ASO Author Reflections: Revisiting the Prognostic Significance of Grade in Papillary Thyroid Carcinoma
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ASO AUTHOR REFLECTIONS
ASO Author Reflections: Revisiting the Prognostic Significance of Grade in Papillary Thyroid Carcinoma Allen S. Ho, MD1,2
, Wendy L. Sacks, MD1,3, and Zachary S. Zumsteg, MD1,4
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; 2Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA; 3 Division of Endocrinology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; 4Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 1
PAST
PRESENT
The management of papillary thyroid carcinoma (PTC) has undergone colossal change, driven largely by the understanding that most disease is low risk. A substantial percentage of PTC can now be managed without total thyroidectomy, without radioactive iodine, and without prophylactic central neck dissection. However, it is important not to overlook the fact that thyroid cancer still encompasses a spectrum of disease. Current guidelines have catalogued more than 20 pathologic features that define risk stratification criteria.1 Interestingly, histologic grade is not included, despite its prominence as a factor in older prognostic acronyms (i.e., AGES, SAG, GAMES) validated by multiple institutions as highly influential regarding survival.2 This exclusion also is curious given that less differentiated cancers (culminating in anaplastic thyroid carcinoma) intuitively appear to present with a greater incidence of aggressive regional and distant spread. The utility of external beam radiation therapy (EBRT) for less differentiated subtypes also has remained controversial.3
This large-scale study4 showed that worsening grade corresponded with a rising incidence of aggressive clinicopathologic features and a parallel increase in mortality. Whereas prior work considered grade as possibly a proxy for other covariates (e.g., tumor size), our multivariable analysis found histologic grade to be an independent predictor of mortality hazard. We furthermore demonstrated that EBRT was associated with longer survival for patients with poorly differentiated tumors, even after landmark analysis to account for an immortal time bias.
Ó Society of Surgical Oncology 2020 First Received: 5 August 2020 Accepted: 15 August 2020 A. S. Ho, MD e-mail: [email protected] Z. S. Zumsteg, MD e-mail: [email protected]
FUTURE The inherent subjectivity of grade in PTC has perhaps limited its adoption in universal prognostic systems. Nevertheless, the prognostic impact of grade observed across a broad cross-section of institutions in this study suggests a generalizable impact that should not be ignored. Moreover, the subjectivity in determining grade has not prevented other cancer types (e.g., prostate, breast, sarcoma, and salivary cancer) from incorporating this metric into clinical decision-making. In practice, efforts in thyroid pathology to overcome interobserver variability already exist, including the increasingly accepted Turin criteria f
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