Higher Prostate-specific Antigen Research Articles

EP008 - Determining the diagnostic value of PSMA-PET/CT imaging in patients with persistent high prostate specific antigen levels and negative prostate biopsies. The SESAME-study

EP008 - Determining the diagnostic value of PSMA-PET/CT imaging in patients with persistent high prostate specific antigen levels and negative prostate biopsies. The SESAME-study

Men with High Prostate Specific Antigen Have Higher Risk of Gleason Upgrading after Prostatectomy: A Systematic Review and Meta-analysis.

To examine the correlation between prostate specific antigen (PSA) and the risk of Gleason sum upgrading (GSU) from biopsy Gleason sum (bGS) to prostatectomy Gleason sum (pGS). Five electronic databases (Web of Science, Ovid Medline, Ovid Embase, SCOPUS and the Cochrane Library) were searched from inception until March 2020. Studies were included if they focused on the relationship between PSA and GSU analyzed in multivariable analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies. The publication bias was evaluated by funnel plot and Egger's test. Our search yielded 19 studies with high quality including 42193 patients. GSU was found in 28.2% of patients. Higher PSA level was associated with a significant increased risk of GSU (pooled OR = 1.14, 95% CI: 1.10-1.18; P < .05; I2 = 92%). For the definition of upgrading from bGS ≤ 6 to pGS ≥ 7, the odds of upgrading with higher PSA level as opposed to lower PSA level was 1.12 (95% CI: 1.11-1.14; P < .05; I2 = 13%), while the odds of upgrading with other definitions were 1.11 (95% CI: 1.05-1.18; P < .05; I2 = 89%). Patients with high level of serum PSA are at high risk of undergoing pathologic upgrading at prostatectomy. Combined with other risk factors, PSA prompts risk reclassification and improve confidence of urologists in management decisions for optimal therapy. Nevertheless, further robust studies are necessitated to confirm these results.

A non-randomized prospective study on the diagnostic performance of perineal prostatic biopsy, directed via diffusion nuclear resonance, in patients with suspected prostate cancer and previous negative transrectal prostate biopsy.

A definition of the best strategy is necessary to optimize the follow-up of patients with previous negative transrectal guided ultrasound biopsy (TRUS-GB) and the persistence of raised prostate-specific antigen (PSA).The purpose of this study was to evaluate the prostate cancer (PCa) diagnostic rate of targeted transperineal ultrasound guided biopsy (TPUS-GB) with cognitive multiparametric magnetic resonance imaging (mpMRI) registration with concurrent systematic biopsy in patients with previous negative systematic TRUS-GB and persistently elevated PSA levels. In this prospective study conducted at the University Infanta Sofia Hospital from April 2016 to November 2017, patients with one previous negative systematic TRUS-GB and persistently high PSA levels were referred for mpMRI prostate scans. All patients underwent systematic TPUS-GB and those patients with suspicious findings on mpMRI scans, Pirads 3 and 4-5, underwent a subsequent cognitive guidance mpMRI-TPUS-GB. In total, 71 patients were included in this study. Suspicious findings on mpMRI scans prior to TPUS-GB were found in 50 patients (70.4%). 16 patients were diagnosed with prostate cancer (22.5%), of whom 14 (87.5%) had a mpMRI scan with Pirads 3 or Pirads 4-5. Patients with Pirads 3, 4 or 5 showed negative results in almost all cores taken by concurrent systematic TPUS-GB. Cognitive mpMRI-TPUS fusion biopsy is a useful tool to diagnose PCa in patients with previous negative prostate biopsy. The samples obtained from the suspicious areas in the mpMRI detect more cases of intermediate and high risk PCa compared to the samples obtained at random or from non-suspicious areas.

Prevalence and Factors Associated with High Concentration of Prostate-Specific Antigen: ELSIA Study.

Prostate cancer (PC) is the second most common cancer among men, behind only non-melanoma skin cancer, and the main method of screening for PC is the prostate-specific antigen (PSA). To analyze the prevalence and the factors associated with high concentration of PSA in the elderly is essential to understand this outcome, and building strategies to decrease their rates of morbidity and mortality. We performed a cross-sectional study with 96 elderly men. A high level of PSA was defined by >4.0 ng/mL. In order to identify sociodemographic, health, functional and behavioral variables, which may be associated with high levels of PSA, we carried out a multivariate analysis using Poisson regression. The prevalence of high levels of PSA was 21.9% (n = 21). High levels of PSA was associated with years of study, race/ethnicity and family arrangement, health perception, systolic blood pressure, diastolic blood pressure, metabolic diseases, alcohol consumption and sedentary behavior. The study found a high prevalence of high PSA concentrations in the elderly and several aspects are associated, which can be a worrying factor for their health, since PSA is an important marker of prostate cancer.

Association of schistosomiasis and risk of prostate cancer development in residents of Murehwa rural community, Zimbabwe

BackgroundProstatic male genital schistosomiasis and prostate cancer co-existence cases are uncommon however, some studies have indicated that schistosomiasis may trigger development of prostate cancer regardless of age. Schistosomiasis is a public health problem in sub-Saharan Africa and may account for some undocumented cases of schistosomiasis prostatic cancer in schistosome endemic rural communities. It is against this background that we investigated the association between schistosomiasis and risk of prostate cancer development in residents of Murehwa Community, a schistosomiasis endemic area.MethodologyWe conducted a cross sectional study involving 366 men residing in Murehwa District, Zimbabwe. Schistosoma haematobium and S. mansoni infection was diagnosed using urine filtration and Kato Katz techniques, respectively. Haematuria was detected using urinalysis reagent strip test. A structured questionnaire was used to obtain history of schistosomiasis infection among study participants. Risk of prostate cancer development was assessed by measuring prostate-specific antigen levels in serum using the ELISA.ResultsPrevalence of S. haematobium and S. mansoni infection was 12.3% and 1.4%, respectively. Individuals with schistosomiasis had higher prostate-specific antigen levels (mean 1.208 ± SD 1.557 ng/mL) compared to those without schistosomiasis (mean 0.7721 ± SD 1.173 ng/mL; p < 0.05). Older individuals > 50 years had higher prostate specific antigen levels (mean 0.7212 ± SD 1.313 ng/mL) compared to individuals < 50 years old (mean 0.4159 ± SD 0.8622 ng/mL; p < 0.05). Prostate-specific antigen levels log10 (mean 0.2584 ± SD 0.2128 ng/mL) and were associated to S. haematobium infection intensity log10 (mean 1.121 ± SD 0.5371 eggs/10 mL), r(s) = − 0.3225, p < 0.05. There was a correlation between prostate-specific antigen levels log10 (mean 0.2246 ± SD 0.1858 ng/mL) and S. haematobium infection intensity log10 (mean 1.169 ± SD 0.5568 eggs/10 mL) among participants with a history of schistosomiasis infection (r(s) = − 0.3520; p < 0.05). There was no correlation between prostate-specific antigen levels of > 4 ng/mL (mean 5.324 ± SD1.568 ng/mL) and schistosome eggs log10 (mean 1.057 ± SD 0.6730 eggs/10 mL; p > 0.05).ConclusionUrogenital schistosome infections and history of schistosome infections were associated with prostate specific antigen levels, an indicator for risk of prostate cancer. Therefore, S. haematobium schistosome egg burden was associated with the risk of prostate cancer development in adult males residing in Murehwa District, Zimbabwe.

Ulcerative colitis that developed during radiotherapy for prostate cancer, deteriorated rapidly and required emergency surgery

BackgroundAlthough there are reports linking ulcerative colitis (UC) to prostate cancer (PC), those reports are of PC patients who were previously diagnosed with UC. There are no reports of the development of UC during radiotherapy. Here we describe the first case of a patient who developed UC during radiotherapy for PC. The UC progressed rapidly and required emergency surgery.Case presentationA 61-year-old Japanese man underwent a prostate biopsy at another hospital due to a high prostate-specific antigen level and was diagnosed with PC. Goserelin and bicalutamide treatment was initiated in 2019, and intensity-modulated radiotherapy (total of 60 Gy/20 Fr) was administered in 2020. Diarrhea began during the radiotherapy and bleeding began post-radiotherapy. He was admitted to another hospital 14 days after the end of the radiotherapy, and colonoscopy revealed a deep ulcer in the colon, which led to the suspicion of UC. He was transferred to our hospital, and colonoscopy showed a widespread map-like ulcer, pseudopolyposis, and very easy bleeding in the colon. We diagnosed severe UC, and it worsened rapidly with uncontrollable bleeding, which we considered an indication for surgery. Emergency surgery (a total colectomy and ileostomy creation) was performed. The specimens confirmed an extensively spreading ulcer throughout the colon. The pathological report was UC in the active phase. The postoperative course was good.ConclusionsWhen a patient exhibits diarrhea while undergoing radiotherapy for PC, clinicians should be aware of the possibility of UC in addition to radiation colitis, and colonoscopy should be considered.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Implementation of repeat biopsy and detection of cancer after a diagnosis of atypical small acinar proliferation of the prostate.

Current guidelines recommend a repeat biopsy within 3-6 months after an initial diagnosis of atypical small acinar proliferation (ASAP) due to the high incidence of cancer detection on repeat biopsy. The current study sought to investigate practice patterns after a diagnosis of ASAP in a real-world setting and examine the clinicopathological outcomes of repeat biopsy. The departmental database of the Hyogo Prefectural Nishinomiya Hospital identified 97 of 1,218 patients with a diagnosis of ASAP on initial biopsy from 2011 to 2016. Clinical and pathological data were retrospectively analyzed. Of the 97 patients, 34 (35.1%) underwent a repeat biopsy. Patients with a repeat biopsy had a significantly higher prostate-specific antigen (PSA) velocity and shorter PSA doubling time than patients without a repeat biopsy (P=0.0002), and of these 34 patients with a repeat biopsy, 16 (47.1%) were diagnosed as having cancer. Multivariate logistic regression analysis revealed that a small prostate (P=0.0250) and advanced age (P=0.0297) were associated with cancer detection on repeat biopsy. Of the 16 cancers identified, 13 (81.6%) were diagnosed with a Gleason score >6. The results indicated that the implementation of a repeat biopsy for patients with ASAP could be affected by clinical characteristics in real-world settings, despite the current recommendation of guidelines endorsing immediate repeat biopsy. Prostate volume and age would aid in the decision-making process to perform repeat biopsy in patients with high PSA velocity and short PSA doubling time after a diagnosis of ASAP.

Infertile Men Have Higher Prostate-specific Antigen Values than Fertile Individuals of Comparable Age

BackgroundInfertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. ObjectiveTo investigate prostate-specific antigen (PSA) values in men presenting for primary couple’s infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40–45 yr of age. Design, setting, and participantsThis is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. Outcome measurements and statistical analysisDescriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. Results and limitationsOverall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02–0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. ConclusionsInfertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Patient summaryIn this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men.

Negative 11C-choline PET/computed tomography imaging in restaging of patients with prostate cancer with serum prostate-specific antigen values >20 ng/mL.

Several studies have reported about the performance of C-choline-PET/computed tomography (CT) (choline) in patients with biochemical recurrent (BCR) prostate cancer, but there is a lack of information regarding negative choline in the same clinical setting. Our aim was to retrospectively analyse negative choline in a cohort of BCR-patients with high prostate-specific antigen (PSA). We retrospectively analysed all choline-scans performed at two high-volume imaging centres between 2005 and 2018, selecting those of interest according to the following inclusion criteria: (1) proven prostate cancer treated either with radical prostatectomy or primary external beam radiation therapy (EBRT), (2) BCR after radical prostatectomy or EBRT, (3) PSA serum values >20 ng/mL at the time of scan and (4) scan reported as negative for active disease. Overall, among 5792 scans performed for BCR-prostate cancer, 14 matched the inclusion criteria and were classified as follows: 5/14(36%) inaccurate reports, 3/14(21%) questionable underestimation of positive findings, originally described as unclear, 6/14(43%) negatives. Choline showed a high detection rate in BCR-prostate cancer patients with PSA >20 ng/mL. Although negative reports can be found in this clinical setting, in our review various disease-relevant findings were identified in more than half of the cases originally reported as negative warranting a double reading in such cases to avoid false-negative reports.

Abstract 5773: Cardiorespiratory fitness and PSA screening patterns in the Henry Ford FIT Project

Abstract Background: High levels of cardiorespiratory fitness (CRF) have been associated with a decreased risk of many cancers, but the association with prostate cancer (PCa) is less clear. A possible explanation for the lack of consistency is that prostate specific antigen (PSA) screening and in turn prostate cancer detection is more frequent in men with higher fitness although the relationship between fitness and PSA screening is not established. Methods: The Henry Ford (HF) FIT Project is a retrospective cohort study of 69,894 consecutive patients who underwent physician-referred exercise stress testing from 1991 through 2009. Cancer diagnosis was identified through linkage to the HF tumor registry. We included men aged 40-70 yr who had CRF testing beginning in 1995 (when PSA screening became widespread), without prevalent cancer, followed at least 3 yrs and up to 10 years, who never develop prostate cancer (n=12,442). CRF was measured in metabolic equivalents of task (METs) and categorized as less than 6 (ref), 6-9, 10-11, and at least 12. PSA values were abstracted from the HF electronic medical record between 1995 and 2010. Individuals with at least 3 screening PSA tests were categorized as high screeners. Logistic regression was used to evaluate the relationship between CRF and high PSA screeners, adjusted for age at stress test and race. Results: Participants had a mean age of 54 ± 8 yrs (67% white; 25% black) and mean follow-up was 7±2 yrs. Compared to individuals with low fitness (less than 6 METs, reference), those with higher fitness (6-9, 10-11, at least 12 METs) had higher odds of being a high PSA screener (Table). When stratified by race, the OR for black patients were not statistically different than white patients (Table). Results were similar among those with comorbidities (myocardial infarction, heart failure, or diabetes) at baseline. Odds ratio of being a high screener (at least 3 PSA tests) in individuals followed 3-10 yearsMETs categoryAll (n=12,442Whites (n=8,356Blacks (n=3,049)Patients w/comorbidities (n=3,924)&amp;lt;6RefRefRefRef6-91.6(1.3-1.8)1.6(1.3-2.0)1.4(1.1-1.9)1.6(1.3-2.0)10-111.9(1.6-2.2)1.9(1.6-2.4)1.7(1.3-2.2)2.0(1.7-2.4)&amp;gt;=122.4 (2.1-2.9)2.5(2.0-3.1)2.1(1.6-2.8)3.2(2.5-4.0) Conclusion: High CRF is associated with more frequent PSA screening. This points towards a healthy screening bias and should be accounted for in studies looking at fitness and incident prostate cancer. Citation Format: Cara Reiter-Brennan, Omar Dzaye, Mouaz H. Al-Mallah, Zeina Dardari, Clinton A. Brawner, Lois E. Lamerato, Steven J. Keteyian, Jonathan K. Ehrman, Kala Visvanathan, Michael J. Blaha, Catherine Handy Marshall. Cardiorespiratory fitness and PSA screening patterns in the Henry Ford FIT Project [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 5773.

Predictors of ISUP score upgrade in patients with low-risk prostate cancer.

The literature contains few studies that focus on the relationship between International Society of Urological Pathology (ISUP) score upgrade and complete blood count (CBC) parameters for patients with low-risk prostate cancer and studies achieved inconclusive results. We retrospectively analyzed our institutional database for patients with prostate cancer who underwent radical prostatectomy (RP) between 1994 and 2017. In total, we included 633 patients with low-risk prostate cancer in the study. We investigated the effects of clinicopathologic factors on ISUP score upgrade. Moreover, we compared RP pathologic outcomes between the patients with and without ISUP score upgrade. The mean age and follow-up periods were 61.09±6.61 years and 41.9±1.8 months, respectively. ISUP score upgrade was observed in 207 patients (32.7%). In multivariate analysis, high prostate-specific antigen (PSA) density and percentage of positive cores were found to be significantly associated with ISUP score upgrade (p = 0.003 and p = 0.003, respectively). The neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, and eosinophil-lymphocyte ratio were found to have no effect on ISUP score upgrade (p = 0.856, p = 0.353, p = 0.128, and p = 0.074, respectively). The percentage of tumors, surgical margin positivity, seminal vesicle invasion rate, and extraprostatic extension rate in RP pathology were higher in patients with ISUP score upgrade (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). Approximately one-third of the patients in our series had ISUP score upgrade in RP pathology. PSA density and the percentage of positive cores were found to be the factors significantly associated with ISUP score upgrade. CBC-related factors had no effect on ISUP score upgrade.

Different clinical presentations of xanthogranulomatous prostatitis: A case series and review of the literature

Objective: Xanthogranulomatous prostatitis (XGP) is a rare entity that has different clinical presentations. This report of three cases illustrates the diversity of clinical features of XGP, together with a comprehensive literature review. Methods: Three elderly male Sri Lankan patients underwent transurethral resection of the prostate for severe lower urinary tract symptoms. Carcinoma of the prostate was suspected in two patients, and one of them had a very high prostate-specific antigen level (324 ng/mL), suggestive of metastatic prostate carcinoma. The third patient had a clinically benign prostate gland. The histology of all three resected prostate chippings revealed XGP. Results: This case series encompasses two cases of XGP that mimicked carcinoma of the prostate clinically and another case that had benign clinical features. Patients with XGP can have clinical, radiological and serological evidence of advanced prostate carcinoma. Other rare modes of presentation of XGP include prostate abscess and haematospermia. Many concerns of XGP such as aetiology, epidemiology, natural history, risk of malignant transformation and possible treatment options remain unclear due to the paucity of the literature. Conclusions: XGP presents with a variety of benign and malignant clinical features. The possibility of encountering XGP in patients with clinically malignant prostates should not be overlooked.

Who can safely evade a magnetic resonance imaging fusion-targeted biopsy (MRIFTB) for prostate imaging reporting and data system (PI-RADS) 3 lesion?

To identify patients who can safely evade the magnetic resonance imaging fusion-targeted biopsy (MRIFTB) for prostate imaging reporting and data system (PI-RADS) 3 lesion. Overall, 755 men with PI-RADS 3-5 lesions who underwent MRIFTB were retrospectively analyzed. Univariate and multivariate analyses were performed to determine significant predictors for clinically significant prostate cancer (CSPCa), defined as Gleason grade group ≥ II. Detection rates and negative predictive values of CSPCa were estimated according to various clinical settings. Median age, prostate-specific antigen (PSA), and PSA density of patients were 66.0years, 7.39ng/mL, and 0.19ng/mL, respectively. Overall detection rates of CSPCa according to PI-RADS 3 (n = 347), 4 (n = 260), and 5 (n = 148) lesions were 15.0%, 30.4%, and 80.4%, respectively. The negative predictive value (NPV) of PI-RADS 3 lesion on MRI was 15.0%. On multivariate analysis, age [≥ 65years, odds ratio (OR) = 0.427], PSA density (≥ 0.20ng/mL2, OR = 0.234), prior negative biopsy history (OR = 2.231), and PI-RADS score (4, OR = 0.427; 5, OR = 0.071) were independent predictors for the absence of CSPCa by MRIFTB. When assessed according to various conditions, NPVs of PI-RADS 3 lesions were relatively high in subgroups with low PSA density (< 0.20ng/mL2) regardless of age or prior biopsy history (NPV range 91.1-91.9%). Contrarily, NPVs in subgroups with high PSA density were relatively low and varied according to age or prior biopsy history groups (NPV range 50.0-86.8%). Men with the PI-RADS 3 lesion and low PSA density might safely evade the MRIFTB, regardless of age or prior biopsy history.

Unusually High PSA Level Allows Diagnosis of a Metastatic Prostate Cancer in Older Man

Prostate cancer is now the most commonly diagnosed cancer amongst men in France despite the absence of a generalized screening program. Prostate-specific antigen (PSA) level can be used as a screening test. We report the case of an 86-year-old patient, whose metastatic prostate cancer was diagnosed on an unusually high PSA level (over 5000µg/L), without urologic signs. The diagnostic was then confirmed by a thoracicabdominal-pelvic CT scan, which found diffuse metastases, before hormonal therapy started.

Is a sampling transition zone important to increase the detection of prostate cancer in systematic prostatic biopsies?

Use of transrectal ultrasound (US)-guided biopsies improved diagnosis and treatment for patients with high prostate-specific antigen (PSA) or abnormal digital rectal exam (DRE). To investigate whether taking two transition zone (TZ) biopsies in addition to routine prostate double-sextant biopsies (12-cores) would improve detection rates of prostate cancer (PCa). A retrospective analysis of 1107 in a single institution database after Institutional Review Board approval, which underwent US-guided prostate biopsies from January 2014 to June 2016. All patients with suspected PCa based on positive DRE or high PSA submitted to US-guided prostate biopsy (double-sextant 12-cores alone and 12-cores with two TZ extra cores) were included. A total of 1107 patients were included; 120 patients underwent double-sextant 12-cores alone and 987 underwent 12-cores with two TZ extra cores. Among patients submitted to two TZ extra cores, TZs of 755 (76.5%) patients were negative to neoplasia and 232 (23.5%) were positive to neoplasia. Among these patients, 26 (2.6%) had their final Gleason score increased with TZ core; TZ fragments of 20 (2.0%) patients led to a treatment change (re biopsy, active surveillance or from active surveillance to radiation therapy or radical prostatectomy). When the complication rate is analyzed (with or without hospital admission), among the patients submitted to TZ cores, 259 (26.2%) complications were observed; between those submitted to double-sextant 12-cores, 26 (21.7%) complications were observed (P=0.279). Extended core biopsy protocol with two TZ extra fragments improves detection rates of cancer when compared to double-sextant biopsy protocol without increasing complication rates. TZ routine cores should be considered.

The relationship between pre-radiation therapy testosterone levels and prostate cancer aggressiveness.

We investigated whether there is an association between testosterone levels and prostate cancer aggressiveness in patients treated with radiation therapy who underwent a prostatectomy or prostate radiotherapy (EBRT). A total of 380 patients who received primary or post-operative radiotherapy were identified. At the time of radiotherapy, baseline testosterone levels and body mass index (BMI) measurements were available. On multivariate analysis (MVA), higher prostate-specific antigen (PSA) levels were predictive of testosterone ≥10.4 (OR=1.3, p=.04) and testosterone ≥12.0nmol/L (OR=1.3, p=.04). Patients with a Gleason score ≥8 were more likely to have testosterone <8nmol/L than patients with a lower score (31% vs. 20%, p=.043). On univariate analysis, a Gleason score ≥8 was associated with a lower likelihood of having a normal (≥8nmol/L) testosterone level (OR=0.51, 95% CI: 0.3-0.9, p=.02), and on MVA adjusted for post-surgical versus primary EBRT and BMI (≥30kg/m2 ), the Gleason score lost its statistical significance (p=.09). While higher PSA levels are associated with higher testosterone levels, the interaction between Gleason score and testosterone is unclear and merits further study.

Evaluation of Notch1 gene expression in prostate carcinoma

Aim: Prostate cancer is one of the most common cancers in the world and its incidence is rapidly increasing. Currently, several new treatment strategies that target specific signaling pathways as well as immunotherapy are being explored for prostate cancer. In the current study, we aimed to investigate the frequency and clinicopathologic features associated with Notch1 gene expression using immunohistochemistry and real-time-polymerase chain reaction in patients with prostate cancer. Methods: This research was planned as a cohort study. Tissue samples of 60 patients with prostate cancer and 20 patients with benign prostatic hyperplasia were selected from the archives. Twenty patients with benign prostatic hyperplasia were used as the control group. The relative expression levels of Notch1 gene were determined by real-time-polymerase chain reaction while Notch1 protein expression was analyzed using immunohistochemistry. Results: We found Notch1 gene expression at a significant level in 17 (28.3%) of 60 patients with prostate carcinoma. We found a significant correlation between high Gleason scores (P=0.007), high ISUP (International Society of Urologic Pathologists) grade group scores (P=0.008) and high prostate-specific antigen levels (P=0.018) for Notch1 gene expression. Conclusions: We conclude that Notch1 is important in prostate carcinogenesis. Therefore, determining Notch1 will be an essential step in targeted therapies in patients with prostate carcinoma.

10-Year Clinical Experience With 18F-Choline PET/CT: An Italian Multicenter Retrospective Assessment of 3343 Patients.

The primary aim of this multicenter retrospective analysis is to examine the role of F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008-2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of F-choline images and in patient selection in the last 5 years.

Prospective evaluation of 18F-DCFPyL PET/CT in biochemically recurrent prostate cancer: Analysis of lesion localization and distribution.

5556 Background: 18F-DCFPyL, a promising PET agent targeting prostate specific membrane antigen (PSMA), is prospectively evaluated in a single academic center for detecting recurrent lesions in prostate cancer patients with biochemical recurrence (BCR). Methods: We prospectively enrolled 150 men (51-91 years old, mean ± SD: 70.3±7.5) with biochemical recurrence (PSA median 2.38 ng/mL, range 0.12 to 698.4) after primary definitive treatment with prostatectomy (65%), radiotherapy (35%) or both (19%). The 18F-DCFPyL positive lesions compatible with prostate cancer were evaluated by two independent readers. Impact of 18F-DCFPyL PET/CT on patient management was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 83% (125 scans), which increased with higher prostate specific antigen (PSA) levels (ng/mL): 63% (PSA &lt; 0.5), 75% (0.5≤PSA &lt; 1), 91% (1≤PSA &lt; 2), 95% (2≤PSA &lt; 5) and 98% (PSA≥5), respectively. In the cohort who underwent prostatectomy, 18F-DCFPyL PET/CT had higher positivity rate in patients with shorter PSA doubling time (PSAdt) (94% in PSAdt 0-3 months vs. 53% in PSAdt &gt; 12 months, P&lt; 0.01). No difference of 18F-DCFPyL positivity rate was observed in post-radiation patients with different PSAdt, nor were there differences between patients with low grade (Gleason 6) or higher-grade prostate cancer (Gleason 7-10). 20 patients (13%) had lesions in the prostate bed only and 41 patients (27%) had oligometastatic disease (1-3 lesions), making them candidates for locally targeted therapy. We identified a total of 1455 18F-DCFPyL positive lesions, including 51 lesions in the prostate bed, 271 pelvic and 463 extra-pelvic lymph nodes, approximately 585 osseous lesions, including 5 patients with diffuse osseous metastases, and 85 lesions in other organs (most commonly in the lungs). 91 out of 150 patients (61%) had change in treatment after 18F-DCFPyL PET and, most noticeably, 48 of these patients (32% total) had lesions only localized on 18F-DCFPyL PET/CT despite negative conventional imaging. Conclusions: 18F-DCFPyL PET/CT holds great potential to be a “one-stop shop” diagnostic tool in the work-up of BCR prostate cancer, with high (61%) impact on the management of these patients. Clinical trial information: NCT03501940 .