The Application Value of 18F-prostate-specific Membrane Antigen PET/CT in Prostate Cancer

Overview

Prostate cancer (PCa) is the most common type of malignant tumor and the third leading cause of cancer-associated mortality among men worldwide. The biological behaviors of PCa at different degrees of malignancy also largely differ, directly impacting disease outcomes and responses to treatment. Therefore, accurate risk stratification of PCa before treatment and the development of an individualized treatment regimen, play a vital role to improve the clinical outcome of patients. However, overdiagnosis and unnecessary biopsies, which are invasive examinations associated with higher costs and adverse effects. When the PSA is less than 20ng/mL, less than 1% of PCa patients have a positive bone scan, and routine bone scans are not recommended for asymptomatic or low-risk PCa patients. Interestingly, due to the variations among evaluators that often occur when defining the T stage, biopsies operate inaccuracy, also low-PSA level can also occur metastasis, there is a need for an objective and accurate imaging biomarker for the diagnosis of different grade PCa. Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein, which has higher expression in cancerous prostate cells than in normal prostate cells. Meanwhile, its expression level is positively correlated with the degree of malignancy, the tendency of metastasis, and the risk of early recurrence. In recent years, 18F-PSMA positron emission tomography/computerized tomography (PSMA PET/CT) has earned widespread attention as a novel imaging modality based on molecular-level analysis, rather than morphological or physiological analysis, to assist in PCa diagnosis and tumor burden evaluation. Currently, Maximum Standardized Uptake Value (SUVmax) is the most commonly used semi-quantitative parameter in PET/CT, which is used to assess tumor burden of PCa, and thus can be used as an imaging biomarker to assess the degree of malignancy of prostate cancers. However, prior studies mainly focused on the correlation between patients' biochemical recurrence lesions and the PSA levels and Gleason score. There is a lack of research to explore the correlation among primary PCa burden, PSA levels, and the degree of prostate cancer malignancy. The aim of this project is to use 18F-PSMA PET/CT SUVmax to analyze the correlation among primary PCa imaging, and clinical indicators, and to evaluate the predictive value for PCa risk stratification, metastasis risk, and biochemical recurrence.

Prostate cancer (PCa) is the highest malignant male tumor and one of the leading causes of mortality among men worldwide. The biological behaviors of PCa malignancy are largely heterogeneous, directly impacting prognostic grouping and treatment options. In addition, assessments of the distant metastatic status for PCa patients have recently received increasing attention due to the heightening mortality rate. Therefore, the precise systemic staging of primary PCa risk stratification before treatment plays a crucial role in designing the management strategy for the individualized treatment option. According to both American Urological Association (AUA) and the European Association of Urology (EAU) guidelines, patients with total prostate-specific antigen (tPSA) \> 20 ng/mL and/or Gleason Score ≥ 8 are high-risk, the probability of distant metastasis and mortality will increase significantly and may not suitable for active surveillance programs, radical prostatectomy or radiotherapy treatment. However, tPSA is organ-specific but not tumor-specific, the biological behaviors of prostate malignancy are largely heterogeneous, and the specificity of the ability of tPSA to reflect distant metastasis remains debatable. Using tPSA as the only indicator for risk stratification discrimination and distant metastases prediction may causing in large numbers of unnecessary prostate biopsies. Also, elderly patients with severe comorbidities or undergoing anticoagulation therapy may not be the optimal candidates for biopsies and may cause adverse effects and higher costs. In these cases, it is urgent to find objective and accurate imaging biomarkers for risk stratification classification with a noninvasive approach based on imaging analysis. The prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is primarily expressed in prostatic tissues, and its expression is correlated with the degree of malignancy and further increases in metastatic. The ability of PSMA to easily penetrate tissues and diffuse with solid tumor lesions can reflect the statuses of metastasis. Prior studies show that PSMA PET/CT is superior to conventional imaging methods for lymph node metastatic detection and that the pre-treatment tPSA level and Gleason Score are associated with the PSMA uptake in primary PCa. Furthermore, the Maximum Standardized Uptake Value (SUVmax) is the most commonly used semi-quantitative parameter in PET/CT and prior studies have already been used to assess the degree of malignancy of PCa and predict extended pelvic lymph node metastases in intermediate to high-risk PCa patients by 68Ga-PSMA-11 or 68Ga-PSMA-617. 18F-PSMA-1007 is advantaged by its higher spatial resolution images and non-urinary excretion that reduces urinary clearance, this approach bears a great potential to facilitate the detection of primary PCa and metastatic lesions. However, to our knowledge, no prior studies have employed 18F-PSMA-1007 PET/CT to evaluate the diagnostic performance in risk stratification and distant metastases prediction in primary PCa. The present study aims to retrospective investigated the role of 18F-PSMA-1007 PET/CT semi-quantitative parameters correlation among newly diagnosed PCa imaging, tPSA levels and Gleason Score, and to evaluate the prediction performance of 18F-PSMA-1007 PET/CT and clinicopathologic characteristics on PCa risk stratification and distant metastatic prediction.