Apparent Survival Benefit of Postoperative Radioactive Iodine in Lymph Node-Positive Papillary Thyroid Carcinoma: A Negative-Control Analysis for Unmeasured Confounding.
- 1Department of Head and Neck Thyroid Surgery, Xingtai People's Hospital of Hebei Medical University, Xingtai, Hebei Province, P. R. China.
- 2Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
- 3Department of Otorhinolaryngology - Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, P. R. China.
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.
Related
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BibTeX
@article{liu2026apparent,
title = {{Apparent Survival Benefit of Postoperative Radioactive Iodine in Lymph Node-Positive Papillary Thyroid Carcinoma: A Negative-Control Analysis for Unmeasured Confounding.}},
author = {Tengfei Liu and Junli Qiao and Mengxuan Mao and Qiang Guo and Fei Yang},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72320},
url = {https://europepmc.org/article/MED/42910564},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Apparent Survival Benefit of Postoperative Radioactive Iodine in Lymph Node-Positive Papillary Thyroid Carcinoma: A Negative-Control Analysis for Unmeasured Confounding.
AU - Tengfei Liu
AU - Junli Qiao
AU - Mengxuan Mao
AU - Qiang Guo
AU - Fei Yang
PY - 2026
DA - 2026/10/01
JO - Cancer medicine
DO - 10.1002/cam4.72320
UR - https://europepmc.org/article/MED/42910564
AB - 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.
SN - 2045-7634
ER -