Elsevier

Seminars in Oncology

Volume 37, Issue 6, December 2010, Pages 619-626
Seminars in Oncology

Endocrine cancer
Practical Considerations in the Evaluation and Management of Adrenocortical Cancer

https://doi.org/10.1053/j.seminoncol.2010.10.011Get rights and content

Adrenocortical cancer (ACC) is a rare, challenging disease with a broad range of clinical presentations. Often presenting in an advanced stage with a large, locally invasive primary tumor or with Cushing's syndrome, it requires a multidisciplinary approach to treatment. We discuss controversies in the evaluation and management of ACC. We conclude that the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) remains unclear and that it should be employed sparingly. Biopsies should be performed only when metastatic disease is present and a primary tumor has not been clearly established. Care should be taken in using the Weiss criteria to make decisions regarding prognosis. Surgery is the preferred intervention initially and at the time of recurrence, and every effort should be made to attempt a surgical resection. The latter should be an open resection; laparoscopic resection should not be performed if there is a high suspicion of ACC. The use of mitotane in patients without evidence of disease remains controversial. Systemic chemotherapy is effective in patients with widely metastatic disease or as an adjunct to a surgical intervention and should focus on regimens that have been shown to effect responses; “novel targeted therapies” should not be employed as first-line treatment. Radiofrequency ablation (RFA) and cryoablation can be very helpful but are still under evaluation; embolization with or without chemotherapy may be used as a surgical adjunct. The role of radiation remains to be defined. Finally, physicians caring for these patients need to recognize that Cushing's disease is a debilitating problem that should be managed aggressively; expecting chemotherapy to solve this complication is not appropriate.

Section snippets

Evaluation and Work-Up

The evaluation of a patient presenting for the first time with an adrenal mass that may be ACC should include a history and physical examination, together with blood and urine tests to ascertain whether the tumor is functional. Imaging studies are an important adjunct to define the extent of disease as accurately as possible. Because surgical resection remains the only curative option for ACC, the approach from the outset should be to determine whether the patient's presentation is one that

The Role of Biopsy

In a patient presenting with an adrenal mass, careful deliberation is warranted in deciding whether a biopsy should be performed. The risk of seeding tumor—although not quantified—and the difficulty differentiating benign from malignant in a small biopsy sample, must be considered in making the decision.17, 18 In a patient with symptoms referable to excess hormone production, manifested either as frank Cushing's syndrome or subclinical hormone excess measured in a 24-hour urine collection, the

Pathologic Assessment

Distinguishing a small, 4- to 6-cm ACC without local spread or distant metastases from a benign adenoma can be challenging. To assist in the differential, several multi-parametric approaches have been proposed for establishing malignancy. Among these, the “Weiss criteria,” first proposed in 1984, is most widely used.19, 20, 21, 22, 23 It is based on nine histopathologic properties of adrenocortical tumors that were established unequivocally as malignant either because they metastasized or

Management of ACC

In general terms, three options are available for the management of ACC: surgical resection, oral mitotane, and intravenous chemotherapy. However, many management issues remain unsolved, in part because of the rarity of the disease and the paucity of data together with the challenges presented by large retroperitoneal tumors that have often metastasized locally and to distant sites. We address these below, again providing relevant background and opinions based on the available information and

Systemic Chemotherapy

As might be expected for a rare disease, the therapy of ACC suffers from a scientific database that is very limited and that might be characterized as a collection of anecdotes, albeit some larger than others. Nowhere is this more apparent than in the chemotherapy of ACC. The mitotane controversy has been addressed above and one might argue the choice of what chemotherapy is best is also a “work in progress.” In general terms when assessing chemotherapeutic efficacy one can look at response

Managing Patients With ACC—A Multidisciplinary Approach

Managing patients with ACC requires a multidisciplinary approach involving medical, surgical, and radiation oncologists, endocrinologists, and interventional radiologists. Both at presentation and at relapse the focus should be on whether a surgical intervention is possible, given this remains the most promising curative option for ACC. Unfortunately, despite aggressive surgery at the time of initial presentation, 70% to 85% of patients relapse locally or develop metastases, explaining a 5-year

Conclusion

Because surgical resection remains the principal curative option for ACC, the approach from the outset should be to determine whether the patient's initial or subsequent presentation is one that can be managed surgically. If the answer is yes, every effort should be made to accomplish this. Chemotherapy, RFA, cryoablation, embolization, and radiation therapy are valuable adjuncts. Future efforts should be directed at improving chemotherapy options and conducting the necessary studies to

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