bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is the most important predictor of renal function after opened and robotic partial nephrectomy? A propensity score matched study.
Authors: Nguyen Ngoc Ha , Joung Jae Young , Lee Sangchul , Lee Hakmin , Yu Young Dong , Jeong Chang Wook , Hong Sung Kyu , Lee Sang Eun , Byun Seok-Soo 
Published: February 2018

701 Background: This study was designed to investigate the parameters that predict the short term and long term renal function after opened partial nephrectomy (OPN) and robot-assisted partial nephrectomy (RPN). Methods: Medical records of 896 patients who underwent OPN and RPN between Feb 2004 to Apr 2017 at our institution were retrospectively reviewed. The propensity scores matching between of OPN and RPN group were performed with a ratio of 1:1. Postoperative outcomes were compared and multivariate logistic regression was performed to identify the parameters influencing acute kidney injury (AKI) and chronic kidney disease (CKD) progression. Results: No significant differences of preoperative characteristics were observed between two study groups after propensity score matching. RPN was significantly associated with longer warm ischemic time (WIT) (p < 0.001); yet, estimated blood loss (EBL), positive surgical margin (PSM) rate, major postoperative complication and CKD progression were significantly lower in RPN group (p values were < 0.001; 0.033; < 0.001; < 0.001 and 0.005 respectively). Multivariate analysis exhibited RPN is more favorable than OPN in terms of preserving renal function. Patients with a higher baseline estimated glomerular filtration rate (eGFR) were significantly associated with greater risk of AKI (OR = 1.036; 95% CI of OR 1.021-1.052; p < 0.001), but reduced risk of CKD progression (OR = 0.975; 95% CI of OR 0.955-0.994; p = 0.011). Other independent predictors of CKD progression included WIT (p = 0.025), age (p = 0.035), higher BMI (0.041) and diabetes mellitus history (p = 0.035). Conclusions: Age, BMI, diabetes mellitus history, baseline eGFR and WIT were the independent predictors of CKD progression after PN. RPN is more favorable than OPN for reducing EBL, PSM, major postoperative complication and renal function preservation.
Creation of a tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma.
Authors: Bhindi Bimal , Lohse Christine M. , Cheville John C. , Mason Ross , Tollefson Matthew K. , Harrington Susan , Dong Haidong , Parker Alexander S. , Boorjian Stephen A. , Thompson Robert Houston , Leibovich Bradley C. 
Published: February 2018

703 Background: Clinical and pathologic factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). We sought to determine if tissue biomarkers, along with our previously reported clinical metastases score, can be used to predict cancer specific survival (CSS) in patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients, 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2,12.8) and 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44; 95%CI 1.16-1.78; p < 0.001), high survivin (HR 1.35; 95%CI 1.08-1.68; p = 0.008), and the metastases score (HR 1.13 per one point; 95%CI 1.10-1.16; p < 0.001) were retained as independent predictors in the final multivariable model (c-index 0.69). Conclusions: We created a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy. External validation will be required prior to clinical use.
The diverse genomic landscape of low−risk prostate cancer.
Authors: Cooperberg Matthew R. , Erho Nicholas , Chan June M. , Feng Felix Y , Zhao Shuang , Simko Jeff , Cowan Janet E. , Lehrer Jonathan , Fishbane Nick , Alshalalfa Mohammed , Kolisnik Tyler , Chelliserry Jijumon , Margrave Jennifer , Aranes Maria , Du Plessis Marguerite , Buerki Christine , Tenggara Imelda , Davicioni Elai , Carroll Peter 
Published: February 2018

74 Background: Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores. In this study, we aimed to study the underlying tumor biology of this patient population, by interrogating patterns of gene expression among men with clinically low-risk tumors. Methods: Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling. These cases were compared to 1290 higher-risk biopsy cases with diverse clinical features from a prospective genomic registry. Average genomic risk (AGR) was determined from 18 published prognostic signatures, and MSigDB Hallmark gene sets were analyzed using bootstrapped clustering methods. These sets were examined in relation to clinical variables and pathologic and biochemical outcomes using multivariable regression analysis. Results: 408 (96%) of biopsies passed RNA quality control. Based on average genomic risk quartiles defined by the high-risk multicenter cases, the UCSF low-risk patients were distributed across the quartiles as 219 (54%), 107 (26%), 61 (15%), and 21 (5%). Unsupervised clustering analysis of the Hallmark gene set scores revealed 3 clusters, which were enriched for the previously described PAM50 luminal A, luminal B and basal subtypes. These three clusters did not associate with existing clinical or known genomic risk characteristics, suggesting a novel and independent classification for low-risk prostate cancer. AGR was associated with both pathological (OR: 1.3, p < 0.001) and biochemical outcomes (OR: 1.5, p = 0.001 ) but the clusters were not. Conclusions: Prostate cancers that are largely homogeneously low-risk by traditional characteristics demonstrate substantial diversity at the level of genomic expression. Molecular sub-stratification of low-risk prostate cancer may facilitate better decision-making with respect to both timing and intensity of cancer surveillance and treatment.
The impact of race on adverse pathologic features at the time of radical prostatectomy in men with prostate cancer and implications for adjuvant radiotherapy.
Authors: Jordan Gregory Arthur , Bhasin Richa , Block Alec , Gorbonos Alex , Quek Marcus Lee , Gupta Gopal Nand , Flanigan Robert Charles , Harkenrider Matthew M. , Solanki Abhishek A 
Published: February 2018

75 Background: Patients with adverse pathologic features (≥pT3 disease or positive margins) at the time of radical prostatectomy (RP) have higher biochemical recurrence (BR). Adjuvant radiotherapy (ART) reduces BR, but has potential toxicities. Also, studies suggest Black men are more likely to have aggressive prostate cancer. Our objective was to identify whether black men undergoing RP are more likely to have adverse pathologic features (APF) that lead to an indication for ART. Methods: We conducted a retrospective cohort study of men with cT1-4 Nx/0 Mx/0 prostate adenocarcinoma in the National Cancer Database who underwent RP. Race was divided into 3 groups (Caucasian, Black, Other). Chi-square tests and analysis of variance (ANOVA) tests were used to compare clinical and socioeconomic covariates between race groups. Univariate (UVA) and multivariable analysis (MVA) were performed using logistic regression (LR) to identify covariates predicting for APF. LR was performed to identify the impact of race on pT3 disease and positive margins. Results: A total of 313,013 patients diagnosed between 2004-2014 and undergoing RP were included. 256,315 (85%) were Caucasian, 33,725 (11%) were Black, and 12,973 (4%) were Other race. Fewer Black men had Gleason group 1 (33% vs. 41%) but more had Gleason group 2 disease (46% vs. 38%, p < 0.001). Black men more frequently had PSA ≥10 ng/ml (18% vs. 16%, p < 0.001) and ≥cT2b disease (18% vs. 14%, p < 0.001). On UVA, Black men were more likely to have APF (Odds Ratio [OR] 1.18; 95% Confidence Interval [CI] 1.15-1.21; [p < 0.001]). On MVA, black race was independently associated with having APF (OR 1.21; 95% CI 1.18-1.24; p < 0.001). Black men were more likely to have positive margins (OR 1.26; 95% CI 1.22-1.29; p < 0.001) but less likely to have ≥pT3 disease (OR 0.77; 95% CI 0.74-0.79; p < 0.001). Conclusions: Independent of socioeconomic and clinical factors, Black men undergoing RP are more likely to have APF, increasing the risk of BR in this group, and more frequently creating an indication for ART. This appears to be more due to positive margins than locally advanced tumor. The underlying cause of this disparity warrants further exploration.
Perspectives of health care professionals on active surveillance for the management of prostate cancer.
Authors: Saad Fred , Pang Kittie , Fitch Margaret , Ouellet Veronique , Chevalier Simone , Drachenberg Darrel , Finelli Antonio , Lattouf Jean-Baptiste , So Alan , Sutcliffe Simon , Tanguay Simon , Mes-Masson Anne-Marie 
Published: February 2018

81 Background: Active surveillance has gained widespread acceptance as a safe approach for patients with low risk prostate cancer. Despite presenting several advantages for both patients and the health care system, active surveillance is not adopted by all eligible patients. In this study, we evaluated the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach. Methods: We conducted five focus groups with a total of 48 health care providers (HCP) including family physicians, urologists, surgeons, radiation oncologists, fellows, and residents/medical students. These participants were all providing care for men with low risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of these HCP from academic hospitals in four Canadian provinces was captured. A content and theme analysis was performed on the verbatim transcripts to understand HCP decisions in proposing active surveillance and reveal the facilitators that affect the adherence to this approach. Results: Participants agreed that active surveillance is a suitable approach for low risk prostate cancer patients, but expressed concerns on the rapidly evolving and non-standardized guidelines for patient follow-up. They raised the need for additional tools to appropriately identify the patients best suited for active surveillance. Collaborations between urologists, radiation-oncologists, and medical oncologists were favoured, however, the role of general practitioners remained controversial once patients were referred to a specialist. Conclusions: Integration of more reliable tools and/or markers, and more specific guidelines for patient follow-up would help both patients and physicians in the decision-making for active surveillance.
The prospective assessment of the prostatic cancer mortality with PSA progression in the groups treated or not treated by salvage local brachytherapy.
Authors: Nietupski Karol Edward , Kulik Anna , Wiechno Pawel , Demkow Tomasz , Peczkowski Piotr , Pilichowska Małgorzata , Poniatowska Grazyna Maria , Michalski Wojciech , Rzymkowska Joanna , Sadowska Malgorzata , Ligaj Marcin , Kucharz Jakub , Jonska-Gmyrek Joanna , Wieczorek Ewa , Stencel Katarzyna 
Published: February 2018

85 Background: The effectiveness of diagnostics of local recurrence of prostatic adenocarcinoma after radical radiotherapy and local retreatment high definition brachytherapy and its influence on the prostatic cancer survival. Methods: 55 patients with locally advanced prostatic adenocarcinoma with rising PSA level after radical radiotherapy and exclusion of distant metastases underwent prostatic biopsy. ECOG performance status 0-1 were eligible. The histopathological confirmation was obtained in 22 cases, and 33 patients had negative biopsy. In the case of positive biopsy radical salvage brachytherapy was performed in all patients. In the case of negative biopsy definitive anti-androgen therapy was administered in patients with PSA progression. Anti – androgen therapy was performed as adjuvant and neoadjuvant treatment after brachytherapy. In the course of the long (median 108months) observation we assessed prostatic specific mortality in both groups. In addition we assessed time to PSA progression during the antiandrogen therapy Results: From Mar 2002 we observed 55 patients with rising PSA after radical radiotherapy for the prostatic adenocarcinoma. We confirmed local recurrence of prostatic adenocarcinoma in 22 cases. The median time to biopsy after radiotherapy was 41months. The median observation time after post-radiotherapy biopsy was 108 months. All of the 22 patients were treated with salvage brachytherapy. There were 8 prostatic cancer specific deaths, 1 in the group treated by brachytherapy and 7 in the non-treated group. Median prostatic cancer survival (PCSOS) was 120 months in the treated group vs 75,6 months non-treated, but this difference was not statistically significant (P value 0,49). Median time to progression PSA was 108 months in the treated group vs 48 months non-treated and was not statistically significant. Significant toxicity were not reported. Conclusions: In long time observation we revealed, including the time of antiandrogen treatment depletion therapy, that in the patients with rising PSA and local recurrence treated with high-dose brachytherapy have no worse prognosis than patients with no local progression.
Adjuvant enzalutamide (Enza) for men with non-metastatic high-risk prostate cancer (HRPCa) after radical prostatectomy (RP).
Authors: Ornstein Moshe Chaim , Stephenson Andrew J. , Elson Paul , Tyler Allison Janine , Profusek Pam , Allman Kimberly D , Barata Pedro C. , Magi-Galluzzi Cristina , Fergany Amr Farouk , Stein Robert , Fareed Khaled , Haber Georges-Pascal , Campbell Steven C. , Kaouk Jihad , Grivas Petros , Rini Brian I. , Klein Eric A. , Garcia Jorge A. 
Published: February 2018

88 Background: Management of HRPCa is a clinical challenge. Novel AR inhibitors could potentially impact outcome in HRPCa men following RP. We conducted a phase II study evaluating the efficacy/safety of Enza in men with HRPCa following RP. Methods: HRPCa pts (≥pT3a, GS≥8, iPSA ≥20 ng/mL, +ve lymph nodes (LN), or ≥35% chance of biochemical recurrence (BCR) at 5 yrs based on MSKCC’s nomogram) with undetectable PSA within 3 months from RP were eligible. Enza 160mg PO daily was given in 28-day cycles until disease progression, intolerability, consent withdrawal, or study completion at 24 months. Accrual goal was N=40 to provide 80% power to detect a 75% decrease in the risk of BCR from historical 55% rate. BCR was defined as PSA ≥0.2ng/mL on 2 consecutive lab results or any PSA rise that resulted in subsequent therapy. Results: 42 men enrolled. Median age 59 (range 43-70), based on biopsy 45% were GS7; 36% GS8, 19% GS9. 76% men had cT1, 24% cT2, median iPSA was 8.2 (range 2-77). On prostatectomy pathology: 50% had pT3b; 52% +ve margins; 50% SVI; 24% had +LN. 37 (88%) pts completed 24 planned cycles. Of the 5 pts who did not complete all cycles, 3 withdrew consent for toxicity (2 had G3 fatigue, 1 had G3 fatigue and arthralgias/myalgias), 1 had rising PSA requiring subsequent therapy, and 1 had financial concerns. With median follow-up of 31 months (range 2.5-44.5), 37 (88%) pts remain free of BCR. Of the 5 pts who developed BCR, 4 completed all 24 months on therapy. Median time to BCR was 31 months (range 13-40). Most common adverse events (AE) are listed (Table). Conclusions: Adjuvant Enza in men with HRPCa following RP is safe and relatively well-tolerated. Long-term safety, efficacy, and genomic correlations (including tumor RNA expression) are ongoing. Clinical trial information: NCT01927627. [Table: see text]
Evaluation of the MiCheck MIA test performance in differentiating aggressive from non-aggressive prostate cancer: The MiCheck-01 prospective trial.
Authors: Shore Neal D. , Pieczonka Christopher Michael , Henderson Ralph Jonathan , Bailen James L. , Beebe-Dimmer Jennifer Lynn , Ruterbusch Julie J. , Saltzstein Daniel R. , Concepcion Raoul S. , Borotkanics Robert , Levin Rachel , Wissmueller Sandra , Campbell Douglas , Walsh Brad ,   Minomic CUSP Authors
Published: February 2018

TPS152 Background: A diagnostic test which can better inform both clinicians and patients regarding a decision to proceed with a prostate biopsy, while still utilizing traditional parameters of Prostate Specific Antigen (PSA) kinetics and/or the digital rectal examination (DRE) is still an unmet need. The MiCheck® test is designed as a triage test to assist clinicians in the decision to proceed to prostate biopsy. The MiCheck®test is a simple blood test that measures the levels of the Glypican-1 protein and related signalling molecules. The MiCheck®-01 prospective trial builds on a previous pilot trial that examined the ability of the MiCheck® test to distinguish between normal subjects, patients with benign disease or Gleason 7 and above prostate cancer. The MiCheck® test showed sensitivity of 60% and specificity of 96% in distinguishing between subjects with Gleason ≥7 and normal or BPH patients. In a separate study, the MiCheck® test could differentiate aggressive (GS ≥3+4) from non-aggressive (GS 3+3) prostate cancer with a sensitivity of 85% and specificity of 90%. Methods: The trial consists of two arms: Arm 1 (normal patients, n = 50) and Arm 2 (prostate biopsy patients, n = 300). Inclusion criteria: Arm 1: Age ≥50, Low PSA (performed at most 12 months prior, defined as PSA < 1.5 ng/mL between ages 50 and 60 and PSA < 3 ng/mL above age 60). Arm2: Age ≥40, all subjects who are referred for or have undergone either a de novo or a repeat prostate biopsy for high PSA (defined as PSA ≥ 1 ng/ml between ages 40 and 49, PSA ≥2 ng/mL between ages 50 and 60 and PSA ≥ 3 ng/mL for age 60 and above age 60). Key exclusion criteria: prior history of cancer, patients taking ADT, DRE or other prostate manipulation within 72 hrs, subjects taking 5 ARIs. Results: The trial has recruited 30 Arm 2 patients to date. Interim analyses will be performed following accrual of 100 and 200 Arm 2 patients. Full accrual is expected by mid Q4 2017. Conclusions: Interim analysis data will be presented showing test performance. COI and Funding: The trial is funded by Minomic International Ltd. Neal Shore is a member of Minomic’s Clinical Advisory Panel.
Phase II study of olaparib (without ADT) in men with high-risk biochemically-recurrent prostate cancer following prostatectomy, with integrated biomarker analysis.
Authors: Teply Benjamin A. , Wang Hao , Sullivan Rana , King Serina , Handy Catherine , Lotan Tamara L. , Antonarakis Emmanuel S. 
Published: February 2018

TPS386 Background: Patients with a high-risk biochemical recurrence (BCR) of prostate cancer after local therapy, defined by a rapid PSA doubling time (≤6 mo), are likely to experience metastases and subsequently death from their disease. Early use of androgen deprivation therapy (ADT) in these patients is controversial and is associated with side effects. Non-hormonal therapies that alter the natural history of BCR disease are needed. Olaparib is a PARP inhibitor that produces responses in some men with advanced prostate cancer, particularly those with dysregulation of DNA repair genes (i.e. synthetic lethality). Preclinical data support the activity of olaparib in prostate cancer beyond the DNA repair-deficient subset, yet the optimal biomarker for treatment selection is unknown. We hypothesized that olaparib monotherapy would show activity in men with high risk BCR and sought to further define the optimal patient population for olaparib in this setting. Methods: In this investigator-initiated multi-center open-label study, eligible patients will have non-metastatic BCR after prostatectomy, with a PSA doubling time of ≤6 mo. Prior limited ADT is allowed, but testosterone must have recovered (≥150 ng/dL). Patients will receive 300mg olaparib twice daily, with disease evaluation by PSA monthly and radiographic studies every 6 mo. Patients continue olaparib until evidence of metastasis or until PSA doubles from baseline, with a minimum exposure of 3 months. The primary endpoint is the rate of decline in PSA to ≥50% from baseline (PSA50 response). Secondary endpoints include safety, progression-free survival, and the rate of durable responses. Exploratory analysis will involve biomarker discovery including somatic DNA mutation analysis, RNA expression analysis, and immunohistochemistry for DNA damage markers, done on prostatectomy specimens. The study will initially enroll an all-comer (unselected) population and will then proceed via a staged-adaptive design; if futility is observed in the all-comer population at interim analyses, enrichment with biomarker-selected patients will occur. Clinical trial information: NCT03047135.