Contemporary Approaches to Adrenocortical Carcinoma
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Alexa J. Hughes, MD, MEdª, Alexandria D. McDow, MDb, Hadley E. Ritter, MDb, Anthony D. Yang, MD, MSa,b, *
KEYWORDS
. Adrenocortical carcinoma . Adrenalectomy . Chemotherapy . Targeted therapy
KEY POINTS
· Adrenal cortical carcinoma (ACC) is a rare, aggressive cancer. All cases should involve expert medical oncologists and fellowship-trained surgical oncologists or endocrine surgeons.
· Surgery is the main treatment for Stage I/II ACC, with clinical trials no longer supporting routine adjuvant mitotane use.
· Unresectable ACC relies heavily on mitotane-based therapies. Additional local therapies have been used but lack a recommended regimen.
· Recurrence rates are high, necessitating routine surveillance with frequent radiographic evaluations to monitor and adjust therapy.
· All patients with ACC should be evaluated for participation in a clinical trial when appropriate.
INTRODUCTION
Adrenocortical carcinoma (ACC) is an uncommon and highly aggressive neoplasm that arises from the adrenal cortex. The incidence of ACC is estimated to range from 0.5 to 2 cases per million persons in the United States annually. Despite its rarity, ACC accounts for 0.02% to 0.2% of all cancer-related deaths.1-3 The disease exhibits a bimodal age distribution, with peak incidences observed in children under the age of 5 years and adults in their fourth to fifth decades of life. The median age of diagnosis is
This article originally appeared in Advances in Oncology, Volume 5, Issue 1, May 2025.
a Department of Surgery, Surgical Outcomes and Quality Improvement Center (SOQIC), Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall, Indianapolis, IN, USA; b Division of Surgical Oncology, Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall, Indianapolis, IN, USA
* Corresponding author. Department of Surgery, Surgical Outcomes and Quality Improvement Center (SOQIC), Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall, Indi- anapolis, IN 46202.
E-mail address: Yangad@iu.edu
Hematol Oncol Clin N Am 40 (2026) 25-37
https://doi.org/10.1016/j.hoc.2025.07.003
| Abbreviations | |
| ACC | adrenocortical carcinoma |
| AJCC | American Joint Committee on Cancer |
| CT | computed tomographic |
| EDP-M | Etoposide, doxorubicin, and cisplatin |
| ENSAT | European Network for the Study of Adrenal Tumors |
| MIA | minimally invasive adrenalectomy |
| OA | open adrenalectomy |
reported between the ages of 46 and 55 years.4-6 Epidemiologic data indicate a fe- male predominance with a female-to-male ratio of 1.5 to 2.5:1.3,6
ACC in adults frequently presents at an advanced stage, with high-grade tumors and metastatic disease at diagnosis. Approximately 20% to 40% of patients present with metastatic disease, most frequently in the form of pulmonary, hepatic, or bony metastases. The prognosis of ACC remains poor with a median survival of 18 months and a 5 year survival rate ranging from 16% to 47% contingent on tumor stage at pre- sentation.1 Historically, key prognostic factors have included completeness of surgical resection, disease stage, and pathologic grade.7 More recent literature has under- scored the importance of integrating clinical and molecular markers to enhance prog- nostication, including hormone secretion profiles, mass-related symptoms, Ki-67 index, and other molecular markers.6,8,9 High Ki-67 levels are associated with poor outcomes, emphasizing the need for its inclusion in prognostic discussions and treat- ment decisions. 10
ACC most often arises sporadically but can be associated with hereditary cancer syndromes. The underlining tumorigenesis in sporadic ACCs has not been fully eluci- dated; however, studies have shown that inactivating mutation in p53 and changes in the IGF2 gene frequently occur. Hereditary disorders are linked to ACC in 10% to 15% of cases, including Li-Fraumeni syndrome (p53), Familial Adenomatous Polyposis (FAP) or Gardner syndrome (APC), Beckwith-Wiedemann syndrome (CDKN1C), Carney complex (PRKAR1A), and MEN1.11 Aside from the previously mentioned ge- netic syndromes, there have been few modifiable risk factors associated with the development of sporadic ACC.
HORMONAL ACTIVITY OF ADRENOCORTICAL CARCINOMA
Upon diagnosis, ACC tumors are categorized as either functional or nonfunctional tu- mors based on their ability to produce hormones. Approximately 60% of ACC cases are functional, the majority of which produce cortisol, while the remaining 40% are nonfunctional tumors.12,13 Patients with functional tumors typically present with clin- ical signs and symptoms with the specific hormone produced (Table 1).
Functional Tumors
· Hypercortisolism is the most common presentation of functional ACCs, occurring in 50% to 80% of hormone-secreting cases. This condition often manifests as Cushing syndrome characterized by proximal muscle weakness, hyperglycemia or new-onset diabetes, facial plethora, abdominal striae, and osteoporosis.3,13
· Androgen excess is the second most common hormone produced by ACC, observed in 40% to 60% of functional ACCs. Clinical manifestations include hir- sutism, virilization, and menstrual irregularities in women. It is important to note that hyperandrogenism in male individuals is frequently underdiagnosed as the symptoms are subtle and unrecognized by physicians. 12,13
| Table 1 Common syndromes from functional adrenocortical carcinoma | ||
|---|---|---|
| Syndrome | Clinical Presentation | Laboratory Evaluation |
| Hypercortisolemia (Cushing Syndrome) | Central weight gain, abdominal striae, hypertension, | Screening should involve 1 of the following tests |
| hyperglycemia, hirsutism, proximal muscle weakness | · 1 mg overnight dexamethasone suppression test · Midnight salivary cortisol . 24 h urinary free cortisol Plasma adrenocorticotropic hormone (ACTH) in AM if confirmed hypercortisolemia to determine whether ACTH dependent or ACTH independent | |
| Androgen Excess | Female individuals: hirsutism, virilization, deepening of the voice, oligo/amenorrhea Male individuals: gynecomastia, testicular atrophy | Adrenal androgens · DHEAS · Androstenedione · Testosterone · 17-hydroxyprogesterone |
| Hyperaldosteronism (Conn Syndrome) | Hypertension, hypokalemia, weakness | Screening: suppressed renin activity and elevated plasma aldosterone level (>10 ng/dL) |
· Hyperaldosteronism: Autonomous aldosterone secretion leads to hypokalemia and hypertension due to disruption of the renin-angiotensin-aldosterone axis. Excess aldosterone production is rare in ACC, accounting for only 2% of func- tional ACCs. 6,14,15
· Multihormonal secretion is also commonly seen in patients with functional tu- mors, further complicating the clinical presentation and management.
Nonfunctional Tumors
Patients with nonfunctional tumors generally present with symptoms related to mass effect from the tumor. These symptoms include nausea, decreased appetite, vomiting, back, and abdominal pain. While some patients are symptomatic due to the size of the tumor, approximately 10% are diagnosed incidentally when found to have an adrenal mass, or incidentaloma, after having a computed tomographic (CT) scan or imaging for other indications.
EVALUATION
All patients found to have an adrenal mass or incidentaloma should undergo a comprehensive evaluation including a biochemical assessment to evaluate for hor- mone hypersecretion (see Table 1) and a morphologic and staging evaluation with proper adrenal-focused imaging.
Biochemical Assessment
The biochemical evaluation of adrenal lesions is crucial to diagnosing excess hormone production, determining the origin of tumor, utilizing steroid hormone levels as tumor markers for surveillance, and assessing the need for hydrocortisone replacement ther- apy in cases of adrenal insufficiency. The hormonal assessment (see Table 1) involves
measuring levels of glucocorticoids, mineralocorticoids, sex steroids, and their pre- cursors. This evaluation can include an overnight low-dose dexamethasone suppres- sion test, late-night salivary cortisol measurement, and 24 h urinary cortisol levels. Additionally, it is crucial to rule out the presence of a pheochromocytoma, by measuring plasma or 24 h urine metanephrines and normetanephrines, prior to per- forming any invasive procedure or surgical intervention.
Radiologic Evaluation
Staging imaging examinations should include CT scans of the abdomen and pelvis, as well as a CT chest to evaluate for metastasis. CT scans with an adrenal intravenous contrast administration protocol, compromising a pre-contrast, arterial phase, portal venous phase, and delayed contrast phase, are recommended to evaluate for washout patterns and for assessment of arterial and venous anatomy. Additional brain imaging is warranted only if distant brain metastasis is clinically suspected. Additional modal- ities such as MRI and PET/CT scan can also be useful in the evaluation of ACC.14
ACC may vary in appearance on CT scans with frequent heterogenous enhance- ment because of necrosis, calcification, and internal hemorrhage present in the malig- nant mass. Concerning CT findings for ACC include
· Lower attenuation (>10 HFU)
· Slow contrast washout of lesion
· Overall, 20% to 50% contrast washout at 10 minutes (benign tumors have a higher washout due to their high lipid content)
· Lesion greater than 4 to 6 cm
· Irregular tumor margins
· Central necrosis or hemorrhage
· Invasion into adjacent structures
· Extension into surrounding vasculature (commonly the renal vein or inferior vena cava)
· Calcifications (Fig. 1)
MRI can be utilized to confirm ACC if CT scans fail to adequately characterize the adrenal lesion. Concerning MRI findings for ACC include
· Isointense to hypointense signal on T1 imaging
· Hyperintense signal on T2 imaging
· Heterogenous signal drop on chemical shift
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PET can be useful for identifying suspected metastatic sites, although it is not routinely utilized as a staging tool in ACC.16 PET may provide useful information when a CT or MRI is unable to determine whether a lesion is benign or malignant. 13
Adrenal Biopsy
Adrenal biopsy is not recommended as part of the routine diagnostic evaluation of pa- tients with suspected ACC unless there is concern for metastatic disease. Biopsy may be useful in the contemporary era to guide oncologic medical management with tar- geted therapies and other novel agents.
STAGING
Prior to 2003, no TNM staging classification existed for ACC. This led the American Joint Committee on Cancer (AJCC) to develop TNM staging in 2004 (Table 2). This classification is used as the foundation for both the AJCC staging system and the Eu- ropean Network for the Study of Adrenal Tumors (ENSAT) staging systems; however, some differences exist (Table 3). The ENSAT staging system has been shown to better reflect patient prognosis than the AJCC classification, although the AJCC classifica- tion is still widely used in the United States and influences National Comprehensive Cancer Network (NCCN) guidelines.17 Other unique staging systems have been pro- posed to further refine prognosis based on patient age, tumor grade, margin status, and patient presentation.9,10,18
SURGICAL MANAGEMENT OF RESECTABLE ADRENOCORTICAL CARCINOMA (STAGES I-III)
Surgical resection remains the primary treatment of nonmetastatic or low-grade and locally advanced ACC (Stages I-III). Complete surgical excision (RO resection) re- mains the only potential curable treatment of ACC. Unfortunately, even low-grade disease is often not curable due to occult micrometastasis, with distant metastases developing in 40% of patients within 2 years following resection.3 Advanced and
| Table 2 TNM staging of adrenocortical carcinoma | ||||
|---|---|---|---|---|
| Primary Tumor (T) | Regional Lymph Nodes (N) | Distant Metastasis (M) | ||
| T0 No evidence of primary tumor | N0 | No regional lymph node metastasis | M0 | No distant metastasis |
| T1 Tumor ≤5 cm, no extra-adrenal invasion | N1 | Regional lymph node metastasis | M1 | Distant metastasis |
| T2 Tumor >5 cm, no extra-adrenal invasion | ||||
| T3 Tumor of any size with local invasion but not invading adjacent structuresª | ||||
| T4 Tumor of any size that invades adjacent organs or large blood vesselsb | ||||
a Adjacent organs include kidney, diaphragm, great vessels, pancreas, liver.
b Large blood vessels include the vena cava and renal veins.
| Stage I | Stage II | Stage III | Stage IV | |
|---|---|---|---|---|
| ENSAT | T1, N0, M0 | T2, N0, M0 | T1-T2, N1, M0 or T3, N0, M0 | Any T, any N, M1 or T3, N1, M0 or T4, any N, M0 |
| AJCC | T1, N0, M0 | T2, N0, M0 | T1-T2, N1, M0 or T3-T4, N0-1, M0 | Any T, any N, M1 |
metastatic ACC relies primarily on systemic chemotherapy since Stage IV ACC is considered unresectable.
Due to the rarity of ACC, it is recommended that all operations are performed by experienced adrenal and oncologic surgeons. The definition of an experienced sur- geon is not well defined. Recent guidelines from the ENSAT recommend a minimal of 6 adrenalectomies per year, but ideally more than 20 per year to qualify as an expert surgeon. 19
Open adrenalectomy (OA) via a transperitoneal approach remains the standard of care for patients with localized disease (Stages I-II) and locally advanced disease (Stage III) when an R0 resection can be achieved.12,20 Complete en bloc resection of adrenal tumors suspected to be ACC should be performed while adhering to surgi- cal oncologic principles. Surgery includes resection of the periadrenal and retroperi- toneal fat, as well as routine loco-regional lymphadenectomy of the periadrenal and renal hilar lymph nodes, in addition to any suspicious nodes identified intraoperatively or on preoperative imaging. The optimal extent of lymphadenectomy has not been defined, and there is only weak evidence to support removal of the celiac, superior mesenteric artery (SMA), para-aortic, or paracaval lymph nodes ipsilateral to the tu- mor.21 Intracaval extension or tumor thrombus is not a contraindication to surgery and patients with these findings should be referred to centers with appropriate exper- tise. For tumors that do not invade the kidney, a nephrectomy is not required because it does not appear to improve overall or disease-free survival.22 It is critical to avoid tumor rupture or spillage intraoperatively as this has been reported to lead to worse outcomes.4 The role of neoadjuvant therapy is evolving but continues not to be recom- mended as standard practice for patients with resectable disease. Approximately 30% of tumors are upstaged from Stage II to Stage III after pathologic examination due to invasion of adjacent tissues or structures (Fig. 2). 16,23
While OA is the recommended approach for adrenal malignancies, minimally inva- sive adrenalectomy (MIA) remains controversial in the setting of ACC. Laparoscopic- assisted or robotic-assisted adrenalectomy is the gold standard for resection of benign adrenal tumors. ENSAT recommends open surgery for suspected ACC with evidence of local invasion but also states that laparoscopic adrenalectomy can be considered for tumors less than 6 cm without evidence of local invasion. They further specify that a laparoscopic approach should be restricted to high-volume centers and there should be a low threshold to convert to an open procedure if there is an increased risk of tumor rupture.20 It should be noted that ENSAT does not comment on robotic surgery in their recommendations.12 Concerns regarding MIA include re- ports of higher recurrence rates, particularly with peritoneal carcinomatosis, tumor rupture and spillage with larger tumors, and decreased rates of RO resection.24-27
Current evidence comparing OA to MIA is based on retrospective case studies and meta-analyses as there are no randomized clinical studies comparing OA to MIA.
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Recently, a few meta-analyses have demonstrated conflicting conclusions regarding the efficacy and oncologic outcomes of MIA compared to OA. Rossi and colleagues reported that there has been an increase in the use of minimally invasive approaches for adrenalectomy in ACC but concluded that the heterogenous results of retrospec- tive studies make it difficult to draw conclusions. Eight of the included studies found that OA was as effective as MIA, while 6 studies concluded that OA was superior to MIA.28 In a different review, Cavallaro and colleagues concluded that there were no significant differences in recurrence rates or cancer-related mortality between open and MIA for Stage I or II disease.16 A separate review article from Giordano and col- leagues evaluated 18 studies comparing MIA to OA and found that there was a higher rate of RO resection (77%-89%) and a lower recurrence rate (24%-29%) with an open approach compared to MIA (67%-85% and 26%-36%, respectively).24 With the mixed findings across review articles, there is a clear need for further investigation.29 Careful selection of patients for whom MIA can be considered should only occur in high-volume centers with expertise in MIA.
ADJUVANT THERAPIES FOR ADRENOCORTICAL CARCINOMA
Adjuvant chemotherapy with mitotane has traditionally been routinely recommended for patients who underwent an RO resection. However, the evidence for mitotane’s effectiveness in this population is unclear, with conflicting evidence based solely on retrospective reviews. Recently, the routine use of adjuvant mitotane in ACC with low-to-intermediate risk of recurrence was not recommended based on findings from the ADIUVO study published in 2023. This was the first multicenter randomized phase 3 clinical trial performed across 7 countries evaluating the use of adjuvant mito- tane in a subset of patients with ACC. Researchers included 91 patients with ACC who underwent an R0 resection with a low-to-intermediate risk of ACC recurrence (Stages I-III, Ki67 <10%). Their results showed no statistical difference in 5 year overall sur- vival and noted that the quality of life for patients with ACC is negatively impacted by adjuvant treatment with mitotane due to side effects, including fatigue, dizziness, gastrointestinal distress, adrenal insufficiency, liver toxicity, hypercholesterolemia, hypertriglyceridemia, anemia, and neutropenia.30
Mitotane remains a foundational part of chemotherapy for resected ACC at high risk for recurrence. European Society of Endocrinology (ESE)-ENSAT recommends that
patients at high risk of recurrence should be offered adjuvant mitotane. This high-risk population includes patients with Stage III disease, R1 or RX reresection, or a Ki-67 Index greater than 10%. Adjuvant therapy should be initiated, usually within 3 months of adrenalectomy. Mitotane blood levels should be monitored with a target of 14 to 30 mg/L and should be administered for at least 2 years as this timeframe has the greatest chance of disease recurrence. Mitotane is a difficult drug to manage due to its long half-life, dose-limiting toxicity, and its narrow therapeutic window, requiring close monitoring. 31
The role of combination mitotane-based chemotherapy is also unclear. The ADIUVO-2 trial is currently recruiting patients. It aims to investigate the efficacy of adjuvant mitotane alone compared to adjuvant mitotane with cisplatin and etoposide in patients with Stages I-III ACC and a high risk of recurrence (ClinicalTrials.gov iden- tifier: NCT03583710).
MANAGEMENT OF RECURRENT ADRENOCORTICAL CARCINOMA
ACC has a reported recurrence rate of up to 85% after surgical resection, with pa- tients with more advanced disease on presentation with higher recurrence rates. 30,32 Though the evidence is limited, locally recurrent disease that is surgically resectable can be managed with repeat surgical excision when time to disease recurrence is greater than 1 year. Patients who present with recurrence more than 12 months after initial resection, low Ki-67 index, and had an R0 resection have the best outcomes. It is not recommended to reoperate in patients who have experienced recurrent disease in less than 12 months. It is contraindicated, to offer re-resection laparos- copically. Although this is a strong recommendation by ENSAT, the evidence level to support this recommendation is low.2º Additional routine tumor debulking is contraindicated.19,20
MANAGEMENT OF UNRESECTABLE ADRENOCORTICAL CARCINOMA Surgical Management of Unresectable Disease
In general, patients who have advanced or metastatic ACC are not candidates for surgery.
Select patients with borderline-resectable ACC may benefit from neoadjuvant chemotherapy prior to consideration of surgery. Borderline-resectable disease is not well defined in the setting of ACC but typically encompasses patients who have a very high risk of morbidity or mortality with resection are at risk of incomplete resec- tion (R1 resection), direct invasion of tumor into the liver, wall of the inferior vena cava (IVC) or renal vein, or abutting the celiac axis or superior mesenteric artery.33 Metasta- tic disease is generally a contraindication for resection; however, surgical resection of solitary or minimal liver and/or pulmonary oligometastases can be considered if an R0 resection is feasible and there is low morbidity and mortality.19,20
For functional tumors that are not resectable, surgical tumor debulking may play a role in improving the efficacy of medical therapy and help decrease hormone hyper- secretion. Routine use of surgery in patients with widespread metastatic disease, for palliative resection, or reoperation for previous R2 (incomplete macroscopic resec- tion) resection is not recommended. 12,19,20
Medical Therapy for Unresectable Adrenocortical Carcinoma
Mitotane in combination with etoposide, doxorubicin, and cisplatin (EDP-M) is the first-line regimen for advanced, unresectable ACC. This recommendation was established based on results from the (First International Randomized Trial in Locally
Advanced and Metastatic Adrenocortical Carcinoma Treatment [FIRM-ACT]) trial. This phase III randomized control trial included 304 patients with advanced ACC to receive mitotane with either EDP-M or streptozotocin. Results from this trial showed that the EDP-M group had a higher response rate and a longer progression-free survival.19,34 Patients who have a good response following chemo- therapy can then be considered for surgery if the goal of an R0 resection is expected to be achieved.35
If patients continue to have progression of disease after EDP-M, patients should be enrolled into clinical trials, if possible. If clinical trials are unavailable, second-line chemotherapy regimens include streptozotocin with mitotane, or gemcitabine plus capecitabine with or without mitotane. The decision to continue mitotane should be discussed with the patient based on toxicities and drug tolerance. If second-line ther- apies are ineffective, salvage therapies with trofosfamide or thalidomide can be considered but have limited effective use.8,34
NONSURGICAL LOCAL THERAPIES FOR ADRENOCORTICAL CARCINOMA Radiation Therapy
Adjuvant radiation therapy should be considered in patients who underwent an R1 or Rx resection, or in Stage III disease, as it has been shown to reduce local recurrence, and help with long-term disease control.36,37 Radiation therapy should be utilized along with adjuvant mitotane. There is no role for radiation therapy in Stage I or II disease. 19
Role for Other Local Therapies
Several other local therapies are suggested to have a role for advanced ACC but there is no definitive consensus on which patients benefit, and which local therapy is supe- rior due to the lack of large studies. These local therapies include thermal ablation (radiofrequency, microwave, and cryoablation), transarterial chemoembolization, and transarterial radioembolization. Typically, the optimal local therapy is determined based on expert opinion, patient preference, and tumor location. A recent retrospec- tive analysis evaluating all subtypes of local therapies found that these treatments benefit many patients with advanced ACC with a reported disease control rate of 70% and a complete response rate of 20%. The authors note that they did not deter- mine whether one type of local therapy was more effective than another due to the small sample size. Furthermore, patients in this study who had mitotane plasma levels greater than 14 mg/L in addition to undergoing their chosen targeted therapy had improved outcomes, suggesting that concomitant use of mitotane with local therapies is potentially beneficial.38,39
NOVEL THERAPIES IN THE TREATMENT OF ADRENOCORTICAL CARCINOMA
There are currently multiple clinical trials investigating the role of targeted therapies such as tyrosine kinase receptors and immunotherapy for treatment of advanced ACC. Preliminary results of many of these studies have not demonstrated success in controlling disease progression; however, there appears to be some benefit of immunotherapy in targeted patient populations, such as those with certain germline mutations and microsatellite instability, as these patients often had higher response rates.8 Multi-tyrosine kinase inhibitors have been studied in small phase II studies. Un- fortunately, many of these drugs have failed to demonstrate significant impact on dis- ease progression and have shown that some of these medications are rapidly metabolized due to mitotane-induced CYP3A4 activity.8,40
SURVEILLANCE
Follow-up for treated ACC in patients without evidence of disease should include repeat laboratory work including a hormone evaluation for functional tumors, a CT scan of the chest and abdomen/pelvis, and a PET scan every 3 months for the first 2 years. Thereafter, every 4 to 6 months based on the risk of recurrence. 12,19 Investi- gators are examining the use of readily available biomarkers, such as cell free DNA, as a surveillance tool to decrease the need for repeated radiation exposure; however, these have yet to be validated.41
SUMMARY
ACC is a rare and aggressive malignancy with a challenging prognosis due to the aggressive nature of disease and the presence of metastasis or advanced disease on presentation. Due to the rarity of disease and aggressive nature, it is recommended that all patients with suspected ACC are treated at centers with oncologic expertise. Surgery with an R0 resection remains the cornerstone of treatment and only possible cure for disease. OA remains the standard of care from a surgical approach, but there are specific instances where a laparoscopic or minimally invasive approach may be warranted in high-volume centers with appropriate expertise. Ongoing research into the molecular and clinical underpinnings of ACC is likely to yield further insights, potentially leading to improved therapeutic options and outcomes for patients with ACC.
CLINICS CARE POINTS
· Given rarity of disease, it is recommended that every patient with suspected ACC be discussed in a multidisciplinary expert tumor board meeting and treated at a tertiary center with high- volume expertise in the treatment of ACC.
· Surgical resection remains the only curative option for ACC with en bloc resection performed by an experienced surgeon. OA is the standard of care, while a laparoscopic approach can be considered for tumors less than 6 cm without evidence of local invasion.
. Mitotane remains the cornerstone of medical treatment of advanced ACC. Findings from the (adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma [ADIUVO]) trial no longer recommend the routine use of adjuvant mitotane for patients with low-risk disease features. Neoadjuvant chemotherapy remains investigational.
. Local therapies can be effective in treating advanced ACC. However, there is a lack of consensus on the optimal regimen, which is largely based on expert consensus. Local therapies such as radiation do not play a role in Stage I or II disease, even as adjuvant therapies.
. It is strongly recommended that all patient who are candidates for a clinical trial be enrolled in one.
DISCLOSURE
The authors have nothing to disclose.
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