Prediction of Survival in Adrenocortical Carcinoma

This article refers to:

Nomograms for Individualized Evaluation of Prognosis in Adrenocortical Carcinomas for the Elderly: A Population-Based Analysis

Adrenocortical carcinoma (ACC) is a highly aggressive endocrine malignancy, very rare, with an overall low incidence rate of 1-2 per million and poor prognosis [1]. Unfortunately, by the time most ACCs are diagnosed, the disease has spread outside the adrenal gland, either locoregionally or commonly metastasizing to other organs (i.e., stage IV). The matter becomes complicated as most ACCs (76%) are functional tumors, with cortisol-secreting tumors associated with poorer prognosis [2]. Because of the rarity of the disease, a comprehensive evaluation of prognostic factors has not been definitively researched. Marked individual variation in disease progression, recurrence, and overall survival has been shown in previous studies. Age at diagnosis correlates with decreased overall survival; however, it remains unclear if this is the case for tumor-free survival. [3] Molecular biology, tumor pathology, and histologic behaviors (high grade, poor differentiation) are usually related to decreased survival. Tumor extent outside the adrenal gland, specifically the presence of distant metastasis, is associated with a worse prognosis [3–6].

The most recent study by Wang et al. [7] is the largest of its kind for adrenocortical carcinoma (ACC) in elderly patients (aged 60 years or older). The study spans over 40 years (between 1975-2016) and includes an analysis of 583 cases of ACC using the Surveillance, Epidemiology, and End Results (SEER) database. The principal aim was to assess the prognosis and the predictors of survival in elderly patients and constructed a predictive model to assess the overall survival (OS) and disease-specific survival (DSS). The overall incidence rate of ACC in the study was 0.88/1,000,000 person-years and was highest in patients aged 60-70 years (1.8/1,000,000 person-years). This is the first study to include the European Network for the Study of Adrenal Tumors (ENSAT) staging system into nomograms based on the SEER registry. The authors performed extensive statistical analysis and validated nomograms internally by evaluating both the calibration and discrimination, and established nomograms to predict the 1-, 3-, and 5-year OS and DSS by incorporating six significant predictors into the model, including: 2 patient factors (age of the patient at diagnosis and sex), two tumor-specific factors (histologic grade and stage), and two therapeutic approaches (surgery, and radiotherapy). Tumor stage was assessed using the ENSAT system adapted by the Union for International Cancer Control (UICC) and World Health Organization (WHO) for its superiority over other staging systems [5]. Overall, the model showed a good correlation between the nomogram prediction and actual observation.

A significant portion of patients in this study presented with ENSAT stage IV disease (39.3%). The most common treatment modalities include surgery (71%), radiotherapy (11.7%), and chemotherapy. The data for chemotherapy was incomplete in 422 (72.4%) cases; therefore, this treatment modality was not included in the analysis, which may have affected the result of the nomograms.

Surgery, whether curative (complete resection) for localized diseases, or palliative (debulking) for advanced disease, remains one of the most important treatment approaches offering the possibility to prolong survival in patients with ACC. Several adjuvant therapies are used depending on the grade and stage of the tumor and other patient-related factors. Unfortunately, with the high recurrence rate after radical surgery (85% of patients develop recurrent disease), the systemic treatment options still have limited efficacy. Platinum-based chemotherapy remains the gold standard in metastatic ACC despite suboptimal efficacy [8]. While the role of radiotherapy has not been defined well, and ACC often is considered radioresistant. It is not clear what the indications for radiation therapy were in this study; prior research has shown that adjuvant radiotherapy to the tumor bed should be considered in patients at high risk for local recurrence, and radiotherapy in a palliative setting may be used for symptomatic metastases to bone, brain, or vena cava obstruction [9]. All therapy of unresectable or metastatic ACC must be considered palliative, a fact that needs to be discussed with the patient so that reasonable expectations are set [6].

The recent emerging targeted therapy from integrated epigenomic and genomic analyses seems promising [10]. This advances in therapy combined with referral of these patients to large cancer centers at the time of initial surgery, development of new trials in patients with well-characterized ACC, networking, and progress in the molecular characterization of ACC indicate a potential paradigm shift in the future for treating ACC.[10]

Despite limitations, this study is based on a very large review of a very rare pathology, and these results show that the validated nomograms are reliable for predicting the survival probability.

Disclosure Statement

No potential conflict of interest was reported by the author(s).