Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis, treatment, and survival analysis of adrenocortical carcinomas: a multicentric study

  • Original Article
  • Published:
Hormones Aims and scope Submit manuscript

Abstract

Introduction

Current guidelines specify controversial areas in adrenocortical carcinomas (ACC), such as optimal follow-up time after remission and identification of prognostic markers. We aim to address these topics by analyzing four reference centers in our country.

Methods

Cross-sectional multicentric study of 69 patients (mean age: 51.7 ± 16.7 years-old; women, 72.5%). Kaplan-Meier survival curves and Cox regression analysis were used to calculate overall survival and its predictors.

Results

Thirty-eight individuals (55.0%) had hormonal autonomous production, and 40.6% of the patients presented with metastasis. Surgery was performed in 84.1% of them. Most of these patients (72.4%) were then assigned to adjuvant therapy, while 27.6% were actively surveilled. Among patients undergoing surgery, those who achieved transient remission presented a longer survival time (66 months) than those who never reached the disease-free status (21 months) (p = 0.021). One patient presented with recurrence more than 7 years after complete tumor resection. The lowest overall survival was observed in patients (n = 11) assigned to palliative care since diagnosis (9 months). Tumor stage was identified as the only independent predictor of survival in our cohort (p = 0.006). Five-year survival was 67% for tumors confined to the adrenal space (stage I/II), 56% for locally advanced disease (stage III), and 0% for metastatic disease (stage IV).

Conclusion

This study reinforces the dismal prognosis of ACC, the need for long-term follow-up, and tumor stage as the most important survival predictor. Reviewing medical records in such rare conditions is an opportunity to identify insufficiencies and to improve medical care.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Diagram 1
Fig. 1

Similar content being viewed by others

References

  1. Ng L, Libertino JM (2003) Adrenocortical carcinoma: diagnosis, evaluation and treatment. J Urol 169(1):5–11. https://doi.org/10.1097/01.ju.0000030148.59051.35

    Article  PubMed  Google Scholar 

  2. Kerkhofs TM, Verhoeven RH, Van der Zwan JM, Dieleman J, Kerstens MN, Links TP, Van de Poll-Franse LV, Haak HR (2013) Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. European journal of cancer (Oxford, England : 1990) 49(11):2579–2586. https://doi.org/10.1016/j.ejca.2013.02.034

    Article  Google Scholar 

  3. Allolio B, Fassnacht M (2006) Clinical review: adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91(6):2027–2037. https://doi.org/10.1210/jc.2005-2639

    Article  CAS  PubMed  Google Scholar 

  4. Fassnacht M, Dekkers O, Else T, Baudin E, Berruti A, de Krijger RR, Haak HR, Mihai R, Assie G, Terzolo M (2018) European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol. https://doi.org/10.1530/eje-18-0608

  5. Kamilaris CDC, Stratakis CA (2018) An update on adrenal endocrinology: significant discoveries in the last 10 years and where the field is heading in the next decade. Hormones (Athens) 17(4):479–490. https://doi.org/10.1007/s42000-018-0072-y

    Article  Google Scholar 

  6. Vassilopoulou-Sellin R, Schultz PN (2001) Adrenocortical carcinoma. Clinical outcome at the end of the 20th century. Cancer 92(5):1113–1121. https://doi.org/10.1002/1097-0142(20010901)92:5<1113::aid-cncr1428>3.0.co;2-i

    Article  CAS  PubMed  Google Scholar 

  7. Kostiainen I, Hakaste L, Kejo P, Parviainen H, Laine T, Loyttyniemi E, Pennanen M, Arola J, Haglund C, Heiskanen I, Schalin-Jantti C (2019) Adrenocortical carcinoma: presentation and outcome of a contemporary patient series. Endocrine 65(1):166–174. https://doi.org/10.1007/s12020-019-01918-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Weiss LM (1984) Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 8(3):163–169. https://doi.org/10.1097/00000478-198403000-00001

    Article  CAS  PubMed  Google Scholar 

  9. Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, Beuschlein F, Terzolo M, Mueller H-H, Hahner S, Allolio B, Group, f.t.G.A.C.R., Tumors, t.E.N.f.t.S.o.A (2009) Limited prognostic value of the 2004 international union against cancer staging classification for adrenocortical carcinoma. Cancer 115(2):243–250. https://doi.org/10.1002/cncr.24030

    Article  PubMed  Google Scholar 

  10. Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, Jolly S, Miller BS, Giordano TJ, Hammer GD (2014) Adrenocortical carcinoma. Endocr Rev 35(2):282–326. https://doi.org/10.1210/er.2013-1029

    Article  CAS  PubMed  Google Scholar 

  11. Didolkar MS, Bescher RA, Elias EG, Moore RH (1981) Natural history of adrenal cortical carcinoma: a clinicopathologic study of 42 patients. Cancer 47(9):2153–2161. https://doi.org/10.1002/1097-0142(19810501)47:9<2153::aid-cncr2820470908>3.0.co;2-6

    Article  CAS  PubMed  Google Scholar 

  12. Wooten MD, King DK (1993) Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer 72(11):3145–3155. https://doi.org/10.1002/1097-0142(19931201)72:11<3145::aid-cncr2820721105>3.0.co;2-n

    Article  CAS  PubMed  Google Scholar 

  13. Gonzalez RJ, Shapiro S, Sarlis N, Vassilopoulou-Sellin R, Perrier ND, Evans DB, Lee JE (2005) Laparoscopic resection of adrenal cortical carcinoma: a cautionary note. Surgery 138(6):1078–1085; discussion 1085-1076. https://doi.org/10.1016/j.surg.2005.09.012

    Article  PubMed  Google Scholar 

  14. Ayala-Ramirez M, Jasim S, Feng L, Ejaz S, Deniz F, Busaidy N, Waguespack SG, Naing A, Sircar K, Wood CG, Pagliaro L, Jimenez C, Vassilopoulou-Sellin R, Habra MA (2013) Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center. Eur J Endocrinol 169(6):891–899. https://doi.org/10.1530/EJE-13-0519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Weiss LM, Medeiros LJ, Vickery AL Jr (1989) Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13(3):202–206

    Article  CAS  PubMed  Google Scholar 

  16. Libe R, Borget I, Ronchi CL, Zaggia B, Kroiss M, Kerkhofs T, Bertherat J, Volante M, Quinkler M, Chabre O, Bala M, Tabarin A, Beuschlein F, Vezzosi D, Deutschbein T, Borson-Chazot F, Hermsen I, Stell A, Fottner C, Leboulleux S, Hahner S, Mannelli M, Berruti A, Haak H, Terzolo M, Fassnacht M, Baudin E (2015) Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European network for the study of adrenal tumor (ENSAT) study. Annals of oncology : official journal of the European Society for Medical Oncology 26(10):2119–2125. https://doi.org/10.1093/annonc/mdv329

    Article  CAS  Google Scholar 

  17. Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, Fassnacht M, Pentheroudakis G, on behalf of the, E.G.W.G (2012) Adrenal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(suppl7):vii131–vii138. https://doi.org/10.1093/annonc/mds231

    Article  PubMed  Google Scholar 

  18. Terzolo M, Baudin AE, Ardito A, Kroiss M, Leboulleux S, Daffara F, Perotti P, Feelders RA, de Vries JH, Zaggia B, De Francia S, Volante M, Haak HR, Allolio B, Al Ghuzlan A, Fassnacht M, Berruti A (2013) Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. European journal of endocrinology 169(3):263–270. https://doi.org/10.1530/eje-13-0242

    Article  CAS  PubMed  Google Scholar 

  19. Terzolo M, Pia A, Berruti A, Osella G, Ali A, Carbone V, Testa E, Dogliotti L, Angeli A (2000) Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer. J Clin Endocrinol Metab 85(6):2234–2238. https://doi.org/10.1210/jcem.85.6.6619

    Article  CAS  PubMed  Google Scholar 

  20. Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker A-C, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A (2007) Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356(23):2372–2380. https://doi.org/10.1056/NEJMoa063360

    Article  CAS  PubMed  Google Scholar 

  21. Kim Y, Margonis GA, Prescott JD, Tran TB, Postlewait LM, Maithel SK, Wang TS, Evans DB, Hatzaras I, Shenoy R, Phay JE, Keplinger K, Fields RC, Jin LX, Weber SM, Salem AI, Sicklick JK, Gad S, Yopp AC, Mansour JC, Duh Q-Y, Seiser N, Solorzano CC, Kiernan CM, Votanopoulos KI, Levine EA, Poultsides GA, Pawlik TM (2016) Nomograms to predict recurrence-free and overall survival after curative resection of adrenocortical carcinoma. JAMA Surg 151(4):365–373. https://doi.org/10.1001/jamasurg.2015.4516

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lughezzani G, Sun M, Perrotte P, Jeldres C, Alasker A, Isbarn H, Budaus L, Shariat SF, Guazzoni G, Montorsi F, Karakiewicz PI (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. European journal of cancer (Oxford, England : 1990) 46(4):713–719. https://doi.org/10.1016/j.ejca.2009.12.007

    Article  Google Scholar 

  23. Asare EA, Wang TS, Winchester DP, Mallin K, Kebebew E, Sturgeon C (2014) A novel staging system for adrenocortical carcinoma better predicts survival in patients with stage I/II disease. Surgery 156(6):1378–1385; discussion 1385-1376. https://doi.org/10.1016/j.surg.2014.08.018

    Article  PubMed  Google Scholar 

  24. Morimoto R, Satoh F, Murakami O, Suzuki T, Abe T, Tanemoto M, Abe M, Uruno A, Ishidoya S, Arai Y, Takahashi K, Sasano H, Ito S (2008) Immunohistochemistry of a proliferation marker Ki67/MIB1 in adrenocortical carcinomas: Ki67/MIB1 labeling index is a predictor for recurrence of adrenocortical carcinomas. Endocr J 55(1):49–55

    Article  PubMed  Google Scholar 

  25. Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, Dousset B, Bertagna X, Bertherat J (2006) Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients. J Clin Endocrinol Metab 91(7):2650–2655. https://doi.org/10.1210/jc.2005-2730

    Article  CAS  PubMed  Google Scholar 

  26. Johanssen S, Hahner S, Saeger W, Quinkler M, Beuschlein F, Dralle H, Haaf M, Kroiss M, Jurowich C, Langer P, Oelkers W, Spahn M, Willenberg HS, Mader U, Allolio B, Fassnacht M (2010) Deficits in the management of patients with adrenocortical carcinoma in Germany. Deutsches Arzteblatt international 107(50):885–891. https://doi.org/10.3238/arztebl.2010.0885

    Article  PubMed  PubMed Central  Google Scholar 

  27. Freire DS, Siqueira SA, Zerbini MC, Wajchenberg BL, Correa-Giannella ML, Lucon AM, Pereira MA (2013) Development and internal validation of an adrenal cortical carcinoma prognostic score for predicting the risk of metastasis and local recurrence. Clin Endocrinol 79(4):468–475. https://doi.org/10.1111/cen.12174

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal

    Pedro Souteiro, Sandra Belo & Davide Carvalho

  2. Faculty of Medicine, Universidade do Porto, Porto, Portugal

    Pedro Souteiro & Davide Carvalho

  3. Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

    Pedro Souteiro & Davide Carvalho

  4. Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

    Sara Donato, Joana Simões-Pereira & Valeriano Leite

  5. Department of Endocrinology, Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal

    Cláudia Costa, Joana Oliveira, Ana Paula Santos & Isabel Torres

  6. Department of Endocrinology, Centro Hospitalar Universitário do Porto, Porto, Portugal

    Catarina A. Pereira & Helena Cardoso

  7. NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

    Joana Simões-Pereira & Valeriano Leite

  8. Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

    Joana Simões-Pereira & Valeriano Leite

Authors
  1. Pedro Souteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Donato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cláudia Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Catarina A. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joana Simões-Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joana Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sandra Belo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ana Paula Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Helena Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Valeriano Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Davide Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Isabel Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pedro Souteiro.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study was approved by the Centro Hospitalar Universitário de São João ethics committee, a member of the National Ethics Committee for Clinical Research (authorization number 113/19). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Authorization to perform this retrospective study without individual consent was granted by Centro Hospitalar Universitário de São João ethics committee providing that patients’ privacy was preserved adequately (authorization number 113/19).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Souteiro, P., Donato, S., Costa, C. et al. Diagnosis, treatment, and survival analysis of adrenocortical carcinomas: a multicentric study. Hormones 19, 197–203 (2020). https://doi.org/10.1007/s42000-019-00161-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42000-019-00161-1

Keywords

Search

Navigation