Early calcitonin levels in medullary thyroid carcinoma: Prognostic role in patients without distant metastases at diagnosis

Introduction Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. Methods A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Results Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Conclusion Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.

[1]  M. Brose,et al.  LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer , 2022, Future oncology.

[2]  Binglu Li,et al.  Clinical Characteristics, Surgical Management, and Prognostic Factors of Medullary Thyroid Carcinoma: A Retrospective, Single-Center Study , 2022, Technology in cancer research & treatment.

[3]  F. Basolo,et al.  Impact of Advanced Age on the Clinical Presentation and Outcome of Sporadic Medullary Thyroid Carcinoma , 2020, Cancers.

[4]  M. Castro,et al.  Predicting Outcomes in Sporadic and Hereditary Medullary Thyroid Carcinoma over Two Decades. , 2020, Thyroid : official journal of the American Thyroid Association.

[5]  M. Zeiger,et al.  Association between age and disease specific mortality in medullary thyroid cancer. , 2020, American journal of surgery.

[6]  S. Awny,et al.  Medullary thyroid cancer: epidemiological pattern and factors contributing to recurrence and metastasis. , 2020, Annals of the Royal College of Surgeons of England.

[7]  K. Lorenz,et al.  Prediction of biochemical cure in patients with medullary thyroid cancer , 2020, The British journal of surgery.

[8]  C. Benbassat,et al.  Clinico-pathologic and dynamic prognostic factors in sporadic and familial medullary thyroid carcinoma: an Israeli multi-center study. , 2019, European Journal of Endocrinology.

[9]  Douglas B. Evans,et al.  Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. , 2015, Thyroid : official journal of the American Thyroid Association.

[10]  M. Kreissl,et al.  Cabozantinib in progressive medullary thyroid cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  E. Baudin,et al.  Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Pinchera,et al.  Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. , 2008, The Journal of clinical endocrinology and metabolism.

[13]  F. Schmidt Meta-Analysis , 2008 .

[14]  A. Pinchera,et al.  Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer. , 2007, Endocrine-related cancer.

[15]  S. Ismailov,et al.  Postoperative calcitonin study in medullary thyroid carcinoma. , 2004, Endocrine-related cancer.

[16]  E. Baudin,et al.  Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging , 2003, British Journal of Cancer.

[17]  E. Baudin,et al.  Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. , 2003, The Journal of clinical endocrinology and metabolism.

[18]  M. Schlumberger,et al.  Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients , 1998 .

[19]  A. Pinchera,et al.  Disappearance Rate of Serum Calcitonin after Total Thyroidectomy for Medullary Thyroid Carcinoma , 1994, The International journal of biological markers.

[20]  F. Raue,et al.  Epidemiology and Clinical Presentation of Medullary Thyroid Carcinoma. , 2015, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[21]  Kathryn J. Rowland,et al.  Biochemical Cure after Reoperations for Medullary Thyroid Carcinoma: A Meta-analysis , 2014, Annals of Surgical Oncology.

[22]  R. Hinze,et al.  Pattern of Nodal Metastasis for Primary and Reoperative Thyroid Cancer , 2001, World Journal of Surgery.

[23]  M. Schlumberger,et al.  Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'étude des tumeurs à calcitonine. , 1998, Clinical endocrinology.

[24]  J. Cooper Ajcc Cancer Staging Manual , 1997 .