Need for a revised staging consensus in medullary thyroid carcinoma

Hypothesis: Assessing prognosis for medullary thyroid cancer remains challenging and inexact. We hypothesize that the 1997 TNM staging criteria, especially for stage IV, are more accurate than the current 2002 staging system. Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: One hundred seventy-three patients surgically treated for medullary thyroid cancer from January 1, 1980, to December 31, 2007. Main Outcome Measures: Patients were staged according to 1997 and 2002 TNM criteria and according to treatment result: biochemically cured (normal calcitonin level); clinically cured (elevated calcitonin level but no evidence of disease by imaging); or not cured. Survival was calculated from initial surgery to death or last follow-up. Analysis used McNemar test to compare paired proportions and Kaplan-Meier estimation with log-rank tests. Results: A significantly higher proportion of patients were classified as having stage IV cancer using 2002 criteria compared with 1997 criteria (33% vs 7%, respectively; P < .001). Stage IV, 5-year overall survival was 82% (95% confidence interval, 72%-93%) with 2002 criteria vs 46% (95% confidence interval, 22%-93%) with 1997 criteria. Despite 15 of 36 clinically cured patients (42%) being classified as having stage IV cancer (13 patients with stage IVa cancer, 2 patients with stage IVb cancer) by the 2002 criteria, the observed overall survival of the clinically cured group at 5, 10, and 15 years was 100%, 100%, and 79%, respectively (P = .7 compared with those biochemically cured). Conclusions: The current 2002 TNM staging for medullary thyroid cancer appears inadequate, especially for patients with stage IV cancer. Elevated but stable calcitonin levels often do not portend unfavorable outcome. Patients with lymph node metastases, irrespective of their location, but without distant disease would seem best classified as having stage III cancer.