Risk Factors Associated With Recurrence and Death in Patients With Tall Cell Papillary Thyroid Cancer: JAMA
Well-differentiated papillary thyroid cancer (PTC) is the most common thyroid cancer subtype and is generally associated with favorable prognosis owing to low rates of local invasion, recurrence, and metastasis. Aggressive variants of PTC—ie, tall cell, diffuse sclerosing, columnar cell, solid, and hobnail—have historically been understudied and underrepresented in clinical trials. Tall cell morphology (TCM) is the most common histopathologic feature within these variants, often presenting in patients of older age, with larger tumor size, and high rates of extrathyroidal extension. Patients with PTC with TCM (PTC-TCM) have worse disease-specific survival than patients with classic PTC.
This study by Shannon S. Wu and team aimed to determine predictive risk factors for long-term locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and overall survival (OS) among patients with PTC-TCM. Authors reviewed our institution’s 21-year experience of treating a large cohort of patients with PTC-TCM and the long-term follow-up, and identified prognostic factors associated with pertinent clinical outcomes.
All patients treated for PTC-TCM at a single tertiary-level academic health care institution from January 1, 1997, through July 31, 2018, were included. Tall cell variant (TCV) was defined as PTC with TCM of 30% or more; and tall cell features (TCF) was defined as PTC with TCM of less than 30%. Patients with other coexisting histologic findings and/or nonsurgical management were excluded. Clinicopathologic features associated with worse outcomes were identified using Kaplan-Meier and Cox proportional-hazards model. Data were analyzed from March 1, 2018, to August 15, 2018.
A total of 365 patients with PTC-TCM (TCV, 32%; TCF, 68%) were evaluable.
Total thyroidectomy was performed in 336 (92%) patients; 19 (5.2%) received radiotherapy; and 15 (4.1%) received radioactive iodine.
Clinical features were pT3 or T4, 65%; node-positive, 53%; and positive surgical margins, 24%. LRRFS at 1-, 3-, 5-, and 10-year was 95%, 87%, 82%, and 73%, respectively.
On multivariable analysis, male sex and age were not independent predictors of inferior 5-year LRRFS, whereas positive surgical margins (HR, 3.5), positive lymph nodes (HR, 2.8), and primary tumor size of 3 cm or more (HR, 3.3) were strongly associated with worse LRRFS.
Age 55 years or older (HR, 3.2), male sex (HR 4.5), positive surgical margins (HR, 2.7), nodal positivity (HR, 3.1), tumor diameter of 1.5 cm or more (HR, 20.6), and TCV vs TCF (HR, 3.1) were associated with worse DRFS.
Male sex (HR, 3.1; 95% 1.4-6.8) and tumor diameter of 1.5 cm or more (HR, 2.8; 95% CI, 1.0-7.4) were associated with worse OS. A findings-based nomogram was constructed to predict 10-year LRRFS (C index, 0.8).
This retrospective cohort study and the institutional analysis of 365 patients with PTC-TCM found that positive margins, positive lymph nodes, and primary tumor size of 3 cm or more were independent risk factors for inferior LRRFS. These findings will contribute to the growing recognition of the heterogeneous behavior between PTC variants and provide evidence for optimal treatments tailored to patient- and tumor specific features. The prognostic nomogram was constructed to predict 10-year LRRFS to personalize risk assessment and inform treatment planning for patients with this aggressive variant of PTC. External validation of our proposed nomogram in an independent data set is needed to enable personalizing of clinical treatment paradigms for specific histologic subtypes within PTC. Intensified locoregional therapy, including adjuvant radiation, may be considered for treating patients at high risk of recurrence.
Source: Shannon S. Wu; Nikhil Joshi; Jonathan Sharrett; JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2022.3781
