Serum Prostate Research Articles

Is Serum PSA a Reliable Indicator to Omit Skeletal Scintigraphy Among Newly Diagnosed Prostate Cancer Patients?

Objectives: Skeletal scintigraphy is most sensitive modality for detection of bone metastases in prostate cancer (PCa). Bone scintigraphy (BS) is currently not recommended for staging of PCa patients with serum prostate specific antigen (S.PSA) <10 ng/ml or in low-risk group (NCCN 2021, EAU-EANM-2020). This study aims to establish cutoff of S.PSA levels to predict metastatic bone disease in newly diagnosed treatment naive patients with carcinoma Prostate, in Uttarakhand region, India. Materials and Methods: We retrospectively reviewed 105 treatment naïve PCa patients referred to Nuclear Medicine Department, All India Institute of Medical Sciences, Rishikesh, for BS. We assessed association between S.PSA levels (performed within 6 weeks of imaging), Gleason Score (GS)/International Society of Urological Pathology (ISUP) grading and metastatic disease diagnosed on BS. Results: A total of 105 patients were included in this study with an average age of 69 ± 9.4 years (42–87 years). Out of 105 patients, 62 (59%) were positive and 43 (41%) patients were negative on BS for skeletal metastasis. According to S.PSA levels, patients were divided into five subgroups. On subgroup analysis, most of the patients with S.PSA of >100 were positive for metastasis on BS (83.7%) but a significant number of patients with S.PSA<10 were also positive for skeletal metastasis (46%–7/15) on BS. Conclusion: In current patient population, a high incidence of bone metastasis is noted even at low S.PSA levels and in low-risk groups. Hence, BS can be considered in carcinoma prostate patients even with PSA levels <10 ng/ml. Although, other parameters such as GS/ISUP grading, pathological grade and clinical stage should also be considered and individualised risk adapted strategy to be followed for initial staging.

A high serum dehydroepiandrosterone concentration is a predictor of candidates for active surveillance in men with serum prostate-specific antigen < 10 ng/mL

BackgroundThere is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy.MethodsA systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC–MS/MS) just before biopsy. Patient’s age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses.ResultsThe median patient’s age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively.ConclusionThe study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.

OR25-5 Adverse Cardiovascular Events and Cause Mortality in Men During Testosterone Treatment: Individual Patient and Aggregate Data Meta-Analyses

Abstract Background The cardiovascular safety of testosterone treatment in low testosterone is widely acknowledged to be unclear. Testosterone increases haematocrit, thereby potentially increasing venous thromboembolism risk. The FDA lists cardiovascular risk and stroke as adverse effects of testosterone. Systematic reviews and meta-analyses of published data have limited ability to confirm source data quality and categorisation. Some published meta-analyses have included participants with distinct risk profiles (e.g. cancer, HIV), with serum testosterone atypical for hypogonadism (&amp;gt;12nmol/L), short durations of testosterone treatment, and studies without placebo treatment. Furthermore, subtypes of cardiovascular or cerebrovascular events (e.g. stable angina) during testosterone treatment are seldom published, so have not been analysed previously. Objective Evaluate frequencies of all-cause mortality, and all cardiovascular or cerebrovascular event subtypes, and analyse efficacy of testosterone monotherapy compared to placebo for men with low testosterone, using individual patient data (IPD) and aggregate data meta-analyses. Methods MEDLINE, EMBASE, Science Citation Index, CENTRAL and clinical trial registries (PROSPERO CRD42018111005) were searched for placebo-controlled RCTs including men with serum testosterone &amp;lt;12nmol/L. One-stage meta-analyses were performed for studies providing IPD and two-stage meta-analyses were performed to integrate IPD and aggregated data. Primary outcomes were all-cause mortality and cardiovascular and/or cerebrovascular events at 12 months or nearest time point. Results IPD were obtained from 17 of 35 eligible RCTs (3431/5601 participants) in men with low testosterone. Most participants had functional hypogonadism. Risks of cardiovascular and/or cerebrovascular events were similar between the testosterone and placebo arms (testosterone 120/1601, 7.5%; placebo, 110/1519, 7.2% OR 1.07, 95% CI 0.81-1.42 p=0.62). Frequencies of all cardiovascular or cerebrovascular event subtypes were also similar between testosterone and placebo arms, but testosterone increased risks of oedema and erythrocytosis. No subgroups at higher cardiovascular and/or cerebrovascular event risk were identified. Fewer deaths were recorded in the testosterone arm, but this difference was non-significant (testosterone, 6/1621, 0.4%; placebo, 12/1537, 0.8% OR 0.46, 95% CI 0.17-1.24 p=0.13). Testosterone significantly reduced serum total cholesterol, high-density lipoprotein (HDL), and triglycerides versus placebo. No significant differences in serum low-density lipoprotein (LDL), blood pressure, glycaemic parameters, diabetes incidence or prostate outcomes were observed between groups. Testosterone had positive, albeit varied, effects on quality of life and sexual function. Conclusions This is the most comprehensive study to date interrogating the safety of testosterone treatment in men with low testosterone. We were unable to find evidence from our IPD meta-analyses that testosterone increases risks of mortality or cardiovascular and/or cerebrovascular events in the short- to medium-term in men with low testosterone, most of whom have various forms of functional hypogonadism. These data provide some reassurance to men with low testosterone and their clinicians about the safety of testosterone in the short-to-medium term although more long-term data are required.Acknowledgement: NIHR TestES Consortium. Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.

The effect of testosterone therapy on haematocrit and prostate specific antigen in the real-life setting

Testosterone therapy (TT) is commonly prescribed in men with androgen deficiency. TT has several common side effects. Moreover, the effect of TT on serum prostate specific antigen (PSA) levels has been a matter of debate over the last decade. We aimed to investigate the effect of TT on PSA and haematocrit levels in a cohort of men with androgen deficiency. Complete demographic, clinical and laboratory data from 106 consecutive hypogonadal men treated with TT were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones, complete blood count and PSA were measured in every patient at baseline and after 3 months of TT. Descriptive statistics and logistic regression models tested the association between clinical parameters and haematocrit and PSA values. Overall, median (IQR) patient's age and BMI were 54 (44-64) years and 26.2 (34.6-29) kg/m2, respectively. Above all, 63 (59.4%), 32 (30.2%) and 11 (10.4%) men were treated with T undecanoate, enanthate and gel formulation, respectively. Out of 106 men, 28 (26.4%) and 12 (11.3%) participants had PSA and haematocrit worsening (any degree), respectively. Patients who had PSA worsening (60.5 vs. 50.1 years, p=0.04) and haematocrit worsening (63 vs. 55 years, p=0.03) were older. At univariable logistic regression analysis, older age (OR 1.1, p<0.01) and lower baseline PSA values (OR 0.6; p=0.04) were associated with PSA worsening after TT. Similarly, older age (OR 1.2, p=0.04) and lower baseline haematocrit values (OR 0.7; p=0.03) were associated with haematocrit worsening after TT. After accounting for clinical and laboratory values no independent predictors of haematocrit rising were found. Approximately 20% and 10% of hypogonadal men treated with TT experienced PSA and haematocrit worsening. The degree of change was not meaningful and we failed to find any independent predictor of PSA and haematocrit rising in the real-life setting. None

Evaluation of Patients with Localized Prostate Cancer in whom Long-Term Successful Androgen Deprivation Therapy was Ceased

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

Unlikely debris in the biliary tree: Metastatic prostate cancer masquerading as a Klatskin tumor

Introduction: Prostate cancer is a common malignancy in the United States and worldwide. Most often patients present with localized disease and are asymptomatic at the time of diagnosis. Rarely, advanced disease is present at the time of initial diagnosis, usually heralded by bone pain, fatigue, or weight loss, but jaundice is typically not a presenting symptom among patients newly diagnosed with metastatic prostate cancer. Case Report: A 74-year-old male presented with painless jaundice. He had severe hyperbilirubinemia and imaging demonstrated mediastinal and abdominal lymphadenopathy in addition to biliary ductal dilation with an enhancing mass at the confluence of the left and right hepatic ducts. While the presentation and imaging were classic for a newly diagnosed Klatskin tumor, or perihilar cholangiocarcinoma, tissue biopsies from the biliary lesion and mediastinal and gastrohepatic lymph nodes were all consistent with metastatic adenocarcinoma of prostatic origin. Prostate specific antigen was elevated to 205 ng/mL. The patient underwent biliary stenting and subsequently began treatment with androgen-deprivation therapy with marked improvement in serum prostate specific antigen and resolution of hyperbilirubinemia. Conclusion: We describe a unique case of a patient who presented with painless jaundice and imaging suspicious for a Klatskin-type cholangiocarcinoma. Multiple imaging modalities and repeated biopsies were required to prove this patient actually had metastatic prostate cancer. This case highlights the importance of finalizing an accurate tissue diagnosis prior to initiating management with systemic therapies specific to disease site and biology.

Accurate diagnosis of prostate cancer with CRISPR-based nucleic acid test strip by simultaneously identifying PCA3 and KLK3 genes

Although serum prostate specific antigen (PSA) testing could decrease the morality of prostate cancer (PCa), its low specificity usually led to misdiagnosis due to prostatitis or benign prostatic hyperplasia (BPH). Prostate cancer antigen 3 (PCA3) as an alternative prostate tumor-specificity biomarker could be used to increase the specificity of PCa diagnosis, however, it usually required sophisticated operation and expensive equipment for routine detection. Herein, we constructed an early detection platform for prostate cancer with reverse transcriptase-recombinase aided amplification (RT-RAA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 based nucleic acid test strip. The amplicons of PCA3 and kallikrein related peptidase 3 (KLK3) gene, which amplified simultaneously by single-amplification unit of RT-RAA were specifically recognized by Cas9-sgRNA and visual on the nucleic acid test strip by naked eyes without instruments. Simultaneously detection of PCA3 and KLK3 gene could improve specificity and accuracy of the diagnosis but avoid mutual interference. In addition, the platform presented a detection limit of 500 fg/μL and 50 fg/μL in PCA3 and KLK3 gene, respectively. Furthermore, the analysis result of signal ratio of PCA3 to KLK3 gene of urine and peripheral blood specimens from 32 men with suspected prostate cancer on test strips illustrated that the area under the curve values of urine and peripheral blood specimens were 0.998 and 1.0 respectively. In summary, our study highlighted a facile strategy to design an accurate prostate cancer gene detection platform which had the potential to conduct prostate cancer early detection in the resource-limited or other point-of-care testing (POCT) environments.

Metabolomic profile of prostate cancer-specific survival among 1812 Finnish men

BackgroundAbnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships.MethodsWe examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9–11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%).ResultsOverall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07–2.14; P-values <5.2×10−5). By contrast, the ascorbate/aldarate metabolite oxalate, xenobiotics S-carboxymethyl-L-cysteine, fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and fibrinopeptide B (1-12) were related to reduced disease-specific mortality (fourth versus first quartile HRs=0.82–0.84; P-value <5.2×10−5). Further adjustment for years from blood collection to cancer diagnosis, body mass index, smoking intensity and duration, and serum total and high-density lipoprotein cholesterol did not alter the results. Participants with a higher metabolic score based on the discovery set had an elevated risk of prostate cancer-specific mortality in the replication set (fourth versus first quartile, HR=3.9, P-value for trend<0.0001).ConclusionsThe metabolic traits identified in this study, including for choline, glutamate, arachidonate, gamma-glutamyl amino acids, fibrinopeptides, and endocannabinoid and redox pathways and their composite risk score, corroborate our previous analysis of fatal prostate cancer and provide novel insights and potential leads regarding the molecular basis of prostate cancer progression and mortality.

Relationship between serum indirect bilirubin and prostate volume in patients with benign prostatic hyperplasia: a cross-sectional study

Due to its anti-oxidative effects, bilirubin may protect against a spectrum of diseases. However, the role of bilirubin in patients with benign prostatic hyperplasia (BPH) is poorly explored. This study aimed to investigate the cross-sectional associations between serum indirect bilirubin (IBIL) and prostate volume (PV) in patients with BPH. The medical records of 722 BPH patients were retrospectively analyzed. Body mass index (BMI) was calculated as body weight (kg)/height (m)2. PV was obtained as height (cm) × width (cm) × length (cm) × π/6. Other biochemical indexes were measured by the automatic biochemical analyzer. A univariable linear regression analysis was performed to detect confounders. The IBIL-PV relationship was examined using unadjusted and covariate-adjusted regression models. Furthermore, a segmented linear regression was conducted to analyze the linear trend of IBIL levels and PV. Finally, the sensitivity analysis was stratified by BMI and low-density lipoprotein cholesterol (LDL-C) cutoffs. In this study, the mean age of the patients was 68 (range, 43-93) years. By univariable line regression test, we observed that PV was positively correlated with age, BMI, and LDL-C (β=0.113, 0.096, and 0.135, respectively). IBIL was negatively associated with PV in full adjusted model in men age ≤75 years (β=-1.01; 95% CI: -1.81, -0.22; P=0.01). A statistically significant inverse trend was observed between serum IBIL intervals and PV in patients aged ≤75 years (adjusted for age, BMI, and LDL-C, P for trend =0.015). In sensitivity analysis, significantly negative IBIL-PV relationship only existed in men with normal BMI (adjusted β=-1.328; 95% CI: -2.467, -0.190; P=0.022), overweight men (adjusted β=-1.296; 95% CI: -2.519, -0.074; P=0.038), and men with normal LDL-C level (adjusted β=-1.017; 95% CI: -1.869, -0.164; P=0.019). IBIL is negatively associated with PV in the non-obese population ≤75 years with normal LDL-C. These results suggest that higher serum IBIL possibly provides a degree of protection to BPH by mitigating oxidative stress (OS) related to aging and lipid peroxidation. Nevertheless, these preliminary findings from a single-center, retrospective study have limitations and need to be confirmed by future studies.

Proteomic Analysis of Prostate Cancer FFPE Samples Reveals Markers of Disease Progression and Aggressiveness.

Simple SummaryProstate cancer (PCa) is the second most frequently diagnosed type of cancer in men. The lack of tools for accurate risk assessment is causing over-treatment of men with indolent PCa but also delayed detection of metastatic disease and thus high mortality. The aim of our study was to identify proteins related to the progression and aggressiveness of PCa that could serve as potential biomarkers for better risk stratification. To this end, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens (n = 86) and compared them based on grade groups and biochemical recurrence status. Based on the valuable data generated by these comparisons, we have selected seven proteins (NMP1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) as common denominators of PCa aggressiveness and persistence that could potentially be used for the development of risk assessment tools. Notably, our observations are largely validated by transcriptomics data and literature.Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy, which might not represent the exact degree of PCa risk. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Comparative analysis of 86 PCa samples among grade groups 1–5 identified 301 significantly altered proteins. Additional analysis based on biochemical recurrence (BCR; BCR+ n = 14, BCR- n = 51) revealed 197 significantly altered proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins (NPM1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness. Notably, all seven proteins were significantly associated with progression in Prostate Cancer Transcriptome Atles (PCTA) and NPM1NPM1, UQCRH, and VCAN were further validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. UQCRH levels were also associated with poorer 5-year survival. Our study provides valuable insights into the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.

Prostate Cancer Diagnostic Methods in Korle Bu Teaching Hospital, Accra, Ghana

Objective: The diagnosis of prostate cancer is based on a combination of digital rectal examination (DRE), serum prostate specific antigen (SePSA) estimation and trans-rectal ultrasound guided biopsy (TRUS-B) of the prostate, the latter being the gold standard for prostate cancer diagnosis. This study compared the diagnostic rate of prostate cancer in patients attending the urology clinic at Korle-bu Teaching Hospital, Accra, Ghana, using these methods.Patients and Methods: One hundred and fifty male patients 45 years and older with abnormal DRE and raised or rising SePSA had TRUS biopsy done. The biopsies were processed routinely and all cancer positive slides were graded using the Gleason scoringsystem. DRE findings were comparatively analysed statistically against SePSA and histological findings.Results: Of the 150 subjects, 71(47.3%) were diagnosed as benign and 79(52.7%) had cancer on TRUS-B. Cancer diagnosis rate using a combination of DRE and SePSA was slightly higher (66.4%) than using DRE (64.5%) or SePSA (53.7%) in isolation.Conclusion: DRE was found to have a high positive predictive value, probably due to the late presentation of majority of the patients in this study. SePSA alone is not very reliable, and results must be interpreted with caution due to significant false positive rates. Combining DRE and SePSA improves cancer diagnosis rates.

Clinical Efficacy and Psychological Impact of Omaha-Based Continuing Care for Prostate Cancer Patients.

Prostate cancer is a common malignancy elderly male urogenital system, because of the special disease position, and postoperative complications such as urinary retention, urinary incontinence, and sexual dysfunction, if not treated, can increase the patients' physical pain, anxiety, and other psychological burden; endocrine therapy after surgery can affect self-image and quality of life of patients. Omaha system was originally used for community health nurses, which contains three main contents: problem classification, nursing intervention, and outcome evaluation. The problem classification dimension includes four dimensions: environment, physiology, social psychology, and health-related behavior. The nursing intervention dimension is composed of 75 intervention objectives and four behavior types. Omaha system is a nursing intervention model based on individual psychological, physiological, educational level, and family and social background. The model has good clinical application effect. This study aimed to explore the continuous nursing intervention effect in the nursing of patients with prostate cancer and its psychological impact. A total of 96 prostate patients with cancer who were admitted to Taizhou First People's Hospital from November 2019 to May 2021 were divided into Omaha system care group and routine care group with 48 cases each by random number table method. The routine care group received routine care and discharge guidance, and the Omaha system care group on the basis of the routine care group; continuation care based on the Omaha system was implemented. The differences in mental state, life quality score, serum prostate specific antigen (PSA) level, average urine flow rate, and self-care ability score were compared between the routine care and Omaha system care group. The results showed that Omaha-based continuation care for prostate cancer is beneficial to reduce bad mood, improve patients' life quality score and self-care ability, and provide certain reference for clinical care of prostate cancer patients.

Does serum prostate specific antigen levels correlate with the prostatic inflammation in elderly patients without clinically proven prostate cancer?

Objectives: To determine the whether histological prostatic inflammation correlates with serum prostate specific antigen (PSA), free PSA (fPSA) and percent of fPSA (%fPSA) levels in elderly patients without clinically proven prostate cancer. Methods: A total of 115 patients without clinically proven prostate cancer with transrectal prostate biopsy were included in this retrospective study. Patients were divided two main groups as patients with and without histologic prostatic inflammation. A grading of the histological prostatic inflammation was performed and patients with prostatic inflammation were divided into three subgroups. The age, prostate volume, serum PSA, fPSA and %fPSA levels were compared between patients with and without prostatic inflammation. Correlation between the parameters and grade of prostatic inflammation was also investigated. Results: Serum PSA and %fPSA levels were significantly higher in men with histologically proven prostatic inflammation (15.47 ± 15.28 ng/mL vs. 11.67 ± 8.12 ng/mL; p = 0.002 and 19.8 ± 0.7 vs. 15.79 ± 0.9; p = 0.01, respectively). The mean serum PSA levels were significantly different among the subgroups (p = 0.02) and prostatic inflammation correlated positively with the PSA levels (r = 0.320, p &amp;lt; 0.001). Conclusions: Our findings suggested that reporting the grade of prostatic inflammation in elderly patients may help avoiding unnecessary repeat biopsies if elevated serum PSA level is the only indication for initial prostate biopsy.

Large Cell Neuroendocrine Carcinoma of the Prostate Gland: A Review and Update

It has been documented that the 2016 World Health Organization’s histological classification of prostate cancer has included well-differentiated carcinoid tumours and small- or large-cell poorly differentiated tumours within the category of neuroendocrine tumours. Up to May 2021, only 20 cases of large-cell neuroendocrine tumours of the prostate gland (LCNTPs) had been reported within the literature, among which are nine cases of primary tumours. LCNTPs are a rare histological entity whose evolutive profile and therapeutic potential do differ from those of conventional adenocarcinoma of the prostate gland. Primary neuroendocrine tumours of the prostate gland could be pure or associated with an adenocarcinoma component. Mixed forms of large cell neuroendocrine cancers of the prostate gland (LCNECPs) tend to associated with better prognosis when diagnosed early at a localized stage. Nevertheless, most cases of (LCNTPs) at the time of initial diagnosis could tend to be advanced, locally advanced or metastatic. Even though LCNECPs that are diagnosed initially tend to primary prostate cancers that may be pure primary prostate cancers, few large LCNECPs have been found to be metastatic large cell neuroendocrine carcinomas that had metastasised from other sites of the body for example the lung. Primary LCNECP does tend to manifest similarly to primary adenocarcinoma of prostate gland with lower urinary tract symptoms, haematuria, or signs of obstruction of the upper urinary tract or inability to empty the urinary bladder. Cases of primary LCNECP that manifest tend also to be associated with symptoms related to the sites of the metastases. Serum prostate specific antigen levels tend to be slightly elevated with cases of primary LCNECP, but the levels generally tend not to be as high as most cases of advanced, locally advanced or metastatic primary adenocarcinomas of the prostate gland. Diagnosis of LCNECPs tend to be made pursuant to the undertaking of histopathology and immunohistochemistry staining studies of specimens of the prostate that had been obtained from prostate biopsies, trans-urethral reception of prostate specimens or prostatectomy specimens. The microscopy histopathology examination features of LCNECP the prostate gland have been summarized as follows: (a) Microscopy histopathology examination of LCNECP gland does tend to demonstrate large islands or sheets of tumour cells. (b) Large tumour cells with prominent neuroendocrine features such as salt and pepper chromatin and small nucleoli tend to be visualised upon microscopy examination of specimens of the prostate tumour. (c) High grade features such as lack of glandular formation, frequent mitoses and apoptotic bodies and tumour necrosis tend to be frequent findings upon microscopy examination of specimens of LCNECP. Immunohistochemistry staining features of LCNECP include: (a) At least one of the ensuing neuroendocrine tumour markers should be demonstrated upon immunohistochemistry staining including exhibition of positive immunohistochemistry staining for: chromogranin A, synaptophysin, neuron specific enolase, and CD56 may be positive: It has been stated that immunohistochemistry staining studies may exhibit positive staining in cases of LCNECP with utilization of the following: o TTFI tends to be positive in less than 50% of cases of LCNECP. o Positive AMACR immunohistochemistry staining, but this may be focal or weaker than for adenocarcinoma of the prostate gland. o Positive markers including: PSA, PSMA, NKX3.1 prostein (P501S) tend to be negative in majority of cases of LCNECP, but they could be focally positive in a small subset of the tumours. It has been iterated that in cases of LCNECP, immunohistochemistry staining studies tend to demonstrate negative staining for the ensuing markers: • Urothelial markers such as GATA3, p63, and high molecular weight cytokeratins such as CK5 / 6. • CD99. • Carcinoid tumour of the prostate gland. • PNET/Ewing sarcoma of the prostate gland. • Adenocarcinoma of the prostate gland with focal neuroendocrine differentiation. • Urothelial carcinoma with neuroendocrine differentiation. A high index of suspicion is required in order to diagnose early cases of primary large cell neuroendocrine carcinomas by undertaking early biopsies of prostate glands in all patients who have significant lower urinary tract symptoms if their serum prostate specific antigen (PSA) levels are slightly high or high even if they are commenced on Tamsulosin in an attempt to help improve the symptoms of voiding. There is no consensus opinion on the best management of LCNECP, therefore, there is an urgent need for the establishment of a global multi-centre trial related to various management options for the disease in order to ascertain the best options of management for LCNECP. gland.

Machine Learning and Clinical-Radiological Characteristics for the Classification of Prostate Cancer in PI-RADS 3 Lesions.

The Prostate Imaging Reporting and Data System (PI-RADS) classification is based on a scale of values from 1 to 5. The value is assigned according to the probability that a finding is a malignant tumor (prostate carcinoma) and is calculated by evaluating the signal behavior in morphological, diffusion, and post-contrastographic sequences. A PI-RADS score of 3 is recognized as the equivocal likelihood of clinically significant prostate cancer, making its diagnosis very challenging. While PI-RADS values of 4 and 5 make biopsy necessary, it is very hard to establish whether to perform a biopsy or not in patients with a PI-RADS score 3. In recent years, machine learning algorithms have been proposed for a wide range of applications in medical fields, thanks to their ability to extract hidden information and to learn from a set of data without previous specific programming. In this paper, we evaluate machine learning approaches in detecting prostate cancer in patients with PI-RADS score 3 lesions via considering clinical-radiological characteristics. A total of 109 patients were included in this study. We collected data on body mass index (BMI), location of suspicious PI-RADS 3 lesions, serum prostate-specific antigen (PSA) level, prostate volume, PSA density, and histopathology results. The implemented classifiers exploit a patient’s clinical and radiological information to generate a probability of malignancy that could help the physicians in diagnostic decisions, including the need for a biopsy.

Abstract 3354: A gene expression signature of high serum cholesterol and prostate cancer outcomes

Abstract Statin use is associated with reduced risk of lethal prostate cancer potentially through effects on serum cholesterol. Using data from a prospective study with measured serum cholesterol among men subsequently diagnosed with prostate cancer, we developed a tumour gene expression score to reflect the pre-diagnosis serum cholesterol environment these tumours developed in, and applied this score to a separate study to examine the relationship with prostate cancer-specific outcomes. We identified 127 men with prostate cancer in the prospective Health Professionals Follow-up Study, whose prostate tumors underwent whole genome gene expression profiling. Pre-diagnosis serum cholesterol was measured a median of 3.3 years (IQR 1.5-4.8 years) prior to cancer diagnosis. We excluded men using statins either at time of blood draw for serum cholesterol measurement or at cancer diagnosis. Using tumor biopsy whole genome transcriptomic data from 232 prostate cancer patients treated with radiotherapy in Northern Ireland (NI), we generated the serum cholesterol score by summing z-score-transformed expression for each gene. PTEN status was measured using a published 50-gene transcriptional signature. Both signatures were dichotomized using the median cut-point. Age-adjusted and multivariable Cox regression analysis was used to compute HRs and 95% CI for associations of the cholesterol gene score with biochemical recurrence and metastasis risk. We identified in HPFS a set of 30 genes associated with pre-diagnostic serum cholesterol with a fold change ≥4 which included PTEN. In the NI Cohort, tumors with above median cholesterol scores had higher expression of the PTEN-null signature (p&amp;lt;0.001). Increased serum cholesterol tumor score was associated with higher Gleason grade (p&amp;lt;0.001); this relationship was stronger in PTEN-null tumours relative to PTEN-intact. Over a median follow-up of 11 years, 68 men experienced biochemical recurrence, and 28 developed metastasis. In age-adjusted analysis, patients with high serum cholesterol score had increased risk of recurrence (HR 1.84; 95% CI 1.13-2.99) and metastasis (HR 1.98; 95% CI 0.91-4.29), though the latter was not statistically significant. Associations with recurrence and metastasis were attenuated following further adjustment for Gleason score (HR 1.65; 95% CI, 0.98-2.77 and HR 1.49; 95% CI 0.66-3.35, respectively). Men with increased tumor gene expression of a serum cholesterol score, derived to reflect tumor development within a high serum cholesterol environment, were more likely to be diagnosed with a PTEN-null prostate cancer. These men had more aggressive prostate cancer at diagnosis and increased risk of recurrence, particularly men with PTEN-null disease. Our results support recent findings showing a reduced risk of PTEN-null prostate cancer in statin users, and inform our understanding of the potential role of serum cholesterol in prostate cancer etiology. Citation Format: Sarah Jane Winter, Sophia R. Halliday, Travis A. Gerke, Lorelei Ann Mucci, Konrad H. Stopsack, Gillian Prue, Suneil Jain, Emma H. Allott. A gene expression signature of high serum cholesterol and prostate cancer outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3354.

Simvastatin inhibits prostatic hyperplasia in rats with metabolic syndrome.

To evaluate the influence of metabolic syndrome (MetS) induced by high fat diet (HFD) on prostate tissue and local inflammatory factors in rats model, and the protective efficacy of statins against pathological changes of prostate. 40 Sprague-Dawley rats were divided into 4 subgroups of normal diet (ND), HFD blank, HFD + saline and HFD + simvastatin. After the establishment of models, all subjects were killed to obtain body weight serum lipid, FBG level, FINS and HOMA-IR level. Hyperplasia level of prostate, as well as expression level of interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were also measured. Models have been successfully established. Level of serum lipid, prostatic weight, hyperplasia as well as expressions of IL-6, TNF-α and IGF-1 in the blank and saline subgroups of HFD group were higher than that of ND group (P < 0.05). While simvastatin has significantly resisted the former effects of HFD on serum lipid and prostate (P < 0.05). No significant difference in serum FBG level was found between groups and subunits. FINS levels of ND group was lower than other groups (P < 0.05). In addition, There isno significant difference in FPG and HOMA-IR levels in blank control subunit, saline control subunit, simvastatin subunit (P > 0.05). MetS induced by HFD is an important factor in the induction of BPH. Simvastatin can alleviate the hyperplasia of prostate through the relief of local inflammation in prostatic tissue.

Primary prostate synovial sarcoma: A case report and review of literature.

Prostate synovial sarcoma (SS) is extremely rare. We report a case of prostate SS diagnosed using fine-needle biopsy. The following findings were found: The serum prostate specific antigen level was low, magnetic resonance imaging shows an irregular soft tissue mass in the right posterior part of the prostate, and computed tomography examinations did not reveal any tumor at other parts of the body. Microscopy showed that the tumor cell morphology was densely arranged by interwoven short strands of deep-stained nuclear spindle cells. Immunohistochemical tests were positive for SS18-SSX and SSX. Molecular testing showed that SS18 break-apart Fluorescence In Situ Hybridization (FISH) results were positive, and a comprehensive analysis of this case was performed. Nine cases of prostate SS reported in the English literature were reviewed. In addition, the differential diagnosis, clinical treatment, and clinical prognosis of prostate SS are comprehensively described.

Management Impact of Metachronous Oligometastatic Disease Identified on 18F-Fluciclovine (Axumin™) PET/CT in Biochemically Recurrent Prostate Cancer.

We assessed the incidence rate and management impact of oligometastatic disease detected on 18F-fluciclovine (Axumin™) PET/CT in men with first biochemical recurrence (BCR) of prostate cancer (PCA) after definitive primary therapy. We retrospectively reviewed our clinical database for men with PCA who underwent 18F-fluciclovine PET/CT for imaging evaluation of BCR with negative or equivocal findings on conventional imaging. We included patients with up to and including 5 metastases (oligometastases) regardless of imaging evidence for local recurrence in the treated prostate bed. We examined the association between mean serum prostate specific antigen (PSA) levels with the number of oligometastases (non-parametric ANOVA) and between patients with or without local recurrence (Student t-test). The management impact of oligometastatic disease was tabulated. We identified 21 patients with oligometastases upon first BCR (PSA 0.2-56.8ng/mL) out of 89 eligible patients. There was a significant difference (p = 0.04) in the mean PSA levels between patients with local recurrence (n = 12) and those without local recurrence (n = 9). In the subgroup of analysis of patients without local recurrence, there was no significant association between mean PSA level and number of oligometastases (p = 0.83). Distribution of oligometastases included 66.7% isolated nodal disease and 33.3% bone only. Twelve (57.1%) patients had change in management to include change in ADT, salvage therapy, or both. Treatment change was initiated in 62.5%, 28.6%, 66.7%, 100%, and 100% of patients with 1, 2, 3, 4, and 5 oligometastatic lesions, respectively. The incidence rate of oligometastatic disease in men with first BCR of PCA undergoing 18F-fluciclovine PET/CT for imaging evaluation of BCR was 23.6% in our eligible patient population. There was no significant association between serum PSA level and the number of oligometastases. Treatment management was affected in 57.1% of patients with oligometastases.

Diagnostic accuracy of 18F-PSMA-1007 PET/CT for prostate cancer in primary staging and biochemical recurrence with different serum PSA levels: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis to evaluate the application value of fluorine-18-prostate specific membrane antigen (18F-PSMA-1007) positron emission tomography/computed tomography (PET/CT) in patients with different serum prostate specific antigen (PSA) levels and primary prostate cancer (PCa) or the biochemical recurrence of PCa. A comprehensive electronic literature search of the PubMed, Embase and Cochrane Library databases was conducted in accordance with the PRISMA statement. We calculated the pooled sensitivity and specificity of 18F-PSMA-1007 PET/CT in PCa. A summary receiver operator characteristic (SROC) curve and the area under the curve (AUC) were used to assess the accuracy of 18F-PSMA-1007 PET/CT for PCa. The final analysis included 11 studies that described 799 patients and 4261 lesions with 18F-PSMA-1007 PET/CT in PCa. The pooled sensitivity and specificity of 18F-PSMA-1007 PET/CT in PCa were 0.836 and 0.946, respectively. The per-patient pooled sensitivity and specificity of 18F-PSMA-1007 PET/CT in PCa were 0.934 and 0.453, and the per-lesion values were 0.816 and 0.979, respectively. The pooled sensitivity and specificity of 18F-PSMA-1007 PET/CT in PCa with PSA>2ng/mL were 0.923 and 0.442 in a patient-based analysis and 0.799 and 0.961 in a lesion-based analysis, respectively. The pooled sensitivity and specificity of 18F-PSMA-1007 PET/CT in PCa with PSA≤2ng/mL were 0.832 and 0.277 in a patient-based analysis, respectively. This meta-analysis showed that 18F-PSMA-1007 PET/CT has a higher diagnostic value for prostate cancer in the setting of primary PCa and biochemical recurrence. As serum PSA levels increase, the diagnostic accuracy of 18F-PSMA-1007 PET/CT also improves.