ENDOCRINE SOCIETY
OXFORD
Letter to the Editor From de Ponthaud et al: “Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients’ Survival”
Charles de Ponthaud, 1,2,3,[D Nathalie Chereau,1,3 Fabrice Menegaux, 1,3 and Sébastien Gaujoux1,2,3, [D
1Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Paris, France 2Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France 3Sorbonne University, Paris, France
Correspondence: Sébastien Gaujoux, MD, PHD, Department of Digestive and Endocrine Surgery, Pitié-Salpétrière Hospital, APHP, Sorbonne University, Paris, France, Bat. Husson Mourier, 47-83 Avenue de l’Hôpital, 75013 Paris, France. Email: sebastien.gaujoux@aphp.fr
Key Words: adrenocortical carcinoma, cytoreductive surgery, overall survival
Abbreviations: ACC, adrenocortical carcinoma; CR, cytoreductive surgery; OS. overall survival.
Dear Editors,
We read with interest the multicenter retrospective study by Srougi and colleagues and we would like to congratulate them for raising this interesting question. Nevertheless, we believe that their conclusion that cytoreductive surgery (CR) of the primary tumor in metastatic adrenocortical carcinoma (ACC) is associated with prolonged survival should be taken with caution.
Firstly, in order to compare overall survival (OS) between CR vs no-CR groups, it is important to match them on main known prognostic factors for metastatic ACC including number of metastatic organs and age but also mitotic count, hormone secretion, response to preoperative chemotherapy, molecular biology, and genetics (1, 2). The simple use of age and number of organs with metastases (≤2 or >2) seems insuf- ficient to ensure comparability between groups. Furthermore, no information on the general condition of patients (ASA score, WHO score, or Charlson score) is given. We can easily assume that the patients who underwent surgery were in better health and were probably selected as stable or good responders to neoadjuvant treatment, which concerned about 20% of patients in the CR group. Besides, we do not have in- formation on the surgeries performed, which have an obvious impact on OS. We can also assume that patients operated on certainly had a well-localized primary tumor without the need for resection of adjacent organs (pancreas, right liver, kidney), unlike the control population, which may have had a more invasive and locally aggressive tumor, thus constituting an- other important selection bias (3). Finally, it would have been interesting to take advantage of this large series to produce a propensity score considering many more relevant prognostic factors in order to give weight to the current results and avoid obvious biases.
Secondly, if surgery of the primary tumor could be benefi- cial in highly selected patients with unresectable metastases,
as hypothesized in the context of metastatic pancreatic neuro- endocrine tumors, this remains highly debatable (4, 5). There are very few other oncological models in which resection of the primary tumor in context of metastases has shown a sur- vival benefit over systemic therapy. This is for example the case in metastatic renal cell carcinoma where retrospective studies suggesting a benefit of nephrectomy in metastatic pa- tients were overturned by a recent prospective randomized controlled trial (6). On the other hand, avoiding surgery may also benefit patients with a faster start of systemic therapies. In addition, recommendations from the European Society of Endocrinology, the Europeans Society of Endocrine Surgery, and the European Network for the Study of Adrenal Tumours suggest that adrenal surgery should not be routinely per- formed in cases of extensive metastatic disease at the time of first diagnosis (7, 8). Nevertheless, we think that in some highly selected cases, debulking surgery for large symptom- atic and/or oversecreting adrenal tumor resistant to medical treatment can be considered in metastatic patients (7).
Consequently, we believe that considering that resection of the primary tumor significantly improves OS of metastatic ACC patients should be taken with great caution.
Conflict of Interest
The authors declare neither conflicts of interest nor financial ties.
References
1. Assié G, Antoni G, Tissier F, et al. Prognostic parameters of metastatic adrenocortical carcinoma. J Clin Endocrinol Metab. 2007;92(1):148-154.
2. Wu K, Liu Z, Li X, Lu Y. Clinical score predicting overall survival after surgery for synchronous metastatic adrenocortical carcinoma: a
surveillance, epidemiology, and end result-based study. Am Surg. 2021;87(5):805-811.
3. Sinclair TJ, Gillis A, Alobuia WM, Wild H, Kebebew E. Surgery for adrenocortical carcinoma: when and how? Best Pract Res Clin Endocrinol Metab. 2020;34(3):101408.
4. Partelli S, Cirocchi R, Rancoita PMV, et al. A systematic review and meta-analysis on the role of palliative primary resection for pancreatic neuroendocrine neoplasm with liver metastases. HPB. 2018;20(3):197-203.
5. Livhits M, Li N, Yeh MW, Harari A. Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease. Surgery. 2014;156(6):1531-1540.
6. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018;379(5):417-427.
7. Gaujoux S, Mihai R, Joint Working Group of ESES and ENSAT. European Society of Endocrine Surgeons and European Network for the Study of Adrenal Tumours recommendations for the surgical man- agement of adrenocortical carcinoma. Br J Surg. 2017;104(4):358-376.
8. 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(4):G1-G46.
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