As grade progresses, survival is considerably worse for this already extremely aggressive disease. The European network for the study of adrenal tumors (ENSAT) staging classification for ADCC demonstrates that the hazard ratio (HR) for grade 4 compared to grade 1 for disease specific survival is 3.2 (C.I 95%; 2.24-4.58).
The management of ADCC has always been and still remains surgery. Therefore, the key is not to jeopardize the success of a surgical intervention. Dr. Fojo emphasized that laparoscopic surgery should not be performed for this specific entity. He presented data showing that peritoneal dissemination occurs in 47% vs. 3.1% in laparoscopic and open surgery, respectively, with a relative risk of 15.1 (C.I. 95% 6.8-33.4), p<0.0001.
CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1, a molecule endowed with potent chemotactic activity for lymphocytes. This receptor is also abundantly expressed in normal and malignant adrenal tissue. This can be used for immunohistochemistry staining for identification of these tumors.
Dr. Fojo continued his talk and focused on adjuvant therapy, quoting a New England Journal of Medicine (NEJM) paper discussing the role of Mitotane, discovered in the 1960’s, as an adjuvant treatment modality for ADCC, emphasizing the fact that in this setting, Mitotane should be given slowly and under strict supervision. Moving on to metastatic disease, Dr. Fojo discussed another NEJM paper discussing the beneficial role of chemotherapy in metastatic ADCC. Unfortunately, there are no significant discoveries regarding targeted therapy in ADCC. Lastly, looking at the now very popular treatment modality of immunotherapy, specifically in the setting of ADCC, TCGA data has shown that the mutational load in ADCC is quite high, following Melanoma and bladder cancer, potentially making it a suitable candidate for this newly discovered therapy. Unfortunately data has shown that PD-L1 expression in ADCC is quite low, thus restricting the potential added benefit for this specific therapy.
In summary, surgery remains to date the only curative option for ADCC. Laparoscopic resection leads to peritoneal dissemination, an incurable iatrogenic problem, and therefore, should not be used. Adjuvant Mitotane should be given to high risk patients in a controlled supervised manner. Chemotherapy has limited albeit beneficial activity in the management of metastatic ADCC. Immunotherapy is still unproven in this entity and should only be given as a last resort and not before conventional chemotherapy. Dr. Fojo concluded his presentation by stressing the importance of enrolling patients with this rare entity into clinical trials.
Presented By: Antonio Tito Fojo, MD, PhD, Columbia University
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA