Surgical management of anaplastic thyroid cancer: indications and limitations

Introduction. Anaplastic thyroid cancer (ATC) accounts for less than 1 % of thyroid neoplasms, but is characterized by high aggressiveness and death in the vast majority of cases. The median survival in this pathology is <6 months. Despite development of multimodal approaches to treatment of ATC (surgery, chemotherapy, radiation therapy), local and systemic control of the disease remains unsatisfactory in most patients. The use of targeted drugs and immunotherapy opens up new possibilities for increasing the survival rate of patients with ATC, but the effectiveness of their combination with surgery and also long-term results remain poorly understood. The role of surgical treatment of primary tumor is subject of discussion: on the one hand, radical resection can improve local control of the disease and reduce symptoms of compression, and on the other, aggressive operations often involve a high risk of complications and do not always lead to increase in life expectancy. Of particular difficulty is definition of criteria for selecting patients who could actually benefit from surgical treatment.

Aim. To evaluate the effectiveness of surgical treatment with various options for combined treatment and determine criteria for its feasibility in ATC.

Materials and methods. The multicenter prospective study included 65 patients with morphologically confirmed stage IvA–C ATC treated in 2016–2022 at the pirogov High medical Technology Clinic of St. petersburg State university, the National medical Research Center of Radiology and the National medical Research Center of Endocrinology. patients are divided into 4 groups: 1) surgical treatment (n = 23); 2) surgical treatment and chemotherapy (n = 26); 3) surgical treatment, chemotherapy and radiation therapy (n = 5); 4) surgical treatment, chemotherapy and targeted therapy (n = 9). patient survival was assessed using the kaplan–meier method. Comparison of clinical-anamnestic data from 3 independent groups was performed using the kruskal–wallis test with further post-hoc analysis; comparison of the study groups – using Cox regression.

Results. median of overall survival in the surgical treatment, chemotherapy, and targeted therapy group was 20 months (95 % confidence interval 12–24), in the surgical treatment group was 2 months (hazard ratio, 0.075; p <0.001). partial response was recorded in 56 % of patients receiving targeted therapy, in other groups it was not observed (p <0.001). Comparison of data from patients who underwent R0 / R1- and R2 resection was not possible due to small number of patients who underwent conditionally radical surgery (n = 12)

Conclusion. Surgical intervention in ATC can be justified only as part of an integrated approach using agnostic targeted therapy. The results of the study highlight the need for molecular genetic testing and interdisciplinary consultation in each case. In the future, it is necessary to study new combinations of targeted drugs and immunotherapy in neoadjuvant regimen.

1. Agosto Salgado S. Evolution of anaplastic thyroid cancer management: perspectives in the era of precision oncology, Ther Adv Endocrinol Metab 2021:12:20420188211054692. DOI: 10.1177/20420188211054692

2. Bible K.C., Kebebew E., Brierley J. et al. 2021 American Thyroid Association Guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2021;31(3):37–86. DOI: 10.1089/thy.2020.0944

3. Romanchishen A.F., Zalmover E.A., Bogatikov A.A. Effectiveness of traditional treatment of patients with anaplastic thyroid cancer. Onkokhirurgiya = Oncosurgery 2010;2(3):100. (In Russ.).

4. Nikiforovich P.A., Polyakov A.P., Sleptsov I. et al. Targeted therapy of anaplastic thyroid cancer. Opukholi golovy i shei = Head and Neck Tumors 2022;12(4):33–8. (In Russ.). DOI: 10.17650/2222-1468-2022-12-4-33-38

5. Taissoun Aslan Z.A., Granados-García M., Luna-Ortiz K. et al. Anaplastic thyroid cancer: multimodal treatment results. Ecancermedicalscience 2014;8:449. DOI: 10.3332/ecancer.2014.449

6. Brignardello E., Palestini N., Felicetti F. et al. Early surgery and survival of patients with anaplastic thyroid carcinoma: analysis of a case series referred to a single institution between 1999 and 2012. Thyroid 2014;24(11):1600–6. DOI: 10.1089/thy.2014.0004

7. Lee D.Y., Won J.K., Lee S.H. et al. Changes of clinicopathologic characteristics and survival outcomes of anaplastic and poorly differentiated thyroid carcinoma. Thyroid 2016;26(3):404–13. DOI: 10.1089/thy.2015.0316

8. Passler C., Scheuba C., Prager G. et al. Anaplastic (undifferentiated) thyroid carcinoma (ATC). Langenbecks Arch Surg 1999;384(3):284–93. DOI: 10.1007/s004230050205

9. Swaak-Kragten T., de Wilt J.H.W., Schmitz P.I.M. et al. Multimodality treatment for anaplastic thyroid carcinoma – treatment outcome in 75 patients, Radiother Oncol 2009l;92(1):100–4. DOI: 10.1016/j.radonc.2009.02.016

10. Hu S., Helman S.N., Hanly E., Likhterov I. The role of surgery in anaplastic thyroid cancer: a systematic review. Am J Otolaryngol 2017;38(3):337–50. DOI: 10.1016/j.amjoto.2017.02.005

11. Hölting T., Meybier H., Buhr H. Status of tracheotomy in treatment of the respiratory emergency in anaplastic thyroid cancer. Wien Klin Wochenschr 1990;102(9):264–6. (In German).

12. Pozdeyev N., Gay L.M., Sokol E.S. et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clin Cancer Res 2018;24(13):3059–68. DOI: 10.1158/1078-0432.CCR-18-0373

13. Cabanillas M.E., Dadu R., Iyer P. et al. Acquired secondary RAS mutation in BRAFV600E-mutated thyroid cancer patients treated with BRAF Inhibitors. Thyroid 2020;30(9):1288–96. DOI: 10.1089/thy.2019.0514