Abstract
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Introduction: Prostate-specific membrane antigen (PSMA) is one of the most widely studied biomarkers in prostate cancer (PCa). However, the limitation of PSMA as a biomarker is its low expression in PCa tissues with low Gleason score, and tumor heterogeneity is another factor. Neurotensin receptor (NTSR) is overexpressed in non-androgen-dependent PCa tissues, as well as in neuroendocrine PCa with low PSMA expression. However, how 68Ga-PSMA and 68Ga-NT PET/CT could be used (or combined) in various types of PCa diagnosis has barely been investigated. We aimed to compare the preclinical data of the role of 68Ga-PSMA and 68Ga-NT PET/CT in initially detecting PCa.
Methods: Patients who were pathologically diagnosed with PCa underwent 68Ga-PSMA PET/CT and 68Ga-NT PET/CT within 15 days as part of the prospective trial were included. Visual assessment of PET images was undertaken and standard uptake value (SUVmax) was measured for the dominant lesion per participant. Each PET scan was interpreted by three independent masked readers and a consensus majority interpretation was generated (two vs. one) to determine positive findings. Pathological specimens obtained from prostate biopsy or radical prostatectomy were used as the gold standard. Because clinical and ethical standards for patient management did not allow surgery or sampling of all detected metastatic lesions, follow-up imaging (68Ga-PSMA PET/CT, MRI, CT, scintigraphy) and clinical follow-up findings were used as a modified reference standard to confirm those metastatic lesions that cannot be confirmed by histopathology. This study is registered with ClinicalTrials.gov, number NCT03516045.
Results: Twenty-four patients who were pathologically diagnosed with PCa were analyzed. Overall, detection rates were significantly lower with 68Ga-NT PET/CT (one [4.2%; 95%CI 0-21] of 24) than with 68Ga-PSMA PET/CT (21 [87.5%; 95%CI 68-97] of 24) at the patient level (Kappa=0.017, p<0.0001); in the subanalysis of primary PCa (one [4.2%; 95%CI 0-21] with 68Ga-NT PET/CT vs. 20 [83.3%; 95%CI 63-95] with 68Ga-PSMA PET/CT); in the subanalysis of the nodes metastasis (none [0%; 95%CI 0-14] with 68Ga-NT PET/CT vs. seven [29.2%; 95%CI 13-51] with 68Ga-PSMA PET/CT); in the subanalysis of the bone metastasis (one [4.2%; 95%CI 0-21] with 68Ga-NT PET/CT vs. four [16.7%; 5-37] with 68Ga-PSMA PET/CT; Kappa=0.357, p=0.25).
Conclusions: This study confirms the higher detection rates of 68Ga-PSMA PET/CT than 68Ga-NT PET/CT in patients with prostate cancer, both in detecting primary and metastatic lesions, indicating that 68Ga-NT PET/CT may not be a direct competitor or has a complimentary role of 68Ga-PSMA PET/CT in fully characterizing PCa with different regions.
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