We retrospectively analyzed the cases of patients with metastatic cervical cancer to investigate the significance of pre-treatment albumin for the prediction of overall survival. The results of a multivariate analysis demonstrated that the presence of hypoalbuminemia predicted a short survival time in this patient cohort. Our analyses also revealed that the patients with albumin >3.3 g/dL who underwent CCRT were likely to survive longer than the patients who underwent other treatments. Pre-treatment albumin is a useful biomarker to identify patients for whom CCRT can be expected to prolong survival.
Similar to the reports on other malignancies, the present results suggest that there is a strong association between pre-treatment serum albumin and the prognosis of cervical cancer patients. Hypoalbuminemia reflects a state of increased catabolism due to tumor-derived cytokines and tumor progression itself. In patients with malignant tumors, the serum albumin level tends to decrease because of malnutrition and systemic inflammatory responses. The present analysis demonstrated a significant negative correlation between albumin and CRP, which reflects systemic inflammation. Cachexia accompanied by hypoalbuminemia is a complex condition involving the tumor, the host response to the tumor, and anticancer therapy. Hypoalbuminemia has been reported to be associated with low quality of life (QOL) and increased risk of adverse effects induced by chemotherapy during the treatment for malignancies [17, 18]. A patient’s pre-treatment serum albumin level may thus be a useful tool for estimating the patient’s tolerance to treatment intensity and survival prognosis. It may also be useful to consider this value with regard to nutritional interventions to elevate a patient’s albumin.
We recently reported that sarcopenia at diagnosis is a prognostic factor in patients with metastatic cervical cancer[16]. We also reported the prognostic value of the neutrophil-to-lymphocyte ratio in early-stage ovarian clear-cell carcinoma [19]. There have also been reports that sarcopenia, cachexia, and malnutrition in gynecological malignancies are useful in predicting prognosis [16, 20, 21]. In the case of metastatic cervical cancer, it is often difficult to decide whether to choose radiotherapy, chemotherapy, chemoradiotherapy, or best supportive care as the primary treatment. The performance status according to the Eastern Cooperative Oncology Group is often taken into consideration, but this PS is sometimes felt to be less objective. The preoperative serum albumin is a more objective biomarker that adequately reflects cancer cachexia.
We also observed that CCRT as the primary treatment was efficient for improving the OS of the patients with distant metastases (HR 3.66, 95%CI: 1.22–10.82). Our hospital’s policy was to choose CCRT as a general rule when the patient’s symptoms due to physical weakness or distant metastasis were not severe. Our finding that CCRT was a favorable prognostic factor in this study may thus have been affected by selection bias. Past studies of the 5-year survival rate of stage IVB cervical cancer have reported rates at 5.5–8.4% [3-6]. Although it is difficult to make a simple comparison, the 5-year survival rate in this study was 35.7%, which is better than previously reported. This is due to high local control rate that 12 out of 32 patients treated with CCRT (37.5%) achieved complete response in locoregional tumor. This suggests the potential of CCRT for stage IVB cervical cancer with distant metastasis.
There are some study limitations to consider. It was a retrospective analysis, and bias and confounding factors were thus present. The small sample size (n=43) could have resulted in a type-II error. In clinical practice, patients with organ metastatic cervical cancer are very diverse, and it is necessary to take into account various parameters such as the mode of metastasis and the patient’s general condition in order to determine the optimal treatment. Our findings are therefore merely hypothesis-generating, but our observation that albumin not only predicts the prognosis of patients with organ-metastatic cervical cancer but also indicates the possibility of more effective treatment for some patients with a promising long-term prognosis is of value. In other words, even in patients with organ-metastatic cervical cancer, if the albumin level is >3.3, CCRT may be more effective in prolonging life as the initial treatment. Prospective clinical trials in patients with organ metastatic cervical cancer using an albumin-based risk assessment are expected in the future.
In conclusion, in the present patient series, the malnourished patients (albumin ≤3.3 g/dL) with organ metastatic cervical cancer had shorter survival than those with albumin >3.3 g/dL.