Work

Apparent Survival Benefit of Postoperative Radioactive Iodine in Lymph Node–Positive Papillary Thyroid Carcinoma: A Negative‐Control Analysis for Unmeasured Confounding

Year: 2026

Type: article

Abstract: BACKGROUND: Observational studies report an overall-survival advantage for postoperative radioactive iodine (RAI) in lymph node-positive papillary thyroid carcinoma (PTC), but such estimates are vulnerable to confounding by indication and to bias from immortal time and the healthy-user effect. We assessed the credibility of this apparent benefit rather than RAI efficacy itself. METHODS: Using SEER (2010-2015), we assembled a cohort of N1b, M0, totally thyroidectomized PTC patients and applied a 3-month landmark analysis (sensitivity analyses at 1 and 6 months) with stabilized inverse-probability-of-treatment weighting. We estimated RAI effects on overall survival, cancer-specific survival, and relative survival, and on a negative-control outcome-non-thyroid-cancer death-that RAI cannot plausibly affect. Residual confounding was quantified with E-values. RESULTS: Among 4275 patients, RAI showed an apparent survival benefit in direction across all three endpoints. However, the negative-control outcome likewise showed an apparent benefit (IPTW hazard ratio 0.713, 95% CI 0.562-0.906), indicating residual confounding not removed by weighting. The apparent survival benefits therefore could not be distinguished from unmeasured confounding. CONCLUSIONS: In registry data lacking key confounders, a negative control identifies the apparent RAI survival benefit as a candidate artifact of unmeasured confounding. The findings neither support nor refute RAI efficacy.

Source: Cancer Medicine

DOI: 10.1002/cam4.72320

Authors: Tengfei Liu, Junli Qiao, Mengxuan Mao, Qiang Guo, Fei Yang

Institutions: Hebei Medical University, Xingtai People's Hospital, Sichuan University, West China Hospital of Sichuan University, Fourth Hospital of Hebei Medical University

Language: English

Topic: Thyroid Cancer Diagnosis and Treatment

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,700