Cancer Research, Statistics, and Treatment

: 2020  |  Volume : 3  |  Issue : 3  |  Page : 655--656

Treatment of adrenocortical carcinoma – Present and future

Saba Samad Memon, Anurag R Lila, Tushar R Bandgar 
 Department of Endocrinology and Metabolism, Seth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India

Correspondence Address:
Tushar R Bandgar
Department of Endocrinology and Metabolism, Seth G S Medical College and KEM Hospital, Parel, Mumbai - 400 012, Maharashtra

How to cite this article:
Memon SS, Lila AR, Bandgar TR. Treatment of adrenocortical carcinoma – Present and future.Cancer Res Stat Treat 2020;3:655-656

How to cite this URL:
Memon SS, Lila AR, Bandgar TR. Treatment of adrenocortical carcinoma – Present and future. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Dec 2 ];3:655-656
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Adrenocortical carcinoma (ACC) is undeniably one of the worst malignancies that endocrinologists encounter. The article by Kapoor et al. about the role of systemic therapy in ACC is indeed commendable.[1] As ACC is a rare disease, there is a paucity of data on its outcomes. Kapoor et al.'s study reports the real-world data from a resource-limited country like India and reiterates the dismal survival for this aggressive malignancy. Although the paper is lucid and well written, a few points in the article merit discussion.

ACC originates from the hormone-producing adrenal cortical tissue; thus, autonomous excess production of steroids and androgens is a common clinical presentation in almost 50%–75% of the patients.[2] However, in the study by Kapoor et al., Cushing's syndrome was the presenting feature in 16.7% of the patients, although biochemically 46.5% had functional hormonal synthesis. Cortisol excess is associated with worse survival and poor prognosis.[2] An additional analysis of the survival outcomes for the secretory versus non-secretory phenotypes could have underscored the same in Kapoor et al.'s data. It could also probably explain the better survival observed in their study compared to the study by Schulick and Brennan, which had a higher percentage of patients with clinically overt hormone excess.[3]

Yet another bone of contention is the use of mitotane in the adjuvant setting. The data supporting such use are largely derived from retrospective single-center studies.[4] The results of the randomized prospective multicenter trial, ADUVIO, are still awaited. The use of mitotane is fraught with many difficulties, of which monetary concerns and unavailability are the foremost. In addition to systemic toxicity, mitotane causes an increase in the levels of hormone-binding proteins, making the interpretation, and replacement of other hormones challenging. In patients requiring replacement of thyroid hormones, testosterone, cortisol, and even aldosterone, the dose of the medication has to be increased by 3–5-fold to prevent morbidity and mortality. In addition, alternative strategies like testing the free hormone levels are warranted for monitoring. It might be interesting to compare the survival of the patients from the current cohort who did not receive mitotane in the adjuvant setting with that of patients from a comparable historical cohort who are able to receive mitotane to justify its use.

Despite the grim overall outlook towards ACC, the genomic and molecular advancements are paving the way for a hopeful future. Profiling the tumor tissue with a transcriptome analysis for the expression of BUB1B-PINK1 and the absence of hypermethylation of the CpG islands can help identify tumors with a better prognosis, even in patients with Stage I/II/III disease, who may merit just watchful waiting.[2] It can thus identify a subset of tumors with worse outcomes, that can receive aggressive management soon after surgery. The p53-RB, insulin-like growth factor (IGF), and Wnt/β-catenin pathways have been identified to play an important role in ACC pathogenesis; however, targeting the IGF pathway did not lead to improved survival.[5] Targeting the use of these specific drugs only for the tumors that express these driver mutations may improve the response rates. Moreover, novel drugs against the steroidogenesis pathway and immunomodulating drugs are currently in trials. Thus, genomics-guided care could be the future of ACC.

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1Kapoor A, Noronha V, Toshniwal A, Menon S, Joshi A, Patil VM, et al. Exploring the role of systemic therapy in adult adrenocortical carcinoma: A single-center experience. Cancer Res Stat Treat 2020;3:192-200.
2Jouinot A, Bertherat J. Management of endocrine disease: Adrenocortical carcinoma: Differentiating the good from the poor prognosis tumors. Eur J Endocrinol 2018;178:R215-30.
3Schulick RD, Brennan MF. Long-term survival after complete resection and repeat resection in patients with adrenocortical carcinoma. Ann Surg Oncol 1999;6:719-26.
4Rajappa S. Treating advanced adrenal cortical carcinoma: The long, winding, and endless road. Cancer Res Stat Treat 2020;3:290-2.
5Mohan DR, Lerario AM, Hammer GD. Therapeutic targets for adrenocortical carcinoma in the genomics era. J Endocr Soc 2018;2:1259-74.