Studies have demonstrated that lymph node ratios carry significant prognostic value in several types of cancer, including medullary thyroid carcinoma (MTC). The ratio is calculated by taking the number of metastatic lymph nodes obtained and dividing that figure by the number of lymph nodes resected.
The prognostic implications of lymph node ratios are important because a higher value tends to represent more advanced disease and thus a poorer prognosis.
As published in the European Journal of Surgical Oncology, Rozenblat and colleagues sought to investigate the relationship between lymph node ratios and MTC characteristics. They also aimed to quantify the performance of lymph node ratios as a prognostic indicator.
The reason for their study? “Although the [lymph node ratio] has been found to serve as a prognostic factor in various cancers such as squamous cell carcinoma of the oral cavity, papillary thyroid carcinoma, and gastric, colorectal and breast cancers, data for MTC are limited,” they explained.
The research team combed through the database of 4 tertiary centers and retrospectively identified patients with MTC who underwent a total thyroidectomy with neck dissection between 1984 and 2016 (n=193). Patient medical records were used to identify key clinical outcomes and prognostic variables. The research team also examined surgical reports to confirm the extent, side, and site of the operation.
A dedicated head and neck pathologist was recruited to analyze all neck dissection specimens, which were thoroughly examined for lymph nodes. The number of lymph nodes was ascertained, allowing for the lymph node ratios to be calculated.
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The results of the study indicated that lymph node ratios correlated with tumor size, but were inversely correlated with the age of diagnosis.
The research team reported that a high lymph node ratio was associated with a variety of disease parameters, such as extrathyroidal extension and bilateral tumor. In addition, it corresponded to postoperative calcitonin levels and carcinoembryonic antigen.
“[Lymph node ratio] was a strong indicator of [disease specific survival], tumor recurrence, and [distant metastases],” the authors of the study wrote. “As the [lymph node ratio] increased, [disease specific survival] decreased and the risk of recurrence and [distant metastases] increased.”
Predicting MTC Recurrence
The study conducted by Rozenblat et al strongly suggests that a high lymph node ratio is a negative prognostic indicator in patients with MTC. In Cancers, Kim and colleagues pursued a slightly different angle in identifying the use of lymph node ratios for predicting the risk of MTC recurrence.
The research team retrieved medical records of patients treated for MTC at a single healthcare center between 1995 and 2017. The team specifically searched for individuals who underwent total thyroidectomy with neck dissection (which was needed to estimate the lymph node ratio). A total of 132 patients were enrolled; 18 had hereditary MTC with confirmed family history.
Their findings on the prognostic value of the lymph node ratio echoed the research conducted by Rozenblat et al: an increase in the lymph node ratio is associated with a poorer prognosis.
In this study, 2 patients demonstrated MTC recurrence. However, they had low lymph node ratios and excellent biochemical responses. Nevertheless, the research team reported that lymph node ratios and serum calcitonin levels calculated postoperatively held predictive power for structural recurrence.
The authors of the study concluded that lymph node ratios had a potential role in predicting structural recurrence as a quantitative investigational tool for lymph node metastasis in patients with MTC.
An independent analysis of this trial suggests its conclusions are not airtight; the 2 patients who experienced MTC recurrence but had low lymph node ratios preoperatively demonstrate the limitations of using this technique to predict MTC recurrence. As for the other limitations of this study, the authors conceded that a retrospective design in a single center opens up the possibility of selection bias.
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It is important to note that lymph node ratios are calculated based on the extent (and quality) of nodal dissections performed intraoperatively. This inevitably means that different outcomes are possible depending on the abilities of the surgeon conducting the operation.
In addition, lymph node ratios are simply one part of the puzzle when it comes to prognostic factors in MTC. Studies have validated a number of important variables that hold prognostic value, such as sex, age at diagnosis, local tumor invasion, lymph node metastasis, as well as calcitonin and carcinoembryonic antigen (CEA) levels. Any of these factors can influence the outcome of patients with MTC, regardless of their lymph node ratios.
It is an inevitability in medicine that researchers continue to seek prognostic variables in any disease, since the manipulation of these variables may bring about better clinical outcomes. Nevertheless, it is important that the evidence for these matters is carefully weighted to avoid rash conclusions from being made. At present, the therapeutic decision to perform a total thyroidectomy with neck dissection still represents the most promising strategy to minimize the risk of recurrence and extend survival in MTC.
Rozenblat T, Hirsch D, Robenshtok E, et al. The prognostic value of lymph node ratio in medullary thyroid carcinoma: a multi-center study. Eur J Surg Oncol. 2020;46(11):2023-2028. doi:10.1016/j.ejso.2020.04.016
Kim J, Park J, Park H, et al. Metastatic lymph node ratio for predicting recurrence in medullary thyroid cancer. Cancers (Basel). 2021;13(22):5842. doi:10.3390/cancers13225842