The association of pregnancy with disease progression in patients previously treated for differentiated thyroid cancer: A propensity score-matched retrospective cohort study

Abstract

IMPORTANCE Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of progression/recurrence of DTC after treatment remains controversial due to the effect of confounding. OBJECTIVE To assess the effect of pregnancy on structural or biochemical progression in patients previously treated for DTC in a retrospective cohort using propensity score matching (PSM). DESIGN, SETTING, AND PARTICIPANTS This cohort study included 123 pregnant women and 1,376 non-pregnant women after initial treatment for DTC at Peking University Third Hospital between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 102) and non-pregnancy groups (n = 297) in terms of age, Hashimoto's thyroiditis, lymph node dissection, extra-thyroid invasion, initial risk of recurrence after treatment, and time interval between treatment and last follow up by using PSM. EXPOSURES DTC patients became pregnant after previous treatment. MAIN OUTCOMES AND MEASURES The risk of structural or biochemical progression was assessed in the pregnancy and PSM matched non-pregnancy groups, respectively. Conditional logistics regression models were used to control important confounders and consider the matching properties of the data. RESULTS At baseline, the pregnancy (n = 102) and non-pregnancy groups (n = 297) were balanced in all matched variables (standardized differences <10% and P > 0.05). After a mean follow-up of approximately 4.5 years, we observed no evidence of difference between the two groups in growth in the size of existing metastatic foci [2 (2.0 %) vs. 2 (0.7 %); P = 0.346], percentage of patients developing new lymph node metastases [4 (3.9 %) vs. 21 (7.1 %); P = 0.519], node growth in the contralateral thyroid lobe [4 (3.9 %) vs. 16 (5.4 %); P = 0.324 ], or biochemical progression [2 (2.0 %) vs. 9 (3.0 %); P = 0.583]. Results from conditional logistic regressions and several sensitivity analyses also showed no evidence of association of pregnancy with the risk of progression, after adjusting for potential confounders of age, tumor size, initial risk stratification, Hashimoto's thyroiditis, lymph node dissection, the time interval between treatment and follow-up, and achievement of TSH inhibition target (P = 0.354). The pregnancy-progression association observed longer than 4.5 years showed no evidence of difference with that observed shorter than 4.5 years (P for interaction was 0.283). We further classified the pregnancy patients into 3 subgroups based on the time interval between treatment and pregnancy (< 1 year, 1-2 years, ≥ 2 years) and found that the shorter the time interval, the higher the risk of DTC progression (P for trend was 0.043). CONCLUSIONS AND RELEVANCE The risk of DTC progression/recurrence in the pregnant women was not higher than that in the well-matched, non-pregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait an appropriate amount of time before pregnancy.