Baseline 18F-FDG PET/CT Parameters as Imaging Biomarkers of Overall Survival in Castrate-Resistant Metastatic Prostate Cancer

The lifetime risk of prostate cancer in developed countries is about 1 in 6 men (1). In the post–prostate-specific antigen (PSA) screening era, most patients (about 93%) present with locoregional disease, whereas metastatic disease is the initial presentation in about 4% of patients, with the remaining 3% categorized as of unknown stage (1). Although men with localized prostate cancer are treated with curative intent, many will eventually develop biochemical recurrence and metastatic disease (2). Most men with metastatic prostate cancer develop a castrate-resistant state having a hallmark of tumor growth despite castrate levels of serum androgens (3). Castrate-resistant metastatic prostate cancer is incurable and is the main cause of disease-related morbidity and mortality. An important unmet need in this clinical context is the optimal selection and sequencing of various drug options guided by the most informative outcome measures to provide maximum benefit to individual patients (4). Given the proclivity of prostate cancer to metastasize to bone, and the limitations of existing imaging tools for assessment of bone metastases, evaluating response quantitatively has been difficult. These difficulties include the inability to use response criteria such as Response Evaluation Criteria in Solid Tumors for assessment of bone metastases on CT, the confounding effect of the flare phenomenon on standard bone scintigraphy, and the ambiguity associated with the clinical significance of changes in serum PSA level (5,6). This notion is also coupled with the current evolution in the treatment paradigm to control, relieve, or eliminate disease manifestations (e.g., PSA, imaging findings, or symptoms) and to delay or prevent future disease manifestations (7). A recognized and relevant outcome measure in castrate-resistant metastatic prostate cancer is overall survival (OS), which may be useful for guiding and optimizing treatment decisions. OS may be predicted by several clinical, laboratory, and imaging parameters. However, given the remarkable heterogeneity of disease in terms of prognosis, a quantitative patient-specific imaging-based predictive model of OS will be of significant clinical value. PET is an ideal imaging tool for noninvasive interrogation of the underlying tumor biology. Several promising radiotracers are being investigated in the imaging evaluation of prostate cancer, including 18F- or 11C-choline, 18F- or 11C-acetate, 16β-18F-fluoro-5α-dihydrotestosterone targeted to the androgen receptor, the synthetic L-leucine analog anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid, and PSMA-based PET radiotracers (8,9). However, the exact diagnostic and prognostic roles of these radiotracers in prostate cancer are undefined and will require continued investigation. 18F-FDG is the most common PET radiotracer used for oncologic applications and is based on elevated glucose metabolism in malignant tissue in comparison to normal tissue. 18F-FDG uptake in prostate cancer depends on tumor differentiation, with low uptake in well-differentiated tumors and high uptake in aggressive poorly differentiated tumors (10). Cumulative current evidence strongly suggests that 18F-FDG PET/CT may be useful in the imaging evaluation of men with metastatic prostate cancer (10). The aim of this prospective investigation was to determine whether parameters derived from 18F-FDG PET/CT bear independent prognostic information on OS in patients with castrate-resistant prostate cancer.