bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between PSA kinetics and detection rate of PSMA-PET in the setting of biochemical recurrent prostate cancer: A systematic review and meta-analysis.
Authors: Pereira Mestre Ricardo , Treglia Giorgio , Ferrari Matteo , Pascale Mariarosa , Mazzara Calogero , Azinwi Ngwa C , Llado Anna , Stathis Anastasios , Giovanella Luca , Roggero Enrico 
Published: March 2019

71 Background: Serum prostate-specific antigen (PSA) may predict the risk of positive positron emission tomography/computed tomography with radiolabeled prostate-specific membrane antigen (PSMA-PET/CT) in patients with biochemical recurrent prostate cancer (BRPCa). However, to date, there are no clear data regarding the correlation between PSA kinetics and PSMA-PET findings. We performed a systematic review and meta-analysis to provide evidence-based data in this setting. Methods: A comprehensive literature search of studies published through October 2018 in PubMed/MEDLINE, EMBASE and Cochrane library databases was performed. A meta-analysis to establish the detection rate (DR) of PSMA-PET using different cut-off values of PSA doubling time (PSAdt) and a pooled analysis to establish whether shorter PSAdt may predict positive PSMA-PET results was performed in patients with BRPCa. Results: Twelve articles were included in the systematic review and eight articles (including 1398 patients) were selected for the meta-analysis. The pooled DR including 95% confidence intervals (95% CI) of PSMA-PET in restaging prostate cancer (PCa) patients was 72% (95% CI: 60-82%), increasing to 83% (95% CI: 75-90%) when PSAdt was ≤ 6 months and decreasing to 60% (95% CI: 37-80%) when PSAdt was > 6 months. PSAdt ≤ 6 months may predict the positive result of PSMA-PET (pooled odds ratio: 3.22; 95% CI: 1.17-8.88). Statistical heterogeneity among the included studies was found. Conclusions: PSA kinetics, and in particular shorter PSAdt, may be predictor of PSMA-PET positivity in patients with BRPCa. Further larger studies in this setting are warranted.
Cascade testing of men with prostate cancer in families with a spectrum of inherited cancers: Importance of attention to race.
Authors: Giri Veda N. , Chandrasekar Thenappan , Hegarty Sarah , Gross Laura , Leong Joon Yau , Gomella Leonard G. 
Published: March 2019

75 Background: Prostate cancer (PCa) is increasingly recognized as a part of hereditary cancer syndromes (HCS) with implications for cascade genetic testing (CGT) of men with PCa in these families. However, race-specific rates of HCS in probands presenting for inherited cancer assessment who report a family history (FHx) of PCa is not known has implications for CGT of men with PCa. Methods: A prospectively maintained genetic testing database at a tertiary care cancer genetics program was queried for all probands reporting a PCa FHx. Pedigrees were analyzed for three HCS linked with PCa: hereditary breast and ovarian syndrome (HBOC), classic Hereditary PCa (HPC), and Lynch syndrome (LS). Associations between HCS and race were evaluated using Fisher’s exact test. Each HCS was evaluated for potential genetic link to the male relative with PCa and associations with race were tested using Fisher’s exact test. Results: 345 probands met inclusion criteria: 53 African-American (AA), 292 Caucasian (Wh), 74.5% female. Proband cancer diagnoses included breast (43.2%), prostate (12.8%), pancreatic (3.8%), ovarian (3.2%), and colorectal (2.9%). Overall, 63.8% of probands met criteria for ≥ 1 HCS based on personal and FHx. Male relatives with PCa in these families with potential genetic link to HCS were found in 75.5% AA families and 61.6% Wh families. HBOC was identified in a higher percentage of AA families with a potentially-linked male relative with PCa compared to Wh families (69.8% vs. 52.4%, respectively; p=0.051). Among probands with HCS potentially linked to PCa (n = 169), 19.5% were found to carry a genetic mutation in a cancer risk gene (17.9% AA and 19.9% Wh). BRCA1/2 mutations accounted for all mutations identified in AA probands and 66.7% of Wh probands. Conclusions: A significant percentage of patients who present for inherited cancer assessment report a FHx of PCa potentially linked with a HCS. Importantly, AA probands with a PCa FHx have comparable rates of HCS as Wh probands, with potentially higher rates of HBOC in AA families accounted for by BRCA mutations. Cascade testing of men with PCa in families with HCS is crucial with a need to address any race-specific barriers.
A genomic classifier shows improved prediction of oncologic outcomes in African-American men treated with radical prostatectomy.
Authors: Freedland Stephen J. , Du Plessis Marguerite , Zhang Jingbin , Howard Lauren , de Hoedt Amanda , Davicioni Elai 
Published: March 2019

8 Background: Accurate risk stratification after radical prostatectomy (RP) is important to help select men at risk of recurrence who will benefit most from postoperative radiation or multi-modal therapy. Increasingly genomic testing is being used in the clinic for this purpose. However, little is known about how these tests predict outcomes in African-American men (AAM), an underserved at risk population. Here we evaluate Decipher within a large Veteran Affairs cohort and compare its performance to the CAPRA-S clinical model for predicting outcomes in patients. Methods: Decipher genomic classifier (GC) scores were generated for 557 patients, who underwent RP at the VA Medical Center Durham between 1989 and 2016. This was a clinically high-risk cohort which all underwent RP. Cox UVA and MVA proportional hazards models and survival c-index were used to compare the performance of Decipher and CAPRA-S for predicting risk of metastasis and PCa specific mortality (PCSM). Results: Overall, 55% (n = 306) of patients in the cohort were AAM. CAPRA-S classified 10.4% as low risk for recurrence while for GC it was 50.4%. With a median follow-up of 9 years, only 40 patients developed metastases and 18 patients died of PCa. In multivariable analyses, both GC (p = 0.044 HR:1.30 95% CI:1.01-1.69) and CAPRA-S (p = 0.037 HR:1.27 95% CI:1.01-1.58) were significant predictors for metastasis within non-AAM; however, only GC (p < 0.001 HR:1.70 95% CI:1.31-2.20), was significant within AAM. GC but not CAPRA-S was a significant predictor of PCSM for both EAM (p = 0.044 HR:1.54 95% CI:1.01-2.53) and AAM (p = 0.002 HR:1.65 95% CI:1.19-2.42). The survival c-index of GC for predicting metastasis 8 years post RP was 0.84 (95% CI: 0.76-0.90) in AAM and 0.70 (95% CI:0.63-0.80) in non-AAM. For PCSM endpoint, it was 0.82 (0.61-0.93) in AAM and 0.73 (95% CI:0.63-0.84) in non-AAM. Conclusions: Our results among non-AAM confirm many prior studies showing that GC is a powerful predictor of metastasis and PCSM. Among AAM, not only was GC a very strong predictor of poor outcome, there was actually a suggestion that GC may perform better among AAM than EAM, though this requires further validation.
Machine learning approaches to improve prostate cancer outcome.
Authors: Rodrigues Pereira Ronnie , Miller Crispin , Baena Esther , Bristow Robert G. 
Published: March 2019

82 Background: High-risk Prostate Cancer (PCa) occurs in as much as 37% of PCa cases in England and Wales. This proportion is much higher than in other developed countries. Furthermore, there is an imprecision in the primary treatment of these patients. More specifically, in the administration of systemic therapy. Currently, surgeons prescribe radical prostatectomy and radiation, while radiation oncologists often combine radiation with androgen deprivation therapy (ADT). However, ADT has significant side effects and not all patients develop Biochemical Recurrence/Metastasis. Furthermore, clinical factors have limited ability to identify these patients. Consequently, we turn to biomarker discovery for more accurate disease management. Methods: We applied a machine learning strategy to identify discriminatory DNA Methylation patterns between patients with biochemical recurrence from those with stable disease in high-risk PCa (D’Amico Classification, T-stage ≤ 3a). Training and feature selection occurred in cross-validation (4 Folds, 10 reps) on 102 patients from the TCGA-PRAD dataset (26 BCR). Gene co-expression networks were derived from mRNA expression (|Pearson correlation| > 0.70). Network clustering maximised global modularity (Louvain algorithm) and unsupervised clustering evaluated complete linkage. Functional enrichment employed MiSigDB Hallmarks and g:ProfileR. Results: A linear support vector machine outperformed Naïve Bayes, Random Forest and Artificial Neural Networks with an AUC = 0.91 ± 0.14 (95% CI). This epigenomic test preferentially sub-stratifies high-risk patients, as it shows no improvement over the “No Information Rate” of intermediate- and low-risk patients (p-value > 0.05, t-test). We identified functional clusters from a co-expression network superimposed with the genes most correlated to the epigenomic test. The most enriched cluster reveals disturbances in MYC targets, cell cycle and RNA splicing. Conclusions: Preliminary results indicate that an epigenomic test identifies a sub-group of patients which could benefit from ADT at the stage of primary treatment, however it requires further validation.
Changing physician PSA screening behavior in men 70 years of age and older by use of the electronic medical record.
Authors: Presti Joseph , Alexeeff Stacey , Horton Brandon , Prausnitz Stephanie , Avins Andrew 
Published: March 2019

85 Background: Since 2013, both the United States Preventive Services Task Force and the Kaiser Permanente National Prostate Cancer Guidelines have recommended against PSA-based screening for prostate cancer in men ≥70 years of age. Adherence to these guidelines has been variable. A “Best Practice Alert” (BPA) was activated in the electronic medical record (EMR) system in October 2015 at Kaiser Permanente Northern California (KPNC). This alerted physicians, in real time, if they attempted to order a PSA test in a man ≥70 years of age with no history of prostate cancer. No additional physician training or education was used. The objective of the present study was to determine the impact of this BPA on the frequency of inappropriate PSA testing. Methods: This was a retrospective study spanning the years 2013 to 2017, in men ≥70 years of age in KPNC with no prior history of prostate cancer. We compared the annual rates of PSA testing between the pre-BPA period, 2013 and 2014; and the post-BPA period , 2016 and 2017 (the post-BPA period began 3 months after the BPA was instituted). The primary outcome was the annual rate of PSA testing. The percent change between the two time periods, the rate ratio and 95% confidence interval (CI) were calculated. Results: The annual number of eligible men (men ≥70 years of age and no history of prostate cancer) and annual number of these men undergoing PSA testing are shown in the Table. Annual screening rates declined from 34.3% in the pre-BPA era to 13.5% in the post BPA era. The rate ratio was 0.394 (95% CI, 0.390-0.398). Conclusions: Following the activation of a simple and inexpensive BPA within the EMR, the rate of inappropriate PSA testing decreased 61% in men ≥70 years of age. This change was durable over the study period, demonstrating that well-conceived, straightforward interventions can have a marked effect on physician behavior. [Table: see text]
Immune infiltrate with CD8 low or PDL1 high associated with metastatic prostate cancer after radical prostatectomy (RP).
Authors: Vicier Cecile , Werner Lillian , Huang Ying , Hamid Anis , Evan Carolyn , Loda Massimo , Sweeney Christopher 
Published: March 2019

86 Background: Given limited information about the prostate cancer (PC) immune infiltrate in men with localized disease, we profiled 6 markers and correlated them with risk of metastases after RP, using a single-institution cohort. Methods: Using a tissue microarray (TMA) with formalin-fixed, paraffin-embedded radical prostatectomy specimens, we performed a multiplex immunohistochemistry (IHC) analysis of immune checkpoint markers (PD1, PDL1), T-cell regulator / helper (FOXP3, CD4) and killer T cells (CD3, CD8). Quantitative multispectral imaging analysis was used to define the “density” of each marker: a ratio between number of positive cells divided by glandular and stromal area. Data collected included patient characteristics, time to biochemical relapse (BCR), time to metastasis (M1) and overall survival (OS). Results: TMA staining resulted data for at least one marker for 129 patients and all 6 markers for 109 patients. Median follow-up for this cohort was 14 years (0.25-27 years). As detailed in the table, either low CD8 or high PDL1 had a statistically significant association with biochemical and metastatic relapse and trend toward poorer OS on univariate analysis (UVA). A risk score of 0, 1 or 2 with CD8 low and PDL1 high each being one point revealed a strong association with higher score and incremental risk of BCR and metastasis. Conclusions: Multiplex IHC profiling of primary prostate cancer revealed high PDL1 and low CD8 density as poor prognostic markers alone and more impactful as part of a risk score for biochemical and metastatic relapse. [Table: see text]
Prospective evaluation of a new patient decision aid to enhance prostate cancer screening decision-making.
Authors: Brooks Michael Austin , Misra-Hebert Anita , Zajichek Alexander , Carlsson Sigrid V. , Hugosson Jonas , Kattan Michael W. , Stephenson Andrew J. 
Published: March 2019

87 Background: We previously developed screening nomograms to predict 15-year risk of all-cause mortality, prostate cancer diagnosis, and prostate cancer mortality, and incorporated them into a graphical patient decision aid (PtDA). Our objective was to prospectively recruit primary care patients interested in shared-decision making regarding prostate specific antigen (PSA) screening and assess the impact of individualized counseling using our new PtDA. Methods: 50 patients from one internal medicine practice were enrolled in a single-arm sequential trial design, with face-to-face clinician counseling and questionnaires. Eligibility criteria included men age 50-69 years old and life expectancy > 10 years. Patients were excluded for a personal history of prostate cancer or PSA screening within the prior year. Participants completed baseline questionnaires regarding prior PSA testing, demographic information, health literacy, and the Control Preferences Scale (CPS). They then received standardized counseling (based on large trial and epidemiologic data) regarding PSA screening, followed by individualized counseling using our new PtDA. Participants then made a screening decision, and completed a post decision questionnaire including a Decisional Conflict Scale. Results: The median age was 60 (IQR 54; 65). 41 (82%) had a prior PSA test, while 9 (18%) had not. 42 (84%) of participants received some education beyond high school, 41 (82%) demonstrated high health literacy, and 45 (90%) desired to have an active role in decision-making based on the CPS. After undergoing counseling, 34 (68%) participants chose to undergo initial or repeat PSA screening, 8 (16%) chose against future screening, and 8 (16%) remained uncertain. 45 (90%) participants found individualized counseling using the PtDA more useful than standardized counseling. Finally, patients reported reduced decisional conflict compared to historical controls (P < 0.001). Conclusions: Our process of standardized counseling followed by individualized counseling using our new PtDA was effective in reducing decisional conflict. The majority of participants found the PtDA more useful for decision making than standardized counseling. Clinical trial information: NCT03387527.
Outcomes of active surveillance for African-American men with prostate cancer: Results of a matched analysis.
Authors: Thomas Lewis , Nyame Yaw A. , El-Shafei Ahmed , Dai Charles , Ganesan Vishnuvardhan , Zampini Anna , Arora Hans , Crane Alice , Hettel Daniel , Fareed Khaled , Stein Robert , Gong Michael C. , Klein Eric A. , Stephenson Andrew J. 
Published: March 2019

89 Background: Prior work has questioned the safety of active surveillance (AS) for African-American (AA) men with prostate cancer. However, studies of AA men on AS are rare, and some show contradictory results as more AA men may undergo definitive therapy leaving a well-selected AS population. To overcome these limitations we performed a retrospective matched cohort study of AA men on AS. Methods: We queried our AS database (2000-2016) for all AA patients. AA men were matched to non-AA men using a 1:1 algorithm based on National Comprehensive Cancer Network (NCCN) risk, age at diagnosis, and year of diagnosis. Cohorts were compared on outcomes of NCCN risk reclassification, receipt of treatment, post-treatment recurrence, development of metastases, and prostate cancer specific mortality. Results: Fifty-nine AA patients were identified and matched, including 18 very low risk (31%), 24 low risk (41%), and 17 intermediate risk patients (29%). Groups were equally matched by NCCN risk and year of diagnosis, and had similar ages at diagnosis (65.6 years AA, 65.9 years non-AA, p=0.97). Initial PSA values were similar between groups (5.2 AA versus 5.1 non-AA, p=0.77). Rates of risk reclassification during AS were higher among AA patients (54% versus 39% p=0.09), though treatment (46% vs 44%) and post-treatment recurrence (11% vs 19%) rates were similar. While AA patients were more often reclassified, many were due to PSA rise (40% AA, 8% non-AA upgraded by PSA alone) rather than pathologic upgrading. AA patients had a longer time to reclassification and treatment than non-AA patients (2.9 and 2.8 years vs 0.9 and 1.0 years, p=0.14). Similar follow-up time was noted (AA 6.0 years versus non-AA 6.4 years, p=0.91). One patient in each group developed metastases. No cancer specific mortalities occurred. Conclusions: In a matched analysis of AA versus non-AA patients on AS, rates of risk reclassification were higher among AA patients, though receipt of treatment and treatment outcomes were similar between groups. Metastatic progression and prostate cancer mortality were rare in both groups. AS appears to be a reasonable option for AA patients with long treatment free periods and reasonable post-treatment outcomes.
Trends in complementary and alternative medicine use among newly diagnosed prostate cancer patients.
Authors: Zuniga Kyle Brian , Zhao Shoujun , Cedars Benjamin E , Cowan Janet E. , Kenfield Stacey , Van Blarigan Erin , Broering Jeanette M , Carroll Peter , Chan June M. 
Published: March 2019

92 Background: Complementary and alternative medicine (CAM) use is common among prostate cancer (PCa) patients. The benefits and risks of the majority of CAM is inconclusive, and thus understanding trends in use is necessary to guide future research. We sought to investigate the prevalence of CAM use and trends in newly diagnosed PCa patients using the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Methods: Between 1996-2017, 7,989 CaPSURE subjects completed questionnaires on use of over 50 CAM types. For prevalence, subjects were identified as users if they ever indicated CAM use. We then performed univariate analyses to examine associations between sociodemographic and clinical characteristics with CAM use using chi-squared tests. To observe trends in CAM use among newly diagnosed patients, we limited subject responses to questionnaires completed within 24 months of diagnosis (7,358 subjects). We then grouped subjects by diagnosis year and calculated percent change in use. Results: Overall, 56% of subjects reported any CAM use. Commonly used CAM were multivitamins (40% of participants) and essential fatty acids and omega-3 (24% of participants). Compared to non-CAM users, a greater proportion of CAM users were college-educated, had a higher household income, and lived in the West and Midwest regions of the U.S (all p < 0.01). In exploring trends, we found that overall CAM use increased by +203% (19% to 56%) between those diagnosed in 1996-1999 and 2010-2017. Between those diagnosed in 2005-2009 and 2010-2017, the largest changes in use were seen in acupuncture (+289%), Vitamin D (+204%), selenium (-59%), and vitamin E (-39%). Conclusions: PCa patients reported widespread CAM use in 1996-2017. Multivitamins were the most prevalent CAM, and use of acupuncture and Vitamin D increased dramatically. This information may help to prioritize research needs and reinforces the importance of discussing CAM use with patients, with referral to specialists (e.g., nutritionists) when indicated.
Preoperative radiotherapy for high-risk prostate cancer (PORT-PC) trial.
Authors: Nagar Himanshu , Formenti Silvia , Scherr Douglas , Hu Jim C. , Schlegel Peter , Kang Josephine , Robinson Brian D. , Khani Francesca , Nanus David M. , Tagawa Scott T. , Molina Ana M. , Faltas Bishoy Morris , Margolis Daniel , Barbieri Christopher 
Published: March 2019

TPS137 Background: Prostatectomy has become the most common treatment for high-risk prostate cancer. After prostatectomy, risk features for local recurrence include extra-capsular extension and/or seminal vesicle invasion (pT3 disease) and positive surgical margins. Post-operative radiotherapy is recommended for patients with pT3 disease, positive margins and/or Group Grade 4-5 and has been shown to reduce the risk of recurrence. In planning adjuvant radiotherapy, the clinical target volume is the prostate bed which is difficult to delineate once the prostate has been surgically removed and can be overestimated by following the location of surgical clips. As such, controversy exists as to the optimal target volume. Guidelines suggest including a significant portion of the posterior and inferior aspects of the bladder, and anterior aspect of the rectum exposing a significant amount of normal tissue to high dose radiation. Pre-operative radiotherapy potentially offers the following advantages: 1) reduced radiation dose to normal tissues; 2) ability to utilize stereotactic body radiotherapy (SBRT) with real-time MRI guidance 3) patient convenience with less fractions and 4) radiobiologic advantage of high dose per fraction treatment delivery. Methods: This is a modified dose escalation trial for patients with high-risk prostate cancer defined as cT3 on MRI or Group Grade 4-5 disease. Patients will sequentially undergo 1) placement of a rectal SpaceOAR, 2) SBRT on the ViewRay MRIdian linear accelerator and 3) prostatectomy. As a modified dose escalation study, patients will be accrued starting at 5 Gy x 5 (up to 8 Gy x 5) with 3 patients per cohort with Grade 4 or 5 gastrointestinal (GI) and/or genitourinary (GU) adverse event related to preoperative radiotherapy as an unacceptable dose limiting toxicity.The primary endpoint is that a patient can undergo a radical prostatectomy after SBRT without a post-operative GI or GU grade 4 or 5 toxicity within 30 days related to preoperative radiotherapy. Secondary objectives include assessment of acute toxicity and quality of life scores. Exploratory analyses include analysis of tumor and normal biopsied and resected tissue and serum markers and interpretation of pre- and post-SBRT MRIs. Clinical trial information: NCT03663218.