The overall estimated risk of recurrence after an apparently complete thyroid cancer resection ranges from <1% to 55%, and the high-quality pathology report is crucial for proper risk stratification. The neck ultrasound (US) and serum thyroglobulin (Tg) and anti-Tg antibody (TgAb) assays are the mainstays for Differentiated Thyroid Cancer (DTC) follow-up. However, the neck US includes a high frequency of nonspecific findings and despite the serum, Tg unmasks the presence of thyrocytes, it is not discriminating between normal and malignant cells. In this study, to improve post-surgery follow-up of minimal residual disease in papillary thyroid cancer (PTC) patients, blood-derived cytology specimens were evaluated for the presence of circulating tumor cells (CTCs). The presence of CTCs of thyroid origin was confirmed by cytomorphological and tissue-specific antigens analysis (Thyroid Transcription Factor-1/TTF-1 and Tg) and proliferative profile (percentage of cells in S-phase). Our data revealed an unfavorable' prognostic risk in patients with >5% CTCs (p = 0.09) and with >30% S-phase cells at baseline (p = 0.0015), predicting ≤1 year relapsing lesion event. These results suggest a new intriguing frontier of precision oncology forefront cytology-based liquid biopsy.

Although the role of liquid biopsy (LB) to measure minimal residual disease (MRD) in the treatment of epithelial cancer is well known, the biology of the change in the availability of circulating biomarkers arising throughout treatments such as radiotherapy and interventional radio-oncology is less explained. Deep knowledge of how therapeutic effects can influence the biology of the release mechanism at the base of the biomarkers available in the bloodstream is needed for selecting the appropriate treatment-induced tumor circulating biomarker. Combining existing progress in the LB and interventional oncology (IO) fields, a proof of concept is provided, discussing the advantages of the traditional risk assessment of relapsing lesions, limitations, and the timing of detection of the circulating biomarker. The current review aims to help both interventional radiologists and interventional radiation oncologists evaluate the possibility of drawing a tailor-made board of blood-based surveillance markers to reveal subclinical diseases and avoid overtreatment.