ADRENOCORTICAL CARCINOMA: AN ORPHAN MALIGNANCY: FROM THE PATIENT TO THE BENCH AND BACK.

Adrenocortical carcinoma (ACC) is an orphan cancer with 35% five-year survival that has been unchanged for last five decades. Patients often present with severe hypercortisolism or with mass effects. The only Food and Drug Administration (FDA)-approved drug for ACC is mitotane, an insecticide derivative, which provides only limited additional months of survival, but with toxicities. Little progress in the field has occurred due to a lack of preclinical models. We recently developed new human ACC in vitro and in vivo research models. We produced the first two new ACC cell lines for the field, CU-ACC1 and CU-ACC2, which we have distributed for global collaborations. In addition, we developed 10 ACC patient-derived xenograft (PDX) and two humanized ACC-PDX models to test new therapeutics and examine the mechanism of mitotane action in combination with immunotherapy. These new preclinical models allow us to identify novel targets and test new therapeutics for our patients with adrenal cancer.

Adrenal cortical carcinoma: Paediatric aspects - literature review.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare malignancy in children. Because of this, each patient with suspected ACC requires individualised management, which should be determined at a meeting of a team of multidisciplinary experts in the field. AIM OF THE STUDY: To summarise data on symptoms, genetic predisposition, and diagnostic procedures for ACC in children. MATERIAL AND METHODS: Papers were searched in the PubMed database to identify published randomised clinical trials, reviews, systematic reviews, meta-analyses, and case reports. RESULTS: Most cases of ACC in children occur under the age of 5 years. The most common presenting symptom in 60-80% of paediatric patients is rapidly progressive virilisation. Diagnostics are based on laboratory and imaging evaluation. The mainstay of treatment is surgery, with laparotomy being the preferred method of surgery. Diagnosis is based on histological examination of surgically removed tissue. The Wieneke index is most commonly used in paediatric practice. However, some cases are still classified as "indeterminate histology". Predisposing genetic factors are found in most children with ACC, most commonly a mutation of the TP53 gene. CONCLUSIONS: Patients should be diagnosed in large clinical centres with experience in this field. The treatment strategy should be individualised. Genetic testing for TP53 gene mutations is indicated in patients with ACC.

Systemic Management of Advanced Adrenocortical Carcinoma.

OPINION STATEMENT: Adrenocortical cancer (ACC) is a rare and aggressive disease. Surgery has traditionally been the primary treatment for locally advanced disease with ongoing controversy around the optimal neoadjuvant and adjuvant treatment options. Unfortunately, local recurrence and the eventual development of metastatic disease is common and five-year survival rates are poor. While many trials have evaluated novel systemic agents to treat advanced adrenocortical cancer, only a few drugs have demonstrated any response at all. To date, only one drug, mitotane, is approved in the US for ACC and no regimen has clearly shown an increase in overall survival. In advanced metastatic or unresectable disease, data supports the first line regimen of EDP chemotherapy + mitotane as the primary treatment modality. In the second line, while data is limited, we would recommend consideration of immunotherapy using a PD(L)1 agent combined with a TKI/VEGF inhibitor or combination immunotherapy with PD1/CTLA-4 drugs. In all cases, we always prefer a clinical trial as available. This article reviews data from multiple studies evaluating novel systemic agents against ACC and discusses current systemic therapy combinations and ongoing clinical trials.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Prognostic factors of adrenocortical carcinoma in children and adolescents: a population-based study.

PURPOSE: Adrenocortical carcinoma (ACC) is an uncommon adrenal gland endocrine tumor that has a poor prognosis in children. We aimed to conduct a population-based cohort study to predict overall survival (OS) in pediatric patients with ACC. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to conduct a retrospective cohort research on pediatric patients diagnosed with ACC between 1975 and 2018. We examined demographic characteristics, tumor stage and size, treatment options, and survival results. Kaplane-Meier estimations were used to generate survival curves based on several parameters. To compare survival curves, the log-rank test was applied.Cox proportional-hazards regression was used to determine the variables related with OS. In addition, we created a nomogram to predict overall survival in pediatric ACC patients. RESULTS: A total of 143 pediatric ACC patients were identified. Females were the most impacted (60.8%). Overall 1 year, 3 year, and 5 year survival rates were 75.0%, 57.6%, and 53.7% for all patients, respectively. In comparison to older patients (5-19 years), younger patients (≤ 4 years) were shown to have more positive characteristics, including a higher likelihood of local disease (29.4% vs. 14%, P < 0.001), tumors less than 10 cm (23.1% vs. 14.7%, P < 0.001), and improved overall survival (5 year OS 89.6% vs. 27.7%, P < 0.001). Age at diagnosis, SEER stage, and surgery were significant independent predictors of OS in this model, according to the results of Cox proportional hazard regression. After that, we developed a nomogram for predicting OS in children with ACC. Patients older than 4 years old had a higher chance of dying. Furthermore, the higher the SEER stage, the higher the risk of death. Patients who do not have surgery have a worse survival rate than those who do. CONCLUSIONS: Our study revealed that age at diagnosis, SEER stage, and surgery were found to be the most important predictors of the overall survival of pediatric ACC. These findings contribute to the existing body of knowledge and emphasize the importance of continued research to advance our understanding of pediatric ACC and improve patient care.

Validated predictive model for treatment and prognosis of adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma has a poor prognosis and multiple clinical, pathological, and treatment variables. Currently, we lack a prognostic and treatment calculator to determine the survival and efficacy of adjuvant chemoradiation. We aimed to validate a calculator to assess prognosis and treatment. METHODS: We searched the National Cancer Database to identify patients with adrenocortical carcinoma surgically treated from 2004 to 2020 and randomly allocated them into a training (80%) or validation set (20%). We analyzed the variables of age; sex; Charlson Comorbidity Index; insurance status; tumor size; pathologic tumor, node, and metastasis categories; surgical margins; and use of chemotherapy and radiation therapy. We used Cox regression prediction models and bootstrap coefficients to generate a mathematical model to predict 5- and 10-year overall survival. After using the area under the curve analysis to assess the model's performance, we compared overall survival in the training and validation sets. RESULTS: Multivariable analysis of the 3,480 patients included in the study revealed that all variables were significant except sex (P < .05) and incorporated into a mathematical model. The area under the curve for 5- and 10-year overall survival was 0.68 and 0.70, respectively, for the training set and 0.70 and 0.72, respectively, for the validation set. For the bootstrap coefficients, the 5- and 10-year overall survival was 6.4% and 4.1%, respectively, above the observed mean. CONCLUSION: Our model predicts the overall survival of patients with adrenocortical carcinoma based on clinical, pathologic, and treatment variables and can assist in individualizing treatment.

Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-related molecular subtypes were identified by unsupervised consensus clustering. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were employed to further establish immune-related gene signatures (IRGS). An evaluation of immune cell infiltration, biological function, tumor mutation burden (TMB), predicted immunotherapy response, and drug sensitivity in ACC patients was conducted to elucidate the applicative efficacy of IRGS in precision therapy. ACC patients were divided into two molecular subtypes through consistent clustering. Furthermore, the 3-gene signature (including PRKCA, LTBP1, and BIRC5) based on two molecular subtypes demonstrated consistent prognostic efficacy across the TCGA and GEO datasets and emerged as an independent prognostic factor. The low-risk group exhibited heightened immune cell infiltration, TMB, and immune checkpoint inhibitors (ICIs), associated with a favorable prognosis. Pathways associated with drug metabolism, hormone regulation, and metabolism were activated in the low-risk group. In conclusion, our findings suggest IRGS can be used as an independent prognostic biomarker, providing a foundation for shaping future ACC immunotherapy strategies.

Advances in translational research of the rare cancer type adrenocortical carcinoma.

Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1-2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately one third of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT-ß-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP-protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutations and the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome.

Adrenocortical carcinoma: Diagnosis, prognostic classification and treatment of localized and advanced disease.

Adrenocortical carcinoma (ACC) is a rare cancer with an estimated incidence of 0.7 to 2.0 cases per 1 million population per year in the United States. It is an aggressive cancer originating in the cortex of the adrenal gland with a poor prognosis. The 5-year survival rate is less than 15% among patients with metastatic disease. In this article, we review the epidemiology and pathogenesis of ACC, the diagnostic procedures, the prognostic classification of ACC, and the treatment options from localized and resectable forms to advanced disease detailing recent therapeutic developments such as immunotherapy and molecularly targeted therapy.

Elucidating the clinical and immunological value of m6A regulator-mediated methylation modification patterns in adrenocortical carcinoma.

N6-methyladenosine methylation (m6A) is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients. However, it is unknown how the m6A regulator affects the tumor microenvironment (TME) cell infiltration in adrenocortical carcinoma (ACC) and how it affects the prognosis of ACC patients yet. The m6A alteration patterns of 112 ACC patients were evaluated, furthermore, the association with immune infiltration cell features was investigated. The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients. The principal component analysis (PCA) technique was taken to create the m6A score to assess the alteration pattern in specific malignancies. We found two independent patterns of m6A alteration in ACC patients. The TME cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both patterns. The m6Ascore also served as an independent predictive factor in ACC patients. The somatic copy number variation (CNV) and patients prognosis can be predicted by m6A alteration patterns. Moreover, the ACC patients with high m6A scores had better overall survival (OS) and higher efficiency in immune checkpoint blockade therapy. Our work demonstrated the significance of m6A alteration to the ACC patients immunotherapy. The individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice.

New Findings on Presentation and Outcome of Patients With Adrenocortical Cancer: Results From a National Cohort Study.

CONTEXT: Because of the rarity of adrenocortical cancer (ACC), only a few population-based studies are available, and they reported limited details in the characterization of patients and their treatment. OBJECTIVE: To describe in a nationwide cohort the presentation of patients with ACC, treatment strategies, and potential prognostic factors. METHODS: Retrospective analysis of 512 patients with ACC, diagnosed in 12 referral centers in Italy from January 1990 to June 2018. RESULTS: ACC diagnosed as incidentalomas accounted for overall 38.1% of cases, with a frequency that increases with age and with less aggressive pathological features than symptomatic tumors. Women (60.2%) were younger than men and had smaller tumors, which more frequently secreted hormones. Surgery was mainly done with an open approach (72%), and after surgical resection, 62.7% of patients started adjuvant mitotane therapy. Recurrence after tumor resection occurred in 56.2% of patients. In patients with localized disease, cortisol secretion, ENSAT stage III, Ki67%, and Weiss score were associated with an increased risk of recurrence, whereas margin-free resection, open surgery, and adjuvant mitotane treatment were associated with reduced risk. Death occurred in 38.1% of patients and recurrence-free survival (RFS) predicted overall survival (OS). In localized disease, age, cortisol secretion, Ki67%, ENSAT stage III, and recurrence were associated with increased risk of mortality. ACCs presenting as adrenal incidentalomas showed prolonged RFS and OS. CONCLUSION: Our study shows that ACC is a sex-related disease and demonstrates that an incidental presentation is associated with a better outcome. Given the correlation between RFS and OS, RFS may be used as a surrogate endpoint in clinical studies.

Prognostic predictors of adrenocortical carcinoma: A single-center thirty-year experience.

Background: The prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and to determine the prognostic predictors of overall and progression-free survival. Methods: Medical records of patients, who were diagnosed with ACC at Taipei Veterans General Hospital between January 1992 and June 2021, were reviewed. Patient demographics, tumor characteristics, and subsequent treatment were analyzed with regard to overall survival and progression-free survival using Kaplan-Meier methods and a Cox regression model. Results: Sixty-seven patients were included. Females (65.7%) were more susceptible to ACC, with a younger onset and active hormonal secretion. One-half of the patients exhibited distant metastases at the time of diagnosis. The European Network for the Study of Adrenal Tumours (ENSAT) stage (hazard ratio [HR] 3.60 [95% confidence interval (CI) 1.25-10.38]; p=0.018), large vessel invasion (HR 5.19 [95% CI 1.75-15.37]; p=0.003), and mitotane use (HR 0.27 [95% CI 0.11-0.70]; p=0.007) were significantly associated with overall survival (OS). There was no single factor independently associated with progression-free survival. Conclusion: ENSAT stage had a substantial impact on overall survival though there was no difference in OS between patients with stage II and stage III ACC. Large vessel invasion portended poor prognosis and influenced OS significantly. Moreover, mitotane only improved clinical outcomes of patients with stage IV disease.

The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery. METHODS: We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan-Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery). RESULTS: Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0-12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22-258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery. CONCLUSIONS: Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.

Pregnancy in patients with adrenocortical carcinoma: a case-based discussion.

Although adrenocortical carcinoma (ACC) during pregnancy is rare, a retrospective review of a case series at our hospital revealed that almost one third of our patients were women in childbearing age. Given that the age of maternity is increasing, dealing with a tumor diagnosis during pregnancy and the need for fertility planning in cancer survivors is likely to become more frequent.We thus carried out a case-based discussion regarding: i) diagnosing and treating an ACC during pregnancy; ii) patients conceiving while on mitotane; iii) ACC survivors with a maternal desire.In each of these cases, it is important to provide patients with sufficient information, to offer medical advice and psychological support, to personalize treatments in accordance with the wishes of the patient and her relatives, and to collaborate with other specialists since a multidisciplinary expert team is required to manage each case individually.

Ferroptosis Biomarkers for Predicting Prognosis and Immunotherapy Efficacy in Adrenocortical Carcinoma.

BACKGROUND: Numerous studies have suggested that ferroptosis plays an important regulatory role in cancer cell death. Nonetheless, the potential effects of ferroptosis regulators on the prognosis, the expression of immunomodulatory factors in the tumor microenvironment and on the efficacy of immunotherapy in adrenocortical carcinoma (ACC) remain largely unknown. METHODS: Public ACC datasets were used to investigate the relationship between ferroptosis regulators and prognosis and clinical features. A ferroptosis scoring system was established for individual cases of ACC using principal component analysis algorithms. Hub ferroptosis-related genes involved in immunoregulation and immunotherapy efficacy in ACC were further identified. RESULTS: Twenty ferroptosis regulators were differentially expressed in ACC and 17 ferroptosis regulators were closely related to prognosis in ACC. A ferroptosis scoring system was developed based on ACSL4, FANCD2, and SLC7A1 expression, and the ferroptosis regulators could serve as an independent prognostic factor for ACC. Further analyses indicated that the ferroptosis score integrated with the tumor mutation burden (TMB), and immune-checkpoint gene expression could predict prognosis in ACC. RNA isolation and reverse transcription­quantitative polymerase chain reaction (RT-qPCR) demonstrated significant differences in the expression levels of ACSL4, FANCD2, and SLC7A1 between ACC and normal tissues. Furthermore, FANCD2 was significantly related to immunotherapy efficacy and prognosis in ACC. CONCLUSION: Our study demonstrated that ferroptosis was significantly associated with prognosis, clinical characteristics, immune-checkpoint gene expression, and tumor microenvironment immune cell infiltration in ACC. The current study provides comprehensive evidence for further research on ferroptosis regulators in ACC and provides new insight into the epigenetic regulation of the antitumor immune response.

Effective multimodal management of a giant adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma is a rare and aggressive tumour. The only curative treatment is surgery with negative margins. In most series, the average lesion size ranges from 5.5 to 15 cm. METHODS: We report the case of a 27-year-old female with hyperandrogenism and Cushing syndrome due to a right adrenocortical carcinoma of 19.7 cm. RESULTS: The tumour abutting on liver and vena cava and the presence two nodules in liver required extensive surgery including a right posterior sectionectomy and an en bloc resection of the adrenal mass together with the right kidney and the gallbladder. The vena cava was also resected with a reconstruction using a pericardial patch since it was invaded on its border. Pathological examination confirmed an adrenocortical carcinoma, with tumour invasion of vessels, tumour capsule, vena cava and two metastases in the liver (pT4N0M1). All margins were negative. Three months after surgery, two lung nodules, cardio-phrenic and internal mammary adenomegalies were noticed on a PET/CT scan, justifying the initiation of chemotherapy, alongside with mitotane. After a 10-month follow-up, CT scan was stable excepted for a lung nodule growing from 4 to 7 mm. Targeted stereotaxic radiotherapy was then administered. Twenty-two months after surgery, the patient has improved considerably and all signs of hyperandrogenism and Cushing syndrome have resolved. CONCLUSION: This case of adrenocortical carcinoma illustrates one of the largest tumours among those reported. It demonstrates the feasibility and effectiveness of a multimodal approach in its treatment even if it is giant and at high risk.

Pediatric adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy of the adrenal gland with an unfavorable prognosis. It is rare in the pediatric population, with an incidence of 0.2-0.3 patients per million in patients under 20 years old. It is primarily associated with Li-Fraumeni and Beckwith-Wiedemann tumor predisposition syndromes in children. The incidence of pediatric ACC is 10-15fold higher in southern Brazil due to a higher prevalence of TP53 mutation associated with Li-Fraumeni syndrome in that population. Current treatment protocols are derived from adult ACC and consist of surgery and/or chemotherapy with etoposide, doxorubicin, and cisplatin (EDP) with mitotane. Limited research has been reported on other treatment modalities for pediatric ACC, including mitotane, pembrolizumab, cabozantinib, and chimeric antigen receptor autologous cell (CAR-T) therapy.

Long-term survival outcomes of pediatric adrenal malignancies: An analysis with the upstaged SEER registry during 2000-2019.

Objective: To investigate the clinicopathological characteristics and long-term survival outcomes of pediatric adrenal malignancies. Method: This study retrospectively analyzed children with pathologically confirmed pediatric adrenal malignancies from Surveillance, Epidemiology, and End Results Database from 2000 to 2019. Kaplan-Meier curve was used to assess the overall survival (OS) and cancer-special survival (CSS), and the Log-Rank method was used to calculate statistical differences. Cox proportional hazards model and Fine-and-Grey model were used to calculate the hazard ratio (HR) of all-cause mortality risk and the sub-distribution HR (sHR) of disease-specific mortality risk, respectively, and their corresponding 95% confidence intervals (CI). Results: 1601 children were included in the study in which 1335 (83.4%) neuroblastoma, 151 (9.4%) ganglioneuroblastoma, 89 (5.6%) adrenocortical carcinoma, and 26 (1.6%) were diagnosed with other types malignancies. Metastatic disease accounted for the largest proportion (69.3%), and the proportion of metastases diagnosed by neuroblastoma was higher than that of adrenocortical carcinoma and ganglioneuroblastoma (73.9% vs. 45.7% vs. 47.2%). The 5-year OS and CSS of all cohort were 69.5% and 70.5%, respectively. Adrenal cortical carcinoma had the worst prognosis, with 5-year OS and CSS of 52.5% and 53.1%, respectively. Patients in recent years had no better OS and CSS than in previous years at diagnosis. The tumor stage remained the main prognostic predictor. Compared to metastatic adrenal tumors, the risk of all-cause mortality (adjusted HR: 0.12, 95% CI: 0.06-0.25, P < 0.001) and the risk of disease-specific mortality (adjusted sHR: 0.11, 95% CI: 0.05-0.25, P<0.001) was significantly lower for patients with localized diseases. Additionally, higher age, adrenal cortical carcinoma, and lack of complete tumor resection are independent risk factors for poor prognosis. Furthermore, it was found that the prognosis of patients who received chemotherapy was worse than those who did not, mainly because the former mostly had metastasis at the presentation and complete resection of the tumor cannot be achieved. Conclusion: The clinicopathological characteristics of pediatric adrenal malignancies have not changed significantly in the past two decades, while the prognosis of patients has improved. Early diagnosis of disease and complete resection of local tumors are the keys to improving prognosis.