ENDOCRINE SOCIETY
OXFORD
Response to Letter to the Editor From Berruti et al “Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients’ Survival”
Victor Srougi, 1,2,1D Mouhammed A. Habra,3,[D and Maria C. B. V. Fragoso4,5
1Division of Urology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
2Division of Urology, Hospital Moriah, São Paulo 04083-002, Brazil
3Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 4Unidade de Suprarrenal, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil; and 5Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
Correspondence: Victor Srougi, MD, Hospital das Clinicas de São Paulo, Av. Enéas de Carvalho Aguiar, 255, São Paulo, SP, Brazil 05403-000. Email: vsrougi@ gmail.com.
Key Words: adrenocortical carcinoma, cytoreduction surgical procedures, surgery, survival
Dear Editor,
We are grateful for the commentary by Berruti et al re- garding our paper on cytoreduction of the primary tumor for patients harboring metastatic adrenocortical carcinoma (ACC) (1). We recognize the limitations of our study, mainly related to its retrospective nature and the potential for selec- tion bias, well pointed out by Berruti et al. Taking that into consideration, we found that cytoreduction followed by sys- temic treatment prolongs survival when compared with sys- temic treatment alone.
We fully agree that some patients benefit from having neoadjuvant chemotherapy followed by resection of the pri- mary tumor and, if possible, metastatic foci. In our paper, 17.9% of the cytoreduction group received neoadjuvant chemotherapy. We stated that preoperative chemotherapy would help in selecting patients with treatment response who would benefit from a maximal effort approach (ie, chemo- therapy followed by surgery). To date, because of the rarity of ACC and the hurdles of patient recruitment, there is a paucity of high-quality data to support what is the ideal treatment for patients with metastatic disease. We concur that the study by Laganà et al, which reported that neoadjuvant chemotherapy might help select patients for surgical treatment, fuels this dis- cussion (2).
On the one hand, it is expected that patients who respond to systemic therapy are the best candidates for a maximum effort approach, including surgery and metastasectomy. Deploying upfront cytoreduction to this group could delay systemic therapy during the convalescence period and worsen their prognosis. On the other hand, most patients with ACC historically have a limited long-term response to chemo- therapy, and we do not have good predictors for a response (3). Furthermore, upfront surgery helps control hormonal and local symptoms of bulky tumors and may provide a better
quality of life. Hence, performing neoadjuvant or adjuvant treatment is not an obvious choice.
Although the existing data are insufficient to delineate the ideal moment for systemic therapy and we wait for a pro- spective trial, our efforts should focus on improving patient selection for the different treatment approaches. Currently, we know that tumor grade, patient age, metastasis burden, me- tastasis location, and hormonal excess are important markers of survival (4). These parameters might tailor an individual- ized treatment plan to fit patients’ needs and conditions.
In summary, our data suggest that resection of primary tumor should not be overlooked in patients with metastatic ACC if deemed safe and feasible. Nevertheless, some pa- tients who require multiorgan resection are likely to benefit from neoadjuvant chemotherapy that can help in selecting candidates for surgery and may reduce the need for exten- sive resection in those who respond well to systemic therapy. We strongly believe that the best answer to the neoadjuvant chemotherapy approach should come through collaborative multi-institutional, prospective studies.
Conflict of Interest
The authors declare neither conflicts of interest nor financial ties.
References
1. Cosentini D. Letter to the Editor from Cosentini et al. Cytoreductive surgery of the primary tumor in metastatic adrenocortical car- cinoma: impact on patients’ survival. J Clin Endocrinol Metab 2022.
2. Laganà, M, Grisanti S, Cosentini D, Ferrari VD, et al. Efficacy of the EDP-M scheme plus adjunctive surgery in the manage- ment of patients with advanced adrenocortical carcinoma: the
Brescia experience. Cancers (Basel). 2020;12(4):941. doi:10.3390/ cancers 12040941.
3. Fassnacht M, Terzolo M, Allolio B, et al. Combination chemo- therapy in advanced adrenocortical carcinoma. N Engl J Med. 2012;366(23):2189-2197.
4. Baechle JJ, Marincola Smith P, et al. Cumulative GRAS score as a predictor of survival after resection for adrenocortical car- cinoma: analysis from the U.S. Adrenocortical Carcinoma Database. Ann Surg Oncol. 2021;28(11):6551-6561. doi:10.1245/ s10434-020-09562.