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Background: Positron emission tomography/computed tomography (PET/CT) with prostate specific membrane antigen ligands (PSMA) is established for use in primary staging of prostate cancer to screen for metastases. It has also shown promise in local tumor staging, including detection of extraprostatic extension (EPE) and seminal vesicle invasion (SVI). Previous studies have shown high heterogeneity in methods and results. Our aim was to compare [18F]PSMA-1007 PET/CT to magnetic resonance imaging (MRI) in evaluation of EPE and SVI, building on a previously described method for standardized evaluation. We retrospectively included 124 patients who had undergone MRI, PSMA PET/CT and prostatectomy. PSMA PET/CT images were evaluated by two nuclear medicine physicians. Using a standardized method, they measured length of capsular contact (LCC) and assessed EPE and SVI visually with the use of 5-point Likert scales. A radiologist evaluated MRI images using criteria based on Prostate Imaging–Reporting and Data System version and incorporating LCC measurement and Likert scales. We evaluated diagnostic performance with histopathology as reference, and the interrater reliability of the PET evaluations. Results: The sensitivity and specificity for detecting EPE with the quantitative LCC method for PSMA PET/CT was 0.46/0.91, for the visual method 0.28/0.82 and for the combination of the two 0.54/0.76. AUC in ROC analysis for the LCC method was 0.70. For MRI the sensitivity and specificity were 0.80/0.64. For SVI, PET/CT and MRI had sensitivity and specificity of 0.14/1.0 and 0.50/0.92 respectively. The intraclass correlation coefficient for the PET LCC measurement was 0.68, the kappa values for the visual Likert scales for PET were 0.53 for EPE and 0.63 for SVI. Conclusions: In this study, we attempted to standardize quantitative and qualitative PSMA PET/CT evaluation of EPE and SVI and compare the method with MRI. MRI had a higher sensitivity for EPE while PSMA had a higher specificity. For SVI, both methods had high specificity. The interrater reliability for the PSMA PET/CT evaluations was moderate to substantial. [ABSTRACT FROM AUTHOR]

Abstract Objectives This study aimed to clinically validate the six‐gene prognostic molecular clinical risk score (MCRS) for the prediction of aggressive prostate cancer in diagnostic biopsy tissue. Methods MCRS was evaluated in prostate biopsy tissue from a Swedish cohort of men with prostate cancer (UPCA, n = 100). The primary outcome of adverse pathology and secondary outcomes of high primary Gleason (≥G4) and high pathological T‐stage (≥T3) were assessed by likelihood ratio statistics and area under the receiver operating characteristic curves from logistic regression models; time to biochemical recurrence was assessed by likelihood ratio statistics and C‐indexes from Cox proportional hazard regression models. Results Biopsy MCRS was significantly prognostic (p

Background: The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3 Tyr705 ) or serine at 727 (pSTAT3 Ser727 ). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway. However, not much is known about how androgen deprivation therapy (ADT) in advanced disease affects pSTAT3 expression. The aim of this study was to determine the influence of ADT on pSTAT3 expression in PCa tissue., Methods: The study cohort came from a PCa tissue microarray resource containing prostate specimens from patients before and post-initiation of ADT. Tissue samples from 111 patients were immunostained for pSTAT3 Tyr705 and pSTAT3 Ser727 . H-score was used to evaluate the intensity and the percentage of pSTAT3 expression in malignant epithelial and stromal compartments. Univariate and multivariable Cox regression analyses were used to assess pSTAT3 Tyr705 and pSTAT3 Ser727 as biomarkers of oncological outcome in patients undergoing ADT., Results: Post-ADT PCa samples demonstrated increased nuclear and cytoplasmic levels of pSTAT3 Ser727 in the stroma compared to pre-ADT samples, whereas pSTAT3 Tyr705 expression was increased significantly in both stromal and malignant epithelial compartments except for stromal cytoplasm. High cytoplasmic pSTAT3 Ser727 in stromal compartments correlated with reduced overall survival, shorter time to castration-resistant PCa development, and decreased metastasis-free survival. An increase in nuclear and cytoplasmic pSTAT3 Ser727 expression within the stromal compartment of post-ADT samples corresponded to a shorter time to CRPC development, which was not observed for pSTAT3 Tyr705 . Multivariable survival analysis using Cox's regression identified that high cytoplasmic pSTAT3 Ser727 expression in the stroma of post-ADT samples and pT3 or pT4-stage were associated with worse overall survival and 5-year metastasis-free survival (MFS)., Conclusions: This study presents novel insights into the impact of ADT on the expression levels of pSTAT3 Tyr705 and pSTAT3 Ser727 in PCa. Cytoplasmic pSTAT3 Ser727 status of cancer-associated stromal cells in post-ADT samples may serve as an independent prognostic marker for OS and 5-year MFS, identifying prostate cancer patients prone to developing resistance to ADT., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)