Gleason Sum Research Articles

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol

Features of the physiological distribution of <sup>68</sup>Ga-PSMA and its importance in the differential diagnosis of metastatic lesions of lymph nodes in patients with prostate cancer

Introduction. The appearance of new radiopharmaceuticals based on prostate-specific membrane antigen has significantly increased the accuracy of prostate cancer diagnosis. The physiological accumulation of 68Ga-PSMA in the sympathetic ganglia is important in the diagnosis of metastatic lesions of the lymph nodes. Erroneous interpretation of images can lead to an incorrect choice of tactics for the treatment of prostate cancer.Purpose: improving the diagnosis of prostate cancer with the help of updated data on the physiological accumulation of 68GaPSMA. Identify the sources of potential errors in the interpretation of PET/CT with 68Ga-PSMA.Materials and methods. In order to stage the verified prostate cancer, PET was performed in our center/CT with 68Ga-PSMA in 109 men. All patients were divided into groups by the level of prostate-specific antigen, Gleason sum, and d’Amico.Results. In all patients, we observed the accumulation of RFP in the cervical, abdominal and presacral ganglia. The capture level of the radiotracer was in the range of SUV=1,6–2,3 (median SUV=1,9). In the control PET/CT study after treatment, the accumulation of RFP in the cervical, abdominal and presacral ganglia remained at the same values, which made it possible to identify the detected changes as a variant of the physiological norm.Conclusions. It is necessary to take into account the peculiarities of the physiological distribution and accumulation of radiotracer in organs and tissues, in particular, the capture of 68Ga-PSMA by sympathetic ganglia. This will avoid false-positive cases when describing PET-CT images and will make it possible to increase the informative value of the method.

Impact of 18F-fluciclovine PET/CT on salvage radiotherapy plans for men with recurrence of prostate cancer postradical prostatectomy.

ObjectivesImaging options to localize biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) are limited, especially at low prostate-specific antigen (PSA) levels. The FALCON study evaluated the impact of 18F-fluciclovine PET/CT on management plans for patients with BCR. Here, we evaluate salvage radiotherapy decisions in patients post-RP.MethodsWe conducted a subgroup analysis of post-RP patients enrolled in FALCON who had a prescan plan for salvage radiotherapy (± androgen-deprivation therapy). Patients’ treatment plans post-18F-fluciclovine PET/CT were compared with their prescan plans. Fisher exact test was used to determine the impact of PSA and Gleason sum on positivity and anatomical patterns of uptake.ResultsSixty-five (63%) FALCON patients had undergone RP. Of these, 62 (median PSA, 0.32 ng/mL) had a prescan plan for salvage radiotherapy. Twenty-one (34%) had 18F-fluciclovine-avid lesions. Disease was confined to the prostate bed in 11 patients (52%) and to the pelvis in a further 5 (24%), while 5 (24%) had extrapelvic findings. Trends towards more disseminated disease with increasing PSA or Gleason sum were observed but did not reach statistical significance. Postscan, 25 (40%) patients had a management change; 17 (68%) were changed to the treatment modality (8 to systemic therapy, 8 to active surveillance, 1 other) and 8 (32%) were radiotherapy field modifications.ConclusionsIncorporating 18F-fluciclovine PET/CT into treatment planning may help identify patients suitable for salvage radiotherapy, help augment planned radiotherapy to better target lesions and support the clinician to optimise patient management.

MP27-02 DOES THE RISK OF OBSTRUCTIVE SLEEP APNEA (OSA) AFFECT ERECTILE FUNCTION RECOVERY (EFR) AFTER RADICAL PROSTATECTOMY (RP)?

You have accessJournal of UrologySexual Function/Dysfunction: Evaluation I (MP27)1 Sep 2021MP27-02 DOES THE RISK OF OBSTRUCTIVE SLEEP APNEA (OSA) AFFECT ERECTILE FUNCTION RECOVERY (EFR) AFTER RADICAL PROSTATECTOMY (RP)? Jose M. Flores, Carolyn A. Salter, Karin Ruiz, Nicole Benfante, Elizabeth Schofield, Miranda Tan, Vincent Laudone, and John P. Mulhall Jose M. FloresJose M. Flores More articles by this author , Carolyn A. SalterCarolyn A. Salter More articles by this author , Karin RuizKarin Ruiz More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Elizabeth SchofieldElizabeth Schofield More articles by this author , Miranda TanMiranda Tan More articles by this author , Vincent LaudoneVincent Laudone More articles by this author , and John P. MulhallJohn P. Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002024.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Obstructive sleep apnea (OSA) affects as many as 7% of adult men in the general population, higher in men with obesity and large neck sizes. OSA is associated with ED. No data to date has assessed EFR after RP in men with OSA. The objective of this study was to define EFR rates 2 years post-RP. METHODS: Records of men who underwent RP with 24-month post-RP follow-up were reviewed. ADT and radiation therapy were exclusions. Men completed the OSA screening questionnaire, STOP-BANG (SB) pre-RP. Men were divided into OSA risk groups: high, intermediate, and low. EFR was recorded using IIEF-EFD score, with a score of at least 24 indicating recovery. Univariable and multivariable logistic regression analyses assessed predictors of EFR. RESULTS: 454 men were analyzed. Mean age 62±7 years. Of the studied population, 12% had a history of OSA, 10% had diabetes, 12% were current smokers, and 37% were former smokers. The median STOP-BANG (SB) score was 2. High, intermediate, and low risk of OSA scores were 8%, 41% and 51% respectively. Mean baseline testosterone (T) was 495 ng/dL, PSA 7.4 ng/mL, and EFD score 22. Most men had a Gleason sum of 7 (87%). 73% of patients had bilateral or unilateral neurovascular bundle preservation. At the 2-year follow up, median EFD score in high, intermediate and low OSA risk groups: were 9, 16, and 18 respectively. The low OSA risk group was significantly more likely to recover (OR = 1.6, 1.1–2.4) than the moderate/high group. Younger age (OR = 0.92, 0.89–0.95), absence of diabetes (OR = 0.31, 0.14–0.72), higher baseline T (OR per 100 units = 1.40, 1.04–1.89), higher baseline EFD score (OR = 1.16, 1.11–1.22), and lower Gleason score (OR = 0.53, 0.34–0.82) were also associated with recovery at 2 years. CONCLUSIONS: In our cohort, at 2 years post-RP, increasing OSA risk is associated with poorer EFR in men post-RP. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e472-e472 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jose M. Flores More articles by this author Carolyn A. Salter More articles by this author Karin Ruiz More articles by this author Nicole Benfante More articles by this author Elizabeth Schofield More articles by this author Miranda Tan More articles by this author Vincent Laudone More articles by this author John P. Mulhall More articles by this author Expand All Advertisement Loading ...

MP36-01 TESTOSTERONE (T) CHALLENGE IN MEN POST-RADICAL PROSTATECTOMY (RP) WITH PROFOUNDLY LOW TESTOSTERONE

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-01 TESTOSTERONE (T) CHALLENGE IN MEN POST-RADICAL PROSTATECTOMY (RP) WITH PROFOUNDLY LOW TESTOSTERONE John P. Mulhall, Serkan Deveci, Jose Flores, Kazuhito Matsushita, Jose Torremade, and Carolyn A. Salter John P. MulhallJohn P. Mulhall More articles by this author , Serkan DeveciSerkan Deveci More articles by this author , Jose FloresJose Flores More articles by this author , Kazuhito MatsushitaKazuhito Matsushita More articles by this author , Jose TorremadeJose Torremade More articles by this author , and Carolyn A. SalterCarolyn A. Salter More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate specific antigen is the primary marker of prostate cancer recurrence. PSA secretion is T dependent with T levels below saturation point associated with sub-optimal PSA production. Men with an undetectable PSA level after RP with very low T levels might have an artificially low PSA level. We aimed to evaluate the effects of raising T level in such men. METHODS: Study population consisted of (i) men post-RP (ii) with undetectable PSA level (iii) total T levels <200 ng/dl (two levels, LCMS) who (iv) underwent in-office intramuscular injection of 100mg of T cypionate (v) had a PSA level checked 5 days later, and if undetectable every month after that, 3 months later then every 6 months and (vi) follow-up of at least 24 months on T therapy. RESULTS: 22 men have been challenged thus far. Mean age 62±18 years. Mean preoperative PSA 6.2. Mean post-RP TT value 140±35 ng/dL 2.2. Median Gleason sum 7. 23% had GS ≥8. Mean post-RP, pre-challenge T value 140± 35 ng/dL. Mean time post-RP to challenge was 7±9 months. Mean TT value 5 days after IMT challenge 640±220 ng/dL, all with TT levels above 400. 5/22 has a PSA elevation, 2 immediately after IMT challenge (PSA values 0.07, 0.08). All other men started T therapy immediately and had PSA elevation at 9, 14 and 22 months after commencing T therapy (PSA values 0.08, 0.12, 0.11). All patients with PSA elevation had continued rise in PSA and had detectable disease on imaging. All men with PSA recurrence had either GS 7 with unfavorable pathology (2) or GS ≥8 (3). CONCLUSIONS: This T challenge approach permits the early detection of prostate cancer recurrence permitting early intervention. About 10% of such men had a PSA rise immediately after T challenge. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e636-e636 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information John P. Mulhall More articles by this author Serkan Deveci More articles by this author Jose Flores More articles by this author Kazuhito Matsushita More articles by this author Jose Torremade More articles by this author Carolyn A. Salter More articles by this author Expand All Advertisement Loading ...

Current Opinion Regarding Multidisciplinary Cancer Clinic Utilization for the Management of Prostate Cancer.

Objectives:Multidisciplinary cancer clinic (MDC) is an evaluation option for the management of prostate cancer (PCa). The purpose of MDC is to provide the patient with a comprehensive assessment and risk/benefit discussion of all pertinent treatment options. Our objective was to obtain a contemporary measure and analysis of urologists’ opinion regarding PCa MDC.Material and Methods:We created a 14-item questionnaire for respondent baseline characteristics, subjective and objective inquiries regarding MDC for PCa management. The survey was distributed through email to members of the Society of Urologic Oncology and the Endourological Society. Data were analyzed using R (R Core team, 2017).Results:One hundred and seven (51%) respondents reported participation in MDC; the majority of which were male (97.6%), academic (61.4%) urologists with urologic oncology fellowship training (50%), and >20 years in practice (40.3%). MDC patients were most commonly referrals (78.5%) and with high-risk disease (Gleason sum 8–10) (83.2%). A majority of the respondents felt that MDC was very or extremely beneficial for PCa research (45% and 19%, respectively) and treatment (35% and 20%, respectively). Responses dissuading the use of MDC included lack of infrastructure (41%) and time commitment (21%). On multivariate analysis, urologists with >10 years in practice were less likely to find MDC beneficial in the management of PCa (11–20 years, P = 0.028 and >20 years P = 0.009).Conclusion:A contemporary sampling of urologists’ opinion and practice patterns alludes to the benefits that advocate for and the resource demand that hinders routine use of MDC for PCa evaluation. Urologist training and practice environment can affect participation in PCa MDC.

Association of increased intensity of prostate-specific antigen screening in younger African American men with improved prostate cancer outcomes.

5004 Background: African-American (AA) men are substantially more likely to present with lethal prostate cancer (PCa) at younger ages than non-Hispanic White men. Despite this disparity, AA men are poorly represented in the prostate-specific antigen (PSA) screening studies on which evidence-based PCa screening guidelines are based. This limits proper PSA screening guidance for AA men, especially for those younger than 55. We examined associations of PSA screening intensity with disease severity at diagnosis and prostate cancer-specific mortality (PCSM) in AA men &lt; 55 years of age. Methods: The earliest recommended age to begin discussion of PSA screening is 40 years. We identified AA men aged 40-55 years, diagnosed with PCa from 2004 to 2017 within the Veterans Health Administration. PSA screening was identified using procedural codes. Screening intensity was defined as percentage of years screened within the pre-diagnostic observation period. This included up to 5 years prior to diagnosis. Multivariable logistic regression assessed the influence of PSA screening intensity on metastatic disease at diagnosis. Lead-time correction using published screening-dependent lead times was performed. PCSM was evaluated using Fine-Gray regression and non-cancer death as a competing event. Additional analysis was performed stratifying PSA screening into ‘High’ and ‘Low’ groups centered on the mean. Results: The cohort included 4,654 AA men at a mean age of 51.8 years with mean PSA screening rate of 53.2%. The pre-diagnostic observation period ranged from 1 to 5 years (median = 5 years). Median follow-up was 7 years. At diagnosis, there was a higher prevalence of Gleason sum ≥ 8 (Grade Group ≥ 4) and metastatic disease in the ‘Low’ group compared with the ‘High’ group ([Gleason sum ≥ 8 (Grade Group ≥ 4)]: 18.6% vs. 14.4%, p &lt; 0.01; Metastatic disease at diagnosis: 3.7% vs. 1.4%, p &lt; 0.01). Increased PSA screening intensity was associated with significantly reduced odds of metastatic disease at diagnosis (odds ratio: 0.61, 95% confidence interval (CI) = [0.47-0.81], p &lt; 0.01) and decreased risk of PCSM (sub-distribution hazard ratio: 0.75, 95% CI = [0.59-0.95], p = 0.02). Conclusions: In this large national cohort of AA men aged 40 to 55 years, PSA screening increased intensity was associated with decreased risk of lethal disease and metastases at time of diagnosis and decreased PCSM. These data support the hypothesis that PSA screening and early prostate cancer detection may improve outcomes in younger AA men.

Clonal hematopoiesis in prostate cancer inferred from somatic tumor profiling.

e17001 Background: Clonal hematopoiesis (CH) is a process associated with normal aging and may complicate the interpretation of liquid-biopsy genomic testing in oncology. Little is known about the prevalence of CH in prostate cancer as detected on somatic tumor profiling, or its association with clinical parameters and outcomes in prostate cancer. We sought to estimate the prevalence and clinical characteristics of patients with CH identified from tissue-based prostate cancer specimens. Methods: This was a retrospective study of men with prostate adenocarcinoma who underwent clinical somatic tissue-based next-generation sequencing using commercial platforms (n = 364). Patients with known hematologic malignancies (n = 7), and those with only liquid biopsies were excluded (n = 34), leaving 323 cases. Classical CH mutations were defined as those in DNMT3A, TET2 or ASXL1. Additional CH mutations included were defined as those in BCORL1, GNAS, SF3B1, JAK2 or PPM1D. Chi-squared tests were used to compare prevalence by categorical variables, Kruskal-Wallis tests to compare means across groups, and Cox proportional hazards were used for time-to-event analyses. Results: The prevalence of CH mutations in prostate cancer was 9% (30/323), and the prevalence of classical CH mutations was 7% (22/323)(Table). The most common mutations were in DNMT3A (n = 9), TET2 (n = 8) and ASXL1 (n = 5); other less common CH alterations were in GNAS and SF3B1 (n = 3 each), followed by CBL and JAK2 (n = 1 each). The most common site of tumor biopsy was the prostate (N = 266) followed by visceral (n = 19) and lymph node (N = 19) metastases. Men with any CH mutation were not significantly older at age of prostate cancer diagnosis (64 vs 62 years; p = 0.19) than those without; however, men with classical CH mutations were statistically older at diagnosis than those without (66 vs 62 years; p = 0.04). There was no difference in prevalence of CH mutations by Gleason sum (P = 0.67). Among men with localized disease at diagnosis, the median metastasis-free survival was 3.9 years in those with overall CH mutations and 6.6 years in those without CH mutations (HR [adjusted for age and Gleason] 1.3; 95% CI 0.7-2.3; p = 0.4). OS from the time of diagnosis to death was also numerically shorter in those with any CH mutation (median 9.7 years in those with and 14.2 years in those without CH mutations; HR 1.2, 95% CI 0.6-2.5; p = 0.6). Conclusions: CH can be detected in about 7-9% of prostate cancer patients from tissue-based tumor samples, is associated with older age, and may be linked to adverse oncological outcomes. The prognostic impact of CH in the context of specific systemic therapies (hormonal, chemotherapeutic) remains to be elucidated.[Table: see text]

Differential responses to taxanes and PARP inhibitors (PARPi) in ATM- versus BRCA2-mutated metastatic castrate-resistant prostate cancer (mCRPC) patients (pts).

5040 Background: PARPi have shown promise in mCRPC pts with mutations in DNA repair, but ATM- and BRCA2-altered pts may respond differently to PARPi. We hypothesized that differences may also exist for taxane therapy, aiding in treatment sequencing decisions. Methods: mCRPC pts (N = 137) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were identified from 8 US academic centers. Demographic, treatment, and survival data were collected. Kaplan-Meier analyses were performed for time-to-treatment-discontinuation (TTD), as well as overall survival (OS), from time of first taxane or PARPi therapy. Cox hazard ratio (HR) regression analyses were performed, adjusting for Gleason sum (≤7 vs. 8-10). For OS, receipt of subsequent therapies following first taxane or PARPi was also included as a covariate. Results: 50 ATM- and 87 BRCA2-mutated pts were identified. 40/50 (80%) of ATM-mutated pts received taxane only or taxane prior to PARPi, while 10/50 (20%) received PARPi only or PARPi prior to taxane. ATM-mutated pts showed a trend towards longer TTD when taxane was given first vs PARPi given first (P = 0.08, adjusted HR for taxane treatment 0.50 [95% CI: 0.24–1.08]). Considering all pts who received taxane first, ATM-mutated pts had longer TTD than BRCA2-mutated pts who received taxane first ( P= 0.04, adjusted HR for ATM 0.61 [CI: 0.37–0.99]). Among ATM-mutated pts, OS was longer in those receiving taxane first ( P= 0.06, adjusted HR for taxane treatment 0.33 [CI: 0.10–1.05]). Among BRCA2-mutated pts, 43/87 (49%) received taxane first and 44/87 (51%) received PARPi first. BRCA2-mutated pts had longer TTD when PARPi was given first vs taxane given first ( P&lt; 0.0001, adjusted HR for PARPi treatment 0.32 [CI: 0.19–0.56]). Considering all pts who received PARPi first, BRCA2-mutated pts also had longer TTD than ATM-mutated pts who received PARPi first ( P= 0.0031, adjusted HR for BRCA2 0.29 [CI: 0.12–0.66]). There was no significant OS difference in BRCA2-mutated pts regarding which treatment was given first ( P= 0.63, adjusted HR for PARPi treatment 1.18 [CI: 0.59–2.35]). Conclusions: Our data in ATM- and BRCA2-mutated mCRPC pts suggests a trend towards improved clinical outcomes when taxanes are used prior to PARPi in ATM-mutated pts, while the reverse sequence appears to be better for BRCA2-mutated pts.[Table: see text]

Positive association between preoperative lymphocyte-to-monocyte ratio and risk of the status of positive surgical margins by prostate cancer: results in 497 consecutive patients treated only by radical prostatectomy.

BackgroundPositive surgical margins (PSM) is one of the most important factors affecting the prognosis of prostate cancer (PCa) patients after radical prostatectomy (RP). Although some studies have found the preoperative systematic inflammation-based scores the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) can predict the incidence and prognosis of PCa, few studies have explored the predictive value of preoperative systematic inflammation-based scores on the PSMs for PCa patients after RP.MethodsFrom June 2014 to September 2020 a total of 497 patients underwent RP at our institution. Blood samples from all patients were collected within one week before surgery. Preoperative clinical characteristics including age, body mass index (BMI), prostate-specific antigen (PSA), and biopsy Gleason sum (BGS) were assessed. Postoperatively pathological specimens were assessed for pathological Gleason sum (PGS), pathological stage, and margin status.ResultsIn the multivariable analysis including preoperative variables, PSA and LMR were the independent predictive factors for PSM (OR: 2.817; 95% CI, 1.836–4.320, P<0.001; OR: 1.124; 95% CI, 1.018–1.240, P=0.021. Considering pre-, intra-, and postoperative variables, BGS, perineural invasion, seminal vesicle invasion (SVI), pathologic Gleason sum (PGS) combined, were associated with increased risk of PSM in the univariable analysis (P<0.001 for all variables). However, in the multivariable analysis, perineural invasion (OR: 2.672; 95% CI, 1.649–4.330; P<0.001), PGS (OR: 2.52; 95% CI, 1.556–4.082; P<0.001) were independent predictive factors for the incidence of PSM. Finally, LMR was shown to be an independent predictive factor (OR: 0.881; 95% CI, 0.779–0.996; P=0.043) for apical PSMs, with increasing LMR predicting the lower incidence of apex location. And we also found that LMR was an independent factor that predicts multifocal positive margins (OR: 1.179; 95% CI, 1.023–1.358; P=0.023).ConclusionsPreoperative LMR could be used as an independent predictor to predict the incidence of PSMs after RP. And Considering pre-, intra-, and postoperative variables, we also found that preoperative LMR could predict the occurrence of apical and multifocal PSMs.

EMPIRE-1: Randomized Trial Comparing Conventional- vs Conventional Plus Fluciclovine (18F) PET/CT Imaging-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer

Background: Molecular imaging is increasingly used to guide prostate cancer decisions and treatment planning. The specific aim was to evaluate the role of fluciclovine (18F) PET/CT [PET] in improving cancer control over conventional imaging for post-prostatectomy radiotherapy. Methods: Patients with prostate cancer with detectable PSA post-prostatectomy and negative conventional imaging were randomized to radiotherapy directed by conventional imaging (Arm 1) vs conventional imaging+PET (Arm 2). The treatment setting was an academic medical center with community affiliates. In Arm 2, radiotherapy decisions were rigidly determined by PET, which was also used for target delineation. Using a standard post-radiotherapy failure definition, failure rates at 3 years (primary study endpoint) were compared. Univariate and multivariable analyses were performed for demographic, disease, and treatment factors. Secondary endpoints included provider-reported gastrointestinal and genitourinary toxicities. Findings: From September 18, 2012 to March 4, 2019, 165 patients were randomized. PET findings resulted in a 35·4% rate of decision changes, including 4 patients having radiotherapy aborted. Median follow-up was 3·52 years. Three-year failure-free survival rate for Arm 1 vs Arm 2 was 63·0 vs 75·5% (difference,12·5; 95% CI:4·3-20·8; p=0·0028) and at 4-years was 51·2 vs 75·5% (difference,24·3; 95% CI:15·6-33·0; p<0·0001). On univariate analysis, Arm achieved a statistical trend(p=0·0540); Gleason sum, extracapsular extension, seminal vesicle invasion, pelvic field, and PSA reached significance. On multivariable analysis, Arm (HR=2·04[95%CI: 1·06-3·93], p=0·0327), extracapsular extension, pelvic field, and PSA reached significance. Toxicity was similar in both Arms. Interpretation: Inclusion of fluciclovine (18F) PET into post-prostatectomy radiotherapy decisions and planning resulted in a significant improvement in failure rate. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. Trial Registration: Enrollment was done under ClinicalTrials.gov registration (NCT 01666808) which is closed to new participants. Funding: NIH R01 CA169188 [major source]; Blue Earth Diagnostics, Ltd. [cassette arrangement with Emory]. Declaration of Interests: ABJ reports personal fees from Blue Earth Diagnostics, Ltd. in the role of advisory board service outside the submitted work. ES - none. SG - none. RH - none. BH - none. PJR - none. JWS - none. PRP - none. KMX - none. MG discloses he is entitled to a royalty derived from sale of products related to the research described in this manuscript. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. For human research studies the consent forms it is stated that he is entitled to a share of sales royalty received by the University from Nihon under that agreement. The terms of this arrangement have been reviewed and approved by the University in accordance with its conflict of interest policies. VAM - none. SSJ - none. OK - none. BCC - none. MAB - none. OAA - none. AAA - none. VRD - none. DMS participates through the Emory Office of Sponsored Projects in sponsored grants including those funded or partially funded by Blue Earth Diagnostics, Ltd; Nihon MediPhysics Co, Ltd.; Telix Pharmaceuticals (US) Inc.; Advanced Accelerator Applications; FUJIFILM Pharmaceuticals U.S.A., Inc; Amgen Inc. Also reports consultant fees outside the submitted work from: Syncona; AIM Specialty Health; Global Medical Solutions Taiwan; Progenics Pharmaceuticals, Inc. Ethics Approval Statement: Signed informed consent was obtained from every trial participant. The treatment setting was at Winship Cancer Center of Emory University (academic medical center with community affiliates); institution review board approval was through Emory University.

Stage and Grade Migration in Prostate Cancer Treated With Radical Prostatectomy in a Large German Multicenter Cohort.

Overdiagnosis and overtherapy in prostate cancer (PCa) treatment should be avoided, which has led to an awareness of the need to decrease treatment in cases of low-risk PCa with radical prostatectomy (RP). Simultaneously, prostate-specific antigen testing has become less popular in the last few years, which has resulted in higher cancer grade and stage at diagnosis. We evaluated stage and grade migration in the disease of patients treated with RP in a large German cohort. Overall, 4842 patients undergoing RP between 2000 and 2019 were included. Age, prostate-specific antigen level, biopsy, and pathologic Gleason score as well as clinical and pathologic stage were collected. D'Amico risk groups and Gleason score were evaluated over different time points. We detected a significant grade migration toward higher grade. The proportion of biopsy Gleason sum≤ 6 dropped from 45.8% to 20.6% between≤ 2010 and 2017-2019. Further, the proportion of patients with low D'Amico risk scores also decreased by almost 50% (20.8% vs 12.2%). Finally, the proportion of non-organ-confined PCa increased over time, and the proportion of postoperative Gleason sum≤ 6 decreased from 20% to 10% over time. Taken together, data indicate a significant preoperative grade and stage migration toward disease of higher grade in RP-treated PCa. Between the years 2000 and 2019, the proportion of biopsy Gleason sum≤ 6 and the proportions of D'Amico low risk disease decreased by approximately 50% (respectively, 45% to 20% and 20.8% to 12.2%). This might indicate better patient selection for RP, but might also be a telltale sign of the rising mortality and morbidity of PCa.

Predicting Gleason sum upgrading from biopsy to radical prostatectomy pathology: a new nomogram and its internal validation

BackgroundTo explore the rate of Gleason sum upgrading (GSU) from biopsy to radical prostatectomy pathology and to develop a nomogram for predicting the probability of GSU in a Chinese cohort.MethodsWe retrospectively reviewed our prospectively maintained prostate cancer (PCa) database from October 2012 to April 2020. 198 patients who met the criteria were enrolled. Multivariable logistic regression analysis was performed to determine the predictors. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Calibration curve was used to assess the concordance between predictive probabilities and true risks.ResultsThe rate of GSU was 41.4%, whilst GS concordance rate was 44.4%. The independent predictors are prostate specific antigen (PSA), greatest percentage of cancer (GPC), clinical T-stage and Prostate Imaging Reporting and Data System (PI-RADS) score. Our model showed good discrimination (AUC of 0.735). Our model was validated internally with good calibration with bias-corrected C-index of 0.726.ConclusionsUtilization of basic clinical variables (PSA and T-stage) combined with imaging variable (PI-RADS) and pathological variable (GPC) could improve performance in predicting actual probabilities of GSU in the 24-core biopsy scheme. Our nomogram could help to assess the true risk and make optimal treatment decisions for PCa patients.

Development of a Multiparametric Magnetic Resonance Imaging-Based Nomogram for Clinically Insignificant Prostate Cancer

Purpose Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. Materials and Methods We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. Results Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. Conclusions We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker. Key Words: Clinically insignificant prostate cancer; Magnetic resonance imaging; Nomogram.

Extended 14-core schematic diagram mapping prostate biopsy increases both the cancer detection rate and the accuracy of Gleason Score

Objective: To evaluate the effectiveness of extended 14-core schematic diagram mapping prostate biopsy for improving the cancer detection rate (CDR) and accuracy of Gleason score. Material and Method: This study included 184 patients who underwent transrectal ultrasound (TRUS)-guided lateral sextant biopsy (group I) and 196 patients who underwent extended 14-core biopsy (group II). Inclusion criteria for prostate biopsy were elevated serum prostate-specific antigen (PSA) levels (&gt;4.0 ng/ml) and/or suspicious digital rectal examination (DRE). Results: Median patient age was 69.68 years (±7.89) and 70.07 years (±8.83) for group I and II, respectively. Median pre-biopsy PSA was 18.04 (range: 8.42-22.35) and 15.83 ng/ml (range: 6.54-21.72) for group I and II. Out of the first group, 65 (35.3%) patients had prostate cancer, whereas 78 (40.0%) patients of group II had cancers. The overall cancer detection rate was significantly higher in group II (40.0%) than group I (35.3%), p=0.034, and in particular showed a significant increase in the cancer detection rate in the subgroup with PSA level between 4-10 ng/ml. Moreover, rising Gleason sum after radical prostatectomy was 1 in 3 (11.1%) patients and 2 in 1 (3.7%) patient. Conclusion: Extended 14-core schematic diagram mapping prostate biopsy significantly increased the cancer detection rate of prostate cancer and increased the accuracy of biopsy Gleason score. Thus, schematic diagram mapping prostate biopsy should be the standard ultrasound guided prostate biopsy in our institute for increasing the cancer detection rate and also for planning treatments.

Abstract PO-201: Smoking as a risk factor for the aggressive prostate cancer for African-American men from the North Carolina–Louisiana Prostate Cancer Project (PCaP)

Abstract Background. Significant racial disparities exist in PCa, with the incidence in African- Americans (AAs) being 50% higher than European Americans (EAs) and PCa mortality rates in AAs being more than two-fold higher. However, the disparity cannot be explained by screening, access to treatment, and genetics can only partially explain the disparity that does little to confer actionable clinical relevance. Currently, only 3 definitive risk factors for PCa have been identified: age, race, and family history of PCa. Smoking has not been an established risk factor for prostate cancer (PCa), and has not been emphasized in PCa prevention. However, recent studies have shown increasing evidence that there is a higher risk of biochemical recurrence, PCa mortality, and metastasis among current smokers, presenting an urgent need in re- evaluating the association between smoking and aggressive PCa. This study aimed to determine whether smoking increase the likelihood of developing a more aggressive prostate cancer. Methods. The study used data from the North Carolina–Louisiana Prostate Cancer Project (PCaP), which is a population-based study of incident PCa conducted between years 2004-2009 in 2 southern states where significant racial disparities in PCa are observed. Because PCa is over diagnosed and most PCa is not clinically relevant, this study will include only subjects with high (Gleason score ≥ 8; PSA &amp;gt; 20 ng/mL; Gleason score = 7 and stage T3–T4) or low (Gleason score &amp;lt; 7 and stage T1–T2 and PSA &amp;lt;10 ng/mL) PCa aggressiveness. 1,497 participants were included in the analysis. Chi square and t-tests were used for the variables of interest and possible confounders, and multivariable logistic regression models were used for the odds ratio estimate. Results. There were 44.9% AAs and 55.1% EAs in the study. AA participants were significantly younger (mean=61.8, SD=7.9) compared with EAs (mean=64.0, SD=7.9), with lower education levels, shorter smoking cessation period, less screening tests in the past, less cigarettes per day, and higher Gleason sum. From the analysis, more AAs (57.6%) and those who were current smokers (22.7%) were diagnosed with high aggressive PCa. Current smokers had a 2.4 times- higher risk of high aggressive PCa (unadjusted OR=2.42, adjusted OR=2.39); when stratified by race, the risk diminished for EAs (OR=1.30) but increased for AAs (OR=3.36). Conclusion. Our study shows increased risk of aggressive PCa for current smokers, especially among AAs. Previous study had shown that self-reported cigarettes per day predicts smoke intake more poorly in AAs than in EAs. Thus, there is an urgent need in validated research using biomarkers to confirm the relationship of smoking and aggressive PCa, since cigarette smoking is preventable but have not been emphasized in PCa prevention. Citation Format: Ping-Ching Hsu, Shelbie Stahr, Christopher Brazeal, Elizabeth H. Fontham, L. Joseph Su. Smoking as a risk factor for the aggressive prostate cancer for African-American men from the North Carolina–Louisiana Prostate Cancer Project (PCaP) [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-201.

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.

Presenting Pattern and Treatment Modalities of Prostate Cancer in Nicrh

Objective: The aim was to describe the clinicopathological presentation of prostate cancer and the treatment modality in patients seen in Uro-oncology department of National Institute of Cancer Research &amp; Hospital (NICRH), Bangladesh. Methods: Data were collected prospectively from all patients with diagnosed prostate cancer and managed in Uro-oncology department of NICRH from January 2016 to December 2017. Patient’s age, clinical presentation, prostate specific antigen(PSA) level, mode of diagnosis, Gleason sum score, stage of the disease at presentation and modality of treatment were recorded and analyzed. Results: There were 407 cases of histologically proven prostate cancer. Mean patient age was 69 years. About 87% presented as diagnosed prostate cancer. Twenty one(5%) patient presented with features of metastasis with unknown primary , we confirmed after prostate biopsy. About 77% of patients had a serum PSA above 20 ng/ml. Gleason sum score was 8 or more in 46% of patients. Metastases were found at the time of presentation in 85% of patients. Ten (2.5%) patients underwent radical radiotherapy, while two patients had radical prostatectomy. Most (68%) of the 347 patients who required androgen deprivation therapy had surgical orchiectomy. Conclusion: Bangladesh appear to be having a low incidence of prostate cancer, but a larger proportion of advanced and high grade cancers in comparison to the UK and USA. Although genetic differences may exist, a dietary or an environmental factor is more likely to be the cause for these changes. The protective effect of this factor appears to wane as South Asians emigrate and live in UK and USA. Bangladesh Journal of Urology, Vol. 21, No. 2, July 2018 p 56-61

Prostate cancer presentation, treatment selection, and outcomes among men with HIV/AIDS: A clinical stage, race, and age-matched contemporary analysis

PurposeTo compare the clinical presentation, treatment receipt, and oncologic outcomes between human immunodeficiency virus-seropositive (HIV+) and seronegative (HIV−) men with prostate cancer (CaP) matched by age, clinical stage, and race. Materials and methodsA retrospective review of 3,135 men treated for CaP from 2000 to 2016 was performed. HIV+ patients (N = 46) were matched 1:2 to 3 to HIV− men (N = 137) by age, race, and clinical stage. Clinicopathologic features and primary treatment received were compared between cohorts. Associations between HIV status and progression-free, cancer-specific, and overall survival were compared by HIV status using the Kaplan-Meier method and Cox proportional hazards analysis. ResultsAfter matching, men with and without HIV were similar with respect initial prostate-specific antigen, Gleason Sum, and Eastern Cooperative Oncology Group (ECOG) performance status. Among HIV+ men, 67.4% had a history of acquired immune deficiency syndrome, and 91.3% were on highly active antiretroviral therapy at CaP diagnosis. Among men with localized disease, HIV+ men were more likely to receive radiation (59.5% vs. 44.8%) or no therapy (13.5% vs. 4.3%) and less likely to receive surgery (16.2% vs. 30.2%), or to initiate active surveillance (10.8% vs. 16.4%; P = 0.04 overall). There were no differences in rates of clinical progression, development of castration resistance, or CaP death by HIV status. However, HIV+ status was associated with inferior overall survival (hazard ratio 2.89, P = 0.04). ConclusionsWhile most HIV+ patients had a history of acquired immune deficiency syndrome; HIV was well controlled in the majority of patients at the time of CaP diagnosis. While oncologic outcomes were similar between HIV+ and HIV− men, significant differences in treatment selection were observed. Further research is necessary to understand differences in treatment election by HIV status and to define optimal CaP treatment selection in men with HIV.

Size of pelvic bone metastasis as a significant prognostic factor for metastatic prostate cancer patients.

To investigate the potential prognostic value of image analysis of pelvic bone metastasis in newly diagnosed prostate cancer patients. Data from 69 patients with both bone scintigraphy and pelvic CT images were selected for this analysis. Open source software (3D Slicer version 4.8.1.) was used for image analysis. Metastatic pelvic bone lesions were manually contoured, and radiomic features were extracted. As risk factors for overall survival (OS) and cause-specific survival (CSS), 105 radiomic features and clinical risk factors including age, initial prostate-specific antigen, Gleason score, TNM stage, lactate dehydrogenase (LDH), hemoglobin (Hb), alkaline phosphatase, extent of disease, visceral metastases, and radiotherapy were assessed by uni- and multivariate analyses. Median follow-up was 41months (range 0-157months). Five-year overall survival and cause-specific survival rate were 37.9% and 43.5%, respectively. After multivariate analysis, LDH, Hb, and "maximum 2D diameter" defined as maximum tumor size in the axial plane were detected as risk factors for OS. Gleason sum, LDH, and maximum 2D diameter were detected as risk factors for CSS. Maximum 2D diameter was detected as a significant prognostic factor for metastatic prostate cancer patients.