A Mathematical Model to Assess the Effect of Residual Positive Lymph Nodes on the Survival of Patients With Papillary Thyroid Microcarcinoma

Front Oncol. 2022 Jun 30:12:855830. doi: 10.3389/fonc.2022.855830. eCollection 2022.


Background: Active surveillance (AS) has been considered the first-line management for patients with clinical low-risk papillary thyroid microcarcinoma (PTMC) who often have lymph node micrometastasis (m-LNM) when diagnosed. The "low-risk" and "high prevalence of m-LNM" paradox is a potential barrier to the acceptance of AS for thyroid cancer by both surgeons and patients.

Methods: Patients diagnosed with PTMC who underwent thyroidectomy with at least one lymph node (LN) examined were identified from a tertiary center database (n = 5,399). A β-binomial distribution was used to estimate the probability of missing nodal disease as a function of the number of LNs examined. Overall survival (OS) probabilities of groups with adequate and inadequate numbers of LNs examined were estimated using the Kaplan-Meier method in the Surveillance, Epidemiology, and End Results (SEER) database (n = 15,340). A multivariable model with restricted cubic splines was also used to verify the association of OS with the number of LNs examined.

Results: The risk of residual m-LNM (missed nodal disease) ranged from 31.3% to 10.0% if the number of LNs examined ranged from 1 and 7 in patients with PTMC. With 7 LNs examined serving as the cutoff value, the intergroup comparison showed that residual positive LNs did not affect OS across all patients and patients aged ≥55 years (P = 0.72 and P = 0.112, respectively). After adjusting for patient and clinical characteristics, the multivariate model also showed a slight effect of the number of LNs examined on OS (P = 0.69).

Conclusions: Even with the high prevalence, OS is not significantly compromised by persistent m-LNM in the body of patients with low-risk PTMC. These findings suggest that the concerns of LNM should not be viewed as an obstacle to developing AS for thyroid cancer. For patients with PTMC who undergo surgery, prophylactic central LN dissection does not provide a survival benefit.

Keywords: active surveillance; lymph node metastasis; observation; overtreatment; papillary thyroid cancer; survival analysis.