Higher PSA Levels Research Articles

Determination of critical cut-off values of PCA3 index in patients with prostate gland pathology

Introduction. Prostate cancer antigen-3 (PCA3) is a genetic biomarker, which got widespread and demonstrated high diagnostic potential. This gene expresses only in prostate gland tissue, furthermore, malignant prostate neoplastic transformation leads to 70 – 100 time overexpression of it. Polyadenylated matrix RNA (mRNA) is a functional product of this gene, which do not translating into protein. Gene contains of four introns and three exon. Product of PCA’s gene detecting in post massage urine using polymerase chain reaction (PCR) in combination with reverse transcription. It could use as prognostic biomarker in patients with first negative biopsy or before it performing. Moreover, index of PCA3 can be useful in detecting tumor aggressiveness and decisions about further treatment options. Taking into account these facts, patients with high initial PSA level can avoid unnecessary biopsies. Objective: to determine critical cut-off value of PCA3 index as prognostic biomarker of PCa development. Materials and methods. Research based on routine and special test’s data of 243 men in Institute of Urology, National Academy of Medical Sciences of Ukraine in period of 2015–2020 year. RNA extraction from postmassage urine samples performed using RNeasy (Qiagen) kit. Statistical analysis performed using SPSS Statistics 19.0 (IBM SPSS Statistics 19.0) та SAS 12.0 (IBM Statistical Analysis System 12.0). Critical cut-off values determined using three methods: calculating of average value and (Xave) and standard deviation (SD) of it, Heiner index, and Youden’s index. Evaluation of optimality of determined critical cut-off values performed by comparative analysis using index of positive prognosis (IPP), index of negative prognosis (INP), diagnostic accuracy of method (DAM), Sp and Se for each of used methods. Results and discussion. First method demonstrated than 97,5 % of all results, which means absent of disease, was below critical cut-off values, due to statistical deviations and accurate demonstrate than in case of asymmetry or multimodal distribution this method was unsatisfied. Wherein IPP was 95 %, INP – 72 %, DAM – 78 %, Sp – 97,5 % and Se – 52 %. Calculation of PCA3 index area under ROC-curve was 0,810 (0,771–0,849). Using Heiner’s method critical cut-off value of PCA3 index was 14,0 с. u., where in IPP was 75 %, INP – 82 %, DAM – 78 %, Sp – 78 % and Se – 78 %. Critical cut-off values of PCA3 index 33,4 c. u. which calculated by Youden’s index demonstrated IPP – 98 %, INP – 73 %, DAM – 80 %, Sp – 99 % and Se – 57 %. Conclusions. The most optimal critical cut-off value for PCA3 index was determined using Youden’s index and was 33,4 c. u. Keywords: prostate cancer, PCA , prostate cancer antigen-3, PCA3, prostate cancer antigen-3 index, PCA3 index, critical cut-off values of PCA3 index.

Stereotactic Body Radiotherapy for Oligoprogressive Lesions in Metastatic Castration-Resistant Prostate Cancer Patients During Abiraterone/Enzalutamide Treatment

<h3>Purpose/Objective(s)</h3> Metastasis- directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor–targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer–specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. <h3>Materials/Methods</h3> The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1–5) were treated with MDT. The primary end points were PCSS and PFS. The secondary end points were time to switch to NEST and NEST-FS. <h3>Results</h3> The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the PSA response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than six months after beginning of ARTA [HR = 3.20 (95% CI, 1.12–9.15); <i>P</i> = 0.03] and higher PSA levels after MDT [HR = 1.01 (95% CI 1.00–1.01), <i>P</i> = 0.02] were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. <h3>Conclusion</h3> MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.

Survival trends for patients with primary metastatic prostate cancer before and after the introduction of new antitumor drugs.

During the past two decades, new antitumor drugs (Abiraterone, Enzalutamide, Radium-223, Cabazitaxel, and Docetaxel) have been introduced for treatment of prostate cancer with distant metastases (mPCa). Each drug have demonstrated a survival gain in studies, but little is known about the impact in a general population of mPCa patients. In this study we assessed survival before and after introduction of the new drugs for Norwegian mPCa patients. Survival was assessed in 5542 patients with primary mPCa. The patients were diagnosed between 2004 and 2018, identified in the Norwegian Cancer Registry. We also analyzed a subgroup of 2738 patients possibly eligible for treatment with new drugs (age <80 years, WHO performance status ≤2 and not dead within 3 months from diagnosis). We estimated overall (OS) and cause-specific survival (CSS) across three diagnostic time periods reflecting to the drugs' introduction in Norway: Before (2004-2009), "in between" (2010-2014) and after the introduction (2015-2018). We used Kaplan-Meier survival analysis and multivariable Cox regression. Median OS increased from 2.3 years in 2004-2009 to 3.3 years in 2015-2018. 3-year OS improved from 41% in 2004-2009 to 51% in 2015-2018. An earlier diagnostic period, a more advanced T stage, higher ISUP grade group, lower WHO status and higher PSA levels were associated with a lower CSS. Similar results was found for the subgroup. Median OS of mPCa has increased by one year since 2004 for mPCa patients in Norway. Survival improvement persisted after adjustment for recognized prognostic factors and may be related to the introduction of new drugs in Norway.

MP24-13 PERCENTAGE AND RATIONALE OF GUIDELINE-DISCORDANT ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-13 PERCENTAGE AND RATIONALE OF GUIDELINE-DISCORDANT ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER PATIENTS Renée Hogenhout, Ivo de Vos, Sebastiaan Remmers, Martijn Busstra, Lionne Venderbos, Monique Roobol, and the ERSPC Rotterdam Study Group Renée HogenhoutRenée Hogenhout More articles by this author , Ivo de VosIvo de Vos More articles by this author , Sebastiaan RemmersSebastiaan Remmers More articles by this author , Martijn BusstraMartijn Busstra More articles by this author , Lionne VenderbosLionne Venderbos More articles by this author , Monique RoobolMonique Roobol More articles by this author , and the ERSPC Rotterdam Study Group More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recommendations on Androgen Deprivation Therapy (ADT) for prostate cancer (PCa) patients arise from a critical appraisal of scientific evidence which is a lot of work. Despite these efforts, the known side-effects of ADT and the lack of benefit in certain risk groups, guidelines may not always be adhered to. Here, we determined guideline adherence to ADT recommendations and analyzed the physicians’ motivation in case of disconcordance. METHODS: We included subjects from the Rotterdam section of the European Randomized Study of Screening for PCa who were diagnosed with PCa in all stages since the publication of the first EAU guidelines on PCa in 2001 up to and including 2019, and received any form of ADT within the first year after diagnosis. They were categorized into guideline-concordant or -discordant ADT according to the EAU guidelines recommendations within the study period. RESULTS: A total of 1037/3211 (32%) men diagnosed with PCa received ADT within the first year after diagnosis, of which 162/1037 (16%) men received guideline-discordant ADT. In 79% (823/1037) ADT was administered guideline-concordant and in 4% (45/1037) adherence was not assessable due to incomplete medical files. In seven patients (4%) who were unfit/unwilling for curative treatment, lower urinary tract symptoms (LUTS) contributed to the decision to prescribe ADT monotherapy. These cases were also considered as not assessable since LUTS is not clearly defined as “symptomatic” in the guideline. Most of the guideline discordance was noticed in patients receiving ADT monotherapy for intermediate- and high-risk PCa (73%). A common reason for discordant prescription of ADT as monotherapy in this group was suspicion of (lymph node) metastases due to high PSA level (28%). Other reasons were unwillingness (24%) and/or unfitness (51%) to undergo curative treatment without being symptomatic. Three patients (3%) were symptomatic but not unfit or unwilling for curative treatment. In 16% of the discordant cases, prescription of ADT monotherapy was not motivated. CONCLUSIONS: Guidelines and clinical practice do not necessarily correspond. Physicians did not adhere to EAU guidelines on ADT in a Dutch cohort in 16% of the cases. However, guideline-discordant prescription of ADT may not always indicate “inappropriate” treatment. Physicians are able to make a more nuanced clinical assessment taking into account comorbidities, patients’ wishes and social context. Although guidelines support clinical decision-making, better defined and more tailored guidelines are needed. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e416-e417 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Renée Hogenhout More articles by this author Ivo de Vos More articles by this author Sebastiaan Remmers More articles by this author Martijn Busstra More articles by this author Lionne Venderbos More articles by this author Monique Roobol More articles by this author the ERSPC Rotterdam Study Group More articles by this author Expand All Advertisement Loading ...

Dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation

BackgroundAlthough it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation.Case presentationA 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid.ConclusionsWe successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.

Increased expression of CELSR3 indicates a poor prognostic factor for Prostate Cancer.

Background: Cadherin EGF LAG Seven-Pass G-Type Receptor 3 (CELSR3) gene was reported to be overexpressed in various human cancers and involved in the regulation of neurite-dependent neurite outgrowth and may play a role in tumor formation. However, the clinical significance of CELSR3 in prostate cancer (PCa) has not been fully studied.Methods: The expression of CELSR3 was detected by crossover analysis of the public datasets and cell lines. MTT assay and migration assay were performed to evaluate the cells' physiological functioning. Co-expressed genes and enrichment analysis was performed to investigate the biological significance of CELSR3 in PCa. Quantitative real-time polymerase chain reaction was used to detect the expression levels of hub genes (CENPE, CENPA, CDC20, NUF2, ESPL1, PLK1) related to CELSR3.Results: We found a significant increase in CELSR3 expression in PCa patients and cell lines. Furthermore, immunohistochemical analysis showed that CELSR3 protein expression was significantly more highly expressed in the PCa tissues compared to the non-cancerous PCa tissues. CELSR3 downregulation significantly suppressed cell proliferation and migration potential. CELSR3-related hub genes (CENPE, CENPA, CDC20, NUF2, ESPL1, PLK1) were selected and the functions of these hub genes showed that the function of CELSR3 was closely related to the cell cycle-related signaling pathways. The upregulation of CELSR3 mRNA expression in the PCa tissues significantly correlated with the presence of high serum PSA levels, high pathological stage, high Gleason score, short overall survival time and short disease-free survival time.Conclusion: Our data suggest that CELSR3 may play an important role in the progression of PCa. More importantly, an increase in CELSR3 expression may be indicative of poor disease-free survival and poor prognosis in PCa patients.

Spondylodiscitis, an Exceptional Complication of Prostate Biopsy: Case Report

Background: Transrectal prostate biopsy is a major prostate cancer diagnosis procedure that can cause infectious complications. Osteoarticular localization is uncommon. Aim: To report a case of spondylodiscitis due to a transrectal prostate biopsy and highlight therapeutical principles. Case Presentation: A 60-year-old male underwent transrectal prostate biopsy performed because of high PSA level, and presented 48 hours later with back pain, fever at 40°C associated with an obnubilation. He was treated for malaria without favorable evolution. Persistance of pain and occurrence of neurologic manifestations motivated dorso-lumbar Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) which permitted diagnosis of spondylodiscitis. The treatment was made by triple antibiotic therapy combining Imipenem 500 mg/8h (IV); Ofloxacin 200 mg/12h (IV) and Metronidazole 500 mg/8h (IV) over four weeks. Evolution under treatment was favorable. Conclusion: Spondylodiscitis is an exceptional complication of transrectal prostate biopsy. It may be evocated in case of bones pain after prostate biopsy.

Early Continence and Extravasation After Open Retropubic Radical Prostatectomy - Interrupted vs Continuous Suturing for Vesicourethral Anastomosis.

PurposeTo compare running suture (RS) and interrupted suture (IS) of vesicourethral anastomosis (VUA) during open retropubic radical prostatectomy (RRP) on early urinary continence and extravasation.Patients and MethodsSingle center analysis of 211 patients who underwent RRP performed by a single surgeon during 2008 to 2017 was retrospectively analyzed. For VUA, we used the standard interrupted suture technique (n=100) with a 3–0 PDS suture. The RS (n=111) was performed with 12-bite suture using 3–0 PDS. The primary endpoints were extravasation and early continence. Demographic and peri-operative data were collected and analyzed using Pearson’s chi-square, t-Test and Mann–Whitney U-test. A binary logistic regression analysis was carried out to explore predictors that affected early continence after catheter removal.ResultsThe rates of early urinary incontinence (UI) were 7.7% vs 42.2% (p<0.001). The duration of catheterization and hospitalization was significantly shorter in the interrupted group (4 days vs 5 days, p<0.001 and 5 days vs 6 days, p<0.001). The groups did not differ significantly in body mass index or prostate volume. There were older patients and higher PSA levels in the group with RS technique. No significant difference was found in the postoperative extravasation rates between both groups (13.5% vs 12%, p=0.742).ConclusionRunning vesicourethral anastomosis increased the rate of early urinary incontinence. Both anastomosis techniques provided a similar rate of postoperative urine extravasation. VUA should only be one of the many criteria that must be considered for the preservation of urinary continence of patients after RRP.

Abstract PO-088: Low levels of PSA in diabetic Nigerians: A call for a separate reference range for prostate cancer screening among type-2 diabetics?

Abstract INTRODUCTION Diabetic patients are at higher risk of developing malignancies. Studies have however suggested a contrasting data, indicating lower risk of prostate cancer in type 2 diabetics. Studies in some parts of the world showed lower PSA levels in diabetic patients, but yet to be verified in African living in Africa. AIM The aim was to determine the levels of PSA in Diabetic and Non-diabetic men in Maiduguri-Nigeria and to ascertain similar lower values in African living in Africa. MATERIALS AND METHODS This was a hospital based case-control study that included a total of 132 participants whose ages were from 40 years and above and voluntarily consented to be part of this study. Ethical clearance was obtained from Ethics and Research Committee of the University of Maiduguri Teaching Hospital, structured questionnaire was self-administered. One hundred and four (104) were confirmed type 2 DM male attending Metabolic Clinic University of Maiduguri Teaching Hospital and twenty eight (28) non-diabetic men, who had no history of hypertension, not using antihypertensives or steroid drugs, no history of cardiovascular diseases, not using anti-lipid drugs; not having cancer; non-smokers and non-alcoholic consented and served as control. Data on family history of DM, duration of the disease, hypertension and social lifestyle recorded for diabetic patients. Weight, height and BMI were calculated, Blood pressure, fasting glucose and serum for PSA were determined. RESULTS The mean ages of diabetic and non- diabetic men were 53.3 ± 11.8 and 53.9 ± 6.1 years, respectively. The mean total serum PSA was significantly lower in diabetic compared to non-diabetic (0.72 ± 0.09 ng/ml vs. 2.50 ± 0.44 ng/ml, respectively, p = 0.000). The mean fasting glucose was significantly higher among diabetic compared to non-diabetic p = 0.006). Diabetics were grouped into 5 according to their age (40 -49, 50-59, 60-69,70-79, ≥ 80). The age 70-79 years has the highest mean PSA level than all other groups (1.19 ± 0.45ng/ml), while age group ≥ 80 years has the least PSA value of (0.15 ± 0.05ng/ml). The mean fasting glucose is lowest in age group of ≥ 80years and highest in age groups of 50-59 and 40-49years (7.78 ± 0.68 and 7.56 ± 0.63mmol/L) respectively. The treatment modality was grouped into five; insulin 5(4.8%), oral 73(70.2%), oral and insulin 8(7.7%) and diet 18 (13.6%). Oral and insulin treatment has higher level of PSA (1.29 ±1.03 ng/ml) compared to all the other groups. The PSA levels were grouped based on the duration of diagnosis of DM (0-5, 6-10, 11-15, 16-20 and ≥ 21years) and 11-15 years duration have high levels of PSA than the other group. There was significant Pearson’s Correlation between PSA and age, systolic and diastolic (p=0.000, p=0.002 and p=0.006) respectively. CONCLUSION serum PSA level is significantly lower in type 2 diabetics than in non-diabetics in this study. This study and other findings recommend establishment of separate reference interval for Type 2 diabetic men for appropriate evaluation of their prostatic diseases using the PSA Citation Format: Rebecca Mtaku Gali, Dahiru Saleh Mshelia, Jessy Thomas Medugu, Musa Dungus, Hassan Dogo, Haruna Asura Nggada, Bata Mtaku Gali, Mwajim Bukar, Ahmad Gadam Ibrahim, Galadima Gadzama, Abubakar Farate. Low levels of PSA in diabetic Nigerians: A call for a separate reference range for prostate cancer screening among type-2 diabetics? [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-088.

Biochemical Persistence of Prostate-Specific Antigen After Robot-Assisted Laparoscopic Radical Prostatectomy: Tumor Localizations Using PSMA PET/CT Imaging.

Since the introduction of radiolabeled prostate-specific membrane antigen (PSMA) PET/CT, the ability to visualize recurrent prostate cancer has improved substantially. However, diagnostic accuracy is largely lacking for radiolabeled PSMA PET/CT in patients with biochemical persistence (BCP; that is, persistently measurable prostate-specific antigen [PSA] values after robot-assisted laparoscopic radical prostatectomy [RARP]). Therefore, the aim of this study was to determine the role of PSMA (i.e.,18F-DCFPyL or 68Ga-PSMA-11) PET/CT imaging in patients who experience BCP after RARP and to evaluate the sites of persistent disease on PSMA PET/CT. Methods: In total, 150 consecutive patients with BCP after RARP who underwent radiolabeled PSMA PET/CT imaging were retrospectively evaluated. BCP was defined as any detectable first serum PSA value after RARP (≥0.1 ng/mL) at least 6 wk after surgery, in the absence of an undetectable PSA value after RARP. A multivariable logistic regression analysis was performed to identify predictors for the detection of metastases outside the prostatic fossa (≥miN1) on PSMA PET/CT. Results: PSMA PET/CT was performed at a median PSA value of 0.60 ng/mL (interquartile range, 0.3-2.4) after a median of 6 mo (interquartile range, 4-10) after RARP. In total, 101 of 150 patients (67%) had lesions with PSMA expression on PET/CT, and 89 of 150 (59%) had lesions with increased PSMA expression sites outside the prostatic fossa. Moreover, 39 of 150 patients (26%) had PSMA-positive lesions outside the pelvis. On multivariable analysis, higher PSA values after RARP (P = 0.004) and positive pathologic lymph node status (P = 0.006) were independent predictors for ≥miN1. Conclusion: In the presence of BCP, a high proportion of patients already had disease metastatic to the pelvic lymph nodes or showed evidence of distant metastases, as indicated by PSMA PET/CT. Higher PSA levels after RARP and positive pathologic lymph node status were significantly associated with metastases outside the prostatic fossa. In patients with BCP, PSMA PET/CT imaging is warranted to guide salvage treatment strategies.

Prostat Spesifik Antijenin Akut Üriner Retansiyon Sonrası Üretral Kateter Yerleştirilen ve Benign Prostat Hiperplazisi Olan Hastalarda Prostat Adenokarsinomu Saptamadaki Rolü

Objective : Acute urinary retension (AUR) is one of the most important complications in benign prostate hyperplasia (BPH) patients and its treatment is generally urethral catheterization in acute period. There are studies showing that AUR and urethral catheter placement may cause an increase in serum PSA levels. Our objective in this study was to investigate the relation between increased PSA levels and prostate cancer (PCa) incidence in the patient group after AUR and urethral catheter placement. Materials and Methods : 77 patients who had an indwelling urethral catheter due to AUR, performed prostate biopsy due to high PSA levels and then surgical treatment for clinic BPH were retrospectively examined. Age, prostate volumes, pre-biopsy total serum PSA and PSA densities were noted. Total serum PSA rates, PSA densities and prostate volumes were compared for the groups that PCa was detected (n=6) and not detected (n=71) according to biopsy or surgical specimen results. Results : Mean age of the patients was 65.2±3.9 years. Mean prostate volume was measured as 64.1±12.8 g, mean serum total PSA level as 9.2±4.2 ng/mL and mean serum PSA density as 0.15±0.08 mg/mL/g. In PSA groups with a serum total PSA level of ≤4.0, 4-10, 10-20 and >20, PCa prevalence rates were detected 0%, 4.3%, 13.4% and 20%, respectively. Total PSA levels and PSA densities were found statistically higher in PCa detected group. Conclusion : PCa incidence is low in patients who were placed urethral catheter after AUR. For these patients prostate biopsy should be performed only in chosen cases.

Correlation between peripheral blood neutrophil-lymphocyte ratio and CD34 expression in prostate cancer

BackgroundsThe association of neutrophil-lymphocyte ratio (NLR) and CD34 expression level with PSA level, Gleason score, and clinical stage was investigated in patients with prostate cancer. The correlation between NLR and CD34 expression was also investigated to provide evidence supporting the use of NLR for predicting the prognosis of prostate cancer patients.MethodsClinical data of 75 patients diagnosed with prostate cancer by prostate aspiration biopsy were retrospectively analyzed. The correlation between NLR, CD34 expression, and clinicopathological characteristics was analyzed using the χ2 test and one-way analysis of variance. The correlation between NLR and CD34 was determined using the Pearson coefficient. Disease free survival was estimated by Kaplan-Meier analysis.ResultsBoth NLR and CD34 expression were significantly positively correlated with PSA, Gleason score, and clinical stage (P < 0.05 both). Patients in the NLRHigh/CD34High group were characterized by high PSA level and Gleason score and late clinical stage. NLR was positively correlated with CD34 expression (r = 0.529, P < 0.001).ConclusionsPretreatment NLR was a valuable marker of prognosis in prostate cancer. NLR is positively correlated with CD34 expression.

Abstract 3513: Genome-wide scan for novel prostate cancer susceptibility loci with clinical consequence utilizing increased genetic drift of the Finnish population

Abstract Background: Prostate cancer (PC) is the second most common cancer in men worldwide with a rising prevalence. However, only limited number of clinically actionable variants are known. The objective of this study is to identify novel PC susceptibility loci with potential clinical relevance utilizing the increased genetic drift and reduced selective pressure of the recently bottlenecked powerful resource of the Finnish population. Methods: We meta-analysed &amp;gt;185.000 germline single nucleotide polymorphisms (SNPs) in 2738 PC cases and 2401 controls of Finnish origin in the Collaborative Oncological Gene-Environment Study (COGS) using Illumina iSelect custom SNP genotyping platform. Results: Altogether 160 variants remain significant on GWAS level (p&amp;lt;5 × 10−8) in 18 different gene regions. Out of the 160 identified PC susceptibility hits 78 (49%) are novel variants not reported earlier in association with PC. PC associated signals are in close proximity to one another forming genetic hot-spots on chromosomes 8, 7, 11, 17 and 19. The strength of association varies for 101 PC risk variants (OR 1.24-1.86) and 59 protective SNPs (OR 0.59-0.80). The strongest risk gene is CASC8 (OR=1.86; p=1.214 × 10−11). The most significant signals were found at the 8p21.2 chromosomal region (p&amp;lt;7.6 × 10−16). Functional annotation identified a missense coding SNP at KLK3 gene to be a candidate causal variant. We showed evidence for association both with early-onset PC (OR 1.73; P=0.02), high serum PSA level at diagnosis (OR 1.36; P=0.024) and with aggressive PC (Gleason score ≥8; OR 1.44; P=0.02) at 17q21. Conclusion: The results facilitate risk stratification for screening, clinical studies, treatment choices and functional research of PC Citation Format: Csilla Sipeky, Teuvo L. Tammela, Anssi Auvinen, Johanna Schleutker. Genome-wide scan for novel prostate cancer susceptibility loci with clinical consequence utilizing increased genetic drift of the Finnish population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3513.

The significance of a high preoperative PSA level for the detection of incidental prostate cancer in LUTS patients with large prostates.

To evaluate the diagnostic value of a high preoperative PSA level for the detection of incidental prostate cancer (iPCa) in LUTS patients with very large prostates (> 100cc). We conducted a retrospective analysis of 1125 men treated for LUTS with holmium laser enucleation of the prostate (HoLEP). Patients were stratified according to a preoperative PSA level higher (high PSA; n = 365) or lower than 10ng/ml (low PSA; n = 760). Preoperative and histopathological parameters were compared between both cohorts. Logistic regression models were used to identify independent predictors of iPCa. Demographic parameters were similar between both cohorts. The median PSA levels were 14.2ng/ml (11.5-19.9) and 4ng/ml (2.4-6.0). The prostate volume was significantly higher in the high PSA group (105cc vs. 75cc; p < 0.001). Correspondingly, the PSA density was significantly increased in the high PSA cohort compared to the low PSA cohort (0.14 vs. 0.05; p < 0.001). The overall detection rate of iPCa showed no difference between groups (9.5% vs. 9.9%). More preoperative prostate biopsies were performed in the high PSA group compared to the low PSA group (46.8% vs. 17.6%; p < 0.001). However, the rate of false negative results was comparable between groups (12.7% vs. 11.1%; p = 0.726). In logistic regression models all PSA-related parameters failed to predict iPCa. PSA-guided approaches to predict iPCa in LUTS patients with very large prostates are not accurate. This finding is useful in clinical practice for counselling our patients and to prevent unwarranted diagnostic procedures.

Abstract A066: Performance of the prostate health index (PHI) assay in black men

Abstract Introduction: The low specificity of PSA in prostate cancer (PCa) screening has caused excessive biopsies and PCa over-detection. PHI is more specific for clinically significant (cs) PCa (i.e. Gleason &amp;gt;6 PCa) and includes serum PSA, [-2]proPSA, and free PSA in its formula. Validation studies in diverse populations have suggested that PHI should be used as a reflex test and the optimal cutoffs for PHI vary across ethnic groups, but have not been determined in Black men. We sought to 1) assess the distributions of PHI and PSA in healthy controls and men with high-grade PCa and 2) assess the accuracy of PHI vs. PSA for detection of csPCa in Black men with elevated PSA. Methods: The present study population consists of two biopsy-naïve cohorts. The first cohort serves as healthy controls and includes Black men with PHI and PSA drawn at community screening events through the social networks of eight lay Black male Citizen Scientists. The second PHI Biopsy Study cohort consists of Black men referred with elevated PSA and/or abnormal digital rectal exam (DRE) who had PHI drawn immediately before prostate biopsy. We excluded men with prior biopsies or known PCa. Distributions of PHI and PSA were compared across controls and men with negative biopsies, Gleason 6 PCa and csPCa. Among men with biopsy, we compared the area under the receiver operating characteristics curves (AUC) for PSA and PHI for detecting csPCa and assessed specificity at selected sensitivities as a proxy of avoided biopsies. We descriptively assessed theoretically avoided biopsies and missed csPCa at previously established PHI cut points [27.0, 28.6, 29.9, and 35.0]. Results: For the first objective, 139 men (42.5%) were included as controls from the Citizens Scientist Study and 188 (57.5%) were from the PHI Biopsy Study cohort, out of which 82 (43.6%) had a negative biopsy for PCa, 40 (21.1%) had low-grade PCa, and 66 (35.1%) had a Gleason &amp;gt;6 PCa. Compared to the healthy control group, the PHI Biopsy Study cohort was older (median age 61 vs. 55 years), with higher PSA levels (7.1ng/mL vs. 0.9ng/mL) and PHI scores (61.1 vs. 20.1), and more commonly had a family history of PCa (19.4% vs. 5.0%) and benign prostatic hyperplasia diagnosis (21.3% vs. 2.2%) (all p&amp;lt;0.001). Relative to PSA, PHI has a higher degree of overlap in the distribution between controls and csPCas (p &amp;lt;0.05), suggesting PHI would not perform well as a primary screening test in Blacks. In men with PSA between 4-10, PHI outperformed PSA in the detection of HGPCa with an AUC of 0.70 (95% CI: 0.59-0.81) compared to 0.57 (95% CI: 0.46-0.69). As a reflex test in men with PSA of 4-10ng/mL and normal DRE, a PHI cutoff of 35.0 would spare 20 (27.8%) low-risk men a biopsy while missing 2 (7.4%) csPCas. Conclusion: PHI should not be used for primary screening but has higher accuracy and specificity than PSA in Black men with PSA levels of 4-10ng/mL as a reflex test. At a cutoff of 35.0, 28% of low-risk men avoid biopsy while missing 7% of csPCas. Citation Format: Samuel Carbunaru, Oluwarotimi Nettey, Edward M Schaeffer, Peter H Gann, Michael Abern, Courtney M.P Hollowell, Karriem Watson, Tiffany McDowell, Rick A Kittles, Adam B Murphy. Performance of the prostate health index (PHI) assay in black men [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A066.

Superscan: Superiority of xSPECT/CT over OSEM SPECT/CT in bone scans of prostate cancer patients.

Prostate cancer is one of the most common cancers affecting men. Bone scan is part of the staging modality commonly used to evaluate bone metastasis. A bone scan with diffused increased skeletal tracer uptake relative to soft tissue, combined with faint renal activity is known as a superscan. However, a primary concern are false negatives associated with bone scans, where diffuse metastasis is indistinguishable on superscans. In this study, we performed xSPECT/CT Bone and standard OSEM SPECT/CT reconstruction algorithm in ten prostate cancer patients with high PSA levels, where they initially seem relatively unremarkable on planar images. All patients with extensive bone metastases showed either relatively unremarkable scans or did not demonstrate the true extent of metastatic burden as seen on planar images. Uptake was further confirmed by the correlative diffuse bone lesions on CT images. Our reports also indicated that xSPECT/CT reconstructed images were far superior in delineating focal areas of osteoblastic bone metastasis, when compared with whole body planar images or SPECT/CT images. The extent of metastatic evidence is delineated with excellent clarification by xSPECT/CT images. We propose that whole body xSPECT/CT image reconstruction, or at least SPECT/CT, should be performed in patients with high PSA levels, along with planar imaging, to improve diagnostic accuracy of bone scans in prostate cancer staging.

Clinical analysis of the extracellular vesicle-fingerprint score blood test to refine the prediction of clinically significant prostate cancer and avoid prostate biopsy.

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]

The role of programmed death-ligand 1 and non-epithelial circulating tumor cells in locally advanced prostate cancer.

e17557 Background: Circulating tumor cells (CTCs) is considered as an effective prognostic biomarker in malignancies. It is recently recognized that detections of programmed death-ligand 1 (PD-L1) and mesenchymal markers in CTCs may improve the predictive value. Therefore, we aimed to determine the cut-off values of these CTCs biomarkers in prostate cancer (PCa), assess the rates of PD-L1 positive and non-epithelial (NE) subgroup in CTCs among patients with high-risk (HRPC) and locally advanced PCa (LAPC) before surgery, and evaluate the clinical values of these markers. Methods: Four PCa cell lines selected from Cancer Cell Line Encyclopedia were applied in spiking experiments to establish the cut-offs of PD-L1 positive and NE CTCs. 182 HRPC and 89 LAPC patients were enrolled from June 2016 to December 2018. All patients underwent radical prostatectomy after blood sample collection. CTCs enumeration and biomarkers identification were conducted by Canpatrol CTC enrichment system and the RNA in situ hybridization technique. Lastly, using the cut-offs,we evaluated the association between CTCs markers and other variables in terms of clinical data, disease outcome, tumor tissues immunochemistry (IHC) staining, and the response of immunotherapy. Results: The cut-offs were determined as the lowest rates of NE and PD-L1+ CTCs among the cell lines, 45% and 25%, respectively. In HRPC patients, a higher PSA level and more advanced T stage were observed in the NE CTCs positive group (≥45%), compared with the negative group ( P= 0.041 and P= 0.004). Multivariate analysis showed that the NE CTCs rate, instead of total CTCs number, was an independent risk predictor for progression-free survival (PFS) (HR = 3.85, P= 0.013). In LAPC patients, the PD-L1+ CTCs positive group (≥25%) presented a higher PSA level and higher percentage of lymph node metastasis than negative group ( P= 0.027 and P= 0.028). The median PFSs between the two groups were 16.6 mouths vs. 21.8 mouths, respectively. (HR = 2.87, P= 0.002 ). No significant correlation was found between PD-L1 expression in CTCs and in tumor tissue IHC staining. However, we observed a significant correlation between PD-L1+ CTCs rate and ERG or PTEN expression in tissues ( P= 0.010 and P= 0.009). In addition, patients in PD-L1+ CTCs positive group presented a better PSA response to Durvalumab treatment than those in negative group. Conclusions: PD-L1+ and NE CTCs were an effective prognosis predictors for HRPC and LAPC patients with radical prostatectomy. LAPC patients with PD-L1+ CTCs might benefit from adjuvant immunotherapy

99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center

BackgroundProstate-specific membrane antigen (PSMA) SPECT imaging in prostate cancer (PCa) could be a valuable alternative in regions where access to PSMA-PET imaging is restricted. [99mTc]Tc-PSMA-I&S is a new 99mTc-labeled PSMA-targeting SPECT agent, initially developed for radio-guided surgery. We report on the diagnostic use of [99mTc]Tc-PSMA-I&S-SPECT/CT in PCa.Results[99mTc]Tc-PSMA-I&S-SPECT/CT was performed and evaluated in 210 outpatients with PCa at a single center. Patients were imaged for biochemical recurrence (BCR, n = 152, mean PSA 8.7 ng/ml), for primary staging of high-risk PCa (n = 12, mean PSA 393 ng/ml), and restaging in advanced recurrent PCa (n = 46, mean PSA 101.3 ng/ml). Number and location of positive lesions were determined for the different subgroups. For BCR, detection rates were calculated, defined as the proportion of scans with at least one PSMA-positive lesion.PSMA positive lesions were detected in 65.2% of all 210 patients. Tumor tissue was mainly detected in lymph nodes (59%), in the bone (42%), and in the prostate (fossa) (28%). In the subgroup of patients referred for detection of BCR the detection rate increased from 20% at a PSA level < 1 ng/ml to 82.9% and 100% at PSA levels > 4 ng/ml and > 10 ng/ml, respectively. In the subgroup of high-risk patients referred for primary staging, 42% demonstrated metastatic disease. Restaging of advanced recurrent PCa revealed detectability of PSMA positive tumor lesions in 85% of the scans.Conclusions[99mTc]Tc-PSMA-I&S-SPECT/CT was useful in PSMA-targeted imaging of PCa at various clinical stages. At low PSA levels (< 4 ng/ml), detection rates of [99mTc]Tc-PSMA-I&S-SPECT/CT in BCR are clearly inferior to data reported for PET-imaging and should thus only be considered for lesion detection if imaging with PET is unavailable. However, at higher PSA levels (> 4 ng/ml) [99mTc]Tc-PSMA-I&S-SPECT/CT provides high detection rates in BCR. [99mTc]Tc-PSMA-I&S-SPECT/CT can also be used for primary staging and for restaging of advanced recurrent PCa. However, further studies are needed to assess the clinical value in these indications.

MP75-07 A TERRITORY-WIDE STUDY ON THE PREDICTORS OF 30-DAY COMPLICATIONS IN TRANSRECTAL VERSUS TRANSPERINEAL PROSTATE BIOPSY

INTRODUCTION AND OBJECTIVE: As the "trexit" initiative continues to gain popularity around the world, we aimed to conduct a territory-wide study to investigate the complications rates of transrectal (TR) versus transperineal (TP) prostate biopsy, and to investigate for predictors of complications. METHODS: All data were extracted from a territory-wide electronic patient record system, which records details of every emergency attendance and hospital admission in all public hospitals in Hong Kong. Consecutive patients with transrectal or transperineal prostate biopsies performed in all public hospitals in Hong Kong from January 2016 to October 2019 were included. Baseline characteristics including age, PSA level, diabetes, and drug use (alpha-blockers, anti-cholinergic, antiplatelet, and anti-coagulants) were recorded. 30-day complications requiring emergency attendance or hospital admission, including per-rectal bleeding, hematuria, acute urinary retention, urine culture proven urinary tract infection (UTI), and blood culture proven sepsis were recorded. Multivariate logistic regression analyses were performed to investigate for predictors of complications. RESULTS: The cohort included 9918 TR prostate biopsy and 1001 TP prostate biopsy patients. The TP group had a higher PSA level (67.2±402.6ng/mL vs 54.8±373.8ng/mL, p<0.001) and higher proportion of diabetes (12.9% vs 10.8%, p<0.001). The TR group had higher rates of per-rectal bleeding (0.6% vs 0%, p=0.015), urine culture proven UTI (3.3% vs 1.7%, p=0.007) and blood culture proven sepsis (1.5% vs 0.3%, p=0.002). The TP group had a higher rate of acute urinary retention (5.3% vs 3.2%, p<0.001). The overall complication rates were similar between the TR and TP groups (8.3% vs 8.1%, p=0.805). Multivariate analysis showed that TP biopsy was a significant protective factor for UTI (OR 0.57, 95%CI 0.35-0.93, p=0.025) and sepsis (OR 0.23, 95% CI 0.07-0.72, p=0.012). TP biopsy was a significant risk factor for acute urinary retention (OR 1.81, 95%CI 1.32-2.47, p<0.001). Prior use of alpha-blocker was a significant risk factor of per-rectal bleeding (OR 1.96, 95%CI 1.08-3.56, p=0.028), acute urinary retention (OR 2.72, 95%CI 2.15-3.43, p<0.001) and overall complications (OR 1.71, 95%CI 1.45-2.01, p<0.001). CONCLUSIONS: Transperineal approach could reduce post-biopsy UTI and sepsis. However, our results suggested a higher rate of acute urinary retention especially in TP patients with pre-existing benign prostatic obstruction requiring use of alpha-blockers. Source of Funding: nil