperative grade did not (P = 0.5). Overall, at five-year follow-up, while there were no deaths among the women with preoperative serum CA125 less than 12 U/mL, eleven of the twenty-three deaths (47.82%) in the study occurred in women with a preoperative CA125 more than 28 U/mL. Conclusions. A preoperative CA125 assay for women with uterine cancer is a relatively inexpensive, reproducible, and objective test which provides valuable information regarding the risk of metastatic disease and overall likelihood of long term survival. Patients with a low likelihood of metastatic/nodal disease (favourable tissue type and CA125 level < 28 U/mL) and significant comorbidities may benefit from avoiding an extended complete staging procedure. Alternatively, a high level of CA125 may prompt further imaging and multidisciplinary discussions to plan for individualised management and consideration for recruitment to clinical trials.
Highlights
Endometrial cancer is the fourth most common cancer in women in the UK with 7,703 cases diagnosed in 2008 accounting for 5% of all female cancers [1,2,3]
Patients were divided into two groups based on preoperative CA125 levels ( 28 U/mL) following a Receiver Operative Curve (ROC) analysis
On univariate analysis using a threshold of preoperative CA125 levels correlated with older age group (>80 years), unfavourable tumour grade, unfavourable tissue type, nodal status, and overall survival at 5 years (Table 2)
Summary
Endometrial cancer is the fourth most common cancer in women in the UK with 7,703 cases diagnosed in 2008 accounting for 5% of all female cancers [1,2,3]. The number of cases diagnosed annually is expected to rise [5, 6]. The rise in deaths follows the increase in the number of women being diagnosed with uterine cancer, with its incidence rising by 43 percent since the mid-1990s, from 13.7 to 19.6 per 100,000 [3]. Survival from uterine cancer continues to improve gradually, more women are dying from the disease, because of the rise in numbers of women being diagnosed [7]. Many women presenting with endometrial cancer are elderly [3, 8] and often have significant co-morbidities. Patients who present with disease confined to the uterus have a good prognosis while those with advanced stage disease have a higher risk of recurrence and death.
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