ACC is considered as a rare tumor with few effective regimen and poor prognosis[7]. Although this heterogeneous and aggressive malignancy captured increasing focus gradually, the treatment and prognostic evaluation of ACC is still a challenge for clinicians worldwide. Due to the absence of randomized controlled trials, so far, radical resection represents the only potential curative treatment and no chemo/radiotherapy or other adjuvant therapies could show long-term benefit for patients with ACC[8]. Besides, limited medications in adjuvant setting are still comprised of obsolete agents with substantial side effects, and the clinical outcomes remains dismal.
In order to evaluate the prognosis precisely and hereby constitute the basic treatment decisions for ACC patients, many prognostic studies have been performed and several predictors developed[9]. Out of these, resection status, tumor stage and grade are regarded as most predictive factor of ACC[8]. However, the amount of studies in prognosis is very small and current markers are characterized by intrinsic limitations which might reduce their utility in ACC[10, 11]. Consequently, exploiting a common parameter rather than searching for biomarkers in vivo may be more valuable for this rare malignancy to provide rapid application in prognostic evaluation and patients stratification.
As a common biochemical marker in assessment of nutritional status, serum albumin level has demonstrated prognostic value in several benign or malignant disease[12, 13]. In line with previous studies, our study indicates that the preoperative albumin level is a potential prognostic factor for ACC, which appears to be not only accessible but affordable. Specifically, patients with higher albumin level may have a better prognosis, by comparison, those with lower albumin suffered remarkable reduction in RFS and OS (Fig. 2). Unexpectedly, serum albumin did not demonstrate statistical significance as prognostic marker for RFS in Cox multivariate analysis(HR:0.423, 95%CI: 0.176–1.018, P = 0.055). However, it have shown an conspicuous tendency associated with RFS, and the Kaplan-Meier curves of RFS were significantly different (P = 0.0041), indicating that albumin might be a prognostic indicator for RFS (Table 3)(Fig. 2A).
We also noticed that the cutoff value of albumin (39 g/L) in this study is higher than previous studies[5, 14]. For this discrepancy, we hold the opinion that the number of patients with adrenal incidentaloma who accepted early operation is increasing. Although the preoperative diagnosis was histopathologically modified as ACC after primary resection, these patients possessed excellent nutritional performance which may influence ultimate findings. Additionally, this distinction may reflect the enormous heterogeneity and aggressiveness of ACC which might rapidly worsen nutritional status of patients, highlighting the importance of preoperative nutritional intervention.
The concrete mechanism underlying the association between serum albumin and prognosis in many malignancies remains unclear now. Maybe the malnutrition characterized by hypoalbuminemia tends to incur more postoperative complications, increasing the mortality and morbidity in some degree. On the other hand, the serum albumin with short half-life is prone to be impacted by several disorders such as diabetes mellitus, hepatic insufficiency, chronic kidney disease and hypercortisolism, which may have adverse effects on prognosis of ACC. Particularly, it is reported that in ACC patients cortisol-secretion significantly increase the risk of poor outcomes, including recurrence and death, and should be deemed as a negative prognostic factor[15]. Moreover, many cytokines from systemic inflammatory response related to tumor progression may inhibit the albumin synthesis and accelerate albumin loss to interstitial space[16, 17]. In fact, there are various ways to evaluate the nutritional status, such as body mass index (BMI), weight loss, arm circumference and food-intake[18]. However, these measurements based on prospective studies with subjective and qualitative properties are subjective and impracticable for this retrospective study[19].
Resection remains the primary treatment for solid tumors in recent years. Despite the perioperative preparation and surgical procedures progress in recent years, surgery remains a substantially invasive therapy with potential risk to provoke complications, sometime seriously. As above-mentioned, patients with inferior nutritional performance maybe liable to invite serious complications and poor clinical outcomes. Thus, as other malignancies, adequate perioperative nutrient supplementation might be conducive to decrease postoperative complications and improve prognosis for ACC patients[20].
This study has several limitations. Due to the retrospective design, the bias from unmeasured confounding variables is inevitable. Meanwhile, given the heterogeneity of ACC, patients with lower albumin level maybe suffered more aggressive tumor and their condition may deteriorate faster. Additionally, statistical power in present study was impacted by small sample size since the rarity of ACC. Thus, it is indispensable to perform retrospective investigations to facilitate the data accumulation and provide high-level evidence for this rare malignancy.