bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen deprivation therapy and statin therapy in prostate cancer patients.
Authors: Lai Kin Chung , Turknett Toiya , Singh Parminder 
Published: February 2020

205 Background: Metastatic prostate cancer (mPC) is treated with androgen deprivation therapy( ADT). Duration of response to ADT predicts patient’s survival. It has been shown in observational studies that concurrent statin use may prolong response to ADT. Studies in mice have shown negative interactions. We wanted to examine the effect of this interaction in patients being followed at Mayo Clinic Arizona (MCA). Methods: We examined 441 patients with mPC, who received ADT and were treated at MCA from year 2011 to 2017. . Our study evaluated the time to progression (TTP) and overall survival(OS) for patients with mPC on ADT with or without concurrent statin use. Among the patients who were evaluated, there was a subset of 156 patients taking abiraterone (ABI). Characteristics were compared between statin users and nonusers using Chi squared test and Wilcoxon rank-sum tests. The primary outcome was TTP defined as the duration from ADT initiation to disease progression. The association between statin use and TTP was analyzed by multivariable Cox regression to estimate hazard ratios (HRs) and 95% Conference Interval (CI), and adjusted for Gleason score, primary therapy type, prior ADT, metastatic status, and PSA at ADT initiation. Results: There was no significant difference in TTP when comparing patients with statin to those without a statin. The HR for statin use vs no statin use is 1.049 with CI (0.838, 1.314) and p-value is 0.677. There was no significant difference in overall survival when comparing statin vs no statin use. The HR for statin use vs no statin use was 0.928(CI 0.642, 1.342) with p-value at 0.693. In the ABI population, there was no significant difference in TTP for patients with statin vs no statin. HR was 1.00 CI (0.725, 1.377) with p-value at 0.998. For overall survival, there was no significant difference with HR at 0.852 (CI 0.502, 1.446) with p-value at 0.553. Conclusions: Despite retrospective studies showing benefit of use of statin in men with prostate cancer, our study observed no difference in long term outcomes. Possible explanations could be smaller sample size, inability to verify data as medication intake was not verified directly. Also, patient’s compliance with medications could be a confounding variable.
Prospective comparison of 68Ga-RM2 PET/CT and 68Ga-PSMA-617 PET/CT for initial staging of prostate cancer.
Authors: Schollhammer Romain , De Clermont-Gallerande Henri , Robert Gregoire , Yacoub Mokrane , Lamare Frederic , Balamoutoff Nicolas , Vimont Delphine , Hindie Elif , Fernandez Philippe , Morgat Clément 
Published: February 2020

21 Background: PSMA ( Prostate Specific Membrane Antigen) and GRP-R ( Gastrin Releasing Peptide Receptor) are overexpressed on prostatic cancer cells and can be targeted with a PSMA inhibitor such as 68Ga-PSMA-617 (Liu 2018) or a GRP-R antagonist such as 68Ga-RM2 (Touijer 2019). We aimed to compare 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT at initial staging of prostate cancer. Methods: We prospectively enrolled 10 treatment-naïve patients with biopsy-confirmed prostate cancer. Fifteen lesions were found (two with Gleason score (GS) 6; seven GS 7(3+4), two GS 7(4+3) and four GS ≥ 8). 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT were randomly performed before prostatectomy with imaging at 1 and 2 hours after injection (2MBq/kg). Manual (MS) and automatic (AS) segmentation were performed on each PET imaging and then compared to histology (standard-of- truth). Prostatectomy samples were analyzed by an experimented pathologist who identified and staged each lesion according to GS. Each prostatectomy slice available was scanned for comparison between PET and histologic segmentation. Uptake intensity (SUVmax) and signal-to-noise ratio (SNR) relative to non-lesional prostate gland parenchyma were analyzed. Per-lesion analysis was performed on final GS (prostatectomy). Results: Using AS, 68Ga-RM2 PET/CT showed better sensitivity (Se) than 68Ga-PSMA-617 PET/CT: (0.85 vs 0.75) and better specificity (Sp) (0.89 vs 0.60). MS found similar Se (0.94 vs 0.93) but better Sp (0.89 vs 0.80) with 68Ga-RM2 PET/CT. SNR of 68Ga-RM2 PET/CT was high whatever the GS was; while 68Ga-PSMA-617 PET/CT exhibited higher SNR in high GS (p = 0.044). Finally, in low GS, SNR of 68Ga-RM2 PET/CT was significantly higher than 68Ga-PSMA-617 PET/CT (p = 0.004). Conclusions: GRP-R-targeting and PSMA-targeting have been previously compared in patients with biochemically recurrence (Minamimoto 2016) but not at primary staging. Our initial results, in this indication, showed great diagnostic performance of 68Ga-RM2 PET/CT compared to 68Ga-PSMA-617 PET/CT to characterize low Gleason score tumors. 68Ga-PSMA-617 PET/CT is promising for initial staging of high Gleason score tumors. These results need to be confirmed in a larger study.
Role of soft tissue metastases on tumor progression in castrate-resistant metastatic prostate cancer.
Authors: Ruchalski Kathleen , Douek Michael , Raman Steven , Patel Maitraya , Gutierrez Antonio , Sai Victor , Levine Benjamin D. , Allen-Auerbach Martin , Gupta Pawan , Kim Hyun J. , Villegas Bianca , Goldin Jonathan 
Published: February 2020

214 Background: While visceral metastases in castrate resistant prostate cancer (mCRPC) are a negative prognostic factor, patients may still derive treatment benefits. Given varying anatomic sites of tumor may display differing treatment responses we investigated the role of soft tissue metastases in progressive disease (PD) by anatomic site. Methods: A retrospective review of anonymized patients enrolled in phase 3 clinical trials was performed. Patients were excluded if lacked Tc bone scan or CT chest, abdomen and pelvis (CT CAP) on trial. Subjects were included if they had soft tissue disease per RECIST 1.1. Bone disease was defined by automated BSLA criteria. All CT CAPs per clinical trial protocol were assessed by RECIST 1.1. Soft tissue PD was noted as target|nontarget lesion growth and/or presence of new lesions by anatomic site. Bone PD was defined by >20% increase in BSLA score. Results: Of 322 total patients, 138 met criteria of soft tissue disease at baseline. Baseline anatomic sites of metastases per RECIST included: visceral (74, 53.6%), lymph node only (52, 37.7%) and soft tissue bone (12, 7.1%). PD occurred in 46 patients with baseline soft tissue disease; with PD first detected by BSLA (23, 16.7 %), RECIST (19, 13.8 %) or with PD occurring simultaneously by BSLA and RECIST (4, 2.9%). Of the 138 patients with baseline soft tissue disease, PD occurred by RECIST in 25 patients. This occurred due to worsening visceral (11, 68.8%), lymph node (4, 25.0%) or soft tissue bone (1, 6.3%) disease. PD by new lesions only occurred in 9 patients (36.0%), as a result of 77.8% visceral and 22.2% lymph node. Conclusions: In mCRPC with soft tissue disease at baseline, progression by BSLA bone score still accounts for a large portion of PD. Further analyses must be performed to better differentiate disease phenotypes amongst mCRPC with combined visceral/osseous disease.
[18F]Fluciclovine-PET/MRI use in monitoring response to androgen deprivation therapy in men with prostate cancer following initial staging.
Authors: Galgano Samuel Joseph , McDonald Andrew Michael , Rais-Bahrami Soroush , Choudhary Gagandeep , Bhambhvani Pradeep , McConathy Jonathan 
Published: February 2020

216 Background: [18F]Fluciclovine PET is clinically approved for detection of biochemically recurrent prostate cancer (PCa). However, its use for initial staging and treatment monitoring remains uncertain. No published data exists evaluating the use of fluciclovine-PET for monitoring response to androgen deprivation therapy. Thus, the purpose of this study is to evaluate the potential use of fluciclovine-PET in monitoring response to androgen deprivation therapy (ADT) during initial treatment of patients with newly diagnosed high risk PCa. Methods: A prospective study enrolled patients with high-risk PCa who had no imaging evidence of metastatic disease. All patients underwent a pretreatment fluciclovine-PET/MRI for primary staging, 6 weeks of ADT, and had a follow-up PET/MRI. All exams were interpreted by 3 nuclear medicine physicians. Identification of the primary intraprostatic lesion and nodal metastatic disease was performed with mean and maximum SUV of the MRI-defined primary prostatic lesions and lymph node metastases measured before and after ADT. Results: A total of 10 patients were enrolled. Gleason scores of their primary tumor were 3+4 (n = 2), 4+3 (n=2), 8 (n = 3), and 9 (n = 3). The average pretreatment serum PSA value was 33.04 ng/mL (range 2.83–76.5). The average serum PSA 6 weeks following initiation of ADT was 2.13 ng/mL (range 0.29–5.66). The primary intraprostatic lesion was accurately identified in all 10 patients and 7/10 patients demonstrated suspicious lymph nodes on the pretreatment PET/MRI. Following ADT, all 10 patients demonstrated a decrease in tracer activity both within the primary intraprostatic lesion and suspicious lymph nodes. The primary lesion mean SUV prior to treatment was 4.46±1.14 and 2.37±1.07 following initiation of ADT (p=0.0007). The primary lesion maximum SUV prior to treatment was 7.13±1.70 and 3.54±2.04 following initiation of ADT (p=0.0006). Conclusions: Fluciclovine-PET tracer activity in patients with PCa undergoing ADT appears to correlate with decrease in serum PSA. Fluciclovine-PET imaging may be useful in monitoring response to ADT, particularly if there is a failure of appropriate PSA response. Clinical trial information: NCT03264456.
Clinical fracture associated with androgen deprivation therapy: A retrospective study of early phase clinical trial cohorts.
Authors: Myint Zin , Kunos Charles 
Published: February 2020

234 Background: Androgen deprivation therapy (ADT) is the mainstay treatment in both locally advanced and metastatic prostate cancer. Unfortunately, ADT is associated with rapid loss of bone mineral density (a surrogate for fracture risk) within the first 12 months of initial therapy. Methods: A retrospective review of early phase NCI clinical trials from 2006 to 2013 was conducted to assess the risk of fracture for prostate cancer patients treated with ADT. Results: Seven clinical trials of prostate cancer patients who received ADT between 2006 and 2013 were identified. A total of 464 patients were enrolled in the trials. Patient median age was 64 years, the majority were white (90%), and had good performance status. The median baseline prostate specific antigen level was 29.3 ng/ml and the majority of patients had a Gleason score pattern of >7 (71%). Disease was characterized as involving bone only in 43% of patients and multiple sites (bone, node and/or visceral) in 35%. Of 381 patients for which data were available, 36% received prior hormonal therapy, 37% underwent surgical castration, and 16% received radiation therapy. The most common grade 1-2 adverse events reported in the 7 trials were fatigue (36%), followed by hot flashes (27%), anemia (17%) and hyperglycemia (15%). The most common grade >3 adverse events reported were hypertension and hyperglycemia (3% each). Of the total 464 patients, 7 (0.4%) reported having a fracture (5 were baseline and 2 developed while on treatment). Conclusions: Our study reconfirms the association between clinical fracture and ADT exposure; however, the incidence of fracture rate was less than 1%, which was lower than the published population-based cohorts. The difference could be attributed to short-term ADT exposure, and short-duration of follow up. Clinicians should educate patients about risk of fracture with ADT and offer bone health agent earlier in patients at high risk for fracture and also with underlying co-morbidities such as diabetes, poor performance status, chronic steroid use, or undergo radiation therapy.
The efficacy of metastasis-directed radiation therapy (MDRT) for oligometastatic castration-resistant prostate cancer (CRPC).
Authors: Nagahara Akira , Kanaki Tomohiro , Yamamoto Akinaru , Yamamoto Yoshiyuki , Nakai Yasutomo , Nakayama Masashi , Kakimoto Ken-Ichi , Konishi Koji , Teshima Teruki , Nishimura Kazuo 
Published: February 2020

240 Background: We have utilized imaging study, especially whole body magnetic resonance imaging (WB-MRI), to detect oligometastatic disease of castration resistant prostate cancer (CRPC) and performed metastasis-directed radiation therapy (MDRT) for oligometastatic disease. We review our institutional experience of MDRT for oligometastatic CRPC. Methods: We retrospectively reviewed the database comprising 26 oligometastatic CRPC patients treated by MDRT for oligometastatic disease combined with baseline androgen deprivation therapy at Osaka International Cancer Institute from January 2013 to August 2019 and investigated treatment efficacy of MDRT. Diagnosis of oligometastatic disease was performed by computed tomography, bone scintigraphy and/or WB-MRI. Treatment efficacy was assessed by change of serum prostate specific antigen (PSA) level and progression free survival (PFS). PFS was analyzed by Kaplan-Meier method and comparison was made by log-rank test. Results: The median age at treatment was 75.5 years (range, 62-86). The oligometastatic diseases were bone in 22 patients, lymph node in 2 patients and both in 2 patients. The number of treated lesions were as follows: 1 lesion for 21 patients, 2 lesions for 4 patients and 3 lesions for 1 patient. WB-MRI was performed in 19 patients (73%). Median dose of MDRT was 35Gy (range, 30-60) for bone and 60Gy (range, 50-60) for lymph node. The median PSA prior MDRT was 6.3 ng/ml (range, 0.5-191). Post MDRT PSA reduction was observed in 24 patients (92%) and over 50% PSA reduction was observed in 14 patients (54%). Median PFS was 8.7 month and patients with over 90 days PSA doubling time (PSADT) showed longer PFS (p=0.0074). Conclusions: Our data suggest that MDRT can achieve PSA reduction in most CRPC patients with oligometastasis and PSADT could be a predictor of disease progression after MDRT.
Impact of 68Ga-PSMA-11 PET/CT on staging and management of prostate cancer patients in various clinical settings.
Authors: Sonni Ida , Eiber Matthias , Fendler Wolfgang , Alano Rejah M. , Vangala Sitaram S. , Kishan Amar Upadhyaya , Nickols Nicholas George , Rettig Matthew , Reiter Robert Evan , Czernin Johannes , Calais Jeremie 
Published: February 2020

26 Background: The goal of this study was to determine the impact of 68Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications excluding the two main classical indications: BCR and pre-surgical staging. Methods: This is a prospective study of 197 patients that aimed to determine the impact of 68Ga-PSMA-11 PET/CT on PCa stage and management. Indications for PSMA PET/CT were initial staging of non-surgical candidates (30 patients) and re-staging after definitive treatment (n=168). The re-staging cohort comprised: patients re-staged with known advanced metastatic disease (n=103), after androgen deprivation therapy only (n=16), after surgery with serum PSA levels <0.2 ng/ml (n=13), after radiation therapy (RT) not meeting the Phoenix criteria (n=22) and after other primary local treatments [i.e. HIFU, focal laser ablation, cryoablation, hyperthermia or irreversible electroporation] (n=13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre- and post-PET questionnaires completed by referring physicians, electronic chart review and/or patient telephone encounters. Results: PSMA PET/CT changed disease stage in 135/197 (69%) patients (38% up-stage, 30% down-stage and no changes in stage in 32%). Management was affected in 104/182 (57%) patients. PSMA PET/CT had its greatest management impact in patients who were re-staged after RT. Conclusions: PSMA PET/CT has a profound impact on stage and management of PCa patients outside of the two main classical indications (BCR and presurgical staging) across all examined clinical scenarios. Clinical trial information: NCT04050215.
Transcriptome profiling of NRG Oncology/RTOG 9601: Validation of a prognostic genomic classifier in salvage radiotherapy prostate cancer patients from a prospective randomized trial.
Authors: Feng Felix Y , Sandler Howard M. , Huang Huei-Chung , Simko Jeffry , Davicioni Elai , Nguyen Paul L. , Efstathiou Jason A. , Dicker Adam P. , Dignam James J. , Seiferheld Wendy , Lukka Himanshu , Bahary Jean-Paul , Pisansky Thomas Michael , Hall William Adrian , Shah Amit I. , Pugh Stephanie L. , Pollack Alan , Spratt Daniel Eidelberg , Shipley William U. , Tran Phuoc T. 
Published: February 2020

276 Background: Decipher is a genomic classifier (GC) that estimates risk of prostate cancer (PCa) distant metastases (DM) post-radical prostatectomy (RP). Herein, we validate the GC within the context of a randomized phase 3 trial. Methods: RP specimens from patients on the NRG/RTOG 9601 phase 3 placebo-controlled randomized trial of salvage radiotherapy (sRT) +/- 2 years of bicalutamide (NCT00002874) were centrally reviewed and the highest-grade tumor underwent RNA extraction. Samples passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to assign the GC score (scale 0-1). Our NCTN-CCSC approved pre-specified statistical plan (NRG-GU-TS002 CSC0075) included the primary objective of validating the ability of the GC to independently prognosticate the cumulative incidence of DM, with secondary endpoints of prostate cancer-specific mortality (PCSM) and overall survival (OS). Results: Of patients with tissue available, 352 passed QC and were included for analysis. The final GC cohort was a representative sample of the overall cohort, with a median follow-up of 13 years. On multivariable analysis, the GC (continuous variable) was independently associated with DM (HR 1.19 [95%CI 1.06-1.35], p=0.003), PCSM (HR 1.37 [95%CI 1.18-1.61], p<0.001), and OS (HR 1.16 [95%CI 1.06-1.28], p=0.002) after adjusting for age, race, Gleason score, T-stage, margin status, entry PSA, and treatment arm. The estimated absolute impact of bicalutamide on 12-year OS was less in patients with lower vs higher GC scores (2.4% vs 8.9%), further demonstrated in men receiving early sRT at PSA <0.7 ng/mL (-2.0% vs 5.0%). Conclusions: This is the first validation of this GC in a prospective randomized trial cohort and demonstrates association of the GC with DM and PCSM independent of standard clinicopathologic variables. The GC may help personalize shared decision-making to weigh the absolute benefit from the addition of bicalutamide to sRT.
Impact of MRI on outcomes in active surveillance (AS) for localized prostate cancer in a hospital registry.
Authors: Ravi Praful , Martin Neil E. , Trinh Quoc-Dien , Shaw Grace , Pomerantz Mark , Preston Mark A. , Pedregal Manuel , Taplin Mary-Ellen , Kibel Adam S. , Sweeney Christopher 
Published: February 2020

280 Background: MRI is increasingly used in follow-up of men undergoing AS for localized prostate cancer. Large cohorts predating the MRI era have shown that the risk of disease progression or stopping an AS protocol is ~20-30% at 5 years, but the impact of MRI on outcomes in AS is unclear. Methods: We studied men who initiated AS at Dana-Farber Cancer Institute between 2001-2017 for Gleason 6 prostate cancer diagnosed on transrectal ultrasound-guided biopsy, and who underwent a prostate MRI as part of their AS protocol. Progression on AS was defined as finding Gleason ≥7 cancer on repeat biopsy or at radical prostatectomy. Early MRI was defined as one performed within 1 year of diagnosis. Results: A total of 148 men were identified from a prospective IRB-approved database. Median PSA at diagnosis was 4.8 (range 0.7-14.3), median number of positive biopsy cores was 1 (1-7), median maximal core involvement by cancer was 10% (1-65), and most men (87%) had T1c disease. Overall, 54 (36%) progressed on AS over a median follow-up of 5.6 years (95% CI 5.1-6.0), with the majority (n=44, 81%) progressing at repeat biopsy; the 5-year progression rate was 32% (25-41). There were no major differences in baseline clinicopathologic characteristics between men undergoing early (n=103, 70%) or delayed (n=45, 30%) MRI, but men who had an early MRI underwent fewer subsequent biopsies (median 2 vs. 3, p=0.010) and more targeted biopsies (47% vs. 36, p=0.212). Men who underwent early MRI had a higher rate of progression compared to those who had a delayed MRI (5-year rate 43% [33-55] vs. 12% [5-26], log-rank p=0.001). However, when immortal time bias was accounted for by considering MRI receipt as a time-dependent covariate, early MRI was not associated with progression (HR=0.74 [0.50-1.09], p=0.129). Conclusions: The 5-year progression rate on AS was ~30% in the MRI era, a rate similar to that reported in series that predate the adoption of MRI. A higher rate of progression was seen in men undergoing MRI within 1 year of diagnosis, but MRI timing did not influence risk of progression when accounting for the time interval before an MRI was performed. Longer follow-up is needed to determine the impact of MRI on cancer-specific survival in men undergoing AS.
Pathologic outcomes of MRI invisible tumors in prostate cancer.
Authors: Gurram Sandeep , Lebastchi Amir H. , Ahdoot Michael , Wang Alex Z. , Wood Bradford J. , Turkbey Baris , Pinto Peter A. 
Published: February 2020

282 Background: Magnetic resonance imaging (MRI) invisible tumors are a diagnostic challenge in prostate cancer due to the lack of ability to reliably monitor these lesions radiographically or pathologically. The progression and natural history of these lesions are unknown and outcomes over time are unclear. Methods: Men with multiparametric MRI of the prostate and MRI/Transrectal ultrasound (TRUS) fusion guided biopsy were assessed for the presence of MRI invisible tumors (MIT). An MIT is defined as cancer detected only on extended sextant biopsy and not visible on MRI. All men first underwent an MRI/TRUS fusion biopsy with tracked extended sextant biopsy which originally detected the MIT. The original biopsy needle course sampling these MITs was tracked and set as a future target using the MRI/TRUS fusion platform. Men subsequently underwent a combined MRI/TRUS fusion biopsy, systematic extended sextant biopsy, and a Targeted Tracked biopsy of the MIT (TT-MIT) that was recorded and tracked from the original biopsy. We describe the outcomes of tracking these MITs and compare the ability to monitor them with TT-MIT biopsy as opposed to systematic extended sextant biopsy. Results: 105 MITs were identified, 84 (80%) of which were originally Gleason 6 tumors. The median time between biopsies was 16.6 months. The overall cancer detection rate with TT-MIT was 77.4% compared to 59.7% using systematic extended sextant biopsy. Using TT-MIT, these invisible tumors showed higher Gleason scores in 16 (15.2%) tumors. When TT-MIT was compared to the systematic extended sextant biopsy sampling the corresponding location, it showed increased Gleason scores in 30 (28.6%) MITs while 58 (55.2%) showed concordant pathology and 17 (16.2%) showed less aggressive pathology. Conclusions: The ability to follow MRI invisible tumors suggests that these tumors are more effectively tracked using TT-MIT biopsy technique. These MITs change over time and 15% of them will upgrade to higher Gleason scores. Tracking these tumors with TT-MIT biopsy increases cancer detection rate compared to standard sextant biopsy and more accurately samples these MITs, unveiling a more aggressive pathology.