In a groundbreaking study published in BMC Cancer, researchers have shed new light on the optimal dosing strategy for adjuvant radioactive iodine (^131I) therapy in patients with differentiated thyroid cancer (DTC) exhibiting unexplained elevation of TSH-stimulated thyroglobulin (sTg). Given the ongoing debate regarding the most effective and least toxic radioiodine dose, this comprehensive retrospective analysis evaluated the efficacy and long-term prognostic implications of two commonly used ^131I doses—3.7 gigabecquerels (GBq) and 5.55 GBq—providing critical insights that could influence clinical practice worldwide.
Differentiated thyroid cancer, the most prevalent form of thyroid malignancy, often undergoes surgical resection followed by adjuvant radioactive iodine therapy to eliminate residual microscopic disease. The role of adjuvant ^131I in patients with elevated sTg levels but no definitive imaging evidence of disease has been particularly contentious. sTg serves as a sensitive biochemical marker; however, the optimal therapeutic dosage for these patients has yet to be definitively established, balancing tumor control with potential side effects associated with radiation exposure.
The study retrospectively analyzed data from 224 DTC patients treated at a single institution between January 2015 and December 2016. These individuals underwent adjuvant ^131I therapy at either 3.7 GBq or 5.55 GBq doses following total or near-total thyroidectomy. The patient cohort was closely monitored for both dynamic risk evaluation and clinical outcomes, including persistent and recurrent disease (PRD) rates alongside recurrence-free survival (RFS), over a median follow-up period exceeding six years.
Interestingly, six months post-treatment assessments revealed that 58.9% of patients achieved an acceptable response, defined by biochemical and imaging criteria, regardless of the administered ^131I dose. Conversely, 41.1% displayed an unacceptable response, suggesting the need for further clinical intervention or closer monitoring. Notably, there was no statistically significant difference between the two dosing groups in terms of these early treatment responses, challenging the presumption that a higher ^131I dose automatically confers superior efficacy.
Longitudinal follow-up data underscored the complexity of disease progression in this patient population. Persistent disease was documented in 12 patients, while 24 experienced recurrence during the follow-up. Despite these occurrences, the overall 5-year RFS rate stood impressively at 91.7%, indicating effective disease control with current therapeutic strategies. Yet again, the comparative analysis showed that the higher 5.55 GBq dose did not significantly outperform the 3.7 GBq regimen in preventing disease recurrence.
Advanced statistical modeling yielded further nuanced insights. Univariate analysis linked the results of post-therapy whole-body scans (WBS), including single-photon emission computed tomography (SPECT) imaging, and the number of ^131I treatments with the likelihood of persistent or recurrent disease. Such imaging modalities remain invaluable tools for metastatic detection and treatment planning, suggesting that qualitative and quantitative imaging findings could refine risk stratification beyond merely the administered dose.
More compelling were the results of the multivariate Cox proportional hazards model, which identified several independent predictors of prognosis. The total number of surgeries undertaken emerged as a negative prognostic factor, associated with an increased hazard ratio (HR 3.147) for recurrence, likely reflecting more extensive disease or surgical complexity. Conversely, an increased number of ^131I therapies and a positive treatment response at six months were both significantly associated with improved recurrence-free survival, highlighting the benefit of tailored, iterative therapeutic approaches.
From a clinical standpoint, these findings bear considerable significance. They suggest that escalating the ^131I dose from 3.7 GBq to 5.55 GBq in patients with unexplained sTg elevation after thyroidectomy may not yield proportional benefits in reducing recurrence or enhancing survival outcomes. This challenges existing paradigms advocating for routine higher dosing and emphasizes the need for individualized treatment algorithms based on patient response and risk factors.
The potential implications extend beyond efficacy. Radioactive iodine therapy, while generally safe, carries risks, including sialadenitis, xerostomia, secondary malignancies, and marrow suppression, which can be dose-dependent. Thus, confirming that lower doses maintain comparable therapeutic results could markedly reduce cumulative toxicity and healthcare costs, increasing long-term quality of life for patients.
Experts emphasize the necessity of validating these results through prospective, randomized controlled trials with larger sample sizes and extended follow-up periods to capture late recurrences and rare adverse events. Such studies would cement the optimal dosing paradigm and inform updated clinical guidelines, potentially refining the standard of care for thyroid cancer worldwide.
Furthermore, the integration of advanced molecular and imaging biomarkers into management algorithms could revolutionize therapeutic decisions. The combined use of ^131I WBS/SPECT was shown to correlate with outcomes and may aid in early identification of patients who warrant more aggressive intervention versus those suitable for de-escalation strategies.
This study’s robust methodology and extended monitoring period significantly enhance its clinical relevance. Retrospective reviews often suffer from limited follow-up or heterogeneity, but here, the investigators have effectively demonstrated consistent application of treatment protocols and thorough outcomes assessment, reinforcing the credibility of their conclusions.
In an era of precision medicine, these findings underscore the importance of balancing therapeutic efficacy with the minimization of unnecessary treatment intensity. The data supports a paradigm shift away from one-size-fits-all approaches, advocating instead for nuanced strategies that consider biochemical markers, imaging results, and individualized risk profiles.
Given the increasing incidence of differentiated thyroid cancer worldwide, optimizing adjuvant therapy regimens is not only a clinical imperative but also a public health priority. This study paves the way for more personalized, evidence-based care models that maximize patient outcomes while preserving vital organ function and quality of life.
In conclusion, the current evidence suggests no significant difference in treatment efficacy or prognosis between 3.7 GBq and 5.55 GBq doses of adjuvant ^131I therapy in DTC patients with unexplained sTg elevation. Moving forward, researchers and clinicians must collaborate on prospective large-scale studies to rigorously define dosing standards and leverage emerging diagnostic tools, ensuring the best possible outcomes for this growing patient population.
Subject of Research: Efficacy and prognostic impact of two different adjuvant ^131I doses (3.7 GBq vs. 5.55 GBq) in differentiated thyroid cancer patients with unexplained TSH-stimulated thyroglobulin elevation.
Article Title: Comparison of efficacy and prognostic impact of adjuvant ^131I therapy at 3.7 GBq and 5.55 GBq in DTC patients with unexplained sTg elevation.
Article References:
Sun, N., Liu, M., Xi, C. et al. Comparison of efficacy and prognostic impact of adjuvant ^131I therapy at 3.7 GBq and 5.55 GBq in DTC patients with unexplained sTg elevation.
BMC Cancer 25, 912 (2025). https://doi.org/10.1186/s12885-025-14307-5
Image Credits: Scienmag.com
