Lymph Node Yield Trades Off Surgery Risks in Thyroid Cancer

Adequate lymph node yield for patients with papillary thyroid cancer is associated with longer operations, longer hospitalization, and higher risk of recurrent laryngeal nerve injury and hypocalcemia, according to results of a new retrospective database study.
“The importance of adequate lymph node yield in papillary thyroid carcinoma surgery includes accurate staging and risk stratification, as well as informing the use of radioactive iodine therapy and potentially reducing the risk of recurrence,” said Rachel Conley, BA, a medical student at Loyola University Stritch School of Medicine, Maywood, Illinois.
However, the extent of dissection needed for adequate lymph node yield must be balanced with surgery risks and potential postsurgical complications, she told Medscape Medical News. And surgical factors associated with adequate lymph node yield have not been well studied. 
The results of the retrospective study were presented in a poster at the American Academy of Otolaryngology-Head and Neck Surgery 2024 Annual Meeting.
Adequate lymph node yield in papillary thyroid cancer has been defined as the number of lymph nodes examined per T stage to rule out occult nodal disease with 90% confidence. The current accepted adequate lymph node yield for papillary thyroid cancer stages T1b, T2, and T3 is 6, 9, and 18 lymph nodes, respectively. 
Conley and colleagues used the American College of Surgeons NSQIP database to identify 5635 adults with papillary thyroid cancer who underwent thyroidectomy between 2016 and 2021 and had a least one lymph node examined. 
The researchers analyzed patient demographics, comorbidities, TNM stage, operative time, surgical specialty, postoperative complications, and length of hospital stay. Adequate lymph node yield was assessed over 5 years. 
Overall, 34% of the total cohort had adequate lymph node yield. This percentage decreased with advanced cancer stages — 38%, 33.6%, and 28.6% for T1b, T2, and T3, respectively (P < .001), Conley and her colleagues reported in their poster. However, the proportion of patients with adequate lymph node yield increased during the study period, from 30% in 2016 to 36.4% in 2021.
The findings that adequate lymph node yield is lower with higher T stages is consistent with previous research, Conley told Medscape. 
Patients with adequate lymph node yield had significantly longer mean operation times and hospital stays compare to those without adequate lymph node yield (188 minutes vs 104 minutes; 1-2 days vs 0-1 days, P < .001 for both).
Postoperative hypocalcemia within 30 days also was significantly more likely in patients with adequate lymph node yield than those without (13.7% vs 7.5%, P < .001).
In addition, patients with adequate lymph node yield had higher complication rates including recurrent laryngeal nerve injury or dysfunction, hypocalcemia requiring IV calcium, and surgical site infections, which are more likely following a more extensive neck dissection, Conley noted. 
Males were more likely to have adequate lymph node yield compared to females, but on further analysis this gender difference did not appear to be a function of age or T stage. More research is needed to explore these gender differences, she told Medscape.
The researchers also found no difference in BMI between patients with and without adequate lymph node yield. This “was unexpected,” said Conley “since a higher BMI may be correlated with an increased number of lymph nodes.” 
Limitations of the study include the lack information on papillary thyroid carcinoma recurrence or radioactive iodine therapy; however, the results may inform decision-making, said Conley. 
“The morbidity associated with extensive lymph node dissection must be carefully weighed against its oncologic benefits, since there is a trade-off between accurate staging and postoperative complications,” the researchers concluded. 
Only Part of the Cancer Puzzle
While the potential benefits of lymph node resection include more adequate staging, risk stratification, guidance in radioactive iodine use, and a reduction in the risk of disease recurrence or even mortality, there are potential drawbacks, said Uttam K. Sinha, MD, director of the USC Head and Neck Center with Keck Medicine of USC, Los Angeles, in an interview. These include overtreatment and increased risk of postoperative complications, such as transient hypocalcemia and recurrent laryngeal nerve injury.
Sinha was not surprised by the study findings, but he emphasized the surgery must be complete; “you cannot leave any thyroid tissue to grow back,” he said.
The current study findings were limited by the fact that lymph node metastasis is only part of the cancer puzzle, he told Medscape. 
Knowing how many lymph nodes are involved in papillary thyroid cancer can inform clinical decision-making, but this knowledge will not necessarily improve overall survival, he said. “The complexity of cancer is so high that just examining lymph nodes is not enough, and clinicians must consider other aspects of a patient’s health, including diet, stress, and lifestyle.” 
The biological behavior and molecular characteristics of the tumor also impact lymph node yield, he noted. “Tumors with aggressive molecular profiles, such as those with BRAF or TERT mutations, and high expression of epithelial-mesenchymal transition-related genes are often associated with more extensive nodal metastasis.” 
Looking ahead in the management of papillary thyroid cancer, more sensitive imaging studies are needed, said Sinha. 
The technology is evolving, and the use of intraoperative biodegradable nanoparticle-based imaging and machine learning to identify tumor margins and metastatic lymph nodes; liquid biopsy and next-generation sequencing to identify mutations in tumor-related genes; and targeted therapies will all impact thyroid cancer treatment, he added. 
The study received no outside funding. Conley had no financial conflicts to disclose. Sinha had no financial conflicts to disclose. 
 
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