bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-reported sexual and urinary function after open and robotic radical prostatectomy.
Authors: Klink Joseph C. , Li Jianbo , Klein Eric A. , Kaouk Jihad , Jones J. Stephen , Stephenson Andrew J. 
Published: February 2017

120 Background: Urinary continence (UC) and sexual function (SF) may be impacted differently after robotic-assisted laparoscopic (RALRP) versus open (ORP) radical prostatectomy. We compared UC and SF among patients treated by RALRP and ORP at a high-volume hospital who were enrolled in a prospective, longitudinal quality-of-life (QOL) protocol. Methods: Between 2007 and 2012, 516 patients treated by active surveillance, brachytherapy, cryotherapy, RALRP, and ORP were enrolled in a QOL protocol at our institution. The focus of this study is 361 patients who were treated by RALRP (N=190) and ORP (N=171). Functional outcomes were assessed at baseline and at 1, 3, 6, 12, and 24 months using a validated QOL instrument (Giesler RB et al. Qual Life Res 2000). SF was assessed by adding the scores from questions on the quality and frequency of erections. UC was assessed by adding the scores from three questions about the frequency and quantity of incontinence and pad usage. Wilcoxon rank sum test and linear regression multivariable analysis were used to assess SF and UC at each time point. Results: Treatment groups were similar in age, PSA, clinical stage, Gleason grade, BMI, baseline UC and SF scores and baseline PDE-5 inhibitor use (all P > 0.05), but the RALRP patients were slightly older (60 vs 61 years, p=0.04) and had larger prostates (38 vs 44 grams, p=0.001). On multivariate analysis, UC was worse in the RALRP cohort at 1 month (12.0 vs 10.9, P = 0.02), 3 months (9.9 vs 8.5, P = 0.01), and 6 months (8.1 vs 6.8, P=0.01) but was similar at 12 and 24 months (all P > 0.2). SF was similar between both RALRP and ORP at all time points (all P > 0.3). At 24 months, UC for RALRP and ORP was 7.1 vs. 6.4, respectively which was not significant in multivariable analysis (P = 0.5). Likewise, SF for RALRP and ORP was 5.3 vs. 6.2 (multivariable P = 0.9). On repeated measures analysis there was no difference between the groups in UC or SF (P=0.4 and 0.5, respectively). Conclusions: Prospectively collected, patient reported QOL endpoints for SF are similar after RALRP and ORP at all time points in a high-volume hospital. Final UC is similar between both techniques, although RALRP patients may experience a slightly slower return to continence.
Aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of men with metastatic castration-resistant prostate cancer (mCRPC): Results from the multinational phase III trial (VENICE).
Authors: Tannock Ian , Fizazi Karim , Ivanov Sergei , Karlsson Camilla Thellenberg , Flechon Aude , Skoneczna Iwona Anna , Orlandi Francisco Jorquera , Gravis Gwenaelle , Matveev Vsevolod B. , Bavbek Sevil E. , Gil Thierry , Viana Luciano S. , Aren Osvaldo Rudy , Karyakin Oleg , Elliott Tony , Birtle Alison J. , Magherini Emmanuelle , Hatteville Laurence , Tombal Bertrand , Rosenthal Mark ,   The VENICE Investigators
Published: February 2017

13 Background: Docetaxel/prednisone is standard first-line chemotherapy for mCRPC. Aflibercept (known as ziv-aflibercept in the US) is a recombinant human fusion protein that binds VEGF-A, VEGF-B and Placental Growth Factor (PlGF), thereby inhibiting angiogenesis. Methods: VENICE was a double-blind, randomized phase III study with overall survival (OS) as primary endpoint. Men with mCRPC, ECOG PS 0-2, adequate organ function and no prior cytotoxic therapy were treated with docetaxel (75 mg/m² iv q3w) and oral prednisone (5mg bid) and randomized double blind 1:1 to receive aflibercept (A) 6 mg/kg or placebo (Pbo), IV every 3 weeks. Pts were stratified by ECOG PS (0-1 vs 2). For final OS analysis, 873 deaths were required to detect a hazard ratio (HR) of 0.8 with 90% power (overall 2-sided α = 0.05). Results: From Aug 2007 to Feb 2010, 1224 patients (median age 68 yr, PS 0-1 96%) were randomized. Baseline characteristics were well balanced between arms. Median number of cycles was 8 (A) and 9 (Pbo). Median relative dose intensity was >0.93 for A, Pbo and docetaxel. At final cut-off, median follow-up was 35.4 mos and 873 pts had died. Results for primary and key secondary endpoints with confidence intervals are in the table. Higher incidence of all grade hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache and infections was observed in the aflibercept arm. Conclusions: Aflibercept in combination with docetaxel/prednisone given as first line chemotherapy for mCRPC did not lead to a statistically significant improvement in OS and added toxicity. (NCT00519285 sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.) Clinical trial information: NCT00519285. [Table: see text]
Real-world experience with sipuleucel-T in patients (pts) ≥80 years old with metastatic castration-resistant prostate cancer (mCRPC): Data from PROCEED.
Authors: Nabhan Chadi , Sartor A. Oliver , Cooperberg Matthew R. , Vacirca Jeffrey L. , Concepcion Raoul S. , Berry William R. , Dhawan Manish , Tutrone Ronald , Sandler Andrew , McCoy Candice , Whitmore James Boyd , Tyler Robert Claude , Higano Celestia S. 
Published: February 2017

131^ Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic mCRPC based on data from the phase III IMPACT pivotal trial that showed a significant improvement in overall survival (OS) compared to control (HR: 0.78 [95% CI: 0.61, 0.98]; P=0.03; median OS difference 4.1 mos). Analysis of IMPACT demonstrated evidence of a positive sipuleucel-T treatment effect in men above and below the median age of 71. We sought to understand the disease characteristics and product parameters in pts ≥80 years (yrs) given the high prevalence of older men in the mCRPC pt population. Methods: PROCEED is an ongoing, multicenter (>190 sites), phase 4 registry enrolling pts receiving sipuleucel-T. Information on antigen presenting cell (APC) activation and total nucleated cell (TNC) count were obtained during product manufacture. Results: Of 560 subjects who completed sipuleucel-T treatment to date: 110 (20%) pts were ≥80 yrs-old. Disease characteristics in pts ≥80 yrs vs <80 yrs are detailed in the table below. Product parameters were similar between groups. Conclusions: Pts ≥80 exhibit similar product parameters compared with their younger counterparts. Future follow-up will explore OS and correlations with immune parameters in both groups. Clinical trial information: NCT01306890. [Table: see text]
Predictors and prognostic implication of pathologic fracture (PF), spinal cord compression (SCC), and bone surgery (BS) following diagnosis of metastatic prostate cancer (PCa).
Authors: Onukwugha Ebere , Yong Candice , Mullins C. Daniel , Seal Brian S. , Hussain Arif 
Published: February 2017

133 Background: Information is limited about the predictors of PF, SCC, or BS and their relationship with PCa mortality in older men diagnosed with metastatic PCa. Methods: We analyzed patients aged 66 or older from the linked Surveillance, Epidemiology, and End Results & Medicare (SEER-Medicare) database. Cases were diagnosed with M1 PCa between 2000 and 2007. Patients surviving at least 30 days post-diagnosis were identified and followed until death or censoring in December, 2009. Post-diagnosis occurrence of PF, SCC, and BS was identified using Medicare claims. (Multinomial) logistic and Cox proportional hazards regression models controlled for demographic characteristics, preventive service use, comorbidity status, and performance status proxies. Survival models were estimated in the full sample (FS) and in a propensity-score matched sample (PSMS). The survival requirement was relaxed and patients diagnosed with stage M1b were considered in sensitivity analyses. Results: Application of inclusion criteria resulted in 7,062 patients in FS (2,398 in PSMS). PCa-specific and all-cause mortality were 54% and 80% at a median (mean; min; max) follow up of 609 days (837; 30; 3,653). The average age for the sample was 78 yrs and 14% were non-Hispanic African American. The proportion with any event, SCC, PF, and BS were: 17%; 10%; 5%; 3%. Race, marital status, comorbid conditions, and health services use related to bone metastases were correlated with the likelihood of sustaining a PF, SCC, or BS, with differences based on the type of event. In the PCa mortality model the HR associated with each event was as follows using FS: [SCC] HR 1.12, 1.01 – 1.24; [PF] HR 1.14, 1.00 – 1.31; [BS] 0.61, 0.50 – 0.75. Results using PSMS were: [SCC] HR 1.04, 0.92 – 1.17; [PF] HR 1.11, 0.96 – 1.28; [BS] 0.58, 0.47 – 0.72. Relaxing the assumption of a minimum survival requirement did not change qualitative results. Conclusions: Patient demographics and clinical comorbid conditions correlate with the likelihood of sustaining PF, SCC or BS. Compared to fractures and spinal cord compression, the relationship between bone surgery and PCa-specific survival is more favorable.
Are PSA baseline levels an indicator for suitability of intermittent androgen deprivation in patients with PSA relapse after radical prostatectomy?
Authors: Tunn Ulf W. , Canepa Giorgio , Kienle Erika 
Published: February 2017

136 Background: Intermittent androgen deprivation (IAD) for prostate cancer patients is currently discussed as a treatment option to improve quality of life and to delay hormone resistance. So far only limited data are available indicating whether certain subgroups of patients with PSA relapse without local recurrence after radical prostatectomy are best suited for this therapy. Methods: In a prospective randomized phase III trial, men with unfavourable prognostic factors and a systemic PSA progression (PSA ≥ 1ng/ml) following an initial fall to < 0.5 ng/ml within 3 months after radical prostatectomy were enrolled. They underwent a 6-months androgen deprivation (AD) induction phase with a microencapsulated leuprorelin acetate 3-month depot formulation plus an overlapping antiandrogen to prevent tumor flare-up. Achieving a PSA level < 0.5 ng/ml, they were randomized to either an IAD treatment arm or to continuous AD. In the IAD arm, retreatment was started when PSA rose to ≥ 3 ng/ml. During Off-Treatment-Time (OTT) PSA and Testosterone were controlled on a monthly basis. Results: Analysis of the first IAD cycle, confined as induction phase + OTT, revealed two subgroups of patients with a cycle length ≤ 15 months (group 1) and ≥ 20 months (group 2) respectively. This was due to a significant difference in the time from testosterone normalization (≥ 2.3 ng/ml, TN) to an increased PSA-value ≥ 3 ng/ml. See Table. Conclusions: Our data show a significant (p=0.001) relationship of low PSA baseline levels to delayed biochemical PSA progression during OTT. Thus IAD might be most suitable for patients with low PSA baseline levels leading to a slow increase of PSA after TN during OTT, providing time to improve quality of life and delay potential hormone resistance. Further large scale studies will be necessary to confirm our findings. Clinical trial information: AP 06/95.[Table: see text]
Exploratory analysis of the visceral disease (VD) patient subset in COU-AA-301, a phase III study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Goodman Oscar B. , Flaig Thomas W. , Molina Arturo , Mulders Peter , Suttmann Henrik , Li Jinhui , Kheoh Thian San , De Bono Johann Sebastian , Scher Howard I. 
Published: February 2017

14 Background: VD is a negative prognostic factor in mCRPC patients (pts) and may be less responsive to hormonal therapy. AA, a selective androgen biosynthesis inhibitor, inhibits androgen synthesis from adrenal and intratumoral sources. Improved overall survival (OS) with AA vs prednisone (P) was demonstrated in a randomized trial of pts with mCRPC post-docetaxel (D). Here we further assess the effect of AA on OS and other clinical outcomes in post-D mCRPC pts with VD (liver or lung, but not nodal-only metastases). Methods: In COU-AA-301, pts with mCRPC previously treated with D were randomized 2:1 to AA (1000 mg) + P (5 mg BID) (n=797) or placebo + P (n=398). The primary end point was OS. Data shown herein represent the updated analysis (775 events) of patients with (n=352) or without (n=843) VD. Results: The OS benefit of AA was similarly improved in patients with VD (4.6 m) and without VD (4.8 m) (Table). Treatment with AA led to significant 40% and 32% reductions in the risk of radiographic progression or death in patients with VD or without VD, respectively. Soft-tissue objective response rates were superior with AA in both groups. PSA response rates (50% reduction) were significantly improved by AA in both groups. Grade 3/4 adverse events (AEs) were similar in both groups. Hypertension, hypokalemia, and LFT abnormalities were observed with AA in pts with and without VD. Conclusions: AA has substantial anti-tumor activity and provides clinical benefit including improvements in OS and rPFS in post-D mCRPC pts with VD indicating it is a therapeutically active treatment option for CRPC pts. Safety/tolerability of AA in pts with VD was similar to that reported previously in mCRPC. Clinical trial information: NCT00638690. [Table: see text]
Detection and genomic interrogation of circulating tumor cells (CTCs) and circulating tumor stem cells (CTSCs) from men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Friedlander Terence W. , Ngo Vy , Doty Shaun , Zhao Qiang , Dong Huang , Ryan Charles J. , Chen Wen-Tien , Paris Pamela 
Published: February 2017

144 Background: Isolation, enumeration, and genomic profiling of CRPC CTCs offers the potential to discover genetic changes that occur in advanced disease. The Vitatex VitaCap platform captures CTCs based on their ability to invade collagenous matrices (CAM), allows for CTC and CTSC capture independent of EpCAM status, and yields viable cells suitable for comprehensive genomic analysis. In this study we sought to compare CTC yields between the VitaCap and the Veridex CellSearch platforms, to determine the utility of prostate-specific membrane antigen (PSMA) as a mCRPC CTC biomarker, to identify CTSCs and CTC clusters, and to explore the feasibility of CTC epigenomic analysis. Methods: CTCs were isolated and enumerated simultaneously using the CellSearch and VitaCap platforms in 23 men. CAM isolated CTCs and CTSCs were defined as EpCAM+PSMA+ and CD44+DPPA5+ respectively, and were enumerated immunocytochemically (ICC) and by flow cytometry. CTC clusters were enumerated by ICC. The Illumina HumanMethylation27 BeadChip was used to determine whole genome methylation status for CAM isolated cells. Results: 35 samples were collected for CAM analysis. A median of 27 (range 0-800) and 23 (range 2-390) CAM+ CTCs/ml were detected by ICC and flow respectively. In a subset of 20 samples, a median of 7 CTCs/ml (range 0-85) were detected by the CellSearch platform. CTCs were detectable by either CAM or CellSearch in >95% of samples. CAM isolated CTC clusters were observed in 23% of samples with a median 7 clusters/ml (range 1-200). CTSCs were detected in 70% and 97% of samples by ICC and flow respectively, with a median of 9 CTSCs/ml (range 1-264) by flow. The CTC methylation profile highly resembled mCRPC with hypermethylation occurring more frequently in pathways associated with apoptosis (p<0.006), angiogenesis (p<0.007), and VEGF signaling (p<0.003). Conclusions: CAM and CellSearch platforms yield comparable CTC counts. CTSCs and CTC clusters are detectable using the CAM platform, and the CTC methylome closely resembles that of mCRPC. Correlation with clinical data may yield further insight into the functional significance of these findings.
P10-1 open-label, multicenter study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) previously treated with sipuleucel-T: Evaluation of antigen-presenting cell (APC) activation.
Authors: Beer Tomasz M. , Glode L. Michael , Lance Raymond , Greengold Richard , Sims Robert Brownell , Wang Yang , Sheikh Nadeem A. , Corman John M. 
Published: February 2017

147 Background: Sipuleucel-T is an autologous cellular immunotherapy that has demonstrated an improvement in survival among men with asymptomatic or minimally symptomatic mCRPC. P10-1 (NCT01338012) is an open-label, multicenter study of sipuleucel-T in men with mCRPC previously treated with sipuleucel-T in the androgen-dependent setting on the PROTECT trial (a prospective, randomized, controlled Phase III study of sipuleucel-T in men with prostate-specific antigen recurrence following radical prostatectomy; NCT00779402). This preliminary analysis of P10-1 evaluates the pattern of APC activation in pts re-treated with sipuleucel-T after progression to mCRPC. Methods: Eligible pts include those previously treated with at least one infusion of sipuleucel-T on PROTECT and who progressed to the mCRPC state. Pts receive up to three additional infusions of sipuleucel-T. APC activation is assessed by CD54 upregulation expressed as the ratio of the average number of CD54 molecules on post-culture vs. pre-culture cells. Results: As of September 14, 2012, 7 pts have been enrolled and have received an infusion of sipuleucel-T. The median interval between the last infusion in PROTECT and the first infusion in P10-1 was 8.6 years. The Table shows a higher fold change in CD54 expression in the first P10-1 treatment compared with the initial infusion in PROTECT. Conclusions: This is the first report of pts re-treated with sipuleucel-T after prior treatment in an earlier disease setting. These preliminary data are consistent with the presence of an immunological memory response to the immunizing antigen several years following initial treatment. Clinical trial information: NCT01338012. [Table: see text]
Location of local recurrence after MRI-guided partial prostate brachytherapy targeting only the peripheral zone: Implications for focal therapy.
Authors: Kovtun Konstantin , Penzkofer Tobias , Agrawal Neha , Kapur Tina , Fedorov Andriy , Cormack Robert A. , D'Amico Anthony Victor , Tempany Clare M. , Nguyen Paul Linh 
Published: February 2017

149 Background: Prostate cancer local recurrences usually occur at the same site as the dominant primary tumor in patients treated with radiation therapy to the whole gland. We characterized location of local recurrences in patients who were treated with MRI Guided Partial Brachytherapy in which only the peripheral zone was targeted. Methods: We retrospectively reviewed ten patients with initial cT1c, Gleason score 3+4 or less prostate cancer who developed biopsy proven local recurrences and had available imaging after MRI Guided Partial Brachytherapy targeting the peripheral zone from 1998 to 2006. All 10 patients had 1.5T endorectal coil MRI at diagnosis, performed primarily for staging and not for tumor localization, while at recurrence 8 had 3T endorectal coil MRI and 2 had 1.5T endorectal coil MRI. Scans consisted of at least T1 and T2 sequences. Two radiologists (C.T. and T.P.) blinded to clinical data reviewed diagnosis MRI scans together and quantified likelihood of tumor on a 1 to 5 scale in each section of an eight part prostate in both pre-treatment and recurrence scans. Local recurrence was judged to be in the same location as the baseline tumor if at least 50% of the tumor location overlapped. Results: Only 3 of 10 patients had local recurrences at the same location as the baseline tumor with a mean overlap of 64%. 7 of 10 patients had local recurrences at a different location with a mean overlap of 5%. 5 of 10 patients had recurrences in the central zone of the prostate which did not definitively show tumor on review of the initial 1.5T staging scan. Conclusions: After MRI-guided brachytherapy targeting only the peripheral zone in men initially staged with 1.5T MRI, 50% of the local recurrences occurred at the non-targeted central zone, raising the possibility that focal therapy directed only at the dominant tumor will result in increased out-of-field recurrences. Whether the superior ability of modern 3T multiparametric MRI to detect and precisely localize occult prostate cancer foci will reduce this risk is the subject of current study.
Gleason pattern 5 as a pathologic predictor of recurrence, development of metastasis, and prostate cancer-specific death for patients receiving salvage radiation therapy following radical prostatectomy.
Authors: Jackson William C. , Johnson Skyler B. , Foster Corey , Li Darren , Foster Benjamin , Song Yeohan , Sandler Howard Mark , Palapattu Ganesh S. , Kunju Priya , Mehra Rohit , Hamstra Daniel A. , Feng Felix Yi-Chung 
Published: February 2017

151 Background: The presence of primary, secondary, and tertiary Gleason pattern 5 (GP5) in prostate cancer has been shown to predict outcomes and improve risk stratification following radical prostatectomy (RP) and external beam radiation therapy (EBRT). However, the predictive value of GP5 has not been assessed in salvage EBRT (SRT) for a rising PSA after RP. We sought to assess the prognostic capability of the presence of GP5 in this setting. Methods: 575 patients who received SRT at a single institution for biochemical recurrence after RP were retrospectively reviewed in an IRB approved analysis. We assessed the impact of GP5 on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and Cox Proportional Hazards models. Results: Median follow up was 56.7 months post SRT. On pathologic evaluation, 563 patients had a documented Gleason score (GS). 60 patients (10.7%) had primary, secondary, or tertiary GP5. GP5 was the strongest pathologic predictor of DM (p<0.01 HR: 1.9 [95%CI: 1.3-2.9]) and PCSM (p<0.01 HR: 4.0 [95%CI: 2.1-7.7]) on univariate analysis. The presence of GP5 was a better predictor of BF, DM, PCSM, and OS than stratification by GS8-10. Patients with GP5 had clinically worse outcomes than GS8 patients without GP5. There was no difference in outcome between primary, secondary, and tertiary GP5. On multivariate analysis, GP5 was the strongest pathologic predictor of BF (p<0.01 HR: 2.7 [95%CI: 1.6-4.5]), DM (p<0.01 HR: 11.2 [95%CI: 3.9-32.2]), and PCSM (p<0.01 HR: 6.0 [95%CI: 1.8-19.6]). Conclusions: In SRT, where pathologic factors including extra-capsular extension, seminal vesicle invasion, and margin status are known, the presence of GP5 is the strongest pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual GP’s for SRT patients following RP. Intensification of treatment regimens, such as early use of androgen deprivation therapy or adjuvant radiation, may be appropriate for patients with GP5 in this setting.