The Effect of Neoadjuvant Androgen Deprivation Therapy on Tumor Hypoxia in High-Grade Prostate Cancer: An 18F-MISO PET-MRI Study

Abstract

Tumor hypoxia is associated with radioresistance and poor prognosis after radiation therapy for prostate cancer (PCa). In this prospective pilot study, we assessed the ability of 18F-misonidazole (18F-MISO) positron emission tomography (PET)-magnetic resonance imaging (MRI) to detect hypoxia in high-grade PCa patients who were candidates for curative radiation therapy, and we evaluated 18F-MISO PET-MRI modulation after 3months of neoadjuvant androgen deprivation therapy (nADT). Eleven PCa patients with a Gleason score (GS) ≥ 8 underwent 18F-fluorocholine (18F-FCH) PET-computed tomography at diagnosis and an18F-MISO hybrid PET-MRI examination before nADT; a second 18F-MISO PET-MRI examination was acquired after 3 months of nADT for all patients but one who dropped out because of noncompliance with nADT.Immunohistochemistry for tissue hypoxia- and proliferation-related biomarkers (glucose transporter 1, carbonic anhydrase IX, vascular endothelial growth factor A, Ki-67, hypoxia-inducible factor 1 alpha, and epidermal growth factor receptor) was performed in lesions bearing the highest GS.We used nonparametric tests to assess (1) the presence of 18F-MISO-positive regions (tumor-to-background ratio [TBR]≥1.4) at baseline; (2) the correlation between imaging parameters (PET tracer uptake, Prostate Imaging Reporting and Data System [PIRADS] scores, and dynamic contrast enhancement perfusion markers) at baseline; (3) the difference in immunohistochemistry staining between 18F-MISO-positive and -negative lesions; and (4) the changes in 18F-MISO PET-MRI after nADT. Uptake of 18F-MISO was significant in 7 patients, being coincidental with the highest GS region in 5 of them. A significant correlation was found at baseline between GS and 18F-MISO TBR, between 18F-MISO TBR and MRI perfusion markers, between GS and 18F-FCH maximum standardized uptake value, between GS and PIRADS score, and between 18F-FCH maximum standardized uptake value and PIRADS score.No difference was found between 18F-MISO-positive and -negative biopsy specimens with respect to tissue biomarkers. The TBR of 18F-MISO diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline. PET imaging with 18F-MISO showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3months of nADT in high-grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a reoxygenation effect of nADT.