Keywords
PSMA metastatic thyroid cancer - differentiated thyroid carcinoma - radioactive iodine-refractory
- RAIR-DTC
Introduction
Differentiated thyroid carcinoma (DTC) in Filipinos is linked to a more aggressive
recurring behavior, leading to higher morbidity rates.[1] It is crucial to be vigilant and improve the quality of diagnosis, treatment, and
prognosis of thyroid cancers in the Philippines. With the advent of prostate-specific
membrane antigen (PSMA) PET/CT, multiple studies have described incidental uptake
in the thyroid gland. Such findings may represent both benign and malignant etiologies,
which warrant further clinical investigation. Presently, there is limited evidence
on the potential of PSMA PET/CT scans as a prognostic biomarker in DTC, and opinions
on their use in thyroid cancers, especially compared with 18F-FDG PET/CT scans, are varied.[2]
[3]
[4] We aim to highlight the significance of simultaneous cancers identified by PSMA
PET/CT scan, examine its predictive value in radioactive iodine refractoriness (RAIR)-DTC,
and explore how PSMA radioligand therapy can enhance treatment protocols in the future.
Case Report
A 57-year-old male, diagnosed with prostate adenocarcinoma (Gleason score: 4 + 3 = 7,
ISUP group 3), underwent an 18F-PSMA PET/CT ([Fig. 1A]), which revealed PSMA receptor-overexpressing lesions in the prostate and left lower
lung nodule, measuring 2.5 cm × 2.1 cm × 2.0 cm. Biopsy of the lung nodule, along
with histomorphology and immunohistochemical staining, was consistent with metastatic
thyroid carcinoma. Total thyroidectomy subsequently confirmed papillary thyroid microcarcinoma,
and the patient subsequently underwent RAI therapy. Post-therapy total body scan ([Fig. 1B]) demonstrated functioning thyroid tissue remnants in the anterior neck with a noniodine-avid
left lung nodule. A significant rise in serum thyroglobulin levels (26.82–561 ng/mL
over a 4-month period) prompted a second cycle of RAI therapy, which achieved successful
ablation of the thyroid remnants; however, there was persistent nonradioiodine concentration
in the known lung metastasis ([Fig. 1C]). A follow-up 18F-PSMA PET/CT (4 months since the first scan; [Fig. 1D]) showed decreased PSMA uptake in the prostate and stable PSMA uptake in the lungs,
with interval progression in size and number on CT. The patient is maintained on Pamorelin
and has been initiated on Lenvatinib.
Fig. 1 (A) PSMA receptor-overexpressing lesions in the prostate and left lower lung nodule.
(B) Posttherapy scan after first cycle of RAI therapy showed functioning thyroid tissue
remnants in the anterior neck with a noniodine-avid left lung nodule. (C) Posttherapy scan after the second cycle of RAI therapy showed successful ablation
of the neck remnants and persistent nonradioiodine concentration of the left lung
nodule. (D) Interval decrease of PSMA receptor-overexpressing lesions in the prostate, while
stable PSMA uptake in the lung nodule.
Discussion
The PSMA-avid nodule in the left lower lung is attributed to increased PSMA expression
in tumor-associated neovasculature, a phenomenon seen in aggressive and metastatic
thyroid cancers, particularly in poorly differentiated subtypes. This expression is
driven by angiogenic factors within the tumor microenvironment.[5] It is important to avoid assuming all PSMA-avid lesions in prostate cancer patients
are metastases. In this case, biopsy of the PSMA-avid lung nodule revealed a synchronous
papillary thyroid malignancy.
With the advent of PSMA PET/CT, several studies have reported incidental uptake in
the thyroid gland. Although the PSMA PET/CT identified a metastatic lung nodule originating
from the thyroid, it did not show PSMA uptake in the thyroid gland itself.
RAIR-DTC lacks the sodium iodide symporter in the basement membrane of thyroid follicular
cells for iodine uptake. This absence explains why the lung nodule remains noniodine
avid, despite receiving two cycles of radioactive iodine (RAI) therapy with a cumulative
dose of 305.3 mCi. Identifying patients who are likely to develop RAI refractoriness
is crucial, as these individuals have a 10-year survival rate of under 10%.
Emerging evidence indicates that PSMA expression may serve as a predictive biomarker
for the early identification of RAIR-DTC. Immunohistochemical analyses have demonstrated
upregulated PSMA expression within the tumor-associated neovasculature of RAIR lesions,
a feature that correlates with increased tumor aggressiveness. Moderate to intense
PSMA immunoreactivity has been significantly associated with an elevated likelihood
of progression to radioiodine resistance.[6]
[7]
[8] In this case, PSMA-avid pulmonary metastasis was identified on PSMA PET/CT imaging
prior to definitive biochemical or imaging evidence of RAIR, supporting the utility
of PSMA expression as an early surrogate marker of refractoriness in DTC.
Furthermore, there is limited evidence on the potential of PSMA PET/CT scans as a
prognostic biomarker in DTC.[2]
[3]
[4] It has been demonstrated that PSMA expression is related to malignant disease, poor
prognostic factors, poorer progression-free survival, and a low rate of recurrence-free
survival.[9]
[10]
Due to the PSMA avidity of these metastatic lesions, therapy with Lutetium-177-PSMA
has become a viable option, expanding treatment possibilities for RAIR-DTC.[11] Diagnostic PSMA PET/CT scans offer several added benefits, including detecting lesions
with aggressive characteristics, early identification of radioiodine refractoriness,
evaluating PSMA uptake in metastatic lesions, and assessing suitability for theranostic
therapy. This case indicates that a PSMA PET/CT scan may be able to detect radioiodine
resistance at an early stage and stratify patients in need of close monitoring, further
evaluation, and other treatment options.
Conclusion
This case indicates that PSMA PET/CT scans may be able to detect radioiodine resistance
at an early stage and stratify patients in need of close monitoring, further evaluation,
and other treatment options.
