title: Adrenocortical Cancer: A Molecularly Complex Disease Where Surgery Matters.
abstract: The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered "adrenolytic," is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection. Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date, no targeted therapy has achieved meaningful outcomes. Consequently, first-line therapy for metastatic disease remains a combination regimen of etoposide, doxorubicin, and cisplatinum established in a randomized clinical trial. In addition to evaluating recent studies in adrenocortical cancer, we raise one critical clinical issue-the risk of peritoneal dissemination following laparoscopic resection of adrenocortical cancer. In a retrospective case series of 267 patients referred to the NCI for the treatment of recurrent or advanced adrenocortical cancer, we found extensive peritoneal dissemination in 25 of the 45 patients (55.6%) who had undergone laparoscopic resection, compared with only 7 of the 222 patients (3%) who had undergone an open resection (P < 0.0001). Although this has been debated in the literature, our data argue for an end to laparoscopic resection of adrenocortical cancers to avoid peritoneal dissemination, a complication of laparoscopy that is uniformly fatal. Clin Cancer Res; 22(20); 4989-5000. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS REVISING PARADIGMS".
authors.affiliation: Surgery Branch and Thoracic & GI Oncology Branch, NCI, NIH, Bethesda, Maryland.
authors.forename: Eden C
authors.initials: EC
authors.lastname: Payabyab
authors.affiliation: Division of Oncology Products 1, OHOP, CDER, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Sanjeeve
authors.initials: S
authors.lastname: Balasubramaniam
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Maureen
authors.initials: M
authors.lastname: Edgerly
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Margarita
authors.initials: M
authors.lastname: Velarde
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.affiliation: Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aradhana M
authors.initials: AM
authors.lastname: Venkatesan
authors.affiliation: James J. Peters Veterans Administration Medical Center, Bronx, New York.
authors.forename: Harshraj
authors.initials: H
authors.lastname: Leuva
authors.affiliation: Medical Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.affiliation: James J. Peters Veterans Administration Medical Center, Bronx, New York. Division of Medical Oncology, Department of Medicine, Columbia University Medical Center, New York, New York.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
authors.affiliation: James J. Peters Veterans Administration Medical Center, Bronx, New York. Division of Medical Oncology, Department of Medicine, Columbia University Medical Center, New York, New York. atf2116@cumc.columbia.edu.
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000628:therapy*; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000628:therapy*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D010535:Laparoscopy / Q000009:adverse effects / Q000401:mortality; D008939:Mitotane / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000556:secondary; D012189:Retrospective Studies
chemical_list: D018931:Antineoplastic Agents, Hormonal; D005047:Etoposide; D008939:Mitotane; D004317:Doxorubicin; D002945:Cisplatin