PROSTAT KANSERİNDE SİSTEMİK TEDAVİ YANIT DEĞERLENDİRİLMESİNDE Ga-68 İŞARETLİ PSMA PET-BT İLE BİYOKİMYASAL BELİRTEÇLERİN ROLÜ VE PROGNOSTİK ÖNEMİ

Abstract

Kodaz O. The Role and Prognostic Significance of Ga-68 Labeled PSMA PET/CT and Biochemical Markers in the Assessment of Systemic Treatment Response in Prostate Cancer, Hacettepe University Faculty of Medicine, Department of Nuclear Medicine, Thesis of Residency, Ankara, 2026. Prostate cancer is the second most common cancer in men, and accurate assessment of treatment response in the metastatic stage is critically important for patient management. Although serum prostate-specific antigen (PSA) is the principal biomarker for monitoring treatment response, it may be limited in reflecting the true tumor burden, particularly in the castration-resistant stage. Ga-68 labeled PSMA PET/CT, on the other hand, is a powerful imaging modality capable of demonstrating tumor burden at the volumetric and molecular levels. The aim of this study is to determine the role of PSMA PET/CT and biochemical markers such as serum PSA in the assessment of response to chemotherapy and radionuclide therapy in metastatic prostate cancer, the relationship of these parameters with one another, and their prognostic significance. This retrospectively designed study included three patient groups: patients with de-novo metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen deprivation therapy and docetaxel (Group A, n=49); patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel chemotherapy (Group B, n=26); and patients with mCRPC receiving 177Lu-PSMA radionuclide therapy (Group C, n=96). In all cases, semiquantitative parameters obtained from pre- and post-treatment PSMA PET/CT, primarily total tumor volume (TTV), and serum PSA levels were recorded; treatment response was evaluated using the RECIP 1.0, PSMA PET Progression (PPP), and PCWG3/PCWG4 criteria together with serum PSA response criteria. The agreement (concordance-discordance) between imaging response and PSA response and the relationship of these parameters with overall survival were investigated. Our findings demonstrated that in the hormone-sensitive stage, in which the disease is highly responsive to treatment, there was a high degree of concordance between serum PSA changes and PSMA PET parameters, with discordance remaining low. However, as the disease progressed to the castration-resistant stage, this agreement was markedly disrupted; this suggested that tumor biology changes in mCRPC cases and that PSA may be insufficient to reflect the true tumor burden. In patients with discordance, PSMA PET response was found to be determinant for survival. A positive correlation between PSA and TTV changes was observed in patients receiving systemic therapy, particularly in the group receiving radionuclide therapy. PSMA PET-based response criteria that jointly consider volumetric change or the development of new lesions were found to provide more comprehensive information compared with assessments based solely on clinical and PSA data. In conclusion, particularly in the mCRPC stage, routinely evaluating PSMA PET/CT before making PSA-based treatment-change decisions is important for excluding pseudoprogression and for detecting early relapse before PSA progression develops. These retrospective findings need to be supported by multicenter and prospective studies involving larger patient cohorts.