Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2021

01-03-2021 | Thyroid Cancer | Endocrine Tumors

Prognostic Impact of Histologic Grade for Papillary Thyroid Carcinoma

Authors: Allen S. Ho, MD, Michael Luu, MPH, Laurel Barrios, BA, Bonnie L. Balzer, MD, Shikha Bose, MD, Xuemo Fan, MD, Evan Walgama, MD, Jon Mallen-St. Clair, MD, Usman Alam, BS, Iram Shafqat, BS, De-Chen Lin, PhD, Yufei Chen, MBBS, Jennifer E. Van Eyk, PhD, Ellie G. Maghami, MD, Glenn D. Braunstein, MD, Wendy L. Sacks, MD, Zachary S. Zumsteg, MD

Published in: Annals of Surgical Oncology | Issue 3/2021

Login to get access

Abstract

Background

While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade.

Methods

We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed.

Results

Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04–1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23–3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18–0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17–0.80, p = 0.01).

Conclusions

Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.
Appendix
Available only for authorised users
Literature
1.
Lin JS, Bowles EJA, Williams SB, Morrison CC. Screening for thyroid cancer: updated evidence report and systematic review for the US preventive services task force. JAMA. 2017;317(18):1888–903.PubMedCrossRef
2.
Force USPST, Bibbins-Domingo K, Grossman DC, et al. Screening for thyroid cancer: US preventive services task force recommendation statement. JAMA. 2017;317(18):1882–1887.CrossRef
3.
Ho AS, Davies L, Nixon IJ, et al. Increasing diagnosis of subclinical thyroid cancers leads to spurious improvements in survival rates. Cancer. 2015;121(11):1793–9.PubMedCrossRef
4.
Ho AS, Luu M, Zalt C, et al. Mortality risk of nonoperative papillary thyroid carcinoma: a corollary for active surveillance. Thyroid. 2019;29:1409–1417.PubMedPubMedCentralCrossRef
5.
Ho AS, Chen I, Melany M, Sacks WL. Evolving management considerations in active surveillance for micropapillary thyroid carcinoma. Curr Opin Endocrinol Diabetes Obes. 2018;25(5):353–9.PubMedCrossRef
6.
Ho AS, Daskivich TJ, Sacks WL, Zumsteg ZS. Parallels between low-risk prostate cancer and thyroid cancer: a review. JAMA Oncol. 2019;5(4):556–64.PubMedCrossRef
7.
Walgama E, Sacks WL, Ho AS. Papillary thyroid microcarcinoma: optimal management versus overtreatment. Curr Opin Oncol. 2020;32(1):1–6.PubMedCrossRef
8.
Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.PubMedPubMedCentralCrossRef
9.
Tam S, Amit M, Boonsripitayanon M, et al. Adjuvant external beam radiotherapy in locally advanced differentiated thyroid cancer. JAMA Otolaryngol Head Neck Surg. 2017;143(12):1244–51.PubMedPubMedCentralCrossRef
10.
Ho AS, Luu M, Barrios L, et al. Incidence and mortality risk spectrum across aggressive variants of papillary thyroid carcinoma. JAMA Oncol. 2020;6:706.PubMedCrossRef
11.
Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery. 1987;102(6):1088–95.PubMed
12.
Akslen LA. Prognostic importance of histologic grading in papillary thyroid carcinoma. Cancer. 1993;72(9):2680–5.PubMedCrossRef
13.
Shaha AR, Loree TR, Shah JP. Intermediate-risk group for differentiated carcinoma of thyroid. Surgery. 1994;116(6):1036–40; discussion 1040-1.PubMed
14.
15.
Beckham TH, Romesser PB, Groen AH, et al. Intensity-modulated radiation therapy with or without concurrent chemotherapy in nonanaplastic thyroid cancer with unresectable or gross residual disease. Thyroid. 2018;28(9):1180–9.PubMedPubMedCentralCrossRef
16.
Chow SM, Law SC, Mendenhall WM, et al. Papillary thyroid carcinoma: prognostic factors and the role of radioiodine and external radiotherapy. Int J Radiat Oncol Biol Phys. 2002;52(3):784–95.PubMedCrossRef
17.
Kiess AP, Agrawal N, Brierley JD, et al. External-beam radiotherapy for differentiated thyroid cancer locoregional control: a statement of the American Head and Neck Society. Head Neck. 2016;38(4):493–8.PubMedCrossRef
18.
Haddad RI, Nasr C, Bischoff L, et al. NCCN guidelines insights: thyroid carcinoma, Version 2.2018. J Natl Compr Cancer Netw. 2018;16(12):1429–40.CrossRef
19.
Boffa DJ, Rosen JE, Mallin K, et al. Using the National Cancer Database for outcomes research: a review. JAMA Oncol. 2017;3(12):1722–8.PubMedCrossRef
20.
Venables WN, Ripley BD. Modern Applied Statistics with S. 4th ed. Berlin: Springer; 2002.CrossRef
21.
Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81(3):515–26.CrossRef
22.
Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine-reporting of subgroup analyses in clinical trials. N Engl J Med. 2007;357(21):2189–94.PubMedCrossRef
23.
Ho AS, Kim S, Tighiouart M, et al. Quantitative survival impact of composite treatment delays in head and neck cancer. Cancer. 2018;124(15):3154–62.PubMedCrossRef
24.
25.
Michels JJ, Jacques M, Henry-Amar M, Bardet S. Prevalence and prognostic significance of tall cell variant of papillary thyroid carcinoma. Hum Pathol. 2007;38(2):212–9.PubMedCrossRef
26.
Morris LG, Shaha AR, Tuttle RM, Sikora AG, Ganly I. Tall-cell variant of papillary thyroid carcinoma: a matched-pair analysis of survival. Thyroid. 2010;20(2):153–8.PubMedPubMedCentralCrossRef
27.
Kuo EJ, Goffredo P, Sosa JA, Roman SA. Aggressive variants of papillary thyroid microcarcinoma are associated with extrathyroidal spread and lymph-node metastases: a population-level analysis. Thyroid. 2013;23(10):1305–11.PubMedPubMedCentralCrossRef
28.
Regalbuto C, Malandrino P, Frasca F, et al. The tall cell variant of papillary thyroid carcinoma: clinical and pathological features and outcomes. J Endocrinol Invest. 2013;36(4):249–54.PubMed
29.
Regalbuto C, Malandrino P, Tumminia A, Le Moli R, Vigneri R, Pezzino V. A diffuse sclerosing variant of papillary thyroid carcinoma: clinical and pathologic features and outcomes of 34 consecutive cases. Thyroid. 2011;21(4):383–9.PubMedCrossRef
30.
Silver CE, Owen RP, Rodrigo JP, Rinaldo A, Devaney KO, Ferlito A. Aggressive variants of papillary thyroid carcinoma. Head Neck. 2011;33(7):1052–9.PubMedCrossRef
31.
Akslen LA, LiVolsi VA. Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma. Cancer. 2000;88(8):1902–8.PubMedCrossRef
32.
Mete OS, Asa SL, Bullock MJ, Carty SE, Hodak SP, McHugh JB, Nikiforov YE, Pettus J, Richardson MS, Shah J, Thompson LD. Protocol for the examination of specimens from patients with carcinomas of the thyroid gland. Northfield: College of American Pathologists; 2019.
33.
Lee N, Tuttle M. The role of external beam radiotherapy in the treatment of papillary thyroid cancer. Endocr Relat Cancer. 2006;13(4):971–7.PubMedCrossRef
34.
Tsang RW, Brierley JD, Simpson WJ, Panzarella T, Gospodarowicz MK, Sutcliffe SB. The effects of surgery, radioiodine, and external radiation therapy on the clinical outcome of patients with differentiated thyroid carcinoma. Cancer. 1998;82(2):375–88.PubMedCrossRef
35.
Farahati J, Reiners C, Stuschke M, et al. Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4). Cancer. 1996;77(1):172–80.PubMedCrossRef
36.
Biermann M, Pixberg M, Riemann B, et al. Clinical outcomes of adjuvant external-beam radiotherapy for differentiated thyroid cancer—results after 874 patient-years of follow-up in the MSDS-trial. Nuklearmedizin. 2009;48(3):89–98; quiz N15.PubMedCrossRef
37.
Terezakis SA, Lee KS, Ghossein RA, et al. Role of external beam radiotherapy in patients with advanced or recurrent nonanaplastic thyroid cancer: Memorial Sloan-Kettering Cancer Center experience. Int J Radiat Oncol Biol Phys. 2009;73(3):795–801.PubMedCrossRef
38.
Romesser PB, Sherman EJ, Shaha AR, et al. External beam radiotherapy with or without concurrent chemotherapy in advanced or recurrent non-anaplastic non-medullary thyroid cancer. J Surg Oncol. 2014;110(4):375–82.PubMedCrossRef
39.
Brierley J, Tsang R, Panzarella T, Bana N. Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. Clin Endocrinol (Oxf). 2005;63(4):418–27.CrossRef
40.
Volante M, Collini P, Nikiforov YE, et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol. 2007;31(8):1256–64.PubMedCrossRef
41.
Hiltzik D, Carlson DL, Tuttle RM, et al. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: a clinicopathologic study of 58 patients. Cancer. 2006;106(6):1286–95.PubMedCrossRef
42.
Sanders EM, Jr., LiVolsi VA, Brierley J, Shin J, Randolph GW. An evidence-based review of poorly differentiated thyroid cancer. World J Surg. 2007;31(5):934–45.PubMedCrossRef
43.
Ibrahimpasic T, Ghossein R, Carlson DL, et al. Outcomes in patients with poorly differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2014;99(4):1245–52.PubMedCrossRef
44.
Burman KD. Is poorly differentiated thyroid cancer poorly characterized? J Clin Endocrinol Metab. 2014;99(4):1167–9.PubMedCrossRef
45.
Ibrahimpasic T, Ghossein R, Shah JP, Ganly I. Poorly differentiated carcinoma of the thyroid gland: current status and future prospects. Thyroid. 2019;29(3):311–21.PubMedPubMedCentralCrossRef
46.
Epstein JI. Prostate cancer grading: a decade after the 2005 modified system. Mod Pathol. 2018;31(S1):S47–63.PubMedCrossRef
47.
Rakha EA, Reis-Filho JS, Baehner F, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12(4):207.PubMedPubMedCentralCrossRef
48.
Geetha KM, Leeky M, Narayan TV, Sadhana S, Saleha J. Grading of oral epithelial dysplasia: points to ponder. J Oral Maxillofac Pathol. 2015;19(2):198–204.PubMedPubMedCentralCrossRef
Metadata
Title
Prognostic Impact of Histologic Grade for Papillary Thyroid Carcinoma
Authors
Allen S. Ho, MD
Michael Luu, MPH
Laurel Barrios, BA
Bonnie L. Balzer, MD
Shikha Bose, MD
Xuemo Fan, MD
Evan Walgama, MD
Jon Mallen-St. Clair, MD
Usman Alam, BS
Iram Shafqat, BS
De-Chen Lin, PhD
Yufei Chen, MBBS
Jennifer E. Van Eyk, PhD
Ellie G. Maghami, MD
Glenn D. Braunstein, MD
Wendy L. Sacks, MD
Zachary S. Zumsteg, MD
Publication date
01-03-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 3/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-09023-2

Other articles of this Issue 3/2021

Annals of Surgical Oncology 3/2021 Go to the issue

ASO Author Reflections

ASO Author Reflections: Spotlight on Malignant Peritoneal Cytology in Uterine Sarcoma: A Potential Avenue for Future Research

Pancreatic Tumors

Landmark Series: Neoadjuvant Treatment in Borderline Resectable Pancreatic Cancer

Health Services Research and Global Oncology

Where the Other Half Dies: Analysis of Mortalities Occurring More Than 30 Days After Complex Cancer Surgery

Gastrointestinal Oncology

Impact of Neoadjuvant Therapy on Minimally Invasive Surgical Outcomes in Advanced Gastric Cancer: An International Propensity Score-Matched Study

Health Services Research and Global Oncology

Association of Living in Urban Food Deserts with Mortality from Breast and Colorectal Cancer

Thoracic Oncology

Lymph Node Examination for Stage I Second Primary Lung Cancer Patients Who Received Second Surgical Treatment