bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Detection of significant prostate cancer through magnetic resonance imaging targeted biopsy of PI-RADS3 lesions in African American patients based on prostate specific antigen density threshold of 0.15 ng/ml2: Analysis of patient population from the Vattikuti Urology Institute.
Authors: Alanee Shaheen Riadh , Deebajah Musatafa , Roumayah Zade , Dabaja Ali , Peabody James O. , Menon Mani
Published: February 2020

286

Background: A prostate specific antigen density (PSAD) threshold of 0.15 ng/ml2 have been suggested for significant cancer detection in PI-RADS 3 lesions to avoid unnecessary magnetic resonance imaging targeted biopsy (MRI-TB) of these lesions. However, the performance of this threshold in African American (AA) patients is not well characterized. Methods: We analyzed our institutional data base of MRI-TB to identify the rate of significant prostate cancer (Pca) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of < 0.15 vs. ≥0.15 ng/ml2 and lesion size of < 1 cm vs ≥ 1 cm. Significant prostate cancer was defined as Gleason grade group 2 or higher on MRI-TB of the PI-RADS 3 lesion. Results: Of 768 patients included in the database, 211 (27.5%) patients identified themselves as AAs. Mean age of AA patients was 63 years and mean PSAD was 0.21. Sixty nine (32.7%) AA patients were found to have PI-RADS 3 lesions. Mean PSAD of AA patients with PI-RADS 3 lesions was 0.21 ng/ml2 as well. Fifty percent of AA patients with PI-RADS 3 lesions had PSAD ≥0.15 ng/ml2. Significant Pca detection rate for AA patients with PI-RADS 3 lesions was 9% for PSAD of ≥ 0.15 vs. 0.03% percent for AA patients with PSAD < 0.15 ng/ml2 (OR 7.056, CI 1.017-167.9, P=0.04). Stratification by lesion size (< 1 cm vs. > 1 cm) resulted in missing 0% percentage of significant Pca when only AA patients with PSAD ≥ 0.15 ng/ml2 and lesion size ≥ 1 cm received MRI-TB. Conclusions: We report on the performance of a reported PSAD density threshold in detecting significant Pca in one of the largest series of AA patients receiving MRI-TB of the prostate. Our results have direct clinical implications when counseling AA patients with PI-RADS 3 lesion on whether they should undergo MRI-TB of such lesions.
Deep learning-based approach for automated assessment of PTEN status.
Authors: Jamaspishvili Tamara , Harmon Stephanie , Patel Palak , Sanford Thomas , Caven Isabelle , Iseman Rachael , Mehralivand Sherif , Choyke Peter L. , Berman David Monty , Turkbey Baris
Published: February 2020

294

Background: PTEN loss is associated with adverse outcomes in prostate cancer and has the potential to be clinically implemented as a prognostic biomarker. Deep learning algorithms applied to digital pathology can provide automated and objective assessment of biomarkers. The objective of this work was to develop an artificial intelligence (AI) system for automated detection and localization of PTEN loss in prostate cancer samples. Methods: Immunohistochemistry (IHC) was used to measure PTEN protein levels on prostate tissue microarrays (TMA) from two institutions (in-house n=272 and external n=125 patients). TMA cores were visually scored for PTEN loss by pathologists and, if present, spatially annotated. In-house cohort (N=1239 cores) were divided into 70/20/10 training/validation/testing sets. Two algorithms were developed: a) Class I=core-based, to label each core for biomarker status and b) Class II=pixel-based, to spatially distinguish areas of PTEN loss within each core. ResNet101 architecture was used to train a multi-resolution ensemble of classifiers at 5x, 10x, and 20x for Class I task and a single classifier at simulated 40x for Class II segmentation. Results: For Class I algorithm, accuracy of PTEN status was 88.3% and 93.4% in validation and testing cohorts, respectively (Table). AI-based probability of PTEN loss was higher in cores with complete loss vs partial loss. Accuracy was improved to 90.7% in validation and 93.5% in test cohorts using the Class II region-based algorithm, with median dice scores 0.833 and 0.831, respectively. Direct application to external set demonstrated a high false positive rate. Loading trained model and conservatively re-training (“fine-tuning”) on 48/320 external cohort cores improved accuracy to 93.4%. Conclusions: Results demonstrate feasibility and robustness for fully automated detection and localization of PTEN loss in prostate cancer tissue samples and possibility for time/cost-effectiveness of sample processing/scoring in research and clinical laboratories.[Table: see text]
Clinical utility of PSA density and PI-RADS for deferring biopsy for the detection of clinically significant prostate cancer.
Authors: Truong Matthew , Stevens Erica , Ward Ryan , Bullen Jennifer , Austhof Ethan , Valdez Rogelio , Purysko Andrei , Klein Eric A.
Published: February 2020

298

Background: We sought to identify PSA density (PSAD) and Prostate Imaging-Reporting and Data Systems (PI-RADS) category cut-offs that would allow deferring biopsy in men with suspicion for clinically significant prostate cancer (csPCa). Methods: Our institution’s prostate MRI registry (n = 1718) was queried for patients who had MRI-guided biopsy (MRI-GB) and/or systematic biopsy (SB) performed after prostate MRI between January 2013 and October 2018 (n = 676). Patients in the diagnostic group (either biopsy naïve or with prior negative biopsy) and patients with PCa on active surveillance (AS) were considered eligible. PSA, PSAD, and PI-RADS category were entered into logistic regression models for predicting csPca (grade group [GG] ≥ 2) at biopsy. Receiver operating characteristic (ROC) analysis was performed to assess model accuracy and results were stratified by biopsy indication and PI-RADS categories. Results: Logistic regression models that combined PSAD and PI-RADS categories had the highest ROC’s in both the diagnostic and AS groups (AUC=0.830 and 0.778, respectively). For diagnostic group patients with PSAD ≤0.15, csPCa was found in 6/89 (6.7%) of negative MRI patients (i.e. PI-RADS ≤ 2), 4/90 (4.4%) of PI-RADS 3 patients, 59/159 (37%) of PI-RADS 4-5 patients. If a PSAD cutoff of ≤ 0.15 and PI-RADS category ≤ 3 MRI were used in combination as criteria for biopsy deferral, only 10/526 (1.9%) of patients would have had csPCa missed on subsequent biopsy. Among patients in the AS group with a negative MRI, 0/22(0%) and 3/8 (37.5%) had csPCA if the PSAD was ≤0.15 and >0.15, respectively. Conclusions: For the diagnostic group of patients undergoing prostate biopsy, PSAD cut off ≤0.15 is useful for deferring biopsy only in patients with a PI-RADS ≤ 3. Confirmatory biopsy in patients should be strongly considered before enrolling patients in AS even in the setting of a negative MRI if the PSAD is > 0.15.
Locally advanced scrotal squamous cell carcinoma: Does chemotherapy affect survival?
Authors: Madhira Bhaskara Reddy , Brooks Gary , Khan Rashad , Akhtar Komal , Basnet Alina
Published: February 2020

3

Background: Scrotal squamous cell carcinoma (SSCC)thoughrare, represents the most common forms of scrotal malignancies.40-50% of patients present with locally advanced disease, and treatment is extrapolated from penile cancer. Here we report practice trend and overall survival (OS) outcome of locally advanced SSCC patients who underwent surgery with or without chemotherapy. Methods: We performed a retrospective analysis using the national cancer center database (NCDB) (2004-2016). All patients aged ≥ 18 years with locally advanced SSCC who underwent surgery with or without chemotherapy were included. OS is estimated with Kaplan-Meier curves, with an adjusted hazard ratio (aHR) calculated from Cox proportional hazard regression model. Results: 638 patients were identified with SSCC without distant metastasis. Of these 49 underwent surgery with perioperative chemotherapy and 589 underwent surgery alone. At the median follow up of 39.9 months (mo), median OS is 41.4 mo and 145.7 mo for surgery with chemotherapy group versus surgery alone respectively (P-value <0.0001), with aHR for OS 1.673 (95%CI 0.966-2.897). Patients age ≥ 65 (HR= 3.081, 95% CI=2.107- 4.505, p<0.001), Charlson-Deyo Score (CCI) 2 or more (HR=3.441, 95% CI=2.140- .533, p <0.0001), moderately-poorly differentiated carcinoma (HR=1.713, 95% CI=1.038- 2.829, p=0.0352), and higher clinical nodal status N1,N2 and N3 (HR=2.543, 95% CI=1.42-4.548, p=0.0016)were observed to do worse with surgery and chemotherapy. Patients with CCI of 2 or more, moderate to poorly differentiated carcinoma, higher clinical T and N stage (T2- T4 and N1-N3 respectively) were observed more likely to receive surgery and chemotherapy. Conclusions: No OS improvement was seen in locally advanced SSCC with addition of chemotherapy to surgery. Patients who received chemotherapy along with surgery are observed to have higher risk of mortality vs surgery alone. The study is limited by retrospective nature, lack of randomization, patient selection bias, patient’s choice of therapy, small sample size, and missing information.
Clinical outcomes of abiraterone acetate + prednisone (AA) + bone resorption inhibitors (BRI) versus AA alone as first-line therapy for castration-resistant prostate cancer (CRPC) with bone metastases (BM) in an international multicenter database.
Authors: Francini Edoardo , Montagnani Francesco , Nuzzo Pier Vitale , Gonzalez-Velez Miguel , Alimohamed Nimira S. , Cigliola Antonio , Moreno Irene , Rubio Jaime , Crivelli Francesca , Shaw Grace , Petrioli Roberto , Bengala Carmelo , Francini Guido , Foncillas Jesus Garcia , Sweeney Christopher , Higano Celestia S. , Bryce Alan Haruo , Harshman Lauren Christine , Lee-Ying Richard , Heng Daniel Yick Chin
Published: February 2020

30

Background: BM in patients (pts) with CRPC are associated with shorter overall survival (OS) and higher costs. BRI zoledronic acid and denosumab are frequently used to prevent skeletal-related events (SRE) in pts with CRPC and BM. AA is the most common 1st line therapy for men with metastatic CRPC. We aimed to assess the impact of BRI on OS and time to first SRE (ttSRE) of pts receiving 1st line treatment AA for CRPC with BM. Methods: A retrospective cohort of pts starting AA as 1st line therapy for CRPC with BM between 2013-2016 was identified through 8 hospitals’ IRB approved registries. Pts were classified by use of concomitant BRI and subgrouped by volume of disease (per E3805 definition) at AA start. Kaplan-Meier method and Cox models were used to assess OS and ttSRE with hazard ratio (HR) estimates (95% CI). Results: Of the 745 pts included (543 deaths), 529 (71.0%) had AA alone and 216 (29.0%) AA+BRI. Median follow-up was 23.5 months. Pts receiving concomitant BRI showed a significantly longer OS and a 35% reduced risk of death compared to AA alone (HR=0.65; 95% CI, 0.54-0.79; P<.0001). The OS benefit with BRI was greater for the subgroup with high volume disease (HV) (HR=0.51; 95% CI, 0.38-0.68; P<.0001). The cohort with AA+BRI had a significantly shorter ttSRE (HR=1.27; 95% CI; 1.0-1.60; P=.0439) and, notably, the risk of first SRE was more than doubled for the subgroup with LV (HR=2.29; 95% CI, 1.57-3.35; P<.0001). On MVA, BRI vs. no BRI, prior local therapy (PLT) vs. no PLT, LV vs. HV, baseline VAS pain ≤3 vs. >5, PS 0 vs. ≥1, and PSA are independently associated with longer OS. Conclusions: The addition of BRI to 1st line AA for CRPC men with BM was associated with improved OS, particularly in HV, and worsened ttSRE, more evident in LV. These data suggest a potentially different impact of concomitant BRI on HV vs. LV, which could affect clinical decision making.[Table: see text]
Acute patient-reported toxicities after proton therapy or intensity-modulated radiotherapy for prostate cancer.
Authors: Gergelis Kimberly , Bai Miao , Whitaker Thomas , Routman David M. , Sir Mustafa , Choo Richard
Published: February 2020

305

Background: Toxicity due to radiotherapy (RT) may differ in patients (pts) with prostate cancer who receive intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Methods: Patient-reported bowel function (BF), urinary incontinence (UI), and urinary irritative/obstructive symptoms (UO) domains of the Expanded Prostate Index Composite Questionnaire (EPIC-26) were prospectively collected in pts with localized prostate cancer receiving either IMRT (n=157) or PBT (n=105) to the prostate +/- proximal seminal vesicles for clinical stage T1-T2 N0 prostate cancer at a single tertiary cancer center between 2015 and 2018. Changes in domain scores were analyzed from pretreatment to the end of RT and 3 months post-RT, assessing the acute effects of each modality. A clinically relevant change was defined as a score change that exceeded 50% of the standard deviation of a baseline value. Results: At baseline there was no difference in the scores of BF, UI, and UO domains between IMRT and PBT cohorts. At the end of RT, pts treated with either modality had a statistically significant and clinically relevant worsening of BF and UO compared to baseline. Pts treated with IMRT experienced a significantly greater decrement in BF compared to the PBT cohort (-13 vs -9, p<0.01), including significantly more IMRT pts having a clinically relevant deterioration in BF compared to PBT pts (58% vs 40%, p=0.01). Though there was a statistically significant deterioration in UI in the IMRT cohort (-4, p<0.001), this did not reach the predefined threshold for clinical relevance. Three months following RT, the IMRT group continued to have statistically significant and clinically relevant worsening of BF (-9, p<0.001), whereas the change in BF domain score of the PBT cohort was no longer statistically significant or clinically relevant compared to baseline (-1, p=0.25). There were no statistically significant or clinically relevant changes in UO or UI in either cohort at three months when compared to baseline. Conclusions: Pts who received IMRT or PBT reported unique patterns of toxicity, and pts treated with IMRT had worse decrement in BF immediately after and three months following RT, compared to those treated with PBT.
Influence of node-positive disease after radical prostatectomy on biochemical recurrence and oncologic outcomes in men with prostate cancer.
Authors: Washington Samuel L. , Cowan Janet E. , Herlemann Annika , Zuniga Kyle Brian , Carroll Peter
Published: February 2020

306

Background: The diagnostic and therapeutic value of pelvic lymph node dissection (LND) at radical prostatectomy (RP) remains unclear. Thus, we aim to characterize the oncologic value of LND and secondary treatment on oncologic outcomes for a contemporary cohort of men with nodal disease on surgical pathology at RP. Methods: Men who underwent primary RP with LND for PCa were identified and stratified by pN status. Detectable PSA was defined as a PSA>0.05 ng/ml within 2-6 months after RP. Multivariable Cox proportional hazards regression models were fit for biochemical recurrence-free survival (RFS), overall survival (OS), and PCa-specific mortality (PCSM). Results: Of 1,635 identified patients, 167 (10.2%) had nodal disease. Mean age at diagnosis was 62 years (SD 7.1). Median follow-up after RP was 31 months (IQR 13-58). Those with nodal disease had more extensive LND (mean 17.7, SD 8.3 vs mean 13, SD 7.6, p<0.01). The number of positive LNs was associated with worse 7-year outcomes [RFS, HR 1.2, 95% CI 1.1-1.2, p<0.01; OS, HR 1.2, 95% CI 1.1-1.4, p<0.01] but not PCSM (p=0.2) after adjustments. Median number of positive LN was 1 (IQR 1, 3) in pN1 patients. 31 (19%) had an UDT PSA after RP, 25 (15%) had UDT PSA and received adjuvant therapy, and 106 (66%) had a detectable PSA. On multivariable analysis, number of positive LNs (HR 1.1, 95% CI 1.0-12, p=0.02) and detectable PSA (vs UDT, HR 5.1, 95% CI 1.8-14.3, p<0.01) were associated with increased risk of recurrence after RP but not OS (p>0.05 for all). After salvage treatment, 7-year RFS, OS, and PCSM did not differ significantly between the groups (p>0.05 for all). Conclusions: In a contemporary cohort of men with pN1 disease, more extensive LND was not associated with improved outcomes. Amongst those who underwent secondary treatment after RP, UDT PSA after RP conferred greater biochemical recurrence free survival at 7 years. In this subset of men, adjuvant treatment was not associated with improved post-salvage biochemical or treatment-free survival. Further investigation into the potential therapeutic benefit of LND at RP is warranted to better estimate the potential risk overtreatment of men with nodal disease.
Contemporary racial disparities in PSA screening in a large, integrated health care system.
Authors: Kearns James T. , Adeyemi Oluwaseun , Anderson William E. , Hetherington Timothy C. , Taylor Yhenneko J. , Zhu Jason , Burgess Earle Frederick , Gaston Kris E.
Published: February 2020

308

Background: The USPSTF prostate cancer screening guidelines have changed significantly in the past decade, from a recommendation of do not screen in 2012 to a 2018 recommendation that focuses on shared decision making. Additionally, most guidelines further acknowledge that African American men should be screened more intensively than Caucasian men due to increased incidence of prostate cancer and increased prostate cancer mortality. Our objective was to characterize racial disparities in PSA screening in a large healthcare system with a diverse patient population to understand contemporary trends. Methods: This retrospective cohort study used data from the Atrium Health Enterprise Data Warehouse, which includes clinical records from over 900 care locations across North Carolina, South Carolina, and Georgia. Participants included all men ≥ 40 years seen in the ambulatory or outpatient setting during 2014-2018. PSA testing was determined through laboratory data. Clinical and demographic data were collected. Between-group comparisons were conducted using generalized estimating equations models to account for within-subject correlation. Statistical significance was defined as p < 0.05. Results: There were 582,846 individual men seen from 2014-2018, including 416,843 Caucasians (71.5%) and 85,773 African Americans (14.7%). Screening rates declined among all groups from 2014-2018 (see table). African American men were screened at a similar or lower rate than Caucasian men in each year (from 18.6% vs 19.0% in 2014 to 11.9% vs 12.2% in 2018, respectively). Conclusions: PSA screening declined significantly between 2014 and 2018. African American men screened at a similar or lower rate than Caucasian men each year. Given the consensus that African American men should be more intensively screened for prostate cancer, significant racial disparities remain in prostate cancer screening. Further study is warranted to understand patient, provider, and system factors that contribute to disparities in prostate cancer care and outcomes.[Table: see text]
Phase II trial of definitive radiotherapy with leuprolide and enzalutamide in high-risk prostate cancer.
Authors: de la Calle Claire Marie , Chang Albert , Rashid Ghezal , Wong Anthony C. , Choi Alice , Feng Felix Y , Gottschalk Alexander R. , Menzel Paul Lawrence , Carroll Peter , Nguyen Hao Gia
Published: February 2020

323

Background: Adding enzalutamide to standard LHRH agonist and primary radiation therapy may improve the outcomes in patients with high-risk prostate cancer. Methods: All patients met at least 2 of the following criteria: stage cT3a/b, PSA≥20 ng/mL, Gleason Grade 8-10, ≥33% core involvement on biopsy; or had pelvic lymph node involvement ≥1cm on CT or MRI. All patients were started on 24 months of leuprolide and enzalutamide and then underwent 5 weeks of IMRT (whole pelvis, 45Gy total) followed by a brachytherapy boost. PSA, Testosterone (T) and basic labs were followed during and after treatment. Primary outcome was to assess the safety, tolerability, and feasibility of the protocol and PSA complete response (PSA-CR, defined as PSA nadir ≤0.3). Secondary outcomes included: time to biochemical recurrence (BCR) and progression free survival (PFS). Results: 16 patients were enrolled, 2 were not eligible and 3 withdrew before starting treatment. Mean age at enrollment was 68.6 years (SD 9.4). Median follow up time was 28.27 months (IQR 27.3 – 29.1 months). Median time to PSA-CR was 4.20 months (IQR 3.47 – 4.87 months). Currently all patients still have PSA-CR (Table), and none have BCR per ASTRO Phoenix criteria. All-cause, any grade adverse events (AE) were reported in all 11 (100%) patients with 4 (36.4%) experiencing grade 3 AE. One (9.09%) treatment related serious AE (seizure) occurred. There were no grade 5 AE (death related to AE). 4 subjects stopped treatment early due to: seizure, myalgias, hematuria and social reasons. Most patients however were able to complete the 24 months of leuprolide and enzalutamide: median treatment duration was 24.0 months (IQR 12.1 – 24.0 months). Conclusions: Most patients were able to tolerate and complete the entire 24 months of treatment as originally planned. Currently no patients have met criteria for PSA recurrence. Will plan to follow up patients until month 36 to help determine true BCR rates and PFS. Clinical trial information: NCT02508636. [Table: see text]
Biopsy positivity in prostate cancer patients undergoing mpMRI-targeted radiation dose escalation.
Authors: Meshman Jessica , Farnia Benjamin , Stoyanova Radka , Reis Isildinha , Abramowitz Matthew , Dal Pra Alan , Horwitz Eric M. , Pollack Alan
Published: February 2020

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Background: Radiation (RT) dose escalation improves prostate cancer outcomes, but when the whole gland is treated to high doses complications can arise. We used prostate multiparametric MRI (mpMRI) findings for targeted dose escalation (MTDE) in prospective clinical trials in which prostate biopsy at 2-3 years after completion of RT was planned. Biopsy positivity is a known predictor of biochemical failure. These findings are compared to those in another cohort in which standard whole gland RT doses were used. Methods: Patients enrolled on three investigator initiated clinical trials incorporating MTDE (n=30) were eligible for inclusion. All patients were assessed for response by prostate biopsy 2-3 years after RT. Patients were compared to a reference group treated with standard RT doses to the whole prostate on a randomized trial at Fox Chase Cancer Center (FCCC trial). Univariable and multivariable analysis (MVA) was performed to assess for correlation with biopsy positivity, defined as carcinoma with or without RT effect. Results: Of those treated with MTDE: 3 (10%) were low, 23 (77%) intermediate, and 4 (13%) high risk. Assuming an α/β ratio of 1.5, MTDE patients received an equivalent dose (EQD2) of 76 Gy to the prostate, with focal dose escalation to an EQD2 of 98-122 Gy to mpMRI lesions. The MTDE cohort was compared with 115 patients from the FCCC trial, where 23 (20%) were low, 74 (64%) intermediate, and 18 (16%) high risk. The FCCC trial patients received an EQD2 of 76 Gy (n=64) or 84.24 Gy (n=51) without boost. Median time from RT to biopsy was 2 years (range, 1.6-3.3). The post-treatment biopsy results were negative in 50% (n=73), atypical in 12% (n=17), carcinoma with RT effect in 31% (n=45) and frank carcinoma in 7% (n=10). On MVA, patients with tumor volume >20% were more likely to have positive post-RT biopsies (OR: 3.21, 95% CI: 1.34-7.68, p= 0.009). MTDE patients were less likely to have positive post-RT biopsies, 10% vs. 45%, (OR: 0.13, 95% CI: 0.03-0.46, p=0.002). Conclusions: Focal dose-escalation to mpMRI-defined lesions significantly reduces biopsy positivity, a measure associated with long term outcomes including distant metastasis.
Outcomes of men with ductal prostate cancer undergoing definitive therapy for localized disease.
Authors: Ranasinghe Weranja Kalana Bodhisiri , Shapiro Daniel D. , Reichard Chad A. , Elsheshtawi Mohamed A , Nyame Yaw , Sundi Debasish , Tosoian Jeffrey J. , Wilkins Lamont , Alam Ridwan , Bathala Tharakeswara , Tang Chad , Aparicio Ana , Tu Shi-Ming , Navone Nora , Pisters Louis L. , Stephenson Andrew J. , Klein Eric A. , Allaf Mohamad E. , Chapin Brian Francis , Davis John W.
Published: February 2020

350

Background: Ductal prostate adenocarcinoma (DAC) is an aggressive variant of prostate cancer (PC). We aimed to assess the outcomes of men with localized DAC undergoing radical prostatectomy (RP) or external beam radiotherapy (RTx) compared to acinar adenocarcinoma of the prostate (PAC) and investigate any difference between these treatment modalities. Methods: All patients presenting to our institution with localized DAC from January 2005 - November 2018 were compared to a pooled cohort of patients from 3 tertiary referral centers who underwent RP for Gleason 8 PC and a cohort of high risk PC patients who underwent RTx for PAC. Patient, tumor characteristics and outcome data were analyzed. Results: 257 men with DAC were identified and compared to 803 with PAC. 203 men with DAC and 729 men with PAC underwent RP while 54 men with DAC and 74 men with PAC underwent RTx. Men with DAC were older (65 vs 63 years and 70.5 vs 66 years) and had higher cT3/T4 stage (43% vs 2.8% and 44.5% vs 31.1%) in both groups, respectively (all p <0.05). The median follow-up for men undergoing RP was 34 (range 0.9 to 177) months and 73.4 (range 0.6 – 224.2) months for men having RTx. Presence of DAC was an independent risk factor for metastases (HR 2.5 (95% CI 1.4- 4.8); p<0.01) and death (HR 2.3 (95% CI 1.1 – 4.7); p=0.02) following RP. The 3- year overall survival (OS) rates for DAC and PAC in men undergoing RP were 93.3% vs 99.3% (p<0.01). On adjusting for Gleason score, clinical T stage, PSA and age, DAC was also an independent risk factor for death (HR 6.1 (95% CI 1.7-22.2); p<0.01) in men undergoing RTx with 5-year OS rates of 100% and 81.6% for DAC and PAC, respectively. There was no difference in the OS of men with DAC between RP and RTx. Conclusions: Men undergoing RP or RTx for localized DAC had worse outcomes compared to PAC, but no survival difference was seen between these treatment modalities. DAC behaves clinically differently than PAC. Further evaluation of the underlying biology and potential for specific targeted multimodality therapies in DAC is needed.