Interobserver and intraobserver agreement in PET/CT with [18F]DCFPyL according to TNM molecular and PSMA-RADS 2.0 criteria.

PURPOSE: The aim of this study was to determine the agreement between three observers with different levels of experience using the PSMA-RADS 2.0 criteria and the miTNM system for the interpretation of PET-PSMA with [18F]DCFPyL in males with prostate cancer. MATERIALS AND METHODS: PET-PSMA images from 114 prostate cancer patients were blindly reported twice by three different observers at intervals of 8 weeks. The evaluations were performed according to the molecular imaging TNM (miTNM) and PSMA-RADS 2.0 criteria. We used Fleiss' Kappa to analyse inter and intraobserver agreements. RESULTS: Moderate overall agreement was obtained in the assessment of the PET-PSMA results (Fleiss'k = 0.53; 95% CI 0.45-0.62; p < 0.001), with significant agreement in the miT, miN and miM reports. There was a substantial level of agreement in the reporting of prostatic disease and lymphatic involvement (Fleiss'k = 0.66 and 0.65), being lower than that observed in the reporting of metastatic disease (Fleiss'k = 0.86), especially in the M0 group (Fleiss'k = 0.99). Upon re-evaluation of the images, observer 1 had moderate overall agreement for miT (Fleiss'k = 0.51) and substantial agreement for miN and miM (Fleiss'k 0.75 and 0.63, respectively). CONCLUSIONS: The use of a structured scoring system such as PSMA-RADS 2.0, as well as the miTNM classification system in the interpretation of PET-PSMA images in prostate cancer patients, provides a highly reproducible report format. High levels of interobserver and intraobserver agreement are found, especially when ruling out disease, which supports its use in routine clinical practice.

Utility of 64Cu-Sarcophagine-Bombesin PET/CT in Men with Biochemically Recurrent Prostate Cancer and Negative or Equivocal Findings on 68Ga-PSMA-11 PET/CT.

Despite a high detection rate of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT in biochemical recurrence (BCR) of prostate cancer, a significant proportion of men have negative 68Ga-PSMA-11 PET/CT results. Gastrin-releasing peptide receptor, targeted by the copper-chelated bombesin analog 64Cu-sarcophagine-bombesin (SAR-BBN) PET/CT, is also overexpressed in prostate cancer. In this prospective imaging study, we investigate the detection rate of 64Cu-SAR-BBN PET/CT in patients with BCR and negative or equivocal 68Ga-PSMA-11 PET/CT results. Methods: Men with confirmed adenocarcinoma of the prostate, prior definitive therapy, and BCR (defined as a prostate-specific antigen [PSA] level > 0.2 ng/mL) with negative or equivocal 68Ga-PSMA-11 PET/CT results within 3 mo were eligible for enrollment. 64Cu-SAR-BBN PET/CT scans were acquired at 1 and 3 h after administration of 200 MBq of 64Cu-SAR-BBN, with further delayed imaging undertaken optionally at 24 h. PSA (ng/mL) was determined at baseline. All PET (PSMA and bombesin) scans were assessed visually. Images were read with masking of the clinical results by 2 experienced nuclear medicine specialists, with a third reader in cases of discordance. Accuracy was defined using a standard of truth that included biopsy confirmation, confirmatory imaging, or response to targeted treatment. Results: Twenty-five patients were enrolled. Prior definitive therapy was radical prostatectomy (n = 24, 96%) or radiotherapy (n = 1, 4%). The median time since definitive therapy was 7 y (interquartile range [IQR], 4-11 y), and the Gleason score was 7 or less (n = 15, 60%), 8 (n = 3, 12%), or 9 (n = 7, 28%). The median PSA was 0.69 ng/mL (IQR, 0.28-2.45 ng/mL). Baseline PSMA PET scans were negative in 19 patients (76%) and equivocal in 6 (24%). 64Cu-SAR-BBN PET-avid disease was identified in 44% (11/25): 12% (3/25) with local recurrence, 20% (5/25) with pelvic node metastases, and 12% (3/25) with distant metastases. The κ-score between readers was 0.49 (95% CI, 0.16-0.82). Patients were followed up for a median of 10 mo (IQR, 9-12 mo). Bombesin PET/CT results were true-positive in 5 of 25 patients (20%), false-positive in 2 of 25 (8%), false-negative in 7 of 25 (28%), and unverified in 11 of 25 (44%). Conclusion: 64Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal 68Ga-PSMA-11 PET/CT results. Further evaluation to confirm diagnostic benefit is warranted.

Prognostic significance of invasive cribriform gland size and percentage in Gleason score 7 prostate adenocarcinoma.

OBJECTIVES: Cribriform glands are linked to poorer outcomes in prostate adenocarcinoma. We aimed to assess the prognostic role of the percentage of cribriform glands and the size of the largest invasive cribriform gland in Gleason score 7 prostate adenocarcinomas. METHODS: The presence, percentage, and size of the invasive cribriform glands were investigated and their association with prognostic factors were assessed in 177 Grade Groups 2 and 3 prostate adenocarcinomas. RESULTS: Biochemical recurrence-free survival was statistically significantly lower in cases with a cribriform gland percentage greater than 10% (P < .001) and in cases where the largest invasive cribriform gland size was greater than 0.5 mm (P < .001). Mean largest cribriform gland size and percentage were statistically significant associated with more advanced pT status, lymph node metastasis, biochemical recurrence, and higher preoperative prostate-specific antigen values. CONCLUSIONS: Our findings suggest that the presence of a cribriform pattern, increases in the percentage of such patterns, and increases in the size of the largest cribriform gland within a given tumor are associated with poor prognosis. We suggest that a more aggressive clinical approach may be needed in Grade Group 2 and 3 cases with invasive cribriform glands larger than 0.5 mm and a cribriform gland percentage greater than 10%, especially in prostate needle biopsy specimens.

Does the extent of extraprostatic extension at radical prostatectomy predict outcome?-a systematic review and meta-analysis.

Extraprostatic extension (EPE) of prostate cancer is usually reported as either focal (F-EPE) or established (E-EPE), but data on the implication for outcomes of this subdivision are conflicting and no systematic review (SR) evaluating this exists. This SR aims to address this gap in the literature, focusing on the impact of F-EPE and E-EPE on outcome in radical prostatectomy (RP) patients. Searches on Embase, Medline(R), and Pubmed databases were conducted. Studies were included if they investigated the extent of EPE in RP patients and correlated this with defined outcomes (biochemical recurrence [BCR], death, metastasis). Quality was assessed using the Newcastle-Ottawa Scale. A random effects model was used for studies reporting hazard ratios (EPE extent and biochemical recurrence). 24 studies, including 49,187 men, were included. Six studies were of high quality. 20 studies reported how they measured EPE. 13 studies reported that the extent of EPE was associated significantly with BCR. Meta-analysis showed there was a significant correlation between BCR and both F-EPE and E-EPE when compared to organ-confined disease; no significant difference was found between F-EPE and E-EPE. This is the only SR to investigate the extent of EPE on outcomes after RP. EPE alone predicts outcome, but the value of subdivision by extent could not be demonstrated. Comparisons are limited due to variability in EPE assessment and in the methods used to report outcomes in the literature. Further work to standardize EPE reporting methods, in larger cohorts, may be helpful to resolve remaining questions.

Redefining prostate cancer risk stratification: a pioneering strategy to estimate outcome based on Ki67 immunoscoring.

Accurate prostate cancer (PCa) patient diagnosis and risk assessment are key to ensure the best outcome. Currently, low- and favorable intermediate-risk PCa patients may be offered AS due to the indolent nature of the disease. Nonetheless, deciding between active surveillance and curative-intent treatment remains an intricate task, as a subset of these patients may eventually progress, enduring poorer prognosis. Herein, we sought to construct risk calculators based on cancer biomarkers, enabling more accurate discrimination among patients which may benefit from active interventions.Ki67 immunoscore, GSTP1 and KLF8 promoter methylation levels (me) were assessed in PCa tissues. Study endpoints included overall and biochemical recurrence-free (BCR) survival. Combination with relevant clinicopathological parameters allowed for construction of graphical calculating tools (nomograms).Higher Ki67 index correlated with worse BCR-free survival, whereas higher KLF8me levels were associated with improved overall survival, especially in patients with lower-grade tumors. GSTP1me levels had no prognostic value. Among prognostic models tested, a BCR-risk calculator - ProstARK (including Ki67 and clinicopathologic parameters) - disclosed 79.17% specificity, 66.67% sensitivity, 55% positive predictive value, 86% negative predictive value, and 75.76% accuracy. Similar results were found using an independent PCa biopsy cohort, validating its prognostication ability.Combining clinicopathologic features and Ki67 index into a risk calculator enables easy and accurate implementation of a novel PCa prognostication tool. This nomogram may be useful for a more accurate selection of patients for active surveillance protocols. Nonetheless, validation in a larger, multicentric, set of diagnostic PCa biopsies is mandatory for further confirmation of these results.

Association Between the Decipher Genomic Classifier and Prostate Cancer Outcome in the Real-world Setting.

BACKGROUND AND OBJECTIVE: Although the prognostic significance of the Decipher prostate cancer genomic classifier (GC) has been established largely from analyses of archival tissue, less is known about the associations between the results of Decipher testing and oncologic outcomes among patients receiving contemporaneous testing and treatment in the real-world practice setting. Our objective was to assess the associations between the Decipher GC and risks of metastasis and biochemical recurrence (BCR) following prostate biopsy and radical prostatectomy (RP) among patients tested and treated in the real-world setting. METHODS: A retrospective cohort study was conducted using a novel longitudinal linkage of transcriptomic data from the Decipher GC and real-world clinical data (RWD) aggregated from insurance claims, pharmacy records, and electronic health record data across payors and sites of care. Kaplan-Meier and Cox proportional hazards regressions were used to examine the associations between the GC and study outcomes, adjusting for clinical and pathologic factors. KEY FINDINGS AND LIMITATIONS: Metastasis from prostate cancer and BCR after radical prostatectomy, Decipher GC continuous score, and risk categories were evaluated. We identified 58 935 participants who underwent Decipher testing, including 33 379 on a biopsy specimen and 25 556 on an RP specimen. The median age was 67 yr (interquartile range [IQR] 62-72) at biopsy testing and 65 yr (IQR 59-69) at RP. The median GC score was 0.43 (IQR 0.27-0.66) among biopsy-tested patients and 0.54 (0.32-0.79) among RP-tested patients. The GC was independently associated with the risk of metastasis among biopsy-tested (hazard ratio [HR] per 0.1 unit increase in GC 1.21 [95% confidence interval {CI} 1.16-1.27], p < 0.001) and RP-tested (HR 1.20 [95% CI 1.17-1.24], p < 0.001) patients after adjusting for baseline clinical and pathologic risk factors. In addition, the GC was associated with the risk of BCR among RP-tested patients (HR 1.12 [95% CI 1.10-1.14], p < 0.001) in models adjusted for age and Cancer of the Prostate Risk Assessment postsurgical score. CONCLUSIONS AND CLINICAL IMPLICATIONS: This real-world study of a novel transcriptomic linkage conducted at a national scale supports the external prognostic validity of the Decipher GC among patients managed in contemporary practice. PATIENT SUMMARY: This study looked at the use of the Decipher genomic classifier, a test used to help understand the aggressiveness of a patient's prostate cancer. Looking at the results of 58 935 participants who underwent testing, we found that the Decipher test helped estimate the risk of cancer recurrence and metastasis.

Identification of anoikis-related gene signatures and construction of the prognosis model in prostate cancer.

Background: One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated. Methods: Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub). Results: 113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa. Conclusion: We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.

Impact of frozen section on long-term outcomes in robot-assisted laparoscopic prostatectomy.

OBJECTIVES: To compare 1-year functional and 5-year oncological outcomes of men undergoing robot-assisted laparoscopic prostatectomy (RALP) with neurovascular structure-adjacent frozen-section examination (NeuroSAFE) with those in men undergoing RALP without NeuroSAFE (standard of care [SOC]). SUBJECTS AND METHODS: Men undergoing RALP in our centre between 1 January 2009 and 30 June 2018 were enrolled from a prospectively maintained database. Patients were excluded if they had undergone preoperative therapy or postoperative adjuvant therapy or were enrolled in clinical trials. Patients were grouped based on use of NeuroSAFE. Follow-up was censored at 5 years. The primary outcome was difference in time to biochemical recurrence (BCR) on multivariable analysis, defined as prostate-specific antigen (PSA) >0.2 ng/L on two consecutive measurements. Secondary outcomes were difference in 1-year erectile dysfunction and incontinence. RESULTS: In the enrolment period, 1199 consecutive men underwent RALP, of whom 1140 were eligible, including 317 with NeuroSAFE and 823 with SOC. The median PSA follow-up was 60 months in both groups. Rates of 5-year BCR were similar on Kaplan-Meier survival curve analysis (11% vs 11%; P = 0.9), as was time to BCR on multivariable Cox proportional hazards modelling (hazard ratio 1.2; P = 0.6). Compared with the SOC group at 1 year, the NeuroSAFE group had similar unadjusted rates of incontinence (5.1% vs 7.7%) and lower unadjusted impotence (57% vs 80%). On multivariable analysis, NeuroSAFE patients had equivalent risk of incontinence (odds ratio [OR] 0.59, 95% CI 0.17-1.6; P = 0.4) but significantly reduced risk of erectile dysfunction (OR 0.37, 95% CI 0.22-0.60; P < 0.001). CONCLUSIONS: For men undergoing RALP, compared with SOC, NeuroSAFE patients had equivalent time to BCR and risk of 1-year incontinence, and significantly lower risk of 1-year erectile dysfunction.

Bi-Parametric Magnetic Resonance Imaging Analysis of Biochemical Recurrence of Prostate Cancer after Radical Surgery and Its Predictive Value: A Retrospective Study.

OBJECTIVE: This study aimed to analyse the characteristics of biochemical recurrence after radical prostatectomy via bi-parametric magnetic resonance imaging. METHODS: A total of 200 patients with radical prostatectomy admitted to our hospital from January 2016 to January 2021 were retrospectively enrolled as observation objects. According to whether there was biochemical recurrence after surgery, the patients were divided into the abnormal group (n = 62) and normal group (n = 138). Clinical data, encapsulation infiltration, seminal vesicle infiltration and prostate imaging report and data system (PI-RADS) were collected and compared between the two groups. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Student's t-test and Chi-square test were used to analyse the data. RESULTS: PSM was performed in a 1:1 ratio, and a total of 72 patients were included in the abnormal and normal groups. The baseline data of the patients in each group were not statistically significant. The incidence of extraperitoneal invasion and seminal vesicle invasion was higher in the abnormal group than in the normal group, and we observed a significant difference in PI-RADS scores between the two groups (p < 0.05). Extracapsular invasion, seminal vesicle invasion, PI-RADS score and biochemical recurrence were significantly correlated (p < 0.05). The PI-RADS score has a high value for predicting biochemical recurrence, with an area under the curve value of 0.824, sensitivity of 0.667, specificity of 0.861 and Youden index of 0.528. CONCLUSIONS: Bi-parametric magnetic resonance imaging has a high predictive value in biochemical recurrence after radical prostatectomy, which can provide reference for early intervention measures.

Real-world evidence of 18F-fluciclovine Positron emission tomography/computed tomography performance for recurrent prostate cancer in the Veterans Affairs Health System.

BACKGROUND: There are no population-level studies assessing 18F-fluciclovine (fluciclovine) utilization of Positron emission tomography/computed tomography (PET/CT) for biochemically recurrent prostate cancer (PC). We assessed fluciclovine PET/CT in the Veterans Affairs Health Care System. METHODS: Of 1153 men with claims suggesting receipt of fluciclovine PET/CT, we randomly reviewed charts of 300 who indeed underwent fluciclovine PET/CT. The primary outcome was fluciclovine PET/CT result (positive or negative). Comparison among groups stratified by androgen deprivation therapy (ADT) (yes vs. no) and prostate-specific antigen (PSA) (≤1 vs. >1 ng/mL) at imaging were performed. Logistic regression tested associations between PSA, ADT receipt, and race with fluciclovine PET/CT positive imaging. RESULTS: Fluciclovine PET/CT positivity rate was 33% for patients with PSA 0-0.5 ng/mL, 21% for >0.5-1.0, 54% for >1.0-2.0, and 66% for >2.0 (p < 0.01). A 59% positivity rate ocurred in patients treated with concurrent ADT versus 37% in those not on ADT (p < 0.01). White were more likely to have a positive scan versus Black patients (55% vs. 38%; p = 0.02). Patients whose primary treatment was radical prostatectomy had a lower positivity rate (33%) versus those treated with radiotherapy (55%) (p < 0.001). On multivariable logistic regression, PSA > 1 ng/mL (all men odds ratio [OR]: 4.06, 95% confidence interval [CI]: 2.07-7.96; men on ADT only OR: 4.42, 95% CI: 1.73-11.26) and use of ADT (OR: 3.94, 95% CI: 1.32-11.75), and White (all men OR: 2.22, 95% CI: 1.20-4.17) predicted positive fluciclovine PET/CT. CONCLUSION: This real-world study assessing 18F-fluciclovine PET/CT performance in an equal access health care system confirms higher detection rates than traditional imaging methods, but positivity is highly influenced by PSA at time of imaging. Additionally, patients currently receiving ADT have at least four times higher likelihood of a positive scan, showing that scan positivity isn't negatively affected by ADT status in this study. Finally, White men were more likely to have a positive scan, the reasons for which should be explored in future studies.

Non-alcoholic fatty liver disease increases the risk of biochemical recurrence in high-grade metastatic prostate cancer patients.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients. METHODS: We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables. RESULTS: NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005). CONCLUSIONS: NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Association of Genomic Prostate Score at positive margin with recurrence after radical prostatectomy.

OBJECTIVES: To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR). PATIENTS AND METHODS: We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design. RESULTS: In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design. CONCLUSIONS: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.

Association between mpMRI detected tumor apparent diffusion coefficient and 5-year biochemical recurrence risk after radical prostatectomy.

PURPOSE: To assess the ability of tumor apparent diffusion coefficient (ADC) values obtained from multiparametric magnetic resonance imaging (mpMRI) to predict the risk of 5-year biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: This retrospective analysis included 1207 peripheral and 232 non-peripheral zone prostate cancer (PCa) patients who underwent mpMRI before RP (2012-2015), with the outcome of interest being 5-year BCR. ADC was evaluated as a continuous variable and as categories: low (< 850 µm2/s), intermediate (850-1100 µm2/s), and high (> 1100 µm2/s). Kaplan-Meier curves with log-rank testing of BCR-free survival, multivariable Cox proportional hazard regression models were formed to estimate the risk of BCR. RESULTS: Among the 1439 males with median age 63 (± 7) years, the median follow-up was 59 months, and 306 (25%) patients experienced BCR. Peripheral zone PCa patients with BCR had lower tumor ADC values than those without BCR (874 versus 1025 µm2/s, p < 0.001). Five-year BCR-free survival rates were 52.3%, 74.4%, and 87% for patients in the low, intermediate, and high ADC value categories, respectively (p < 0.0001). Lower ADC was associated with BCR, both as continuously coded variable (HR: 5.35; p < 0.001) and as ADC categories (intermediate versus high ADC-HR: 1.56, p = 0.017; low vs. high ADC-HR; 2.36, p < 0.001). In the non-peripheral zone PCa patients, no association between ADC and BCR was observed. CONCLUSION: Tumor ADC values and categories were found to be predictive of the 5-year BCR risk after RP in patients with peripheral zone PCa and may serve as a prognostic biomarker.

To evaluate the detection rate of local and whole-body recurrence by integrated [18F]F-PSMA-1007 PET/MR assessment of prostate cancer patients treated with prostatectomy with very low biochemical recurrence (<0.5ng/ml). Therapeutic implications.

OBJECTIVE: To analyse the efficacy of integrated assessment of [18F]F-PSMA-1007 PET/MRI on the early detection of local recurrence (LR) for prostate cancer patients with PSA levels <0.5ng/ml after radical prostatectomy. To assess the location of recurrence so that therapy may be tailored to patient. METHODS: Prospective study including 35 patients with prostate cancer (PCa), who were referred for a [18F]F-PSMA-1007 PET/MR after prostatectomy with a very initial PSA value increase (PSA<0,5ng/ml). Simultaneous acquisition in a PET/MRI hybrid equipment (SIGNA-GE), 1h after administration of 370%±10% MBq of [18F]F-PSMA-1007: Prostate selective imaging (20min): multiparametric PET+MRI (MRImp): DIXON, T1, T2, diffusion sequences post-gadolinium administration. Whole body image (30min): PET+MRI: DIXON, T1, T2, diffusion, STIR sequences. A nuclear physician and a radiologist jointly reviewed the studies: In order to assess LR, the "Prostate Imaging for Recurrence Reporting" system was used on MRI, as well as the Likert scale on the PET prostate imaging. The remaining lesions were classified as N1 and M1a. RESULTS: PET/MRI was positive in 25 patients (71,4%) and negative in 10 patients (28,6%). RL was detected in 15 patients (42.9%): in 2 (5.7%) MRI was superior; in 3 (8.6%) PET was superior; integrated PET/MRI showed improved results in 5 patients (14.3%) for the detection of LR. Location of recurrences: LR in 11 patients (44.0%); N1 in 10 (40.0%); LR+N1 (8.0%) in 2; LR+N1+M1a in 2 (8.0%). In 20 patients (80%) the PET/MRI findings allowed radioguided radiotherapy implementation (11 on LR, and 9 on N1), whereas hormonal treatment was decided in 5 patients (20%) due to multimetastases/spread disease. CONCLUSION: [18F]F-PSMA-1007 PET/MRI has a 71.4% recurrence detection rate after prostatectomy with PSA<0.5ng/ml. Its combined PET and MRI study increases the detection of LR by 14.3%, with a high N1+M1a detection rate (56%), allowing radioguided radiotherapy in 80% of patients.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of polychlorinated biphenyls.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

RNA modification Regulators' Co-Expression Score (RMRCoeS) predicts biochemical recurrence and therapy response in prostate cancer: A multi-omics and experimental validation study.

BACKGROUND: Owing to the heterogeneity of prostate cancer (PCa), the clinical indicators traditionally fall short of meeting the requirements for personalized medicine. The realm of RNA modification has emerged as an increasingly relevant domain, shedding light on its pivotal role in tumor heterogeneity. However, the specific contributions of RNA modification regulators within the context of PCa remain largely unexplored. METHODS: In this study, we undertook a literature review to summarize the common 8 types of RNA modifications (ac4c, AI, APA, m1A, m5c, m6A, m7G, Ψ) encompassing a total of 84 regulators. Moreover, we integrated multi-center cohorts with Ridge regression to develop the Regulators' Co-Expression Score (RMRCoeS). Then we assessed the role of RMRCoeS in several clinical aspects such as biochemical recurrence (BCR), responses to chemotherapy, androgen receptor signaling inhibitor (ARSI) therapy and immunotherapy in PCa. Finally, we validated the cancer-promoting performance of five hub genes through immunohistochemistry and in vitro assays. RESULTS: Within the mutation landscape of RNA modification regulators, we observed a relatively low overall mutation rate. Remarkably, RMRCoeS, comprising 81 RNA modification regulators, exhibited a notable capability for accurately predicting the prognosis and therapeutic responses in PCa patients subjected to BCR, chemotherapy, ARSI therapy, and immunotherapy. A high RMRCoeS was indicative of a poor prognosis and unfavorable therapy responses. Functional enrichment analysis unveiled that RMRCoeS may exert its influence on PCa progression through various metabolic pathways. Furthermore, a higher RMRCoeS showed a positive correlation with elevated CNV mutations. Lastly, we validated the oncogene effects of CPSF4, WBSCR22, RPUSD3, TRMT61A, and NSUN5-five hub regulators-within the context of PCa. CONCLUSION: The function of different RNA modifications is interconnected. Comprising eight distinct RNA modifications' regulators, RMRCoeS exhibits multifaceted roles in various aspects of PCa, including disease progression, prognosis, and responses to multiple therapies. Furthermore, we provide the initial validation of the oncogene effect associated with WBSCR22, RPUSD3, TRMT61A and NSUN5 in PCa. Our findings offer novel insights into the significance of RNA modifications in PCa personalized medicine.

Predictive Factors for Early Biochemical Recurrence Following Robot-assisted Radical Prostatectomy.

BACKGROUND/AIM: The primary objective of this study was to identify predictors for biochemical recurrence (BCR) within 2 years following robot-assisted radical prostatectomy (RARP). Identifying predictors will enable insights that enhance personalized patient management and facilitate the ongoing refinement of postoperative therapy strategies. PATIENTS AND METHODS: This retrospective study included patients undergoing RARP from September 2014 to January 2021. Exclusion criteria were preoperative endocrine therapy, BCR beyond 2 years post-surgery, and incomplete postoperative data. Multivariate analyses were conducted to evaluate predictors of BCR, focusing on preoperative prostate-specific antigen (PSA) level, pathological tumor (pT) stage, Gleason score (GS), extraprostatic extension (EPE), and surgical margin status. RESULTS: Among 374 patients, 40 experienced BCR within 2 years. Significant predictors of early BCR included initial PSA level ≥10 ng/ml, pT3 or greater, GS ≥8, EPE, and positive surgical margins (RM1). Multivariate analysis identified pT3 or higher, GS ≥8, and RM1 as independent risk factors for early BCR. CONCLUSION: Early BCR after RARP is significantly associated with advanced pathological stage, high GS, and positive surgical margins. These findings emphasize the need for tailored postoperative management strategies and highlight the importance of precision in surgical technique to improve patient outcomes.

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Background: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Patients and methods: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. Results: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. Conclusion: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.