PSA Increase Research Articles

Plasma-based exploratory biomarker analysis to evaluate GT0918 in a phase I/II study in mCRPC patients.

279 Background: GT0918, a novel potent androgen receptor antagonist, has been evaluated in a ph 1/2 study in mCRPC patients for its safety and efficacy. Here using patient plasma samples, we explored cell-free DNA & RNA-based biomarkers to assess their associations with clinical response of GT0918. Methods: Blood samples were prospectively collected from mCRPC patients at baseline, on- and after study during the trial. PredicinePLUS cfDNA+cfRNA assay, a 180-gene targeted NGS Panel, was used to detect genomic alterations in plasma. Statistical analyses were performed in R 3.5.1. Results: Genomic alterations were detected in all 50 blood samples. Top mutated genes are TP53 (52.5%) and AR (32.5%). When combing variants from genes in a signaling pathway, mutation rates in PI3K axis and homologous recombination pathway are 32.0% and 34.0% respectively. Importantly, AR hotspot mutations (W742C, T878A, and S889G) and amplifications are detected in multiple subjects at baseline, suggesting that it may be the driving events for resistance of prior therapies. AR splicing variants (AR-V3, AR-V7) and TMPRSS2-ERG fusion were also detected by cfRNA profiling. Interestingly, patient 001-001 harboring both AR W742C and T878A mutations detected in cfDNA with high mutation frequency didn’t carry corresponding mutations in cfRNA at the baseline but started to accumulate the mutations in C3D1. Patient 004-002 remained in the study with stable disease for 10 treatment cycles while having continuous increase of PSA. cfDNA profiling indicates frequency of prostate-specific SPOP mutation continued to decrease during the treatment. Conclusions: This is a preliminary analysis to explore potential predictive or pharmacodynamic biomarkers in mCRPC in response to GT0918 treatment. As an non-invasive assay, PredicinePLUS assay was able to detect genomic alterations in blood with a high sensitivity and provided useful molecular insights for treatment monitoring and drug sensitivity & resistance mechanisms. Clinical trial information: NCT02826772.

German health service research with the focus on effectiveness of secondary-antiandrogen deprivation therapy (s-ADT) in prostate cancer patients with buserelin in daily practice.

291 Background: Aim of the health service research was to answer the questions: 1.) Is the s-ADT with buserelin a successful therapy perspective in biochemical progressive PCA patients after any ADT therapy performed prior? 2.) What is the response rate over all and with a PSA decline more than 50% from the starting level? Methods: In a time period of 2.5 years (2013-2016) a study collective of 1233 PCA patients was treated with buserelin of which 355 got a s-ADT therapy after biochemical progress. In follow-up controls the effectiveness was proven in respect to PSA decline after 6 and 12 months. Results: The cohort of 355 men had an age of 77.3 years with a risk distribution of 26.2% low risk, 33% intermediate and 40.8% high risk PCA. The initial PSA level before ADT change ranged from < 0.4 up to > 1000 ng/ml. Therapy effects over 12 month: 17.7% stayed unchanged, 49.7% progressed, 32.7% remitted and 23.8% declined in PSA more than 50% (effective). During the 12 month of follow-up 7.5% showed an initial PSA flair with a following remission, 15.6% an initial remission switching to progression. The PSA progression varied from 10 to 5229% increase and 40% had a PSA increase of more than 100% over 12 month. Conclusions: The s-ADT manipulation by buserelin after any prior ADT therapy induced in 33% over 1 year a positive PSA response and over all in 24% an effective PSA remission ( > 50% PSA decline) over 1 year. On the other hand 50% of the patients will progress with buserelin in s-ADT. The decision if s-ADT will succeed can be maid after 6 month of therapy with buserelin until a treatment change must be decided. Today, in respect to the early onset of abiraterone and docetaxcel in PCA management since 2017 the value of s-ADT must be discussed critically and again re-evaluated.

P2PSA for predicting biochemical recurrence of prostate cancer earlier than total prostate-specific antigen after radical prostatectomy: an observational prospective cohort study.

There is an unmet clinical need for more biochemical specific tests that may detect clinically significant recurrent PCa at an early stage after radical prostatectomy (RP). Our purpose is to test the hypothesis that p2PSA (Index test) detects prostate cancer relapse (BCR) earlier than the current Reference Standard Test (total prostate-specific antigen [tPSA]) in patients who underwent RP for localized PCa. This is an observational, prospective, cohort, follow-up study in patients subjected to RALP (robotic assisted laparoscopic radical prostatectomy) for clinically localized PCa from January 2013 to July 2013 at a high-volume Institution (450 average RP/year). A blood sample, for tPSA and p2PSA, was prospectively drawn after 3, 6, and 12 months and then every 6 months during the following two years. The primary outcome is to determine whether or not kinetics in rising of p2PSA significantly anticipates the tPSA kinetics. Exploratory data analysis was used to identify relationship between different variables. Over 134 patients 20 BCRs were detected according to tPSA cut-off. Five patients showed a contemporary increase of tPSA and p2PSA, 11 presented a p2PSA increase earlier than tPSA increase (13.9 months ±9.7). In four patients, the increase of PSA was not associated with a p2PSA>0.8 pg/mL. The correlation between tPSA and p2PSA according to Sperman's rho coefficient was statistically significant at 3, 6, 18 and 30 months: 0.416 (P<0.01), 0.255 (P<0.01), 0.359 (P<0.01) and 0.413 (P<0.01) respectively. When subjects were stratified according to stage/grade and margins (positive vs. negative), patients with higher stage and positive surgical margins could be considered the target categories. The low rate of observed BCR and high rate of p2PSA false positive are the main limitations. The current findings showed that p2PSA might be more sensitive than tPSA in detecting earlier BCR within 3-year follow-up. Further studies with a longer follow-up and larger population remain mandatory before considering p2PSA for clinical decision-making.

851P - Pharmacokinetic/pharmacodynamic relationship of enzalutamide and its active metabolite N-desmethyl enzalutamide in metastatic castration-resistant prostate cancer patients

Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor approved for the treatment of metastatic Castration-Resistant Prostate Cancer (mCRPC). ENZA is extensively metabolized by CYP 3A4 into N-desmethyl enzalutamide (NDE). Based on in vitro assays, NDE has been identified as pharmacologically active metabolite. We aimed to explore the relationship between ENZA, NDE plasma concentration and progression-free survival (PFS) in mCRPC. Methods: Trough plasma concentrations of ENZA and NDE were measured at steady-state one month after treatment start, using liquid chromatography. Trough ENZA and NDE plasma concentrations were dichotomized into 2 groups (high and low) according to their median value. Progression was defined as clinical progression, PSA increase or imaging progression according to the prostate working group criteria 3 or death. A survival analysis was used to explore relationship between PFS and plasma drug exposure. Results: From January 2015 to May 2017, 18 mCRPC patients treated with ENZA (median age 77.5 years, Interquartile range (IQR) 67.2-82.7) were prospectively included. Median follow-up was 10.6 months (ms) (IQR 5.1-21.3 ms). Median trough plasma concentration of ENZA and NDE were 10.5 ± 3.7 µg/mL (Coefficient of variation (CV) = 33.8%; IQR 8.2-13.2) and 8.1 ± 4.2 µg/mL (CV = 52.7%; IQR 5,4-10,1), respectively. Pearson correlation coefficient value was 0,3 (p = 0.21). Eleven patients (61%) achieved a PSA response. Median PFS in the whole cohort was 11.2 ms (IQR 3.4-12.4). High trough plasma concentration of ENZA was associated with a shorter PFS (9 ms vs 22.6 ms respectively in the high and the low group) (Hazard Ratio (HR) 0.2; 95% CI 0.04-0.57; p = 0.005). Conversely, a high trough plasma concentration of NDE was associated with a longer PFS: 12,8 ms vs 7.2 ms respectively in the high and low group (HR 3.04; 95% CI 1.19-48.45; p = 0.03). Conclusions: Overall, these results suggest that NDE could be more pharmacologically active than ENZA in vivo. Plasma monitoring of ENZA and NDE could lead to early identification of patients who will not benefit from ENZA as well as to optimize their treatment choice. Legal entity responsible for the study: Department of Medical Oncology, Cochin Hospital, Paris Descartes University, Pr Goldwasser. Funding: Has not received any funding. Disclosure: O. Huillard: Consultant/advisor: Astellas Pharma, Sanofi, Janssen Oncology, Bristol-Myers Squibb; Travel, accommodations reimburse: Roche/Genentech, Astellas Pharma, Pfizer; Sanofi. F. Goldwasser: Consultant/advisor: Fresenius Kabi, Baxter. J. Alexandre: Consultant/advisor: Novartis, Roche; Honoraria: Novartis, AstraZeneca, Roche, Ipsen; Research funding: Jansen; Travel, accommodations reimburse: Jansen. All other authors have declared no conflicts of interest.

Histopathological Study of Prostatic Carcinoma in Relation to Gleason Grade, Serum PSA and Ki67 Immunomarker

Introduction- Carcinoma of prostate (CaP) is the second most common cancer in men.Gleason’s score (GS) and pretreatment serum prostate specific antigen (sPSA) levels are important parameters in diagnosis and therapeutic decision making. Recent studies have found that GS tends to undergrade tumors and sPSA levels are not cancer specific. The present study highlights correlation between immunomarker Ki67, GS and sPSA which provides a objective method of grading tumors and helps in better prognostication of patients. Objectives- 1. To study histopathology of prostate carcinoma and its variants and assign them Gleason score as per the Gleason grading system. 2. To study Ki-67 immunoexpression in prostate carcinoma. 3. To correlate Ki-67 expression, Gleason scoring and serum prostate specific antigen levels in prostate carcinoma Methods -A retro-prospective study was done on 100 specimens of prostate carcinoma from the year 2010-2015 in Department of Pathology of ESIC Medical College and PGIMSR, Rajajinagar, Bangalore for a period of 18 months(November2013-April2015).Each case was assigned Gleason score and subjected to immunohistochemistry for Ki67 expression. Results of Ki67 expression was correlated with Gleason score and PSA levels. Results-Out of the 100 cases studied, all case were of acinar/usual adenocarcinoma-WHO type. 40 cases were moderately differentiated, 39 cases were high grade tumors and 21 cases were intermediate grade tumors. Serum PSA levels increased with increase in GS. Ki67 labelling index showed a proportionate increase with increase in GS and serum PSA which was statistically significant. Conclusion- Ki67 is a new emerging biomarker which is significantly associated with tumor grade and pretreatment PSA levels and can be used as an additive parameter or a substitution to known prognostic variables to aid in therapeutic interventions.

Abstract B079: Prospective study on the use of Raman molecular imaging to determine postoperative oncological outcomes in patients with prostate cancer: Analysis of a single center

Abstract Background: Prostate cancer (PCa) is the most common cancer in males and the second leading cause of cancer deaths. One of the most confounding problems faced by urologists is predicting the progression of PCa. Current prognostic tools for PCa rely solely on clinical and pathologic variables that cannot always accurately predict the progression of the disease. More accurate diagnostic tools to aid clinicians and patients to decide the course of treatment, even in the early stage of cancer, have long been sought. In a prospective study, we utilized Raman molecular imaging (RMI) to identify patients at risk for biochemical recurrence following a prostatectomy. RMI is a technology that combines the molecular chemical analysis capability of Raman spectroscopy with high-definition digital image visualization, enabling analysis of the molecular environment of prostate tissue by providing highly specific molecular imaging data. Objective: The aim of this study is to evaluate RMI as a methodology for predicting the outcome of PCa patients following radical prostatectomy. Methods: PCa patients who underwent prostatectomy were prospectively enrolled with informed consent. Surgeries were performed by two practiced surgeons in a single clinical center from 2009–2011, and 60 months’ follow-up time was recorded. Pathology data were reviewed by one genitourinary pathologist. Preoperative and postoperative data (preoperation prostate-specific antigen level [PSA], Nadir PSA, Gleason scores, pathologic stage, biochemical recurrence time) were recorded, and biochemical failure was defined as 2 consecutive increases in postoperative PSA (≥0.2 ng/mL). Patient identifiers were removed. Raman molecular images were collected from unstained prostatectomy tissue sections. Raman spectral data were extracted from epithelial and stromal regions, and multivariate statistical methodologies were applied to these spectra. Partial least squares discriminant analysis (PLS-DA) was employed in conjunction with leave-one-patient-out cross-validation to generate models based on the pathology data and RMI. Results: Initial data analysis was performed on a representative population of 38 PCa patients. In this population the mean (median) age at the time of diagnosis was 60 (61) years; the pathologic stage for 57.9% of the patients was T3 and for 42.1% of the patients T2. Nine patients (23.7%) progressed to biochemical failure in 60 months. Analysis of RMI performed on prostatectomy tissues from these patients indicates that the RMI data are distinguishable between those with biochemical failure (progressors) and those with no evidence of disease (NED). A PLS-DA model comprising 9 progressors and 29 NED patients differentiated between the two tissue classes with 89% sensitivity and 90% specificity, and with an area under the ROC curve of 0.87. In this model, classification accuracy was 90% and the p–value &amp;lt; 0.01. Analysis revealed most notable differentiation between progressors and NEDs when evaluating the epithelium and stroma as separate histologic elements. A PLS-DA model based on epithelial cells from 9 progressors and 10 NEDs discriminated between the two populations with 89% sensitivity and 100% specificity, with AUROC of 0.92 and a p-value &amp;lt; 0.01. A similar model differentiated between the stroma of progressors and NEDs with 100% specificity and 100% sensitivity, and a p-value well below 0.01. Conclusion: RMI is a novel technique that shows promise for identifying patients at risk of progression by visualizing molecular information not seen using other current methods. In Gleason 7 disease, RMI indicates distinctive chemical differences in patients who had biochemical failure postoperatively. This preliminary work lays the foundation for the further study of RMI for evaluating prostate tissue and developing an assay that may impact clinicians and patients with PCa. Citation Format: Arash Samiei, Ralph Miller, Jeffrey Cohen, Heather Gomer, Shona Stewart, Patrick Treado. Prospective study on the use of Raman molecular imaging to determine postoperative oncological outcomes in patients with prostate cancer: Analysis of a single center [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B079.

Effect of Eu(III) and Tb(III) chloride on the gelification behavior of poly(sodium acrylate)

Supramolecular gels are an important class of soft materials: they are basically formed by solvent molecules inside in a 3D network structure and can be considered from soft and weak to hard and tough, depending on the respective mechanical properties. The gelation process can be accomplished in different ways using, for example, the interaction between a charged polymer and a metal ion. In this work, the interaction between poly(acrylic acid) sodium salt (PSA) and the trivalent ion (Eu3+ and Tb3+), to form luminescent gels, has been studied. For that, a phase diagram for polymer-ion mixture was constructed showing that for high molar ratios Ln3+/PSA different phase transitions occur. We have focused our work in the region where the formation of weak and strong gels is occurring. The phase transitions have been assessed by rheological and luminescence measurements. From rheological measurements, we have found that the mechanical strength of gels increases by increasing the concentration of PSA, since the elastic module (G´) increases when the concentration of PSA increases. A similar trend is found in yield stress values, from which the gel begins to behave as a liquid. Thus, the higher the concentration of PSA the higher is the yield stress. The frequency sweeps shows that Ln3+/PSA gels and weak gels exhibit a rheological solid-type behavior, with a storage module (G´) predominating over loss modulus (G´´) in the studied frequency. The formation of the gel phase can also be followed by fluorescence spectroscopy. It can be observed that the emission of fluorescence increases by increasing the molar ratio Ln3+/PSA. Such behavior may be explained by the binding of Ln3+ to deprotonated PSA and a decrease in the number of coordinated water molecules. However, the formation of gel phase is reversible and dependent on the Ln3+ concentration. In fact, by increasing the molar ratio values above a certain critical point, disaggregation of the gel structure occurs, mainly due to electrostatic repulsions between ions Ln3+ and Ln3+/PSA aggregates; this is supported by the decrease in the emission of fluorescence of Ln3+ mixed solutions. The effect of Ln3+ in the PSA gel formation mechanism is complemented with the analysis of FTIR, SEM and EDS mapping data.

MP57-04 THE GERMAN RISK-ADAPTED PROSTATE CANCER SCREENING TRIAL (PROBASE) – FIRST RESULTS AFTER RECRUITMENT OF 30.000 MEN

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2018MP57-04 THE GERMAN RISK-ADAPTED PROSTATE CANCER SCREENING TRIAL (PROBASE) – FIRST RESULTS AFTER RECRUITMENT OF 30.000 MEN Christian Arsov, Nikolaus Becker, Kathleen Herkommer, Jürgen Gschwend, Florian Imkamp, Markus Kuczyk, Boris Hadaschik, Markus Hohenfellner, Roswitha Siener, Glen Kristiansen, Lars Schimmöller, Gerald Antoch, and Peter Albers Christian ArsovChristian Arsov More articles by this author , Nikolaus BeckerNikolaus Becker More articles by this author , Kathleen HerkommerKathleen Herkommer More articles by this author , Jürgen GschwendJürgen Gschwend More articles by this author , Florian ImkampFlorian Imkamp More articles by this author , Markus KuczykMarkus Kuczyk More articles by this author , Boris HadaschikBoris Hadaschik More articles by this author , Markus HohenfellnerMarkus Hohenfellner More articles by this author , Roswitha SienerRoswitha Siener More articles by this author , Glen KristiansenGlen Kristiansen More articles by this author , Lars SchimmöllerLars Schimmöller More articles by this author , Gerald AntochGerald Antoch More articles by this author , and Peter AlbersPeter Albers More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1816AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Population-based PSA screening still is controversially discussed. A risk-adapted approach using a baseline PSA value at age 45 may improve the number needed to screen and to treat. The German risk-adapted PCa screening trial PROBASE is currently the largest ongoing screening trial and aims to accrue 50,000 men within 5 yrs in a prospective and randomized fashion. The trial opened in April 2014. METHODS The PROBASE trial is powered for superiority in terms of specificity of risk-adapted PSA screening starting at age 50 (arm B) as compared to 45 yrs (arm A) with non-inferiority in terms of metastasis from PCa. 45 yrs old men are randomly assigned to risk-adapted screening beginning at age 45 or five years later at age 50. Both groups receive risk-adapted PSA screening based on baseline PSA values: < 1.5 ng/ml (low risk) - 5-yearly PSA (expected 90%), 1.5-2.99 ng/ml (intermediate risk) - 2-yearly PSA (expected 7.5%), >=3.0 ng/ml (high risk) MRI and combined systematic and MRI/TRUS fusion-guided biopsy recommended (expected 2.5%). Screening ends at age 60. RESULTS Overall 30,298 men have been enrolled until October 2017 of which 15,152 were randomized into trial arm A. The majority of the PSA values of trial arm A were < 1.5 ng/ml (n=13,506, 89.1%), few in the range of 1.5 to 2.99 ng/ml (n=1,427, 9.4%) and at 3.0 ng/ml or above (n=219, 1.5%). In the latter group, a PSA value >=3.0 ng/ml was confirmed by a second test in 115/219 subjects (52.5%, 0.8% of all trial arm A participants). Median PSA of these participants was 4.1 ng/ml (range 3.0-28.1).Subsequently, 81 subjects out of the 115 PSA-suspicious men underwent MRI (70.4%). PI-RADS v2 scores were as follows: PI-RADS 1 n=2 (2.5%) PI-RADS 2 n=32 (39.6%), PI-RADS 3 n=23 (28.4%), PI-RADS 4 n=16 (19.8%), PI-RADS 5 n=3 (3.7%).Until now, 81.5% (66/81) also underwent combined biopsy with a PCa detection rate of 33.3% (22/66). Thus, the overall PCa incidence in trial arm A at the first screening round is 0.15%. The rate of cancers with a Gleason score of at least 3+4=7 was 68.2% (15/22). So far, 561 participants initially assigned to the intermediate risk group underwent a second screening round two years later. Altogether, 6.6% (37/561) had a confirmed PSA increase >=3.0 ng/ml (median 3.9, range 3.1-15.7). During this workup, 24 out of these 37 participants had an MRI with combined biopsy. PCa detection rate was 37.5% (9/24) with 5 PCa having a Gleason pattern 4. CONCLUSIONS PROBASE started with a rapid recruitment and the expected distribution of risk-groups could be confirmed. The overall PCa incidence in 45 yrs old men is very low (<1%). Increased PSA levels should be confirmed before performing prostate biopsy. However, men with a confirmed baseline PSA >=3.0 ng/ml or those initially assigned to the intermediate risk group and exceeding the biopsy cut off two years later have a high risk of harbouring significant PCa. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e765 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Christian Arsov More articles by this author Nikolaus Becker More articles by this author Kathleen Herkommer More articles by this author Jürgen Gschwend More articles by this author Florian Imkamp More articles by this author Markus Kuczyk More articles by this author Boris Hadaschik More articles by this author Markus Hohenfellner More articles by this author Roswitha Siener More articles by this author Glen Kristiansen More articles by this author Lars Schimmöller More articles by this author Gerald Antoch More articles by this author Peter Albers More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Multicenter prospective study of switching from GnRH agonists to GnRH antagonist for patients with early stage of castration resistant prostate cancer as a second-line hormonal therapy.

183 Background: It was reported that GnRH antagonist could extend progression free survival for prostate cancer patients significantly longer than GnRH agonist in a first line hormonal therapy. However, the usefulness of switching from GnRH agonist to GnRH antagonist as a second hormonal therapy remains obscure. We performed a multicentral prospective study to investigate whether the switching from GnRH agonist to GnRH antagonist (degalerix) for patients with castration resistant prostate cancer (CRPC) as the 2nd line hormonal therapy was effective. Methods: 37 patients who were pathologically diagnosed as prostatic adenocarcinoma and developed CRPC after 1st line hormonal therapy with GnRH agonist plus anti-androgens were enrolled. After confirming anti-androgen withdrawal syndrome, they were treated with switching from GnRH agonists to degalerix. The primary endpoint was PSA response (PSA decline or up to 10% over baseline PSA). Secondary endpoints were the time to 25% PSA increase from the baseline (PSA response time), PSA progression free survival (PPFS), the time to treatment failure, cancer specific survival, radiographic PFS (rPFS), and safety. Results: Mean age was 76 years old, super high risk; 20 cases (54.1%), high risk; 11 cases (29.7%), intermediate risk; 5 cases (13.5%), low risk; one case (2.7%). PSA responder rate was 24.3% (9 cases). In responders, the median PSA response time was 5.75 months, the median PPFS was 1.77 months, and rPFS rate at 3 months was 96%. Regarding safety, only 2 cases (5.4%) showed G3 of AE. The PSA response had no relationship with the change of serum testosterone, LH nor FSH. Conclusions: The effectiveness of switching from GnRH agonist to GnRH antagonist showed to be limited. Although no predictive factor of the switching was recognized, some long-term responders were seen. We expect the possibility of switching to GnRH antagonist for patients in the early stage of CRPC, especially non-metastatic status. Clinical trial information: UNKNOWN.

Pembrolizumab for recurrent or advanced prostate cancer.

250 Background: Two previous Phase II trials studying pembrolizumab (Pembro) in 38 patients suggest it may be efficacious for prostate cancer (PC). Methods: Fifty-four consecutive men with recurrent or advanced prostate cancer were treated with 1 to 9 cycles of Pembro 200 mg every 3 weeks with or without SBRT at a private medical oncology clinic specializing in PC. Charts were retrospectively reviewed for response and toxicity. Definitions: Response (R) = &gt;50% PSA decline; Progressive Disease (PD) = &gt;50 % PSA increase. Stable Disease (SD)= neither response or progression. Results: 43 men completed 3 cycles of Pembro and were evaluable for toxicity. Toxicity was comparable to reports with other cancers besides PC, with 30.2% (13/43) having Grade 2 or higher toxicity. 31 men completed 4 cycles of Pembro and were evaluable for response. For the 31, the median Gleason score was 4+4=8. Treatment prior to Pembro was enzalutamide (26), abiraterone (18), and sipuleucel-t (23) and docetaxel (20). All but 4 men were castrate resistant (CRPC). Ten men got SBRT to a metastasis shortly before or during Pembro. Number of mutations were determined by the Guardant 360 assay. 17/31 (55%) were responders (19%) or had stable disease (35%). Characteristics of the two subgroups, R (6/31) + SD (11/31) versus PD (14/31), are presented in the table. Conclusions: Disease stabilization or response occurred in slightly more than half of the men treated with 4 or more cycles of Pembro. These positive responses were more common in men with lower PSA, fewer bone mets, fewer mutations, less previous chemotherapy, and there was a trend toward greater benefit in castrate sensitive disease and older men. In a separate abstract related to this patient cohort, the predictive ability of inherited mutations disrupting microRNA signaling were assessed for their capacity to predict toxicity (n=40). The table shows medians of the subgroups in the left 5 columns and the total number of patients in the right 3 columns for the 31 patients evaluable for response. [Table: see text]

Prostate adenocarcinoma presenting with supraclavicular node enlargement: report of a case.

This report describes a case of prostate adenocarcinoma presenting with supraclavicular adenopathy and deep venous thrombosis in the ipsilateral arm. Biopsy revealed the enlarged node to be an undifferentiated adenocarcinoma of unknown origin, while CT scan evidenced widespread adenopathies. Because of the increase in serum PSA, the immunohistochemical staining of the biopsy specimen was reviewed and strong positivity for PSA suggested a prostatic origin. We emphasize the importance of PSA immunohistochemistry and serum PSA level monitoring in men presenting with carcinoma of undetermined origin and generalized lymphadenopathies.

Changes observed in prostate biopsy practices in an inner city hospital with a high risk patient population following the 2012 uspstf psa screening recommendations.

ABSTRACTIntroduction:We compared characteristics of patients undergoing prostate biopsy in a high-risk inner city population before and after the 2012 USPSTF recommendation against PSA based prostate cancer screening to determine its effect on prostate biopsy practices.Materials and Methods:This was a retrospective study including patients who received biopsies after an abnormal PSA measurement from October 2008-December 2015. Patients with previously diagnosed prostate cancer were excluded. Chi-square tests of independence, two sample t-tests, Mann-Whitney U tests, and Fisher's exact tests were performed.Results:There were 202 and 208 patients in the pre-USPSTF and post-USPSTF recommendation cohorts, respectively. The post-USPSTF cohort had higher median PSA (7.8 versus 7.1ng/mL, p=0.05), greater proportion of patients who were black (96.6% versus 90.5%, p=0.01), and greater percentage of biopsy cores positive for disease (58% versus 29.5%, p<0.001). Multivariable analysis supported that the increase in PSA was independent of the increase in the proportion of patients who were black. The proportion of patients who were classified as D’Amico intermediate and high-risk disease increased in the post-USPSTF cohort and approached statistical significance (70.1% versus 58.8%, p=0.12).Conclusions:Our study suggests that the USPSTF recommendations may have led to an increase in pre-biopsy PSA as well as greater volume of disease. Also, a greater proportion of patients were being classified with intermediate or high risk disease. While the clinical significance of these findings is unknown, what the data suggests is somewhat troubling. Future research should further examine these changes in a larger cohort as well as resultant long-term outcomes.

Changes in Clinical Characteristics of Patients with an Initial Diagnosis of Prostate Cancer in Korea: 10-Year Trends Reported by a Tertiary Center.

BackgroundThe Korea Central Cancer Registry reported that incidence rates of prostate cancer have not increased continuously. We used recent trends in the incidence of prostate cancer to generate a preliminary report of the Korean population with prostate cancer.MethodsPatients initially diagnosed with prostate cancer by prostate biopsy from 2006 to 2015 at our tertiary center were selected. All patients were categorized according to age (< 65, 65–75, > 75 years), time period (2006–2010 vs. 2011–2015), and risk classification. Patients with insufficient data were excluded from the analysis.ResultsOf 675 patients (median prostate-specific antigen [PSA], 9.09 ng/mL), those with a Gleason score (GS) of 6 (32.3%) comprised the largest proportion in our cohort. The proportion with a GS of 8 increased for those aged 65–75 years, despite the lack of increase in PSA. Treatment patterns changed for those with very low to low risk cancer. The overall survival (OS) rate and the cancer-specific survival (CSS) rate for all patients at 5 years were 87% and 90%, respectively. Patients with a low body mass index (BMI; ≤ 23 kg/m2) had worse median OS and CSS rates.ConclusionSignificant differences in risk classifications and initial treatments were found between 2006–2010 and 2011–2015. Although PSA did not change, the GS did change. Lower BMI (≤ 23 kg/m2) had worse effects on OS and CSS rates for Korean prostate cancer patients.

PSA kinetics before 40 years of age.

ABSTRACTPurpose:The baseline PSA has been proposed as a possible marker for prostate cancer. The PSA determination before 40 years seems interesting because it not suffers yet the drawbacks related to more advanced ages. Considering the scarcity of data on this topic, an analysis of PSA kinetics in this period seems interesting.Materials and Methods:A retrospective assay in a database of a private diagnostic center was performed from 2003 to 2016. All subjects with a PSA before 40 years were included.Results:92995 patients performed PSA between the ages of 21 – 39. The mean value ranged from 0.66 ng / mL (at age 22) to 0.76 ng / mL (at age 39) and the overall mean was 0.73 ng / mL. As for outliers, 3783 individuals presented a baseline PSA > 1.6 ng / mL (p95). A linear regression model showed that each year there is a PSA increase of 0.0055 ng / mL (β = 0.0055; r2 = 0.0020; p < 0.001). A plateau in PSA between 23 and 32 years was found and there were only minimal variations among the ages regardless of the evaluated percentile.Conclusion:It was demonstrated that PSA kinetics before 40 years is a very slow and progressive phenomenon regardless of the assessed percentile. Considering our results, it could be suggested that any PSA performed in this period could represent the baseline value without significant distortions.

Multi-parametric magnetic resonance imaging monitoring patients in active surveillance for prostate cancer: a prospective cohort study

Objectives: To evaluate the use of multi-parametric magnetic resonance imaging (mpMRI) and mpMRI guided biopsies (MRGB) for monitoring an active surveillance (AS) prostate cancer cohort.Materials and methods: One year after initial diagnostic TRUS guided biopsy (TRUS-bx), baseline mpMRI, and enrolment in an AS program patients underwent a one year follow-up comprising the usual TRUS-bx and an mpMRI. Prostate MRI lesions were scored on the five-point PIRADS scale version 2. In cases without TRUS-bx progression, patients with PIRADS 4 or 5 lesions were scheduled for MRGB. Progression in TRUS-bx was defined as Gleason score (Gs) up-grades, >3 tumor positive cores or a maximal cancer core length (MCCL) > 50%. In MRGB, Gs upgrade or a MCCL ≥6 mm Gs 3 + 3 lesions were considered to reflect progression. PSA increase or progression in clinical T-classification alone was not considered clinical progression.Results: 50 patients were included in the study. In total 10 (20%) patients had per definition progression at one year follow-up. Seven patients (7/50 = 14%) had clinical progression based on TRUS-bx. mpMRI identified seven newly emerged PIRADS 4 lesions. Three patients with PIRADS 4 lesions had no sign of TRUS-bx progression, while MRGB revealed significant cancer (Gs 7 (3 + 4) and Gs 8 (3 + 5)). Consequently, seven patients underwent definitive treatment. Of these, six and four had a progression on MRI and TRUS-bx, respectively.Conclusions: Our study suggests that mpMRI is at least equal to TRUS-bx in detecting progression at one year follow-up in prostate cancer patients undergoing active surveillance.

Oncological follow-up after radical prostatectomy

Radical prostatectomy is the gold standard treatment for patients with localized prostatic cancer, but often the pathological diagnosis reveals a locally advanced stage. The aim of this paper is to present the oncological follow-up after radical prostatectomy on a group of 42 patients, patients which have been diagnosed after surgery with a more aggressive stage, locally advanced PCa. Over a period of four years 136 patients have undergone radical prostatectomy. The pathological examination has established that 42 patients presented extracapsular invasion and/or lymph node invasion. 18 patients (pT3-4N0M0) have undergone radiotherapy alone and 24 patients (8 pN1 and 16 pT3-4N1M0) have received androgen deprivation therapy in association with radiotherapy. Over the next two years 15 patients presented biochemical recurrence. For these patients chemotherapy was initiated, but in two cases PSA increase has been observed during periodic evaluation. Although it is not uncommon that postoperatively the histopathological examination establishes a more aggressive disease stage than that established before surgery, radical prostatectomy remains the solution for the localized prostate cancer, solution that can be boosted by radiotherapy and/or androgen deprivation therapy.

EXPRESSION OF CANCER-ASSOCIATED GENES IN PROSTATE TUMORS

Prostate cancer is one of the most common male cancers in Western countries and takes the third place in morbidity in Ukraine. It is a highly heterogeneous disease. To analyze relative expression levels of the TGFB1, IL1B, FOS, EFNA5, TAGLN, PLAU, and EPDR1 genes in malignant and non-malignant prostate tissues. Total RNA was isolated from 16 prostate adenomas, 37 prostate adenocarcinomas, and 29 conventionally normal prostate tissues. To analyze relative gene expression levels the quantitative real-time polymerase chain reaction was performed. The significant alterations in the relative expression levels were found in all analyzed sample groups for 4 genes: FOS, EFNA5, IL1B, and TGFB1. We have found that FOS and EFNA5 were more frequently overexpressed in carcinomas with Gleason score ≤ 7, compared with adenomas. On contrary, PLAU expression levels were decreased more frequently in prostate cancers, compared with conventionally normal tissues. Noteworthy, we found positive correlation between IL1B expression level and PSA (for patients with slight PSA increase, no more than 20.0 ng/ml). The EFNA5, FOS, IL1B, PLAU, and TGFB1 genes that showed significant expression alterations in prostate tumors, compared with conventionally normal prostate tissue, may play role in prostate cancer development and should be further investigated.

Prostatectomie totale de rattrapage après échec de traitement local pour cancer de prostate : morbidité, résultats oncologiques et fonctionnels

Salvage radical prostatectomy (sRP) for radiorecurrent prostate cancer (PCa) is a challenging procedure. To report our experience with sRP for selected patients with local recurrence after primary treatment for localised PCa. From 2005to 2015, 24patients underwent sRP for recurrent PCa in our center and were included in this retrospective study. Local recurrence was suspected by PSA increase>nadir+2ng/mL and was confirmed by biopsy. Perioperative complications according to Clavien-Dindo classification, oncological and functional results were analysed. Overall, 24patients with a median age of 59years (IQR: 55-60) were included. Median follow-up was 25months (IQR: 9-26). Procedures were performed with open-retropubic approach in 50% and robot-assisted laparoscopic approach in 50%. Overall, 5 (21%) and 2 (8%) patients experienced grade≤IIIa and grade≥IIIb postoperative complication, respectively. Surgical margins were positive in 46% of cases. Three out of 4patients with postoperatively detectable PSA (>0.2ng/mL) had positive surgical margins. Seven patients experienced biochemical recurrence in a median delay of 19months (9-62). Seventy-one percent (5) of these patients experienced clinical recurrence in a median delay of 24months (10-113). Severe urinary incontinence (≥3pads/day) and erectile dysfunction were reported in 25% and 63%, respectively. sRP for patients is a feasible procedure with encouraging local control rate and acceptable morbidity. This technique should be discussed as a treatment option for locally recurrent PCa in well-selected patients. 4.

A randomized phase II cross-over study of abiraterone + prednisone (ABI) vs enzalutamide (ENZ) for patients (pts) with metastatic, castration-resistant prostate cancer (mCRPC).

5002 Background: ABI and ENZ are indicated as 1st line therapy for mCRPC but have not been directly compared. Optimal sequencing of these agents has not been prospectively evaluated and predictive biomarkers are lacking. Methods: Multicenter, phase 2 study randomizing treatment-naïve mCRPC pts to ABI vs ENZ, with cross over at PSA progression. Primary endpoints: response and time to PSA progression (TTPP, PCWG3 criteria) after 2nd line therapy. Reported here are secondary endpoints: PSA ≥50% decline (PSA50) from baseline, TTPP with 1stline therapy, and correlation with deep targeted sequencing of 73 mCRPC genes in circulating tumor DNA (ctDNA). Results: Accrual completed October 2016 with 202 pts randomized (ABI:ENZ = 101:101). Median follow-up 12.8 months. Baseline characteristics were similar between arms: median for age was 75 years (range 49-94), PSA 36.1 (1.7-2817), HGB 130 (89-165), ALK PHOS 105 (31-6600), LDH 207 (77-3098). ECOG PS was 0-1 in 83%, presence of metastases in bone/liver/lung in 83%/6%/10%. With 1stline therapy for ABI vs ENZ, PSA50 at 12 weeks was 53% vs 73% (P = 0.004), no PSA decline occurred in 21% vs 15% (P = 0.243), and median TTPP was 7.4 vs 8.0 months (HR = 0.88, 95% CI 0.61, 1.27). Baseline ctDNA fraction was &gt;2% in 60% of patients, and associated with worse TTPP (HR 1.80, P=0.005). Baseline pathogenic ctDNA alterations in AR, TP53, RB1, and DNA repair (BRCA2, ATM) genes were associated with a shorter TTPP (univariate analysis: TABLE). On multivariate analysis including clinical factors, TP53 and BRCA2/ATM alterations remained significant (HR = 2.54 (95%CI 1.55-4.19) and HR = 2.68 (1.58-4.54)). Pts with a PSA increase as best response were enriched for alterations in DNA repair (P &lt;0.001), TP53 (P = 0.005), RB1 (P = 0.04), and (in 1 pt) a genomically truncated AR. Conclusions: There was a difference in PSA response for 1stline ABI vs ENZ, but no difference for TTPP. Baseline pathogenic ctDNA alterations, particularly in TP53 and BRCA2, identify pts with poor outcomes. Clinical trial information: NCT02125357. [Table: see text]

A phase II randomized trial of observation versus stereotactic ablative radiation for oligometastatic prostate cancer (ORIOLE).

TPS5094 Background: ORIOLE is a randomized, non-blinded Phase II interventional study evaluating the safety and efficacy of SBRT in biochemically recurrent, oligometastatic, hormone-sensitive prostate cancer at 3 centers in the US. Patients will be stratified by clinical characteristics and randomized 2:1 to SBRT or observation. The primary clinical endpoint is progression at 6 months defined by PSA increase, radiologic or clinical evidence, ADT initiation, or death from any cause. Secondary endpoints include local control at 6 months, SBRT-associated toxicity and quality of life, and ADT-free survival. Imaging and laboratory correlates will characterize, in isolation, the effects of SBRT on oligometastatic disease. Methods: Eligible patients are hormone-sensitive, have undergone prior definitive treatment and recurred with 1-3 asymptomatic bone or soft tissue metastases diagnosed within 6 months, PSA doubling time (PSADT) &lt; 15 months, ECOG performance status ≤ 2, and normal organ and marrow function. Minimization will be used to balance assignment by primary intervention, prior ADT, and PSADT. Accrual of 54 patients provides 85% power to detect a decrease in progression rate from 80% to 40% with type I error = 0.05 using one-sided Fisher’s exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival, ADT free survival, and time to locoregional and distant progression will be calculated based on intention-to-treat. Local control will be assessed using RECIST 1.1 criteria. Withdrawal prior to 6 months will be counted as progression. Adverse events will be summarized and quality of life pre- and post-SBRT will be measured by Brief Pain Inventory. The investigational targeted imaging agent 18F-DCFPyL will be compared to bone scan and CT for identifying oligometastases before SBRT and monitoring disease response following SBRT. Biological alterations induced by SBRT will be investigated using circulating tumor cell analysis, deep sequencing of circulating tumor DNA, and T-cell repertoire profiling. A hereditary cancer assay will inform efforts to advance personalized screening and therapy. Clinical trial information: NCT02680587.