Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score in predicting survival after resection of adrenocortical carcinomas
Radu Mihai* İD
Department of Endocrine Surgery, Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
*Correspondence to: Radu Mihai, Department of Endocrine Surgery, Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Old Road, Headington, Oxford OX3 7LE, UK (e-mail: radumihai@doctors.org.uk)
Paper selected for presentation in the BJS Prize session at the European Society of Endocrine Surgeons meeting, Mainz, Germany, May 2023
Adrenocortical carcinoma (ACC) is an exceedingly rare and aggressive tumour1 with great heterogeneity regarding pattern of disease progression. The staging system introduced by the European Network for the Study of Adrenal Tumours (ENSAT)2 has limited ability to predict survival. Different nomograms were developed suggesting widely variable outcomes that correlate poorly with the observed overall survival of individual patients3. Considering these shortcomings, the Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score was recently proposed4 as a more accurate method to stratify patients according to different outcomes and to guide postoperative adjuvant therapy (Table S1).
This study evaluates the potential impact of S-GRAS score stratification on the management of a historical cohort of patients who underwent surgery for ACC in a tertiary referral centre.
Between 2001 and 2022, 70 patients underwent surgery for ACC. The S-GRAS score was calculated for 31 patients included in this study, the limiting factor being the lack of assessment of the Ki67 marker on historical histological specimens (Fig. S1). There was no difference in clinical parameters between patients with or without a complete S-GRAS score (Table S2).
The overall 5-year survival rate of 40% was similar between patients with or without a complete S-GRAS score (mean (s.d.) survival 76(14) months versus 67(12) months; P>0.05) (Fig. S2). Survival rates decreased significantly with a rise in the S-GRAS score (P <0.001) (Fig. 1). Compared with patients with a score of 0-1, the hazard ratio was 1.75 for those with a score of 2-3, 6.2 for those with a score of 4-5 and 20.7 for those with a score ≥6 respectively.
The mean survival time decreased progressively from 9 years in low-risk patients (S-GRAS score 0 and 1) to under 1 year in those classified as high-risk (S-GRAS score 6-7) (Fig. S3). Five patients who were alive at over 10 years after their operation (range 120-142 months) had a median S-GRAS score of 1 (range 0-3) and five patients who died within 6 months of their operation had a median score of 6 (range 6-7).
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Survival function
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Score 2-3
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Score 4-5
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Score 6-7
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Survival (months)
Patients with the same ENSAT stage were distributed over several categories of risk estimated by the S-GRAS score (Table S3). The majority of those with early disease (ENSAT II) had a low score of 0-1 (9 of 13 patients, 70%), yet one patient was in the high-risk group with an S-GRAS score of 5. For patients with locally advanced disease (ENSAT III), the predicted prognosis varied from a low S-GRAS score of 2-3 up to the most severe score of >6.
The use of mitotane treatment did not follow the suggested S-GRAS-based protocol4. According to the proposed algorithm, mitotane is not beneficial for patients with a low S-GRAS score (0-3), yet 8 of 15 patients in our cohort received it. Those with a higher
S-GRAS score (4-5) should receive mitotane and this corresponded with the observed treatment given in 9 of 10 patients. Combination therapy with mitotane and EDP chemotherapy (etoposide- doxorubicin-cisplatin) is recommended for patients with an S-GRAS score of 6 or higher, yet it was never used in this cohort. All six patients with an S-GRAS score of 6-7 were started on mitotane, however five of them died within 6 months of surgery and were deemed too unwell to tolerate EDP chemotherapy.
Full methods and discussion of these findings in the context of the published literature is available online (Supplementary material).
This study confirms that the use of the newly proposed S-GRAS score can stratify patients with ACC and predict survival after radical surgical treatment. Historical decisions regarding adjuvant chemotherapy followed only partially the proposed protocol based on the S-GRAS score, however, its implementation could facilitate these therapy decisions in future patients with ACC.
Funding
The author has no funding to declare.
Acknowledgements
I am grateful for the input of numerous Fellows and trainees who contributed through the years to the maintenance of the departmental ACC database: Tarik Abdul-Aziz, Rajeev Parameswaran, Titus Cvasciuc, Ioannis Christakis, Shad Khan, Mechteld deJong, Yi Sia, May Thwin.
Disclosure
The author declares no conflict of interest.
Supplementary material
Supplementary material is available at BJS Open online.
Data availability
Anonymized data can be made available on request.
Author contribution
Radu Mihai (Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing-original draft, Writing-review & editing)
References
1. Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R 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
2. Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, Beuschlein F 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
3. de Jong MC, Khan S, Christakis I, Weaver A, Mihai R. Comparative performances of nomograms and conditional survival after resection of adrenocortical cancer. BJS Open 2021;5:zraa036
4. Elhassan YS, Altieri B, Berhane S, Cosentini D, Calabrese A, Haissaguerre M et al. S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study. Eur J Endocrinol 2021;186:25-36