Download PDF
CC BY-NC-ND 4.0 · Horm Metab Res 2023; 55(04): 227-235
DOI: 10.1055/a-2042-2431
Original Article: Endocrine Care

A Revised Version of the TNM Classification Leads to Optimized Predictive Performance in Patients with Adrenocortical Carcinoma

Stephan Oliver David‡
1   Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Sarah Krieg‡
2   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Irene Esposito
3   Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Matthias Schott
4   Division for Specific Endocrinology, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Frederik Lars Giesel
5   Department of Nuclear Medicine, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Christoph Roderburg
2   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Sven Heiko Loosen
2   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Tom Luedde
2   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Wolfram Trudo Knoefel
1   Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
,
Andreas Krieg 
1   Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

The prognostic stratification of the current AJCC/UICC TNM classification for adrenocortical carcinoma (ACC) has been validated in only a few studies. In this study, it was hypothesized that redefining the T category cut-off would result in a significant improvement in estimated stage-related survival. In 935 patients with ACC from the SEER database, optimal cut-off values based on tumor size were first determined to redefine T1 and T2 categories. Cox proportional hazards regression analysis and receiver operating characteristics (ROC) were then used to determine the prognostic value of the revised version. A new cut-off value of 9.5 cm tumor size was established to differentiate between T1 and T2 tumors, leading to a revised TNM classification. As a result, a more homogeneous distribution of patients with ACC across all stages was observed. Notably, the predictive value of the newly proposed TNM classification in the ROC analysis exceeded that of the 7th and 8th editions of the AJCC/UICC classification system. Finally, the prognostic superiority of the revised TNM classification was confirmed in a multivariate Cox proportional hazards regression model. In conclusion, the present study demonstrates that updating the current staging system with revised T1 and T2 categories significantly improves the prediction of cancer-specific survival (CSS) in patients with ACC.

Key words

adrenocortical carcinoma - tumor staging - TNM classification - UICC - AJCC


Publication History

Received: 04 February 2023

Accepted after revision: 09 February 2023

Accepted Manuscript online:
24 February 2023

Article published online:
05 April 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Abiven G, Coste J, Groussin L. et al. 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 2006; 91: 2650-2655
    CrossrefPubMedGoogle Scholar
  • 2 Assié G, Antoni G, Tissier F. et al. Prognostic parameters of metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 2007; 92: 148-154
    CrossrefPubMedGoogle Scholar
  • 3 Else T, Kim AC, Sabolch A. et al. Adrenocortical carcinoma. Endocr Rev 2014; 35: 282-326
    CrossrefPubMedGoogle Scholar
  • 4 Hahner S, Fassnacht M.. Mitotane for adrenocortical carcinoma treatment. Curr Opin Investig Drugs 2005; 6: 386-394
    PubMedGoogle Scholar
  • 5 Megerle F, Herrmann W, Schloetelburg W. et al. Mitotane monotherapy in patients with advanced adrenocortical carcinoma. J Clin Endocrinol Metab 2018; 103: 1686-1695
    CrossrefPubMedGoogle Scholar
  • 6 Sabolch A, Else T, Griffith KA. et al. Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma. Int J Radiat Oncol Biol Phys 2015; 92: 252-259
    CrossrefPubMedGoogle Scholar
  • 7 Fassnacht M, Hahner S, Polat B. et al. Efficacy of adjuvant radiotherapy of the tumor bed on local recurrence of adrenocortical carcinoma. J Clin Endocrinol Metab 2006; 91: 4501-4504
    CrossrefPubMedGoogle Scholar
  • 8 Habra MA, Ejaz S, Feng L. et al. A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma. J Clin Endocrinol Metab 2013; 98: 192-197
    CrossrefPubMedGoogle Scholar
  • 9 Lee JE, Berger DH, el-Naggar AK. et al. Surgical management, DNA content, and patient survival in adrenal cortical carcinoma. Surgery 1995; 118: 1090-1098
    CrossrefPubMedGoogle Scholar
  • 10 Luton JP, Cerdas S, Billaud L. et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 1990; 322: 1195-1201
    CrossrefPubMedGoogle Scholar
  • 11 Sullivan M, Boileau M, Hodges CV.. Adrenal cortical carcinoma. J Urol 1978; 120: 660-665
    CrossrefPubMedGoogle Scholar
  • 12 Icard P, Chapuis Y, Andreassian B. et al. Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French association of endocrine surgery. Surgery 1992; 112: 972-979 discussion 979–980
    PubMedGoogle Scholar
  • 13 Macfarlane DA.. Cancer of the adrenal cortex; the natural history, prognosis and treatment in a study of fifty-five cases. Ann R Coll Surg Engl 1958; 23: 155-186
    PubMedGoogle Scholar
  • 14 Lughezzani G, Sun M, Perrotte P. et al. 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 2010; 46: 713-719
    CrossrefPubMedGoogle Scholar
  • 15 Fassnacht M, Wittekind C, Allolio B.. [Current TNM classification systems for adrenocortical carcinoma]. Der Pathologe 2010; 31: 374-378
    PubMedGoogle Scholar
  • 16 Fassnacht M, Johanssen S, Quinkler M. et al. Limited prognostic value of the 2004 international union against cancer staging classification for adrenocortical carcinoma: proposal for a revised TNM classification. Cancer 2009; 115: 243-250
    CrossrefPubMedGoogle Scholar
  • 17 Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence – SEER Research Plus Data, 17 Registries, Nov 2021 Sub (2000-2019) – Linked to County Attributes – Total U.S., 1969-2019 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2021, based on November 2020 submission
    PubMed
  • 18 Camp RL, Dolled-Filhart M, Rimm DL.. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 2004; 10: 7252-7259
    CrossrefPubMedGoogle Scholar
  • 19 DeLong ER, DeLong DM, Clarke-Pearson DL.. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44: 837-845
    Google Scholar
  • 20 van Buuren S, Groothuis-Oudshoorn K.. mice: Multivariate imputation by chained equations in R. J Stat Soft 2011; 45: 1-67
    PubMedGoogle Scholar
  • 21 Robin X, Turck N, Hainard A. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC bioinformatics 2011; 12: 77
    CrossrefPubMedGoogle Scholar
  • 22 Read Excel Files. R package version 1.4.0. https://cran.r-project.org/web/packages/readxl/index.html
    PubMed
  • 23 Drawing Survival Curves using 'ggplot2'. R package version 0.4.9. https://cran.r-project.org/web/packages/survminer/survminer.pdf
    PubMed
  • 24 Survival analysis. R package version 3.3-1. https://cran.r-project.org/web/packages/survival/index.html
    PubMed
  • 25 Therneau TM, Grambsch PM.. Modeling survival data: extending the Cox model. New York: Springer; 2000
    CrossrefGoogle Scholar
  • 26 Fassnacht M, Dekkers OM, Else T. et al. 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 2018; 179: G1-G46
    CrossrefPubMedGoogle Scholar
  • 27 Abdel-Rahman O.. Revisiting the AJCC staging system of adrenocortical carcinoma. J Endocrinol Invest 2022; 45: 89-94
    CrossrefPubMedGoogle Scholar
  • 28 Libé R, Borget I, Ronchi CL. et al. Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European network for the study of adrenal tumor (ENSAT) study. Ann Oncol 2015; 26: 2119-2125
    CrossrefPubMedGoogle Scholar
  • 29 Bilimoria KY, Shen WT, Elaraj D. et al. Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer 2008; 113: 3130-3136
    CrossrefPubMedGoogle Scholar
  • 30 Johanssen S, Hahner S, Saeger W. et al. Deficits in the management of patients with adrenocortical carcinoma in Germany. Dtsch Arztebl Int 2010; 107: 885-891
    PubMedGoogle Scholar
  • 31 Beuschlein F, Weigel J, Saeger W. et al. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab 2015; 100: 841-849
    CrossrefPubMedGoogle Scholar
  • 32 Morimoto R, Satoh F, Murakami O. et al. Immunohistochemistry of a proliferation marker Ki67/MIB1 in adrenocortical carcinomas: Ki67/MIB1 labeling index is a predictor for recurrence of adrenocortical carcinomas. Endocr J 2008; 55: 49-55
    CrossrefPubMedGoogle Scholar
  • 33 Vanbrabant T, Fassnacht M, Assie G. et al. Influence of hormonal functional status on survival in adrenocortical carcinoma: systematic review and meta-analysis. Eur J Endocrinol 2018; 179: 429-436
    CrossrefPubMedGoogle Scholar
  • 34 Asare EA, Wang TS, Winchester DP. et al. A novel staging system for adrenocortical carcinoma better predicts survival in patients with stage I/II disease. Surgery 2014; 156: 1378-1385 discussion 1385–1376
    CrossrefPubMedGoogle Scholar
  • 35 Stojadinovic A, Ghossein RA, Hoos A. et al. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 2002; 20: 941-950
    CrossrefPubMedGoogle Scholar
  • 36 Miller BS, Gauger PG, Hammer GD. et al. Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade. Langenbecks Arch Surg 2010; 395: 955-961
    CrossrefPubMedGoogle Scholar
  • 37 Liang J, Liu Z, Zhou L. et al. The clinical utility of 'GRAS' parameters in stage I-III adrenocortical carcinomas: long-term data from a high-volume institution. Endocrine 2020; 67: 449-456
    CrossrefPubMedGoogle Scholar
  • 38 Elhassan YS, Altieri B, Berhane S. et al. S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study. Eur J Endocrinol 2021; 186: 25-36
    CrossrefPubMedGoogle Scholar
  • 39 Terzolo M, Fassnacht M.. Endocrine tumours: Our experience with the management of patients with non-metastatic adrenocortical carcinoma. Eur J Endocrinol 2022; 187: R27-R40
    CrossrefPubMedGoogle Scholar
  • 40 Terzolo M, Angeli A, Fassnacht M. et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 2007; 356: 2372-2380
    CrossrefPubMedGoogle Scholar
  • 41 Huang H, Fojo T.. Adjuvant mitotane for adrenocortical cancer-a recurring controversy. J Clin Endocrinol Metab 2008; 93: 3730-3732
    CrossrefPubMedGoogle Scholar