Cervical lymph node metastases in patients with differentiated thyroid cancer: A new (and more relevant) indication of active surveillance?

The timeless saying "medicine is an ever-changing science" remains as true as ever. Within the realm of thyroid cancer, recent years have witnessed a significant accumulation of evidence that has ushered in remarkable transformations in the principles that guide management decisions. We are evolving to achieve care that aligns proportionality (administering treatments according to the tumor’s aggressiveness), enhancing value-based and integrating patient preferences to prioritize patient-centered outcomes.

Despite the generally positive outlook for patients with differentiated thyroid carcinoma (DTC), approximately 30% of individuals experience persistent or recurrent disease, frequently found in cervical lymph nodes (¹). Traditionally, the primary approach to managing cervical disease in these patients has been surgical intervention, with some patients undergoing multiple procedures in pursuit of disease control or cure. Unfortunately, these objectives are not consistently met, and surgery carries the risk of potential complications such as hypoparathyroidism and voice disturbances and imposes significant emotional, time, and financial burdens (²,³). Nevertheless, the 2015 American Thyroid Association (ATA) Management Guidelines for Adult Patients with Thyroid Nodules and DTC strongly recommended therapeutic compartmental central or lateral neck dissection for patients with biopsy-proven persistent or recurrent disease in cervical lymph nodes based on specific size criteria. These criteria include a minimum size of ≥ 8 mm in the central compartment and ≥ 10 mm in the lateral compartment (⁴).

In this issue of AE&M, Solórzano and cols. provide insights into the conservative management (active surveillance, AS) of lymph node metastasis of DTC patients (⁵). The authors report a single-center cohort of 32 adult patients with papillary thyroid carcinoma (PTC) from Chile. All patients studied had confirmed (n = 18, 56%) or presumed (n=14, 44%) lymph node metastasis and underwent an AS protocol that involves examination, thyroglobulin, antithyroglobulin antibodies, and neck ultrasound every six months during the first year and after that at 6 to 12-month intervals. After a median follow-up of 4.3 years (range 0.6-14.1 years), only four patients (12.5%) showed locoregional disease progression: two underwent surgery, one was treated with external beam radiation, and the other was awaiting surgery. Importantly, none of the four patients with lymph node progression displayed complications related to tumor growth or treatment of the metastasis. These results are consistent with previous literature that showed a 20% to 24% rate of cervical lymph node enlargement, including two recent cohorts published by Argentinian and Brazilian researchers (⁶,⁷).

Nowadays, AS for primary thyroid tumors (specifically those with less than 1 cm in size) is a well-accepted strategy, although not applied in all healthcare scenarios (⁸). The efficacy and safety of this treatment strategy for low-risk PTC is already demonstrated in several countries, with the most extended experience from Japan (30 years) with more than 3,000 patients followed (⁹). This mounting evidence led to guidelines and societies (including the Brazilian Society of Endocrinology and Metabolism) recommending AS as the initial approach in selected patients with microPTC (¹⁰). Moreover, a systematic review of the cost-effectiveness of AS compared to immediate surgery found that most studies favored AS (¹¹).

The construct of conservative management of primary DTC has been expanded for lymph node metastasis, and accumulating evidence suggests that AS is a feasible strategy for this condition, given that most lymph node metastases identified following total thyroidectomy do not typically exhibit noticeable growth. One should note that AS is a reasonable strategy for small-volume cervical disease that do not threaten noble structures. Additionally, it should be conducted by healthcare teams with resources and knowledge to implement AS protocols for patients that accept conservative management.

One significant limitation of using AS for primary thyroid tumors is that the majority of actual recommendations do not advocate cytological evaluation of thyroid nodules less than 1 cm in size. As a result, most patients eligible for AS should not have been diagnosed at all. On the other hand, most patients with lymph node metastases are today treated surgically and AS has proven to be a viable choice in this scenario. Since these patients already have a diagnosis of DTC, the use of AS in managing persistent cervical disease seems to be a more relevant indication compared to its use in primary tumors.

In summary, the present study contributes to the growing body of evidence supporting the consideration of AS as a viable choice for specific cases among patients with DTC who have suspected or confirmed cervical lymph node metastases. Nevertheless, a definitive determination regarding the appropriateness of AS will ultimately hinge on the findings of prospective studies that meticulously outline criteria for patient and tumor selection and lay out comprehensive protocols for tracking disease progression. These forthcoming trials will play a pivotal role in shaping evidence-based recommendations to guide the AS approach for DTC cervical lymph node metastases.

REFERENCES

• ¹
  Scheffel RS, Zanella AB, Antunes D, Dora JM, Maia AL. Low Recurrence Rates in a Cohort of Differentiated Thyroid Carcinoma Patients: A Referral Center Experience. Thyroid. 2015 Aug;25(8):883-9. doi: 10.1089/thy.2015.0077.
  » https://doi.org/10.1089/thy.2015.0077
• ²
  Rivera-Robledo CG, Velázquez-Fernández D, Pantoja JP, Sierra M, Pérez-Enriquez B, Rivera-Moscoso R, et al. Recurrent papillary thyroid carcinoma to the cervical lymph nodes: Outcomes of compartment-oriented lymph node resection. World J Surg. 2019 Nov;43(11):2842-9. doi: 10.1007/s00268-019-05094-9.
  » https://doi.org/10.1007/s00268-019-05094-9
• ³
  Lamartina L, Borget I, Mirghani H, Al Ghuzlan A, Berdelou A, Bidault F, et al. Surgery for neck recurrence of differentiated thyroid cancer: Outcomes and risk factors. J Clin Endocrinol Metab. 2017 Mar 1;102(3):1020-31. doi: 10.1210/jc.2016-3284.
  » https://doi.org/10.1210/jc.2016-3284
• ⁴
  Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid.2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020.
  » https://doi.org/10.1089/thy.2015.0020
• ⁵
  Solórzano M, Lustig N, Mosso L, Espinoza M, Santana R, Gonzalez H, et al. Active Surveillance is a Feasible and Safe Strategy in Selected Patients with Papillary Thyroid Cancer and Suspicious Cervical Lymph Nodes Detected after Thyroidectomy. Arch Endocrinol Metab. 2024;68:e230146.
• ⁶
  Jerkovich F, Abelleira E, Bueno F, Guerrero L, Pitoia F. Active Surveillance of Small Metastatic Lymph Nodes as an Alternative to Surgery in Selected Patients with Low-Risk Papillary Thyroid Cancer: A Retrospective Cohort Study. Thyroid. 2022 Oct;32(10):1178-83. doi: 10.1089/thy.2022.0302.
  » https://doi.org/10.1089/thy.2022.0302
• ⁷
  Walter LB, Scheffel RS, Zanella AB, Farenzena M, Faccin CS, Graudenz MS, et al. Active Surveillance of Differentiated Thyroid Cancer Metastatic Cervical Lymph Nodes: A Retrospective Single-Center Cohort Study. Thyroid. 2023 Mar;33(3):312-20. doi: 10.1089/thy.2022.0542.
  » https://doi.org/10.1089/thy.2022.0542
• ⁸
  Smulever A, Pitoia F. Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America. Arch Endocrinol Metab. 2019 Sep 2;63(5):462-9. doi: 10.20945/2359-3997000000168.
  » https://doi.org/10.20945/2359-3997000000168
• ⁹
  Miyauchi A, Ito Y, Fujishima M, Miya A, Onoda N, Kihara M, et al. Long-Term Outcomes of Active Surveillance and Immediate Surgery for Adult Patients with Low-Risk Papillary Thyroid Microcarcinoma: 30-Year Experience. Thyroid. 2023 Jul;33(7):817-25. doi: 10.1089/thy.2023.0076.
  » https://doi.org/10.1089/thy.2023.0076
• ¹⁰
  Ward LS, Scheffel RS, Hoff AO, Ferraz C, Vaisman F. Treatment strategies for low-risk papillary thyroid carcinoma: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM). Arch Endocrinol Metab. 2022 Sept 8;66(4):522-32. doi: 10.20945/2359-3997000000512.
  » https://doi.org/10.20945/2359-3997000000512
• ¹¹
  Baek HS, Jeong CH, Ha J, Bae JS, Kim JS, Lim DJ, et al. Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review. Cancer Manag Res. 2021 Aug 26;13:6721-30. doi: 10.2147/CMAR.S317627.
  » https://doi.org/10.2147/CMAR.S317627

Publication Dates

• Publication in this collection
  07 June 2024
• Date of issue
  2024

History

• Received
  01 Nov 2023
• Accepted
  17 Feb 2024