Check for updates
ASO Author Reflections: Cumulative GRAS Score Predicts Outcomes After Resection for Adrenal Cortical Carcinoma
Jordan J. Baechle, BS1, Paula Marincola Smith, MD2, and Colleen M. Kiernan, MD2
1School of Medicine, Meharry Medical College, Nashville, TN; 2Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
PAST
Previous studies have demonstrated that tumor grade [G], resection status [R], patient age [A], and preoperative symptoms of hormone hypersecretion [S] are predictive of postoperative outcomes for patients with adrenal cortical carcinoma (ACC).1 Libé et al.2 have referred to these risk factors together as the “GRAS” parameters. These authors have further demonstrated the individual impact of the GRAS parameters on survival for late-stage ACC patients in Europe. More recently, Liang et al.3 published a single- institution study suggesting the utility of creating a com- posite GRAS score to stratify the prognosis for patients with stages 1 to 3 ACC.
PRESENT
In a retrospective study using the U.S. Adrenocortical Carcinoma Group (US-ACCG) database, the current authors and their colleagues examined adult patients who underwent resection for stages 1 to 4 ACC at 13 collabo- rative institutions4. By examination of the medical records, a sum GRAS score was calculated for each patient who met three or more of the Weiss criteria5 or had a Ki67 of 20% or higher on the final pathology report (grade [G]), had a
microscopically (R1) or macroscopically (R2) positive final surgical margin at the index operation (resection sta- tus [R]), was 50 years old or older at the index operation (age [A]), and had preoperative symptoms of hormone hypersecretion (symptoms [S]). The cumulative “GRAS” score was shown to stratify overall survival (OS) effec- tively for ACC patients of all stages who underwent primary surgical resection5. An increasing cumulative GRAS score was significantly associated with worse OS after index resection (hazard ratio, 1.57; 95% confidence interval, 1.28-1.92; p < 0.01), and the median OS decreased with each additional GRAS point. The median OS was 120.7 months for a GRAS score of 0, 60.7 months for a GRAS score of 1, 38.2 months for a GRAS score of 2, 31.7 months for a GRAS score of 3, and 9 months for a GRAS score of 4. An alternative three-tiered scoring sys- tem that grouped patients with intermediate GRAS scores together (GRAS scores of 0, 1-3, or 4) was additionally examined and demonstrated the further benefit of stratify- ing disease-free survival (DFS) in addition to OS. The median DFS was 36.1 months for a GRAS score of 0, 13 months for a GRAS score of 1 to 3, and 5.6 months for a GRAS score of 4 (p < 0.01).
FUTURE
The consistency with which the GRAS parameters pre- dict postoperative survival across multiple datasets, patient populations, and studies suggests that these factors play an important role in ACC prognostication. As new research provides further insight into genetic and clinical factors contributing to disease biology, the GRAS parameters are likely to serve as a foundation on which additional prog- nostic criteria can be layered. Although the authors demonstrate the benefit of both a three-tiered and a five- tiered scoring system, it is possible that alternate scoring
Jordan J. Baechle and Paula Marincola Smith contributed equally to this paper.
@ Society of Surgical Oncology 2021, corrected publication 2021
First Received: 8 January 2021
Accepted: 8 January 2021;
Published Online: 2 February 2021
C. M. Kiernan, MD e-mail: colleen.m.kiernan@vumc.org
systems or the addition of novel parameters will further improve ACC patient prognostication. Future studies focused on fine-tuning and adding to the GRAS scoring system may have clinical benefit.
DISCLOSURE
There are no conflicts of interest.
REFERENCES
1. Volante M, Bollito E, Sperone P, et al. Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification. Histopathology. 2009;55:535-43. https://doi.org/10.1111/j.1365-2 559.2009.03423.x.
2. 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;26:2119-25. https://doi.org/10.1093/annonc/mdv329.
3. 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. https://doi.org/ 10.1007/s12020-019-02141-2.
4. Baechle JJ, Marincola Smith P, et al. Cumulative “GRAS” score as a predictor of survival after resection for adrenal cortical carcinoma: analysis from the U.S. adrenocortical carcinoma database. Ann Surg Oncol. https://doi.org/10.1245/s10434-020-09 562-8.
5. Lau SK, Weiss LM. The Weiss system for evaluating adrenocor- tical neoplasms: 25 years later. Hum Pathol. 2009;40:1-12. h ttps://doi.org/10.1016/j.humpath.2009.03.010.
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.