bluuebunny/crossref_metadata_2025_split huggingface dataset:
Providers’ inability to estimate health literacy among African American (AA) patients (pts) with early prostate cancer (PCa).
Authors: Martin-Doyle William , Kilbridge Kerry L. , Regan Susan , Filson Christopher Paul , Trinh Quoc-Dien , Williams Sierra , Master Viraj A. 
Published: March 2019

77 Background: Providers’ estimates of a pt’s health literacy are important for communication and shared decision making among men with early PCa. We explored differences between providers’ estimates of health literacy and measured health literacy among AA pts in a prospective cohort study at Grady Memorial Hospital and the Atlanta Veterans Administration Hospital. Methods: Providers (n=18) estimated the health literacy of 124 newly diagnosed, early-stage, AA PCa pts after discussions with each pt regarding his PCa treatment options, categorized as ≤Grade (Gr) 3; Gr 4-6; Gr 7-8; and High school. At a subsequent visit, prior to choosing his cancer treatment, each pt’s health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM), using the same categories. Domains of numeracy, comprehension of common PCa terms, and anatomic knowledge were assessed using published methods. Concordance between estimated and actual health literacy was evaluated via Cohen’s Kappa coefficient (1.00 = perfect agreement). Results: Despite their discussions with the pts, providers consistently overestimated pts’ health literacy. Agreement between provider estimates and pts’ measured values was consistently low (32.0%-37.6%). These rates were approximately what would be expected by chance. Among the 75 patients with the lowest levels of health literacy, agreement was even lower (12.3%-35.6%). In this group 26.7% of provider assessments were off by ≥2 REALM categories. Conclusions: Healthcare providers are surprisingly ineffective at estimating the health literacy of their pts with early stage PCa. This poor accuracy may diminish providers’ ability to communicate successfully with pts and engage in shared decision making, especially among pts with poor health literacy. [Table: see text]
Evaluating non-hormonal therapy in a phase II trial of SM-88 for rising PSA prostate cancer.
Authors: Gartrell Benjamin Adam , Del Priore Giuseppe , Retter Avi S. , Chen Wen-Tien , Sokol Gerald H. , Vandell Alexander G , Roach Mack 
Published: March 2019

83 Background: Absolute PSA change is an imperfect surrogate of clinical benefit; CTCs and PSA doubling time (DT) may also be used as a surrogate of progression (PD). Hormone therapy (HT) often leads to a rapid decline in PSA, however non-HT may be effective without causing a decline in absolute PSA or testosterone (T). SM-88, a non-HT novel combination Warburg effect therapy (amino acid analogue, CYP3a4 inducer, mTOR inhibitor and catalyst) does not affect T. We report outcomes leading to subsequent therapies of an ongoing PSA recurrent, non-metastatic PC trial. Methods: Prospective Phase II of rising PSA (per PCWG3), detectable CTCs, and no baseline lesions. Results: Since September 2016, 31 subjects enrolled with 17 on study for > 12 weeks. Mean age 68.9; BMI 28.7; 38% black and 62% post RT. Mean T increased 61 mg/dl from baseline 319 mg/dl (p=0.19). 82% (14/17) subjects experienced an improvement in PSA DT and 67% (10/15) experienced a decline in CTCs of >30%. Overall median PSA DT time on enrollment was 5.3 (1.4 – 37.6) and improved to 6.5 (Wilcoxon p=0.02) (see table). 3/4 subjects with PD failed to maintain a CTC drop >60% vs 2/17 without PD (p=.03); median time to nadir CTC was 3 cycles (1-7). Subjects avoiding subsequent therapy averaged a 50% CTC decline (15-100%). CTC and PSA DT effects were not correlated to T level. AEs possibly related to drug/unrelated were: No grade (G) 4 or 5; 0/1 G3; 1/7 G2; 13/19 G1. As reported elsewhere, typical HT-related side effects were not observed. Including all patients with >1 month of data, from initial diagnosis of PSA rise (median 9 months; 3-18), 96% (22/23) have remained metastases-free and 78% (18/23) remained free of additional HT (p<.05). Clinical trial information: NCT02796898. Conclusions: SM-88 may be a useful either before or as an additive to current PC treatments where normal T may be preferred. SM-88 might not worsen QOL parameters related to T level. An effect on PSA DT and CTCs were demonstrated even in an aggressive doubling time subgroup. Prospective trials are planned to confirm its utility.[Table: see text]
Cribriform pattern, Genomic Prostate Score, and adverse pathology at radical prostatectomy in a cohort of prostate cancer patients initially on active surveillance.
Authors: Zuniga Kyle Brian , Washington Samuel L. , Simko Jeffry , Greenland Nancy , Stohr Bradley A. , Cowan Janet E. , Tenggara Imelda , Maggi Martina , Chan June M. , Cooperberg Matthew R. , Carroll Peter 
Published: March 2019

88 Background: A growing body of literature suggests that the presence of cribriform pattern (CP) in prostate biopsy specimens portends worse outcomes. Furthermore, CP tumors have been found to harbor a myriad of genomic alterations associated with more aggressive disease. We sought to examine the association between CP and Genomic Prostate Score (GPS) and how this association helps predict adverse pathology (AP) at radical prostatectomy (RP) in patients initially managed with active surveillance (AS). Methods: Using the UCSF Urologic Outcomes Database (UODB), we identified 180 AS patients who underwent GPS testing and subsequently RP. Biopsy specimens were re-reviewed centrally to confirm Gleason grade. AP was defined as GS ≥ 4+3, pT3/4, or pN1 on surgical pathology. Clinical and demographic characteristics were compared by CP status using t-tests and chi-squared tests. Cox proportional hazards regression was performed to identify factors associated with AP after adjusting for age, PSA density (log), percentage of positive biopsy cores, biopsy source (UCSF versus outside), and year of diagnosis. Additional models included the base covariates plus presence of CP, GPS, and both CP and GPS. Results: For the cohort, mean age was 60.7 years (SD 7.1) with median PSA of 5.3 ng/ml (interquartile range, IQR 4.2-6.9) at diagnosis. Median PSAD was 0.14 (IQR 0.10-0.20). Among 180 patients, 27 (15%) had CP at biopsy. Mean GPS was significantly higher in CP+ compared to CP- patients (35, SD 12.7 versus 27, SD13.7, p < 0.01), and a greater proportion of CP+ patients had AP compared to CP- (59% versus 54%, p < 0.01). On multivariate analysis, CP was associated with AP (HR 1.9, 95% CI 1.1-3.4, p = 0.02), but significance was lost after adjusting for GPS (p = 0.19). Conclusions: The presence of CP at biopsy was statistically significantly associated with higher GPS. While both were associated with AP at RP, CP was not associated with AP independent of GPS, suggesting an interaction or commonality between these factors not previously explored.
Small cell carcinoma of the prostate: National patterns of care and outcomes.
Authors: Horne Zachary D. , Smith Ryan P , Beriwal Sushil , Kalash Ronny , Shinde Ashwin , Glaser Scott , Fuhrer Russell , Wegner Rodney E 
Published: March 2019

9 Background: Small cell prostate cancer (SCPC) is a rare entity with treatment patterns extrapolated from small cell cancer of the lung. Outcomes have been evaluated in small series but prognostic factors are relatively poorly defined. Methods: We utilized the National Cancer Data Base to analyze men diagnosed with SCPC from 2004-2015. Only men with known clinical TNM staging, treatment modalities, and follow up were included. Overall survival (OS) was analyzed and compared with Kaplan-Meier, log-rank, and Cox proportional hazards ratios. Associations with baseline and tumor properties were performed with Chi-squared, independent t-test, and bivariate regression analyses. Results: 800 men with SCPC were identified. Median PSA was 79.0 ng/dL. 55.6% of men had cM1 disease at diagnosis, 31.4% had cN0M0 disease, and 13.0% were cN1M0. Median follow up was 12.4 months for all patients and 19.3 months for cM0 patients. Median survival for cM1, cN0M0, and cN1M0 patients was 9.8, 28.5, and 17.1 months, respectively (p<0.001). In cM0 patients, 66 (18.7%) underwent radical prostatectomy (RP), 177 (50.1%) received radiation therapy (XRT), and 195 (45.2%) received chemotherapy (CT). Median survival for men undergoing RP was not reached vs those who did not undergo RP (p<0.001). XRT also showed a trend towards improved median OS (25.2 vs. 19.1 months, p=0.139). On multivariable analysis for cM0 men, only age (HR 1.044 [95% CI 1.025-10.64] p<0.001), cN1 (HR 1.378 [95% CI 1.001-1.898] p=0.050, RP (HR 0.429 [95% CI 0.259-0.709] p=0.001), and XRT (HR 0.520 [95% CI 0.384-0.704] p<0.001) were predictive for overall survival. When examining only men who received systemic therapy, XRT was the only additional treatment modality to exhibit a survival benefit (HR 0.623 [95% CI 0.425-0.912] p=0.015). Of men with cM1 disease, 78 (17.5%) underwent definitive local therapy (RP/XRT), but no difference in OS was observed. Conclusions: Small cell prostate cancer is an aggressive disease with the majority of men presenting with metastases. In those with pelvis-confined disease who are fit for systemic therapy, radiation therapy to the primary should be considered.
Pilot study of dual imaging with 89Zr-IAB2M and 68Ga-PSMA-11 PET/CT prior to prostatectomy.
Authors: Niaz Muhammad Junaid , Jhanwar Yuliya , Flynn Thomas , Vallabhajosula Shankar , Khani Francesca , Robinson Brian D. , Tagawa Scott T. , Bander Neil Harrison , Scherr Douglas 
Published: March 2019

90 Background: Due to high expression of Prostate Specific Membrane Antigen (PSMA), it’s an excellent candidate for targeted molecular imaging. 89Zr-df-IAB2M is a J591 antibody derived minibody and 68Ga-PSMA-11 is a PSMA small molecule. Methods: Patients with clinically significant (defined as: ≥ 0.5 cm3 with Gleason pattern ≥ 4) localized prostate cancer (PCa) on conventional imaging modalities who planned to undergo surgery were imaged by PET/CT 1-3 hours after 5±2mCi of 68Ga-PSMA-11 injection and 89Zr-IAB2M PET 2-4 days after 10mg IAB2M labeled with 2.5 mCi of 89Zr injection. Image results were interpreted by a central reader without knowledge of the surgical pathology, mapped and the mapped findings later compared with surgical pathology map. Results: 9 patients having clinically localized PCa with median age 65 (46-79) and PSA 8.42 (1.6-12.2) were enrolled. All dominant PCa lesions, which had a median Gleason score 8 (6-9), were detected by both IAB2M and PSMA-11. The smallest of these dominant lesions was 8mm in size. Median SUVmax for dominant lesions was 3.3 (2.3-7.5) on IAB2M and 7.1 (1.6-23.2) on PSMA-11; median MR PIRADS was 4 (4-5). Of 9 Gleason 6 lesions identified on pathology, PSMA-11 detected 3 and IAB2M detected 2. Four extra-prostatic lesions in one patient were detected by both PET agents, 3 were confirmed by surgical pathology and 1 confirmed on bone scan 2 months post-op. A total of 8 lesions reported on scans were not reported by path: 3 were false positive on both scans, 3 were false positive on IAB2M scan only and 2 were false positive on PSMA-11 scan only. 5 Gleason 6 and 2 Gleason 3+4 lesions on pathology were missed by both PET agents and could be considered false negatives. Conclusions: In this small pilot series, performance of the both PET agents was very similar. An advantage of IAB2M is its hepatobiliary clearance rather than renal/urinary, which makes it potentially easier to visualize the PCa and/or pelvic disease; an advantage of PSMA-11 is the ability to image within 1 hour. Clinical trial information: NCT03675451.
Cost-effectiveness of a two-gene urine biomarker assay in MRI strategies for the initial detection of prostate cancer.
Authors: Govers Tim , Resnick Matthew J. , Trooskens Geert , Van Criekinge Wim , Schalken Jack A. 
Published: March 2019

91 Background: MRI is increasingly used in men with a suspicion for prostate cancer (PCa) to target abnormal areas next to systematic biopsy. Although, MRI increases the detection of clinically significant PCa compared to systematic biopsy alone, overdiagnosis and overtreatment of insignificant disease still exists. The 2-gene mRNA PCR urine test combined with traditional risk factors SelectMDx (MDxhealth Irvine Ca) predicts clinically significant PCa, and can be used to reduce overdiagnosis and overtreatment. We assessed the cost-effectiveness of SelectMDx in a population of U.S. men who in the current situation undergo initial MRI and biopsies. Methods: We developed a decision-analytic model to simulate the downstream outcomes in the current MRI strategy, i.e. systematic biopsy plus targeted biopsy in case of a positive MRI. SelectMDx was assessed in two different diagnostic pathways: 1) before MRI to select patients for MRI and biopsy, 2) after a negative MRI to select patients for systematic biopsy. Outcomes were quality-adjusted life years (QALYs) and costs. Model parameters were informed by literature. Two scenarios regarding the mortality of missed PCa were used, using SPCG trial data and using data from the PIVOT trial. Results: Using SelectMDx before MRI (1) resulted in a health gain of 0.003 and 0.030 QALY per patient compared to the current MRI strategy, using the SPCG and PIVOT data, respectively. Cost savings were $1590 per patient and about $496 million for the yearly population of men at risk in the U.S. (n = 311,879). SelectMDx after negative MRI (2) resulted in a health gain of 0.008 and 0,011 QALY per patient using the SPCG and PIVOT data.. Cost savings were $436 per patient and about $136 million for the yearly population. Conclusions: The use of SelectMDx to guide prostate biopsy decision-making can improve health outcomes and lower costs. Cost savings were highest when SelectMDx was used before MRI to select patients for MRI and biopsy. With respect to health gain, the use of SelectMDx after negative MRI was most beneficial when assuming higher mortality for missed PCa (SPCG). When the mortality was assumed to be lower (PIVOT) SelectMDx should be used before MRI to result in the highest health gain.
Clinical utility study of confirms mdx for prostate cancer in a community urology practice.
Authors: Yonover Paul , Steyaert Sandra , Cohen Justin J. , Ruiz Celeste , Grafczynska Karolina , Garcia Elizabeth , DeHart Jessica , Brawer Michael , Groskopf Jack , Van Criekinge Wim 
Published: March 2019

94 Background: There is an unmet need for methods to better identify patients most likely to benefit from repeat prostate biopsy after an initial negative biopsy. ConfirmMDx is a molecular test clinically validated for detection of prostate cancer (PCa) in tissue from PCa-negative biopsies. In this clinical utility study, we evaluated the impact of ConfirmMDx on the management of patients being considered for repeat prostate biopsy in a community urology practice. Methods: The study population consisted of 605 men with a prior PCa-negative prostate biopsy, who were counseled on the need to undergo repeat biopsy at a large community urology practice due to persistent elevated risk of PCa. All tissue cores from each PCa-negative patient were tested with the ConfirmMDx methylation-specific PCR test, and positive or negative ConfirmMDx results based on the presence or absence of GSTP1, APC or RASSF1 methylation in the biopsy tissue. ConfirmMDx results were provided to the physician for use in repeat biopsy decision-making. Medical record review was conducted at a minimum of nine months after ConfirmMDx results were reported. Results: Of the 605 subjects enrolled, 308 (51%) had a negative ConfirmMDx test result and 297 (49%) were positive. For the entire study population, average age was 64 (median 64, interquartile range 59 to 69), average serum PSA level 6.8 ng/mL (5.7, 4.3 to 8.1). The median follow-up for both Confirm positives and negatives was 10 months post-testing. Repeat biopsy rates for ConfirmMDx positive and negative men were 32.3% (96/297) and 5.8% (15/308), respectively (P < 0.001). For patients who received a biopsy during the follow-up period, the time between ConfirmMDx and repeat biopsy was shorter for ConfirmMDx positive men versus ConfirmMDx negatives (median 4 vs. 8 months, P = 0.007). Conclusions: In this utility study, ConfirmMDx had a significant impact on repeat prostate biopsy decision-making in a U.S. community urology setting. Repeat biopsy rates in ConfirmMDx positive men were six-fold higher than in ConfirmMDx negatives. These results reflect the clinical utility of ConfirmMDx for biopsy decision-making in real world clinical practice.
A randomized phase Ib/II study of nivolumab with or without BMS-986253 in combination with a short course of ADT in men with castration-sensitive prostate cancer (MAGIC-8).
Authors: Dallos Matthew , Aggen David Henry , Hawley Jessica , Lim Emerson A. , Stein Mark N. , Kelly William Kevin , Nanus David M. , Drake Charles G. 
Published: March 2019

TPS329 Background: Androgen deprivation therapy (ADT) is highly effective in castration-sensitive prostate cancer (CSPC) but is associated with significant side effects. Novel strategies to reduce ADT exposure and prolong disease control are needed. ADT initially induces a complex immune infiltrate within prostate tumors, suggesting that immunologic intervention may be more effective at the time of castration. Emerging data suggests that the cytokine interleukin-8 (IL-8) recruits immunosuppressive polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into the tumor microenvironment (TME) of many malignancies, including prostate cancer and serum IL-8 levels correlate with lack of response to anti-PD-1 therapy. We hypothesize that immunotherapy with nivolumab (a PD-1 inhibitor) with or without BMS-986253 (an IL-8 inhibitor) combined with degarelix (an LHRH antagonist) will be safe and promote an anti-tumor immune response that can prolong time to disease relapse in CSPC. Methods: This is a randomized, multicenter, two-arm, phase 1b/2 trial of patients with biochemically-recurrent or low volume metastatic CSPC and a rapidly rising PSA (≤12 months). 60 patients will receive immunotherapy with nivolumab or nivolumab plus BMS-986253 for 24 weeks. 16 weeks of ADT with degarelix will be added after 8 weeks of immunotherapy alone. The primary endpoints are safety and PSA relapse rate 10 months after the initiation of therapy. Secondary endpoints include relapse-free survival (RFS), time to testosterone recovery, rate of metastatic progression and change in PSA with immunotherapy alone. Correlative studies will quantify the systemic immune response through cytokine analysis and peripheral T cell profiling using serum and whole blood specimens collected from all enrolled patients. Pre- and on-treatment biopsies will also be obtained from the subgroup of patients with metastatic disease to further define changes in the TME using RNA-sequencing and quantitative multiplex immunofluorescence. The study is open with 1 patient currently enrolled at the time of submission. Clinical trial information: NCT03689699.
A phase II, dose finding, placebo-controlled, study of zuclomiphene citrate to amerliorate the frequency and severity of hot flashes caused by androgen deprivation in men with advanced prostate cancer.
Authors: Getzenberg Robert H. , Rodriguez Domingo , Hancock Michael L , Fisch Harry , Steiner Mitchell S. 
Published: March 2019

TPS338 Background: Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. ADT not only lowers testosterone, but also decreases estrogen levels which can cause significant side effects including hot flashes, loss of bone and bone fractures, and decreases in libido. Up to 80% of the men on ADT report hot flashes and 30-40% of men have moderate to severe hot flashes. Concern over hot flashes make patients less likely to begin ADT and can lead to early discontinuation of ADT. While the off-label use of potent steroidal estrogens has demonstrated efficacy, the appropriate dose as well as dosing route or schedule of these potent estrogens, has not been established. Furthermore, the potential for safety issues with potent steroidal estrogens remains a significant limitation to their clinical utility. Zuclomiphene citrate, is novel weak nonsteroidal estrogenic agent that should ameliorate hot flashes caused by ADT, and as one of the isomers of clomiphene, has a 50 year safety history of being well tolerated in men. Methods: The Phase 2, placebo controlled, dose finding clinical trial (V72203) evaluating zuclomiphene citrate (VERU-944) capsules, oral daily dosing, for the treatment of moderate to severe hot flashes in men with prostate cancer on ADT is in progress. Men are randomized to daily doses of placebo or zuclomiphene 10mg, 50mg or 100mg. V72203 is enrolling approximately 36 men per arm in 10 sites in the United States. The primary efficacy endpoint is the mean change in frequency of moderate and/or severe hot flashes from baseline to week 4 and maintained until week 12. Secondary endpoints include changes from baseline in bone turnover markers, free and total testosterone, SHBG, PSA, and safety. Hot flashes are being measured in real time utilizing an electronic data capture device (ePRO) provided to each subject. We anticipate completion of enrollment by the end of 2018 with study results by second quarter of 2019. Clinical trial information: NCT03646162.
PROPEL: A randomized, phase III trial evaluating the efficacy and safety of olaparib combined with abiraterone as first-line therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Clarke Noel W. , Armstrong Andrew J. , Thiery-Vuillemin Antoine , Oya Mototsugu , Ye Dingwei , Mateo Joaquin , Goessl Carsten Dietrich , Kang Jinyu , Liu Sherry , Saad Fred 
Published: March 2019

TPS340 Background: A Phase II trial showed olaparib (tablets, 300 mg bid) in combination with abiraterone (1000 mg od plus prednisone/prednisolone 5 mg bid) significantly prolonged radiologic progression-free survival (rPFS) compared with abiraterone alone (median 13.8 vs 8.2 months; hazard ratio 0.65, 95% CI 0.44–0.97, P=0.034) in patients (pts) with mCRPC in the second-line metastatic setting who received prior docetaxel (Clarke et al. Lancet Oncol 2018). Treatment benefits were achieved irrespective of homologous recombination repair (HRR) mutation status, suggesting potential synergy between the two treatments that could impact a broader patient population. PROpel (EudraCT: 2018-002011-10) is the follow-on study to this, and the first Phase III trial to assess a PARP inhibitor in combination with abiraterone as first-line treatment in a genetically unselected mCRPC pt population. Methods: PROpel is a double-blind, placebo-controlled, international, multicenter study of pts randomized (1:1), as for the Phase II trial, to abiraterone (1000 mg od plus prednisone/prednisolone 5 mg bid) plus either olaparib (tablets, 300 mg bid) or placebo. Pts must not have received prior chemotherapy, new hormonal agents or other systemic treatment at mCRPC stage (except docetaxel at metastatic hormone-sensitive prostate cancer stage [mHSPC]). Randomization is stratified according to site of metastases (bone only vs visceral vs other) and docetaxel treatment at mHSPC stage (yes, no). The primary endpoint is investigator-assessed rPFS (RECIST v1.1 [soft tissue] and Prostate Working Cancer Group 3 [PCWG-3 criteria; bone]). Secondary objectives include time to first subsequent therapy or death, time to pain progression, overall survival, and health-related quality of life. Safety and tolerability will also be described. Exploratory endpoints include HRR subgroup analyses to confirm that efficacy is independent of HRR status. Screening across ~200 sites in 20 countries is being conducted to identify a target sample of ~720 pts. Enrollment is expected to begin in October 2018. (Study 8, NCT01972217). Clinical trial information: NCT03732820.