This study showed that PTIs were found in 1.1% of patients who underwent PSMA PET/CT. Further diagnostic analysis with ultrasound was performed in less than half of the PTI cases (41%). Most of these cases (84%) underwent FNAC. In only few cases (7%) thyroid surgery was performed. Two patients had a histologically proven thyroid cancer, one patient a benign thyroid lesion and one patient a metastasis of a renal cell carcinoma. The majority of cases (20/25) who received additional PTI diagnostics had a less advanced stage of their primary malignancy. Six patients (10%) died due to their primary PCa.
The incidence of thyroid incidentalomas (TIs) has been described before. 18FDG PET/CT TIs have been widely studied.[32–35] FDG TIs are generally regarded as focally elevated thyroid uptake and up to one-third of the FDG TIs are malignant. The most frequent malignant histological subtype is PTC.[32–35] Because the PSMA PET/CT scan is a relatively new diagnostic tool, there is limited clinical experience with incidental detection of synchronous PSMA-avid malignancies. The incidental expression of PSMA was also shown in other cancers such as renal cell carcinoma, neuroendocrine tumors, melanoma, colon carcinoma, lung cancer or breast cancer.[36–39] Recently, PSMA uptake in thyroid cancer has been reported in case-reports and prospective studies. [19, 25–27] Bychkov et al. found that PSMA expression was observed in a wide spectrum of thyroid tumors and that thyroid cancers had significantly higher PSMA expression than benign tumors. However, the detection of PSMA uptake in the thyroid gland did not guarantee thyroid origin of these lesions. The incidence of PTIs was studied by Kirchner et al. who found an incidental uptake of 68Ga-PSMA by the thyroid gland in 22% of 55 patients with urological cancers. This incidence is higher compared to our study population which can be related to a different study design. The current literature reveals one systematic review concerning 68Ga-PSMA PTIs. Most of the included studies were retrospective in nature and consisted of case-reports. This review concluded that the risk of a PTI being malignant is not negligible. Among 23 PTIs with focal uptake, 6 were malignant (5 primary thyroid carcinomas and one renal cell carcinoma metastasis), one was a follicular lesion of undetermined significance and the other lesions were benign. Gossili et al. studied 341 patients with a 68Ga-PSMA PET/CT scan of which 7 patients (2%) had increased focal PSMA uptake in the thyroid gland of which two were confirmed malignant (2/7). In our cohort, 43 PTIs (70%) with focal uptake were included of which 3 had a proven malignant pathology (2 thyroid carcinomas and one metastasis from renal cell carcinoma). The incidence of confirmed malignancy (7.0%) in the current cohort is lower compared to the above-mentioned study. In general, the follow-up in our study was more comprehensive in cases with focal than diffuse PTIs which is similar to the findings of Gossili et al. Diffusely increased uptake of FDG in the thyroid is thought to be associated with autoimmune thyroiditis or hypothyroidism which may also explain the low rate of diagnostic follow-up for diffuse PTIs.
The ATA guidelines for thyroid nodules suggests further workup in all thyroid nodules of 1 cm and larger, also when incidentally depicted on imaging, because they have a greater potential to be clinically significant malignancies. According to the 2015 Dutch guideline, the advice is to analyze thyroid incidentalomas by ultrasound and FNAC in cases without relevant comorbidities. The indication for PSMA PET/CT scan in this study was staging of the primary detected malignancy, predominantly PCa. This specific population therefore has relevant comorbidity. The strategy to actively pursue all PTIs of one cm and above in this cohort may lead to overtreatment of thyroid nodules that might never become clinically relevant. Surgical management of thyroid carcinoma consists of lobectomy or total thyroidectomy with or without neck dissection or radioactive iodine treatment. These strategies are associated with complications such as hypothyroidism (5% of patients), iatrogenic hypoparathyroidism, recurrent laryngeal nerve damage (1% of patients), dysphagia, hemorrhage and wound infection.[41, 42] The current use of additional imaging and treatment for PTIs detected by PSMA PET/CT scans must be critically evaluated to avoid such complications.
In both our hospitals, different types of management strategies were applied. A minority of 4 patients underwent thyroid surgery, of which 3 were histologically proven malignant. The patient’s comorbidity and life expectancy based on the primary non-thyroid cancer should be taken into account while deciding the further evaluation of a PTI. This study indicates that most physicians have indeed considered this, since patients with a less favorable expected outcome, for example with local- or distant metastasis, received PTI workup significantly less often compared to patients with a more favorable prognosis. If more PTI workup was performed, more thyroid cancers may have been detected. However, analysis of the follow-up data indicates that these possible missed thyroid malignancies dit not become clinically relevant for the patients in our study cohort. However, our follow-up period was relatively short.
Strengths and limitations
A strength of this study includes the large study population for a rarely described finding. Study limitations include the retrospective nature of this study. Another limitation is that the PSMA PET/CT scans were predominantly performed in male patients with prostate cancer. Therefore the conclusions cannot be extrapolated to general clinical practice.The physician dependent choices for PTI workup might also be a potential study bias. The nuclear medicine reports were generated by different nuclear medicine physicians in different hospitals, which might have led to heterogenous reporting. Also, only a minority of patients underwent thyroid surgery. Therefore, a final histological diagnosis was only available in few patients.