Exploring the Relationship Between Patient Age and Cancer-Specific Survival in Papillary Thyroid Cancer: Rethinking Current Staging Systems

Abstract

Purpose Patient age is considered to play a unique prognostic role in papillary thyroid cancer (PTC), with a distinct staging dichotomization at 45 years of age. This is based on older, limited data demonstrating a marked rise in mortality around the ages of 40 to 50 years. We hypothesized that age is associated with compromised survival from cancer, with no cutoff denoting survival difference. Patients and Methods Patients with PTC who had surgery were identified from the SEER database (1998 to 2012). Multivariable proportional hazards modeling utilizing several flexible smoothing approaches were used to examine the association between age and cancer-specific survival (CSS) and to determine whether there is an age cut point that is associated with CSS decrement. Results A total of 31,802 patients with PTC were included. Median age was 45 years (range, 2 to 105 years). Ten-year CSS according to age was as follows: 2 to 19 years, 99.8%; 20 to 29 years, 99.9%; 30 to 39 years, 99.8%; 40 to 49 years, 99.5%; 50 to 59 years, 98.1%; 60 to 69 years, 94.8%; 70 to 79 years, 91.5%; 80 to 89 years, 79.2%; and ≥ 90 years, 73.9%. After adjustment for patient demographic and clinicopathologic characteristics, increasing age was associated with increasing mortality from the disease in a dose-dependent fashion, without an apparent cut point. Each of the smoothing approaches demonstrated a similar linearity of risk over all ages and provided close measures of goodness of fit to the data. Conclusion Patient age is significantly associated with death from PTC in a linear fashion, without an apparent age cut point demarcating survival difference. These results challenge the appropriateness of a patient age cut point in current staging systems for PTC and argue for considering a revision in how we anticipate prognosis for patients with PTC.

Fig 1.

Adjusted association between patient age at diagnosis and cancer-specific survival. The restricted cubic spline plot demonstrates the linear association between patient age (x-axis) and the adjusted log hazard ratio of death (y-axis). The blue solid line represents the fitted line of the association between age and the estimated hazard ratio of survival after adjustment; the two gold dashed lines represent the 95% CI. The three blue dots correspond to the location of three knots used in the model placed at the 10^th, 50^th, and 90^th percentiles of patient age. The effects of the following were adjusted for in the model: patient gender, race, tumor size, extrathyroidal extension, lymph node involvement, distant metastases, extent of surgery, year of diagnosis, and radioactive iodine treatment. Ln HR, log hazard ratio.

Fig 2.

Adjusted association between patient age at diagnosis and cancer-specific survival with thin plate splines applied. The blue solid line represents the fitted line of the association between age and the estimated hazard ratio of survival after adjustment; the two gold dashed lines represent the 95% CI. The effects of the following were adjusted for in the model: patient gender, race, tumor size, extrathyroidal extension, lymph node involvement, distant metastases, extent of surgery, year of diagnosis, and radioactive iodine treatment. Ln HR, log hazard ratio.

Fig 3.

Adjusted association between patient age at diagnosis and cancer-specific survival with adaptive smoothers applied. The blue solid line represents the fitted line of the association between age and the estimated hazard ratio of survival after adjustment; the two gold dashed lines represent the 95% CI. The effects of the following were adjusted for in the model: patient gender, race, tumor size, extrathyroidal extension, lymph node involvement, distant metastases, extent of surgery, year of diagnosis, and radioactive iodine treatment. Ln HR, log hazard ratio.