Pre-operative serum albumin is associated with post-operative complication rate and overall survival in patients with epithelial ovarian cancer undergoing cytoreductive surgery

Highlights

• Hypoalbuminemia is a risk factor for severe postoperative complications.

• Hypoalbuminemia is a risk factor for impaired overall survival.

• Albumin levels should be incorporated in pre-operative workup.

Abstract

Objective

Hypoalbuminemia has been reported as a risk factor for post-operative complications and unfavorable survival in cancer patients. We aimed to evaluate the predictive value of preoperative serum albumin levels on post-operative complication rate and the impact on overall survival (OS) in patients with epithelial ovarian cancer (EOC) undergoing primary cytoreductive surgery.

Methods

The present retrospective study included 604 consecutive patients with EOC who underwent primary cytoreductive surgery at two tertiary cancer centers specialized in gynecologic oncology. Hypoalbuminemia was defined as a pre-operative serum albumin level ≤ 35 g/L. Post-operative surgical complications were graded according to the Clavien–Dindo-Classification (CDC). Fisher-test was used to investigate the predictive value of hypoalbuminemia on the rate of severe post-operative complications. Survival analyses were calculated using log-rank test and Cox regression models.

Results

The incidence of pre-operative hypoalbuminemia in the entire cohort was 16.4%. Hypoalbuminemia was a predictive factor for severe post-operative complications (CDC 3–5) (OR 3.65, (CI95% 1.59-–8.39); p = 0.002). Furthermore, median overall survival time of patients with hypoalbuminemia was 24 months compared to 83 months in patients with normal albumin (p < 0.001), respectively. Hypoalbuminemia was independently associated with shortened overall survival (HR 2.2 (95% CI 1.6–3.0); p < 0.001) even after adjusting established prognostic factors such as age, tumor stage, performance status, and post-operative residual disease.

Conclusion

Pre-operative hypoalbuminemia can be used as both an independent predictive factor for severe post-operative complications and as prognostic parameter regarding overall survival in EOC patients. Therefore, albumin levels may be incorporated into future clinical trials as stratification factor.

Introduction

Cytoreductive surgery is one of the mainstays in the treatment of women with epithelial ovarian cancer (EOC). Surgical outcome significantly impacts patients' survival [1], [2], [3], [4]. However, extensive surgery may be associated with considerable adverse events, and major post-operative morbidity has been reported to occur in 33% to 64% [5]. Several factors associated with peri-operative morbidity like age, performance status, surgical complexity, nutritional status and serum markers (e.g., prealbumin and albumin) have been described with heterogeneous results [6], [7], [8], [9]. Many of these factors are difficult to standardize and classification is based on individual clinical judgment. A simple test based on objective values could help to better classify morbidity risks in a uniform, standardized way, independent of clinical and structural heterogeneity.

Albumin is the most abundant plasma protein in humans, comprising for 50%–65% of the measured total serum protein [10]. It plays a key role in maintaining colloid osmotic pressure, as well as acting as a transport vehicle for intrinsic metabolites, drugs, and anti-oxidative agents [11]. Low serum albumin reflects inflammatory activity and has been reported as a risk factor of post-operative complications and survival in various cancer types [9], [12], [13], [14], [15]. Furthermore, serum albumin level has been described to be a crucial parameter of malnutrition [16] and has also been reported to be an indicator of malnutrition in gynecologic patients [17]. Malnutrition at the time of cancer diagnosis occurs in about 20% of gynecologic cancer patients [18] with its highest prevalence in ovarian cancer (67%) [17]. Thus, the pre-operative evaluation of ovarian cancer patients in regard to radical surgery with a significant risk for severe post-operative complications seems to be of particular importance.

The present study focused on two major aims: the first aim was to evaluate the predictive role of pre-operative serum albumin levels on post-operative complications categorized by Clavien–Dindo-Classification (CDC). The second aim was to elucidate the prognostic association between pre-operative serum albumin levels and overall survival (OS) in patients with epithelial ovarian cancer undergoing primary cytoreductive surgery independent of peri-mortality.