bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of significant prostate cancer through magnetic resonance imaging targeted biopsy of PI-RADS3 lesions in African American patients based on prostate specific antigen density threshold of 0.15 ng/ml2: Analysis of patient population from the Vattikuti Urology Institute.
Authors: Alanee Shaheen Riadh , Deebajah Musatafa , Roumayah Zade , Dabaja Ali , Peabody James O. , Menon Mani 
Published: February 2020

286 Background: A prostate specific antigen density (PSAD) threshold of 0.15 ng/ml2 have been suggested for significant cancer detection in PI-RADS 3 lesions to avoid unnecessary magnetic resonance imaging targeted biopsy (MRI-TB) of these lesions. However, the performance of this threshold in African American (AA) patients is not well characterized. Methods: We analyzed our institutional data base of MRI-TB to identify the rate of significant prostate cancer (Pca) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of < 0.15 vs. ≥0.15 ng/ml2 and lesion size of < 1 cm vs ≥ 1 cm. Significant prostate cancer was defined as Gleason grade group 2 or higher on MRI-TB of the PI-RADS 3 lesion. Results: Of 768 patients included in the database, 211 (27.5%) patients identified themselves as AAs. Mean age of AA patients was 63 years and mean PSAD was 0.21. Sixty nine (32.7%) AA patients were found to have PI-RADS 3 lesions. Mean PSAD of AA patients with PI-RADS 3 lesions was 0.21 ng/ml2 as well. Fifty percent of AA patients with PI-RADS 3 lesions had PSAD ≥0.15 ng/ml2. Significant Pca detection rate for AA patients with PI-RADS 3 lesions was 9% for PSAD of ≥ 0.15 vs. 0.03% percent for AA patients with PSAD < 0.15 ng/ml2 (OR 7.056, CI 1.017-167.9, P=0.04). Stratification by lesion size (< 1 cm vs. > 1 cm) resulted in missing 0% percentage of significant Pca when only AA patients with PSAD ≥ 0.15 ng/ml2 and lesion size ≥ 1 cm received MRI-TB. Conclusions: We report on the performance of a reported PSAD density threshold in detecting significant Pca in one of the largest series of AA patients receiving MRI-TB of the prostate. Our results have direct clinical implications when counseling AA patients with PI-RADS 3 lesion on whether they should undergo MRI-TB of such lesions.
Deep learning-based approach for automated assessment of PTEN status.
Authors: Jamaspishvili Tamara , Harmon Stephanie , Patel Palak , Sanford Thomas , Caven Isabelle , Iseman Rachael , Mehralivand Sherif , Choyke Peter L. , Berman David Monty , Turkbey Baris 
Published: February 2020

294 Background: PTEN loss is associated with adverse outcomes in prostate cancer and has the potential to be clinically implemented as a prognostic biomarker. Deep learning algorithms applied to digital pathology can provide automated and objective assessment of biomarkers. The objective of this work was to develop an artificial intelligence (AI) system for automated detection and localization of PTEN loss in prostate cancer samples. Methods: Immunohistochemistry (IHC) was used to measure PTEN protein levels on prostate tissue microarrays (TMA) from two institutions (in-house n=272 and external n=125 patients). TMA cores were visually scored for PTEN loss by pathologists and, if present, spatially annotated. In-house cohort (N=1239 cores) were divided into 70/20/10 training/validation/testing sets. Two algorithms were developed: a) Class I=core-based, to label each core for biomarker status and b) Class II=pixel-based, to spatially distinguish areas of PTEN loss within each core. ResNet101 architecture was used to train a multi-resolution ensemble of classifiers at 5x, 10x, and 20x for Class I task and a single classifier at simulated 40x for Class II segmentation. Results: For Class I algorithm, accuracy of PTEN status was 88.3% and 93.4% in validation and testing cohorts, respectively (Table). AI-based probability of PTEN loss was higher in cores with complete loss vs partial loss. Accuracy was improved to 90.7% in validation and 93.5% in test cohorts using the Class II region-based algorithm, with median dice scores 0.833 and 0.831, respectively. Direct application to external set demonstrated a high false positive rate. Loading trained model and conservatively re-training (“fine-tuning”) on 48/320 external cohort cores improved accuracy to 93.4%. Conclusions: Results demonstrate feasibility and robustness for fully automated detection and localization of PTEN loss in prostate cancer tissue samples and possibility for time/cost-effectiveness of sample processing/scoring in research and clinical laboratories.[Table: see text]
Clinical utility of PSA density and PI-RADS for deferring biopsy for the detection of clinically significant prostate cancer.
Authors: Truong Matthew , Stevens Erica , Ward Ryan , Bullen Jennifer , Austhof Ethan , Valdez Rogelio , Purysko Andrei , Klein Eric A. 
Published: February 2020

298 Background: We sought to identify PSA density (PSAD) and Prostate Imaging-Reporting and Data Systems (PI-RADS) category cut-offs that would allow deferring biopsy in men with suspicion for clinically significant prostate cancer (csPCa). Methods: Our institution’s prostate MRI registry (n = 1718) was queried for patients who had MRI-guided biopsy (MRI-GB) and/or systematic biopsy (SB) performed after prostate MRI between January 2013 and October 2018 (n = 676). Patients in the diagnostic group (either biopsy naïve or with prior negative biopsy) and patients with PCa on active surveillance (AS) were considered eligible. PSA, PSAD, and PI-RADS category were entered into logistic regression models for predicting csPca (grade group [GG] ≥ 2) at biopsy. Receiver operating characteristic (ROC) analysis was performed to assess model accuracy and results were stratified by biopsy indication and PI-RADS categories. Results: Logistic regression models that combined PSAD and PI-RADS categories had the highest ROC’s in both the diagnostic and AS groups (AUC=0.830 and 0.778, respectively). For diagnostic group patients with PSAD ≤0.15, csPCa was found in 6/89 (6.7%) of negative MRI patients (i.e. PI-RADS ≤ 2), 4/90 (4.4%) of PI-RADS 3 patients, 59/159 (37%) of PI-RADS 4-5 patients. If a PSAD cutoff of ≤ 0.15 and PI-RADS category ≤ 3 MRI were used in combination as criteria for biopsy deferral, only 10/526 (1.9%) of patients would have had csPCa missed on subsequent biopsy. Among patients in the AS group with a negative MRI, 0/22(0%) and 3/8 (37.5%) had csPCA if the PSAD was ≤0.15 and >0.15, respectively. Conclusions: For the diagnostic group of patients undergoing prostate biopsy, PSAD cut off ≤0.15 is useful for deferring biopsy only in patients with a PI-RADS ≤ 3. Confirmatory biopsy in patients should be strongly considered before enrolling patients in AS even in the setting of a negative MRI if the PSAD is > 0.15.
Locally advanced scrotal squamous cell carcinoma: Does chemotherapy affect survival?
Authors: Madhira Bhaskara Reddy , Brooks Gary , Khan Rashad , Akhtar Komal , Basnet Alina 
Published: February 2020

3 Background: Scrotal squamous cell carcinoma (SSCC)thoughrare, represents the most common forms of scrotal malignancies.40-50% of patients present with locally advanced disease, and treatment is extrapolated from penile cancer. Here we report practice trend and overall survival (OS) outcome of locally advanced SSCC patients who underwent surgery with or without chemotherapy. Methods: We performed a retrospective analysis using the national cancer center database (NCDB) (2004-2016). All patients aged ≥ 18 years with locally advanced SSCC who underwent surgery with or without chemotherapy were included. OS is estimated with Kaplan-Meier curves, with an adjusted hazard ratio (aHR) calculated from Cox proportional hazard regression model. Results: 638 patients were identified with SSCC without distant metastasis. Of these 49 underwent surgery with perioperative chemotherapy and 589 underwent surgery alone. At the median follow up of 39.9 months (mo), median OS is 41.4 mo and 145.7 mo for surgery with chemotherapy group versus surgery alone respectively (P-value <0.0001), with aHR for OS 1.673 (95%CI 0.966-2.897). Patients age ≥ 65 (HR= 3.081, 95% CI=2.107- 4.505, p<0.001), Charlson-Deyo Score (CCI) 2 or more (HR=3.441, 95% CI=2.140- .533, p <0.0001), moderately-poorly differentiated carcinoma (HR=1.713, 95% CI=1.038- 2.829, p=0.0352), and higher clinical nodal status N1,N2 and N3 (HR=2.543, 95% CI=1.42-4.548, p=0.0016)were observed to do worse with surgery and chemotherapy. Patients with CCI of 2 or more, moderate to poorly differentiated carcinoma, higher clinical T and N stage (T2- T4 and N1-N3 respectively) were observed more likely to receive surgery and chemotherapy. Conclusions: No OS improvement was seen in locally advanced SSCC with addition of chemotherapy to surgery. Patients who received chemotherapy along with surgery are observed to have higher risk of mortality vs surgery alone. The study is limited by retrospective nature, lack of randomization, patient selection bias, patient’s choice of therapy, small sample size, and missing information.
Clinical outcomes of abiraterone acetate + prednisone (AA) + bone resorption inhibitors (BRI) versus AA alone as first-line therapy for castration-resistant prostate cancer (CRPC) with bone metastases (BM) in an international multicenter database.
Authors: Francini Edoardo , Montagnani Francesco , Nuzzo Pier Vitale , Gonzalez-Velez Miguel , Alimohamed Nimira S. , Cigliola Antonio , Moreno Irene , Rubio Jaime , Crivelli Francesca , Shaw Grace , Petrioli Roberto , Bengala Carmelo , Francini Guido , Foncillas Jesus Garcia , Sweeney Christopher , Higano Celestia S. , Bryce Alan Haruo , Harshman Lauren Christine , Lee-Ying Richard , Heng Daniel Yick Chin 
Published: February 2020

30 Background: BM in patients (pts) with CRPC are associated with shorter overall survival (OS) and higher costs. BRI zoledronic acid and denosumab are frequently used to prevent skeletal-related events (SRE) in pts with CRPC and BM. AA is the most common 1st line therapy for men with metastatic CRPC. We aimed to assess the impact of BRI on OS and time to first SRE (ttSRE) of pts receiving 1st line treatment AA for CRPC with BM. Methods: A retrospective cohort of pts starting AA as 1st line therapy for CRPC with BM between 2013-2016 was identified through 8 hospitals’ IRB approved registries. Pts were classified by use of concomitant BRI and subgrouped by volume of disease (per E3805 definition) at AA start. Kaplan-Meier method and Cox models were used to assess OS and ttSRE with hazard ratio (HR) estimates (95% CI). Results: Of the 745 pts included (543 deaths), 529 (71.0%) had AA alone and 216 (29.0%) AA+BRI. Median follow-up was 23.5 months. Pts receiving concomitant BRI showed a significantly longer OS and a 35% reduced risk of death compared to AA alone (HR=0.65; 95% CI, 0.54-0.79; P<.0001). The OS benefit with BRI was greater for the subgroup with high volume disease (HV) (HR=0.51; 95% CI, 0.38-0.68; P<.0001). The cohort with AA+BRI had a significantly shorter ttSRE (HR=1.27; 95% CI; 1.0-1.60; P=.0439) and, notably, the risk of first SRE was more than doubled for the subgroup with LV (HR=2.29; 95% CI, 1.57-3.35; P<.0001). On MVA, BRI vs. no BRI, prior local therapy (PLT) vs. no PLT, LV vs. HV, baseline VAS pain ≤3 vs. >5, PS 0 vs. ≥1, and PSA are independently associated with longer OS. Conclusions: The addition of BRI to 1st line AA for CRPC men with BM was associated with improved OS, particularly in HV, and worsened ttSRE, more evident in LV. These data suggest a potentially different impact of concomitant BRI on HV vs. LV, which could affect clinical decision making.[Table: see text]
Acute patient-reported toxicities after proton therapy or intensity-modulated radiotherapy for prostate cancer.
Authors: Gergelis Kimberly , Bai Miao , Whitaker Thomas , Routman David M. , Sir Mustafa , Choo Richard 
Published: February 2020

305 Background: Toxicity due to radiotherapy (RT) may differ in patients (pts) with prostate cancer who receive intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Methods: Patient-reported bowel function (BF), urinary incontinence (UI), and urinary irritative/obstructive symptoms (UO) domains of the Expanded Prostate Index Composite Questionnaire (EPIC-26) were prospectively collected in pts with localized prostate cancer receiving either IMRT (n=157) or PBT (n=105) to the prostate +/- proximal seminal vesicles for clinical stage T1-T2 N0 prostate cancer at a single tertiary cancer center between 2015 and 2018. Changes in domain scores were analyzed from pretreatment to the end of RT and 3 months post-RT, assessing the acute effects of each modality. A clinically relevant change was defined as a score change that exceeded 50% of the standard deviation of a baseline value. Results: At baseline there was no difference in the scores of BF, UI, and UO domains between IMRT and PBT cohorts. At the end of RT, pts treated with either modality had a statistically significant and clinically relevant worsening of BF and UO compared to baseline. Pts treated with IMRT experienced a significantly greater decrement in BF compared to the PBT cohort (-13 vs -9, p<0.01), including significantly more IMRT pts having a clinically relevant deterioration in BF compared to PBT pts (58% vs 40%, p=0.01). Though there was a statistically significant deterioration in UI in the IMRT cohort (-4, p<0.001), this did not reach the predefined threshold for clinical relevance. Three months following RT, the IMRT group continued to have statistically significant and clinically relevant worsening of BF (-9, p<0.001), whereas the change in BF domain score of the PBT cohort was no longer statistically significant or clinically relevant compared to baseline (-1, p=0.25). There were no statistically significant or clinically relevant changes in UO or UI in either cohort at three months when compared to baseline. Conclusions: Pts who received IMRT or PBT reported unique patterns of toxicity, and pts treated with IMRT had worse decrement in BF immediately after and three months following RT, compared to those treated with PBT.
Influence of node-positive disease after radical prostatectomy on biochemical recurrence and oncologic outcomes in men with prostate cancer.
Authors: Washington Samuel L. , Cowan Janet E. , Herlemann Annika , Zuniga Kyle Brian , Carroll Peter 
Published: February 2020

306 Background: The diagnostic and therapeutic value of pelvic lymph node dissection (LND) at radical prostatectomy (RP) remains unclear. Thus, we aim to characterize the oncologic value of LND and secondary treatment on oncologic outcomes for a contemporary cohort of men with nodal disease on surgical pathology at RP. Methods: Men who underwent primary RP with LND for PCa were identified and stratified by pN status. Detectable PSA was defined as a PSA>0.05 ng/ml within 2-6 months after RP. Multivariable Cox proportional hazards regression models were fit for biochemical recurrence-free survival (RFS), overall survival (OS), and PCa-specific mortality (PCSM). Results: Of 1,635 identified patients, 167 (10.2%) had nodal disease. Mean age at diagnosis was 62 years (SD 7.1). Median follow-up after RP was 31 months (IQR 13-58). Those with nodal disease had more extensive LND (mean 17.7, SD 8.3 vs mean 13, SD 7.6, p<0.01). The number of positive LNs was associated with worse 7-year outcomes [RFS, HR 1.2, 95% CI 1.1-1.2, p<0.01; OS, HR 1.2, 95% CI 1.1-1.4, p<0.01] but not PCSM (p=0.2) after adjustments. Median number of positive LN was 1 (IQR 1, 3) in pN1 patients. 31 (19%) had an UDT PSA after RP, 25 (15%) had UDT PSA and received adjuvant therapy, and 106 (66%) had a detectable PSA. On multivariable analysis, number of positive LNs (HR 1.1, 95% CI 1.0-12, p=0.02) and detectable PSA (vs UDT, HR 5.1, 95% CI 1.8-14.3, p<0.01) were associated with increased risk of recurrence after RP but not OS (p>0.05 for all). After salvage treatment, 7-year RFS, OS, and PCSM did not differ significantly between the groups (p>0.05 for all). Conclusions: In a contemporary cohort of men with pN1 disease, more extensive LND was not associated with improved outcomes. Amongst those who underwent secondary treatment after RP, UDT PSA after RP conferred greater biochemical recurrence free survival at 7 years. In this subset of men, adjuvant treatment was not associated with improved post-salvage biochemical or treatment-free survival. Further investigation into the potential therapeutic benefit of LND at RP is warranted to better estimate the potential risk overtreatment of men with nodal disease.
Contemporary racial disparities in PSA screening in a large, integrated health care system.
Authors: Kearns James T. , Adeyemi Oluwaseun , Anderson William E. , Hetherington Timothy C. , Taylor Yhenneko J. , Zhu Jason , Burgess Earle Frederick , Gaston Kris E. 
Published: February 2020

308 Background: The USPSTF prostate cancer screening guidelines have changed significantly in the past decade, from a recommendation of do not screen in 2012 to a 2018 recommendation that focuses on shared decision making. Additionally, most guidelines further acknowledge that African American men should be screened more intensively than Caucasian men due to increased incidence of prostate cancer and increased prostate cancer mortality. Our objective was to characterize racial disparities in PSA screening in a large healthcare system with a diverse patient population to understand contemporary trends. Methods: This retrospective cohort study used data from the Atrium Health Enterprise Data Warehouse, which includes clinical records from over 900 care locations across North Carolina, South Carolina, and Georgia. Participants included all men ≥ 40 years seen in the ambulatory or outpatient setting during 2014-2018. PSA testing was determined through laboratory data. Clinical and demographic data were collected. Between-group comparisons were conducted using generalized estimating equations models to account for within-subject correlation. Statistical significance was defined as p < 0.05. Results: There were 582,846 individual men seen from 2014-2018, including 416,843 Caucasians (71.5%) and 85,773 African Americans (14.7%). Screening rates declined among all groups from 2014-2018 (see table). African American men were screened at a similar or lower rate than Caucasian men in each year (from 18.6% vs 19.0% in 2014 to 11.9% vs 12.2% in 2018, respectively). Conclusions: PSA screening declined significantly between 2014 and 2018. African American men screened at a similar or lower rate than Caucasian men each year. Given the consensus that African American men should be more intensively screened for prostate cancer, significant racial disparities remain in prostate cancer screening. Further study is warranted to understand patient, provider, and system factors that contribute to disparities in prostate cancer care and outcomes.[Table: see text]
Phase II trial of definitive radiotherapy with leuprolide and enzalutamide in high-risk prostate cancer.
Authors: de la Calle Claire Marie , Chang Albert , Rashid Ghezal , Wong Anthony C. , Choi Alice , Feng Felix Y , Gottschalk Alexander R. , Menzel Paul Lawrence , Carroll Peter , Nguyen Hao Gia 
Published: February 2020

323 Background: Adding enzalutamide to standard LHRH agonist and primary radiation therapy may improve the outcomes in patients with high-risk prostate cancer. Methods: All patients met at least 2 of the following criteria: stage cT3a/b, PSA≥20 ng/mL, Gleason Grade 8-10, ≥33% core involvement on biopsy; or had pelvic lymph node involvement ≥1cm on CT or MRI. All patients were started on 24 months of leuprolide and enzalutamide and then underwent 5 weeks of IMRT (whole pelvis, 45Gy total) followed by a brachytherapy boost. PSA, Testosterone (T) and basic labs were followed during and after treatment. Primary outcome was to assess the safety, tolerability, and feasibility of the protocol and PSA complete response (PSA-CR, defined as PSA nadir ≤0.3). Secondary outcomes included: time to biochemical recurrence (BCR) and progression free survival (PFS). Results: 16 patients were enrolled, 2 were not eligible and 3 withdrew before starting treatment. Mean age at enrollment was 68.6 years (SD 9.4). Median follow up time was 28.27 months (IQR 27.3 – 29.1 months). Median time to PSA-CR was 4.20 months (IQR 3.47 – 4.87 months). Currently all patients still have PSA-CR (Table), and none have BCR per ASTRO Phoenix criteria. All-cause, any grade adverse events (AE) were reported in all 11 (100%) patients with 4 (36.4%) experiencing grade 3 AE. One (9.09%) treatment related serious AE (seizure) occurred. There were no grade 5 AE (death related to AE). 4 subjects stopped treatment early due to: seizure, myalgias, hematuria and social reasons. Most patients however were able to complete the 24 months of leuprolide and enzalutamide: median treatment duration was 24.0 months (IQR 12.1 – 24.0 months). Conclusions: Most patients were able to tolerate and complete the entire 24 months of treatment as originally planned. Currently no patients have met criteria for PSA recurrence. Will plan to follow up patients until month 36 to help determine true BCR rates and PFS. Clinical trial information: NCT02508636. [Table: see text]
Biopsy positivity in prostate cancer patients undergoing mpMRI-targeted radiation dose escalation.
Authors: Meshman Jessica , Farnia Benjamin , Stoyanova Radka , Reis Isildinha , Abramowitz Matthew , Dal Pra Alan , Horwitz Eric M. , Pollack Alan 
Published: February 2020

336 Background: Radiation (RT) dose escalation improves prostate cancer outcomes, but when the whole gland is treated to high doses complications can arise. We used prostate multiparametric MRI (mpMRI) findings for targeted dose escalation (MTDE) in prospective clinical trials in which prostate biopsy at 2-3 years after completion of RT was planned. Biopsy positivity is a known predictor of biochemical failure. These findings are compared to those in another cohort in which standard whole gland RT doses were used. Methods: Patients enrolled on three investigator initiated clinical trials incorporating MTDE (n=30) were eligible for inclusion. All patients were assessed for response by prostate biopsy 2-3 years after RT. Patients were compared to a reference group treated with standard RT doses to the whole prostate on a randomized trial at Fox Chase Cancer Center (FCCC trial). Univariable and multivariable analysis (MVA) was performed to assess for correlation with biopsy positivity, defined as carcinoma with or without RT effect. Results: Of those treated with MTDE: 3 (10%) were low, 23 (77%) intermediate, and 4 (13%) high risk. Assuming an α/β ratio of 1.5, MTDE patients received an equivalent dose (EQD2) of 76 Gy to the prostate, with focal dose escalation to an EQD2 of 98-122 Gy to mpMRI lesions. The MTDE cohort was compared with 115 patients from the FCCC trial, where 23 (20%) were low, 74 (64%) intermediate, and 18 (16%) high risk. The FCCC trial patients received an EQD2 of 76 Gy (n=64) or 84.24 Gy (n=51) without boost. Median time from RT to biopsy was 2 years (range, 1.6-3.3). The post-treatment biopsy results were negative in 50% (n=73), atypical in 12% (n=17), carcinoma with RT effect in 31% (n=45) and frank carcinoma in 7% (n=10). On MVA, patients with tumor volume >20% were more likely to have positive post-RT biopsies (OR: 3.21, 95% CI: 1.34-7.68, p= 0.009). MTDE patients were less likely to have positive post-RT biopsies, 10% vs. 45%, (OR: 0.13, 95% CI: 0.03-0.46, p=0.002). Conclusions: Focal dose-escalation to mpMRI-defined lesions significantly reduces biopsy positivity, a measure associated with long term outcomes including distant metastasis.