World Journal of Surgery

, Volume 38, Issue 6, pp 1318–1327 | Cite as

Borderline Resectable Adrenal Cortical Carcinoma: A Potential Role for Preoperative Chemotherapy

  • Brian K. Bednarski
  • Mouhammed Amir Habra
  • Alexandria Phan
  • Denai R. Milton
  • Christopher Wood
  • Nicholas Vauthey
  • Douglas B. Evans
  • Matthew H. Katz
  • Chaan S. Ng
  • Nancy D. Perrier
  • Jeffrey E. Lee
  • Elizabeth G. Grubbs



Adrenal cortical carcinoma (ACC) may have tumor or patient characteristics at presentation that argue against immediate surgery because of an unacceptable risk of morbidity/mortality, incomplete resection, or recurrence. This clinical stage can be characterized as borderline resectable ACC (BRACC). At present, systemic therapies in ACC can reduce tumor burden in some patients, creating an opportunity in BRACC for a strategy of preoperative chemotherapy (ctx) followed by surgery.

Materials and Methods

A single-institution retrospective review was conducted of all patients considered for surgery for primary ACC. Patients with BRACC treated with preoperative ctx were categorized as follows: group A, imaging suggesting a need for multiorgan/vascular resection; group B, imaging suggesting potentially resectable oligometastases; and group C, patients having marginal performance status/comorbidities precluding immediate surgery. Both the disease-free survival (DFS) and the overall survival (OS) were compared in BRACC patients treated with preoperative ctx+surgery and those who had upfront surgery.


Fifty-three patients with primary ACC were considered for surgery (median follow-up: 49.9 months). Thirty-eight patients (71.7 %) had initial surgery and 15 of them (28.3 %) were considered BRACC and received preoperative therapy. Of these 15 patients, 12 (80 %) received combination therapy with mitotane and etoposide/cisplatin-based ctx, 2 (13 %) received mitotane alone, and 1 (7 %) received ctx alone. Six patients were defined as group A, 5 as group B, and 4 as group C. Thirteen (87 %) BRACC patients underwent surgical resection. BRACC patients were younger but had more advanced disease than the patients having initial surgery (stage IV in 40 vs 2.6 % [p < 0.01]). By Response Evaluation Criteria In Solid Tumors criteria, 5 patients (38.5 %) had a partial response, 7 (53.8 %) had stable disease, and 1 (7.7 %) had disease that progressed. Postoperative mitotane use was similar between groups (p = .15). Median DFS for resected BRACC patients was 28.0 months [95 % confidence interval (CI), 2.9–not attained] vs 13 months (95 % CI, 5.8–46.9) (p = 0.40) for initial surgery patients. Five-year OS rates were also similar: 65 % for resected BRACC vs 50 % for initial surgery (p = 0.72).


The favorable outcome of patients with BRACC, despite more advanced stage of disease compared to those treated with surgery first, together with uncommon disease progression, suggests a benefit of neoadjuvant treatment sequencing in patients with BRACC.


Tumor Thrombus Preoperative Therapy Mitotane Multivisceral Resection Adrenal Cortical Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have no disclosures.


  1. 1.
    Fassnacht M, Johanssen S, Quinkler M et al (2009) Limited prognostic value of the 2004 international union against cancer staging classification for adrenocortical carcinoma: proposal for a revised TNM classification. Cancer 115:243–250PubMedCrossRefGoogle Scholar
  2. 2.
    Maluf DF, de Oliveira BH, Lalli E (2011) Therapy of adrenocortical cancer: present and future. Am J Cancer Res 1:222–232PubMedCentralPubMedGoogle Scholar
  3. 3.
    Kerkhofs TM, Verhoeven RH, Van der Zwan JM et al (2013) Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer 49:2579–2586PubMedCrossRefGoogle Scholar
  4. 4.
    Stigliano A, Cerquetti L, Sampaoli C et al (2012) Current and emerging therapeutic options in adrenocortical cancer treatment. J Oncol 2012:408131PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Grubbs EG, Callender GG, Xing Y et al (2010) Recurrence of adrenal cortical carcinoma following resection: surgery alone can achieve results equal to surgery plus mitotane. Ann Surg Oncol 17:263–270PubMedCrossRefGoogle Scholar
  6. 6.
    Terzolo M, Angeli A, Fassnacht M et al (2007) Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356:2372–2380PubMedCrossRefGoogle Scholar
  7. 7.
    Fassnacht M, Terzolo M, Allolio B et al (2012) Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med 366:2189–2197PubMedCrossRefGoogle Scholar
  8. 8.
    Katz MH, Pisters PW, Evans DB et al (2008) Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 206:833–846 discussion 846–848PubMedCrossRefGoogle Scholar
  9. 9.
    Tempero MA, Arnoletti JP, Behrman S et al (2010) Pancreatic adenocarcinoma. J Natl Compr Cancer Netw 8:972–1017Google Scholar
  10. 10.
    Lughezzani G, Sun M, Perrotte P et al (2010) The European network for the study of adrenal tumors staging system is prognostically superior to the international union against cancer-staging system: a North American validation. Eur J Cancer 46:713–719PubMedCrossRefGoogle Scholar
  11. 11.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Compr Cancer Netw 92:205–216CrossRefGoogle Scholar
  12. 12.
    Bourdeau I, Mackenzie-Feder J, Lacroix A (2013) Recent advances in adrenocortical carcinoma in adults. Curr Opin Endocrinol Diabetes Obes 20:192–197PubMedCrossRefGoogle Scholar
  13. 13.
    Zini L, Porpiglia F, Fassnacht M (2011) Contemporary management of adrenocortical carcinoma. Eur Urol 60:1055–1065PubMedCrossRefGoogle Scholar
  14. 14.
    Gonzalez RJ, Tamm EP, Ng C et al (2007) Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma. Surgery 142:867–875 discussion 875PubMedCrossRefGoogle Scholar
  15. 15.
    Abrams RA, Lowy AM, O’Reilly EM et al (2009) Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 16:1751–1756PubMedCrossRefGoogle Scholar
  16. 16.
    Evans DB, Farnell MB, Lillemoe KD et al (2009) Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 16:1736–1744PubMedCrossRefGoogle Scholar
  17. 17.
    Vauthey JN, Dixon E (2009) AHPBA/SSO/SSAT consensus conference on resectable and borderline resectable pancreatic cancer: rationale and overview of the conference. Ann Surg Oncol 16:1725–1726PubMedCrossRefGoogle Scholar
  18. 18.
    Berruti A, Fassnacht M, Baudin E et al (2010) Adjuvant therapy in patients with adrenocortical carcinoma: a position of an international panel. J Clin Oncol 28:e401–e402 author reply e3PubMedCrossRefGoogle Scholar
  19. 19.
    Datrice NM, Langan RC, Ripley RT et al (2012) Operative management for recurrent and metastatic adrenocortical carcinoma. J Surg Oncol 105:709–713PubMedCrossRefGoogle Scholar
  20. 20.
    Gaujoux S, Al-Ahmadie H, Allen PJ et al (2012) Resection of adrenocortical carcinoma liver metastasis: is it justified? Ann Surg Oncol 19:2643–2651PubMedCrossRefGoogle Scholar
  21. 21.
    Kemp CD, Ripley RT, Mathur A et al (2011) Pulmonary resection for metastatic adrenocortical carcinoma: the National Cancer Institute experience. Ann Thorac Surg 92:1195–1200PubMedCrossRefGoogle Scholar
  22. 22.
    Hermsen IG, Kerkhofs TM, den Butter G et al (2012) Surgery in adrenocortical carcinoma: importance of national cooperation and centralized surgery. Surgery 152:50–56PubMedCrossRefGoogle Scholar
  23. 23.
    Miller BS, Gauger PG, Hammer GD et al (2012) Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy. Surgery 152:1150–1157PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2014

Authors and Affiliations

  • Brian K. Bednarski
    • 1
  • Mouhammed Amir Habra
    • 2
  • Alexandria Phan
    • 3
  • Denai R. Milton
    • 4
  • Christopher Wood
    • 5
  • Nicholas Vauthey
    • 1
  • Douglas B. Evans
    • 6
  • Matthew H. Katz
    • 1
  • Chaan S. Ng
    • 7
  • Nancy D. Perrier
    • 1
  • Jeffrey E. Lee
    • 1
  • Elizabeth G. Grubbs
    • 1
  1. 1.Department of Surgical OncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Endocrine Neoplasia and Hormonal DisordersUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Medical OncologyMethodist Cancer CenterHoustonUSA
  4. 4.Department of BiostatisticsUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of UrologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Department of SurgeryMedical College of WisconsinMilwaukeeUSA
  7. 7.Department of RadiologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations