Parathyroid Carcinoma: Incidence, Survival Analysis, and Management: A Study from the SEER Database and Insights into Future Therapeutic Perspectives

SIMPLE SUMMARY: Parathyroid carcinoma (PC) is a rare endocrine malignancy and an uncommon cause of primary hyperparathyroidism. It is more common in older Caucasians, with a slight male predominance. Among the patients with available data in a large national cancer registry of the U.S. population, PC was usually 2–4 cm in size, histologically defined as well-differentiated adenocarcinoma, and localized to the native glands with negative lymph nodes. The overwhelming majority (>95%) of the patients underwent surgery, with the remaining few receiving radiation or chemotherapy. The 5-year survival rate after surgery was 84%. Factors such as large tumor size (>4 cm), older age (>40 years), male sex, Caucasian race, distant spread, and poor tumor differentiation were associated with an increased risk of death. ABSTRACT: Introduction: Parathyroid carcinoma (PC) is an extremely rare entity, with a frequency of 0.005% of all malignancies. Most data related to this rare disease are limited to case series and a few database studies. We present a large database study that aims to investigate the demographic, clinical, and pathological factors, prognosis, and survival of PC. Methods: Data of parathyroid carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) diagnosed between 1975 and 2016. Results: PC had a slightly higher incidence in men (52.2%, p < 0.005), the majority of cases affected Caucasians (75.4%, p < 0.005), and the mean age at diagnosis was 62 years. Histologically, 99.7% were adenocarcinomas not otherwise specified (p < 0.005), well-differentiated (p < 0.005), and 2–4 cm (p < 0.001) in size among the patients with available data. In cases with staging provided, most PC were organ-confined (36.8%, p < 0.001). Lymph nodes were positive in 25.2% of cases where lymph node status was reported. The main treatment modality was surgery (97.2%), followed by radiation alone (2%), and very few received chemotherapy alone (0.8%), p < 0.005. Five-year follow-up was available for 82.7% of the cases. Those who underwent surgery only or radiation alone had 5-year survivals of 83.8% and 72.2%, respectively (p < 0.037). Multivariable analysis identified tumor size >4 cm, age > 40 years, male sex, Caucasian race, distant spread, and poorly differentiated grade as independent risk factors for mortality (p < 0.001). Conclusion: PC is a very rare tumor mostly affecting Caucasian individuals in the fifth decade. Older age, poor histologic differentiation, and distant metastasis are associated with a worse prognosis. Surgical resection offers the best survival outcome. To better understand the pathogenesis and factors affecting survival, all PC patients should be enrolled in national and international registries.