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

Stephan Oliver David; Sarah Krieg; Irene Esposito; Matthias Schott; Frederik Lars Giesel; Christoph Roderburg; Sven Heiko Loosen; Tom Luedde; Wolfram Trudo Knoefel; Andreas Krieg

doi:10.1055/a-2042-2431

Hormone and Metabolic Research, Table of Contents

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‡

¹Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Sarah Krieg‡

²Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Irene Esposito

³Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Matthias Schott

⁴Division for Specific Endocrinology, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Frederik Lars Giesel

⁵Department of Nuclear Medicine, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Christoph Roderburg

²Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Sven Heiko Loosen

²Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Tom Luedde

²Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Wolfram Trudo Knoefel

¹Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

,

Andreas Krieg

¹Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany

› Author Affiliations

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

Full Text

References

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
2 Assié G, Antoni G, Tissier F. et al. Prognostic parameters of metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 2007; 92: 148-154
3 Else T, Kim AC, Sabolch A. et al. Adrenocortical carcinoma. Endocr Rev 2014; 35: 282-326
4 Hahner S, Fassnacht M.. Mitotane for adrenocortical carcinoma treatment. Curr Opin Investig Drugs 2005; 6: 386-394
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
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
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
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
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
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
11 Sullivan M, Boileau M, Hodges CV.. Adrenal cortical carcinoma. J Urol 1978; 120: 660-665
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
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
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
15 Fassnacht M, Wittekind C, Allolio B.. [Current TNM classification systems for adrenocortical carcinoma]. Der Pathologe 2010; 31: 374-378
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
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
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
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
20 van Buuren S, Groothuis-Oudshoorn K.. mice: Multivariate imputation by chained equations in R. J Stat Soft 2011; 45: 1-67
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
22 Read Excel Files. R package version 1.4.0. https://cran.r-project.org/web/packages/readxl/index.html
23 Drawing Survival Curves using 'ggplot2'. R package version 0.4.9. https://cran.r-project.org/web/packages/survminer/survminer.pdf
24 Survival analysis. R package version 3.3-1. https://cran.r-project.org/web/packages/survival/index.html
25 Therneau TM, Grambsch PM.. Modeling survival data: extending the Cox model. New York: Springer; 2000
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
27 Abdel-Rahman O.. Revisiting the AJCC staging system of adrenocortical carcinoma. J Endocrinol Invest 2022; 45: 89-94
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
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
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
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
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
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
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
35 Stojadinovic A, Ghossein RA, Hoos A. et al. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 2002; 20: 941-950
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
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
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
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
40 Terzolo M, Angeli A, Fassnacht M. et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 2007; 356: 2372-2380
41 Huang H, Fojo T.. Adjuvant mitotane for adrenocortical cancer-a recurring controversy. J Clin Endocrinol Metab 2008; 93: 3730-3732