Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes

We performed this retrospective cohort analysis using data from SEER database which was designed and maintained by the National Cancer Institute. All patients with CPTC, FVPTC, or FTC diagnosed between 2004 and 2014 were identified using histopathological codes of the International Classification of Disease for Oncology, third edition (ICD-O-3). Non-invasive follicular thyroid neoplasm with papillary-like nuclear features presents extremely low recurrence and metastasis, and it cannot be distinguished from other subtypes of FVPTC due to the limitation of SEER database [17, 18]. Histology codes were listed below to select patients of each subtype accordingly.

CPTC included 8050 (papillary carcinoma not otherwise specified, NOS), 8260 (papillary adenocarcinoma, NOS), and 8343 (papillary carcinoma, encapsulated); FVPTC included 8340 (papillary carcinoma, follicular variant); FTC included 8330 (follicular adenocarcinoma, NOS), 8331 (follicular adenocarcinoma well differentiated), 8332 (follicular adenocarcinoma trabecular), and 8335 (follicular carcinoma, minimal invasive).

Patients whose tumor size, tumor extension, lymph node metastasis, distant metastasis, or removal of lymph nodes were unknown were excluded from this study. Cases without survival times were classified as unknown and were also removed from the study.

Our analysis included demographic variables: sex (male or female), age at diagnosis (< 45 or ≥ 45 years), and race (white or black). Cancer characteristics were classified according to the tumor stage, and tumors were grouped based on the sizes: < 1 cm, 1.1–2 cm, 2.1–4 cm, and > 4 cm. These sizes were chosen according to the American Joint Committee on Cancer T staging. Tumor extension included intrathyroidal extension (codes 100, 200, 300, 400), minimal extrathyroidal extension (code 450), and gross extrathyroidal extension (codes 480, 500, 520, 550, 600, 620, 650, 700, 730, 800); lymph node metastasis (code 000, no lymph nodes metastasis; code 120, metastasis to level VI; codes 135, 155, 158, 160, metastasis to level I, II, III, IV, V, or VII); distant metastasis (code 00, no distant metastasis; code 12, 40, 51, 60, distant metastasis disease). Treatment characteristics included lobectomy, total thyroidectomy, total thyroidectomy with postoperative radioactive iodine (RAI) therapy, and insurance status. All the variables were defined using the SEER specific codes.

Overall survival (OS) and disease-specific survival (DSS) were the two main indexes obtained using the multivariate Cox proportional hazard regressions in our study. Survival time (in months) was calculated for each patient using the “Completed Months of Follow-up” given in the SEER database.

Based on the inclusion criteria, a total of 70,346 cases between 2004 and 2014 were eligible for our study. The demographics and clinicopathologic features of DTC were compared between the white and black Americans in Table 1. Among them, 65,171 were white Americans (92.6%), and only 5175 were black Americans (7.4%). The median follow-up time was 50 months for white patients and 46 months for black patients. Of the total death of 2980, 408 died of thyroid cancer. In white patients, 377 died of thyroid cancer (0.6%), and in black patients, 31 died of thyroid cancer (0.6%).

White Americans were more likely to have CPTC (62.0%) than black Americans, while black Americans had a higher percentage of FVPTC (41.4%) and FTC (10.9%) than white Americans. Larger tumor (> 4 cm) were more common in black patients (15.2%) than in white patients (7.9%). Lymph node metastasis occurred more frequently in white patients (19.5%) than in black patients (9.0%). Distant metastasis appeared rarely in both white (0.7%) and black patients (0.9%).

Outcomes of OS and DSS were obtained using the multivariate Cox analysis. Black patients had significantly worse OS than white patients (aHR = 1.127, P = 0.002), while DSS were comparable between white and black patients (aHR = 1.045, P = 0.819). Even when patients are classified into CPTC, FVPTC, and FTC subgroups, no statistical difference of DSS was found between white and black patients (Fig. 1).

Cox proportion hazards models were applied to investigate the association between DSS and potential risk factors in white and black Americans in Table 2. In white Americans, female had better prognosis than male. FVPTC patients had better DSS than CPTC, and FTC patients had significantly worse DSS. Older age (≥ 45 years), advanced stage, larger tumor size, extrathyroidal extension, lymph node metastasis, and distant metastasis had negative effects on DSS in white Americans. For black Americans, despite female had comparable better DSS, no statistical difference was revealed. CPTC, FVPTC, and FTC had very similar DSS. Only tumor size > 4 cm had negative effects on DSS. Minimal extrathyroidal extension and central compartment lymph node metastasis (level VI) did not reveal any significant difference on DSS, while lateral neck nodes (level I, II, III, IV, V, or VII) had negative effects. In addition, black patients did not benefit from a more aggressive therapy than lobectomy, only white patients with total thyroidectomy and postoperative RAI therapy had improved DSS. To further assess the effects of RAI therapy, patients were categorized into three groups: tumor < 2 cm, tumor > 2 cm without lymph node metastasis, and tumor > 2 cm with lymph node metastasis (as RAI was recommended for node-positive and tumor > 2 cm). We found that only white patients with tumor > 2 cm and lymph node metastasis benefited from RAI therapy (Fig. 2). In addition, our results revealed that a number of patients did not receive guideline concordant care (Table 3). As for lymph node dissection, because of the limitation of SEER database, we used the removal of lymph nodes as lymph node surgery. Only black patients with more than four lymph nodes removed had improved DSS.

To determine whether black patients with DTC associated with higher potential of lymph node and distant metastases, we constructed a multivariate logistic regression model (Table 4). In CPTC and FVPTC patients, black Americans were protective against lymph node metastasis, while for FTC, race was not independently associated with lymph node metastasis. As for distant metastasis, black FVPTC, but not CPTC or FTC, patients had more distant metastasis.