bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant androgen deprivation (AD) +/- mitoxantrone + prednisone (MP) in patients with high-risk prostate cancer (PC) post radical prostatectomy (RP): Phase III intergroup trial S9921.
Authors: Hussain Maha , Tangen Catherine M. , Thompson Ian Murchie , Swanson Gregory P. , Wood David Peter , Sakr Wael , Dawson Nancy Ann , Haas Naomi B. , Flaig Thomas W. , Dorff Tanya B. , Lin Daniel W. , Crawford E. David , Quinn David I. , Vogelzang Nicholas J. , Glode L. Michael 
Published: September 2018

5019 Background: Patients (pts) with high-risk PC post RP are at risk of systemic relapse with related morbidity/mortality. Adjuvant AD can reduce this risk. In 1999, based on available data, we hypothesized that adjuvant MP + 2 years (ys) of AD can further reduce mortality. Methods: Eligible pts had cT1-T3, N0 PC with post RP > = 1 high risk factors defined as Gleason sum (GS) ≥ 8, pT3b, pT4, pN+, GS 7 + positive margin or any of these preoperative findings (in pts with neoadjuvant AD): preoperative PSA of > 15 ng/ml, bx GS score > 7, or PSA of > 10 ng/ml + bx GS > 6. Pts had to have post RP PSA = < 0.2 ng/ml, were stratified by T, N, GS, and adjuvant radiation plan and randomized: Arm 1 AD (bicalutamide + goserelin for 2 ys) or Arm 2 AD + 6 cycles m 12 mg/m2 + P 5mg BID. Primary endpoint: overall survival (OS). Median OS was estimated to be 10 ys in AD arm requiring 680 pts/arm to detect a hazard ratio (HR) of 1.30 with 92% power and one-sided α = 0.05. Results: 983 pts (961 eligible intent to treat) with median age 60 ys and median PSA 7.6 ng/ml were randomized to AD or AD + MP from 10/99 -1/07 when the DSMC recommended stopping accrual due to higher leukemia rate in Arm 2. 16% had N1 (Group “Gr” 1), 61% GS ≥8 or pT3b (Gr 2),23% other risk factors (Gr 3). Median time to testosterone recovery was 9.5 months. Median follow-up (f/u) 11.2 ys. Conclusions: OS was higher than anticipated in both arms; MP did not improve OS and increased other malignancy risk. These data illustrate that systemic therapy benefit cannot be extrapolated from different disease stages and the importance of adequate f/u in adjuvant PCa trials. The remarkable DFS and 10 y OS, irrespective of risk extent, may be result of risk definition, and/or 2 ys AD. Pending definitive data 2 ys adjuvant AD for high-risk PCa post RP is a reasonable option to consider. Clinical trial information: NCT00004124. [Table: see text]
Stereotactic ablative radiation therapy for the treatment of oligometastatic prostate cancer.
Authors: Tran Phuoc T. , Moyer C. Leigh , Phillips Ryan , Radwan Noura , Ross Ashley , Reyes Diane K. , Wright Jean , Antonarakis Emmanuel S. , Song Daniel Y. , Deville Curtiland , Walsh Patrick C. , DeWeese Theodore L. , Carducci Michael Anthony , Schaeffer Edward M. , Pienta Kenneth J. , Eisenberger Mario A. 
Published: September 2018

5020 Background: The importance of local treatment in oligometastatic prostate cancer (OPC) is unknown. Stereotactic ablative radiotherapy (SABR) is highly focused, high-dose radiation that is well suited for treatment of oligometastases. Here we report on the safety and preliminary clinical outcomes of SABR in a modern cohort of OPC men. Methods: Eighty four men who satisfied criteria of OPC diagnosed on imaging underwent consolidative SABR were then followed prospectively on our IRB approved registry by our GU multidisciplinary team. We collected demographic, clinical, toxicity and efficacy information. We examined the first 66 men in this preliminary report to allow for a minimum of 4.5 months follow-up. SABR was delivered in 1-5 fractions of 5-18 Gy. Kaplan-Meier method was used to assess local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir+2), distant progression free survival (DPFS), ADT-free survival (ADT-FS) and time-to-next intervention (TTNI). Results: Of the 66 OPC patients analyzed, 25 (38%) men presented as synchronous OPC and the remaining 41 had recurrent OPC. Median and mean follow-up was 61 and 66 weeks, respectively. Patient and disease factors as listed in the Table. Crude Grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no Grade > 2 toxicity. SABR was delivered to 134 metastases: 89 bone (66%), 40 nodal (30%) and 5 (4%) visceral metastases. Overall LPFS at 1-year was 92%. The bPFS and DPFS at 1-year were 69% and 69%, respectively. Median TTNI was not reached yet. Of the 18 men with hormone sensitive prostate cancer who had their ADT deferred, 11/18 (56%) remain free of disease following SABR (1-year ADT-FS was 78%) and in 17 castration resistant men, 11 had > 50% PSA declines with 1-year TTNI of 30% with a median of 45 weeks. Conclusions: Consolidative SABRfor OPCis feasible and well tolerated. The preliminary clinical outcomes in our series is limited by heterogeneity and size but our data suggests that this approach is worthy of further prospective study. [Table: see text]
Circulating tumor cells (CTCs) N-terminal androgen receptor expression to identify patients (pts) with castrate resistant prostate cancer (CRPC) who are more sensitive to chemotherapy.
Authors: Slovin Susan F. , Knudsen Karen E. , Halabi Susan , Carbone Emily , Fernandez Celina , Chen Yu , Autio Karen A. , Rathkopf Dana E. , Kampel Lewis J. , Morris Michael J. , Arauz Gabrielle , Graf Ryon P , Kelvin James , Dittamore Ryan Vance , De Leeuw Renee , Sullivan Amanda , Tse Kin , Molina Ana M. , Scher Howard I. , Kelly William Kevin 
Published: September 2018

5034 Background: Loss of the retinoblastoma tumor suppressor (RB) function was identified as a major means to develop CRPC; the expression of the androgen receptor (AR) is under stringent RB control; and tumors devoid of RB function are hypersensitive to treatment with chemotherapy. Exploratory analysis evaluated baseline N-terminal AR expression in CTCs in men with chemotherapy-naïve CPRC and correlated to changes in PSA, leading us to inquire if this biomarker may identify pts sensitive to chemotherapy. Methods: In a multicenter phase II randomized trial of approved doses of abiraterone acetate/prednisone (AA-Arm 1) or combination AA and standard doses of cabazitaxel (AA/CBZ-Arm 2). Patients on AA received CBZ upon progression. Baseline CTCs were obtained on all pts and expression of N-terminal AR expression was performed by Epic Sciences. Positive AR N-terminal expression (AR+) was based on the presence of at least 1 CTC or CK- cell with AR N-terminal signal expression above the 3.0 positivity threshold. Serial PSAs were determined at baseline and every 3 weeks with routine labs and imaging every 12 weeks. Results: To date, 42 of 80 pts have been enrolled: 22 pts to AA, and 20 pts to AA/CBZ. Both regimens were well tolerated with 8/42 (19%) pts experiencing treatment-related grade 3 or 4 toxicities. Blood from 35 patients underwent CTC analysis. Seventy-seven percent of pts (27/35) had detectable CTCs; 11 of 35 pts (31%) had AR overexpression. Of the pts with AR+ CTCs, 1/5 pts treated with AA, and 5/6 pts treated with AA/CBZ had a PSA decline > 50% from baseline. Conclusions: Real-time CTC analysis of N-terminal AR expression was feasible and data suggests that this may identify a cohort of pts who may benefit from the combination of CBZ with AA. Further studies are ongoing to evaluate whether cellular heterogeneity and RB expression in CTCs play a role in identifying pts who would benefit from chemotherapy. The trial is coordinated by the Prostate Cancer Clinical Trials Consortium, LLC and funded by Sanofi US Services Inc. and Prostate Cancer Foundation. Clinical trial information: NCT02218606.
Assessment of quality of life (QOL), cognitive function and depression in a randomized phase II study of abiraterone acetate (ABI) plus prednisone (P) vs enzalutamide (ENZA) for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Khalaf Daniel , Sunderland Katherine , Eigl Bernhard J. , Finch Daygen L. , Oja Conrad D. , Vergidis Joanna , Parimi Sunil , Zulfiqar Muhammad , Gleave Martin , Chi Kim N. 
Published: September 2018

5036 Background: ABI + P and ENZA treatments are associated with side effects that may impair QOL. ENZA has been associated with cognitive and memory impairment. There has been no direct comparison between these agents and their effect on these domains. Methods: Randomized phase II trial of ABI + P vs ENZA as 1st-line therapy for mCRPC (ClinicalTrials.gov: NCT02125357). FACT-P QOL questionnaire, patient health questionnaire (PHQ-9) and Montreal Cognitive Assessment (MoCA) were completed throughout the study. The proportion of patients with a clinically significant change in FACT-P (10 points total FACT-P score, 3 points FACT-P subscales), worsening of PHQ-9 depression symptom severity (none = 0-4, mild = 5-9, moderate = 10-14, moderate-severe = 15-19, severe ≥20) and decline in MoCA cognitive impairment level (normal = 27-30, mild = 18-26, moderate = 10-17, severe ˂ 10) at week 12 was compared between study arms for this analysis. Results: From 202 patients (pts) accrued, there were 162, 145 and 142 pts with baseline and 12-week FACT-P, PHQ-9 and MoCA assessment. Median baseline FACT-P, PHQ-9 and MoCA scores were similar in both arms. From baseline to 12 weeks, the median total FACT-P score improved in the ABI + P arm (115 to 128, P = 0.02), but there was no change in the ENZA arm (114 to 114, P = 1.00). There was a higher rate of significant worsening for the physical well-being (PWB) subscale for ENZA vs ABI + P (TABLE), but not for the other FACT-P subscales. There was a higher rate of worsening in depression severity in the ENZA arm (TABLE), although worsening to a moderate-severe/severe level occurred in only 2 patients. There was also a trend for worsening in cognitive impairment for the ENZA arm (TABLE). Conclusions: These data suggest there are distinct differences between ABI + P vs ENZA and their effects on QOL, mood symptoms and cognitive function. Clinical trial information: NCT02125357. [Table: see text]
Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Morris Michael J. , Vogelzang Nicholas J. , Sartor Oliver , Armour Alison , Groaning Michael , Robarts Adam , Petrylak Daniel Peter , Tolcher Anthony W. , Gordon Michael S. , Babiker Hani M. 
Published: September 2018

5038 Background: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, but not in most normal tissues, making it a potential therapeutic target. We are conducting a two-part phase 1 dose escalation/expansion study of EC1169, a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide in mCRPC. The utility of the PSMA-targeted companion imaging agent 99mTc-EC0652 is also being evaluated as a patient selection tool. The safety, efficacy, and imaging-based PSMA selection strategy are being investigated in Part A (dose escalation) and Part B (2-stage, 2-cohort expansion). Methods: Part A pts were eligible if they progressed on abiraterone or enzalutamide, and were treated with a taxane. EC1169 was administered as an IV bolus on days 1, 8 every 21 days. Part B pts are enrolled in 1 of 2 cohorts, mCRPC taxane naïve (cohort 1, 45 pts) and taxane exposed (cohort 2, 40 pts). Prior to treatment, pts undergo a 99mTc-EC0652 SPECT scan. The primary endpoint of Part B is median radiographic progression-free survival (rPFS). Other study evaluations are OS, PSA, and CTC-based biomarkers. Results: Part A is now complete: the RP2 dose is 6.5 mg/m2, on the basis of non-DLT transaminitis. 20 Part A/B pts have been treated at the RP2 dose (7 taxane naïve, 13 taxane exposed). Median age is 69 (range: 59-82). Median number of cycles is 2 (range: 1-7). 10 pts (50%) reported at least 1 treatment related AE. Most treatment related AEs are Gr1 and 2; G3 thrombocytopenia, fatigue, and constipation have occurred in 1 pt each. No Grade 4 treatment related AEs have been reported. No DLT or toxicity requiring dose reductions occurred. Four taxane-exposed pts in Part B have reached their first 9 wk radiographic assessment, of which two have soft tissue disease. One of those two patients (50%) has achieved an unconfirmed RECIST PR. Conclusions: The RP2 dose of EC1169 is 6.5 mg/m2. EC1169 has been well tolerated in 20 pts at the RP2 dose. Imaging with 99mTc-EC0652 suggests excellent disease localization supporting a PSMA-targeted therapeutic strategy. There is evidence of anti-tumor activity in both the dose escalation and expansion cohorts. Clinical trial information: NCT02202447.
Comparison of biochemical recurrence free survival after radical prostatectomy triggered by grade reclassification on active surveillance, and men newly diagnosed with similar grade disease.
Authors: Diniz Clarissa P. , Carter Ballentine , Epstein Jonathan I. , Mamawala Mufaddal 
Published: September 2018

5047 Background: Evaluate the biochemical recurrence free survival (bRFS) in men after radical prostatectomy (RP) triggered by Gleason score (GS) grade reclassification (GR) during active surveillance (AS) in order to inform patient decisions. Methods: We conducted a retrospective analysis of men undergoing RP from 1995 - 2015 at Johns Hopkins and identified 4 groups; 94 men in AS that underwent RP following GR from Gleason score (GS) 6 to GS ≥ 7(3+4) [grade groups ≥ 2], 3,504 men that underwent IRP following a diagnosis of grade groups ≥ 2, 56 men in AS that underwent RP following GR to GS 7(3+4) [grade group 2], and 1,979 men that underwent IRP following a diagnosis of grade group 2. The outcome of interest was bRFS, assessed using Kaplan Meir analysis and a multivariate Cox regression model. Results: Men on AS had a lower PSA density distribution (0.11 vs. 0.13, p = 0.022; 0.12 vs. 0.12, p = 0.043), and a higher proportion of low volume cancers (46.2% vs. 15.3%, 46.4% vs. 16.7%, both p < 0.001) as compared to the IRP groups for both biopsy grade groups ≥ 2 and biopsy grade group 2, respectively. The proportions of men with biochemical recurrence (BCR) in the AS and IRP groups were 13.8% vs. 29.1% (p = 0.008 for grade groups ≥ 2) and 8.9% vs. 21.7% (p = 0.022 for grade group 2), respectively. One, 5, 10-year bRFS for men in the AS group vs the IRP group was 97.9%, 76.6%, 69.0% vs 85.5%, 65.1% ,54.2%%, respectively for biopsy grade groups ≥ 2 (log-rank test, p = 0.009), and 96.4%, 89.6%, 89.6% vs 91.2%, 74.0%, 63.9%, respectively for biopsy grade group 2 (log-rank test, p = 0.071). For biopsy grade groups ≥ 2, there was no significant difference in BCR between groups after adjustment for age at treatment, biopsy extent of cancer, and PSA density; HR = 0.78 (95% CI 0.43 – 1.43, p = 0.426). Conclusions: AS patients that are reclassified to grade groups ≥ 2 have no greater risk of treatment failure as compared to men newly diagnosed with similar grades. These data could help inform decisions regarding management of low grade prostate cancer.
Predictors of post-surgical race-specific prostate cancer progression.
Authors: Cullen Jennifer , Kuo Huai-Ching , Hurwitz Lauren , Rosner Inger L. , Rebbeck Timothy , D'Amico Anthony Victor , Lu-Yao Grace L. 
Published: September 2018

5048 Background: Disparity in prostate cancer (CaP) incidence and mortality for African American (AA) versus Caucasian American (CA) men may reflect tumor biology, comorbidity, treatment, follow-up care, and/or health care access. In a racially diverse cohort of patients undergoing radical prostatectomy (RP), this study examined how race, comorbidity, and PSA doubling time (PSADT) impact CaP progression. Methods: Enrollees in the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1989-2014 who underwent RP within 12 months of CaP diagnosis were eligible. Biochemical recurrence (BCR) was defined as PSA ≥0.2 ng/mL post-RP. Comorbid conditions included coronary artery disease (CAD), cerebral vascular incident (CVI), Type II diabetes (DB), hypertension (HT), elevated cholesterol (EC), lung disease (COPD), prostatitis (PS), renal insufficiency (RI) and other cancer (OC). Multivariable Cox proportional hazards (PH) analysis was used to examine comorbid conditions (yes vs. no) and PSADT ( < 3, 3-8.9, 9-14.9, and ≥15 mos) to predict BCR, controlling for age at RP, D’Amico risk stratum, pathology features, and adjuvant treatment. Results: A total of 6,785 patients were eligible; 22% AA and 78% CA. Median age and follow-up was 62 and 6.1 years, respectively. Across race, comparable median follow-up time, distributions of pathologic features and adjuvant treatments were observed. However, AA vs. CA patients had greater HT (53 vs. 39% p < 0.0001), DB (17 vs. 7%, p < 0.0001), and RI (3 vs. 1%, p = 0.002). Alternatively, CA vs. AA patients had greater CVD (10 vs. 7%, p = 0.0008) and OC (3 vs. 0.5%, p < 0.0001). Cox PH analysis showed poorer BCR-free survival for AA vs. CA men (HR = 1.28, CI = 1.11, 1.48, p = 0.0009) adjusting for D’Amico risk stratum, pathology, and treatment. PSADT, not comorbidity, was a critical predictor of BCR, with poorest outcome at extremes: HR PSADT < 3 vs. > = 15 months = 41.5, CI = 33.6, 51.3, p < 0.0001). Conclusions: Despite comparable health care access and distribution in clinical risk stratum and pathology features, race persisted in predicting poor CaP outcome. Disparate comorbidity for AA and CA men did not eliminate this difference. PSADT remained the most striking determinant of poor BCR-free survival.
HSD3B1 genotype and response to androgen deprivation therapy for biochemical recurrence after radiotherapy for localized prostate cancer.
Authors: Hearn Jason W.D. , Xie Wanling , Nakabayashi Mari , Almassi Nima , Reichard Chad A. , Pomerantz Mark , Kantoff Philip W. , Sharifi Nima 
Published: September 2018

5050 Background: The enzyme encoded by the HSD3B1(1245C) variant allele has been shown to promote castration-resistant prostate cancer by increasing intratumoral dihydrotestosterone synthesis. In the setting of biochemical recurrence (BCR) following prostatectomy, inheritance of the variant allele has been associated with inferior clinical outcomes for men treated with androgen deprivation therapy (ADT). Whether the same is true in the context of BCR after radiotherapy (RT) is unknown. Methods: We determined HSD3B1 genotype retrospectively in men treated with ADT for post-RT BCR using an established biorepository at a large academic center. We analyzed time-to-progression (TTP), time-to-metastasis (TTM), and overall survival (OS) according to HSD3B1genotype using an additive genetic model with the log-rank trend test. Multivariable analyses (MVA) were performed to adjust for known prognostic factors with Cox regression. Results: We identified 218 men treated with ADT for BCR after RT, of whom 213 (98%) were successfully genotyped (46%, 45% and 9% carrying 0, 1, and 2 variant alleles, respectively). Median follow-up was 7.9 years (yrs). Demographic and treatment factors were similar across genotypes. Median TTP was 2.3 (95% CI: 1.6, 3.1) yrs in men who inherited 0 variant alleles, 2.3 (1.5, 3.3) yrs with 1 variant allele, and 1.4 (0.7, 3.3) yrs with 2 variant alleles (P = 0.683). Median TTM diminished with the number of variant alleles inherited (7.4 [6.7, 9.7], 5.8 [4.9, 6.5] and 4.4 [3.0, 5.7] yrs, respectively (P = 0.030). No difference in OS was detected (P = 0.305). On MVA with 0 variant alleles as the reference, the adjusted hazard ratio (HR) for metastasis was (1.19 [0.74, 1.92]; P = 0.480) for 1 allele and (2.01 [1.02, 3.97]; P = 0.045) for 2 alleles. MVA did not demonstrate significant differences in TTP or OS. Conclusions: The HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis is associated with time-to-metastasis in men treated with ADT for BCR after RT for prostate cancer. Notably, 49% of men had received prior ADT as part of local therapy and 56% received an anti-androgen during ADT for BCR, which may blunt the effect of the variant allele.
Association of CTC detection by AdnaTest with outcome on enzalutamide in chemotherapy-naïve castration-resistant prostate cancer: Exploratory results from PREMIERE—A SOGUG trial.
Authors: Font Pous Albert , Vazquez-Estevez Sergio , Gonzalez del Alba Aranzazu , Mellado Begoña , Fernandez Calvo Ovidio , Mendez Maria Jose , Juan Fita María José , Rodriguez Sanchez Angel , Pérez-Valderrama Begoña , Gallardo Enrique , Santander Carmen , Sáez M Isabel , Puente Javier , Alonso Teresa , Fernandez Perez Maria Piedad , Martínez Alberto , Lopez-Andreo Maria Jose , Grande Enrique , González-Billalabeitia Enrique , Castellano Daniel 
Published: September 2018

5052 Background: Circulating tumor cells (CTCs) enumeration using CellSearch correlates with clinical outcome in prostate cancer, but is limited for gene expression analysis. AdnaTest ProstateCancer is a commercially available CTC immune-enrichment and PCR-related detection method that allows gene expression studies (Antonarakis E, NEJM 2014). It has demonstrated incremental detection of CTCs in patients with no CTCs identified by CellSearch (Samoila A, ASCO 2013) but needs to be clinically qualified. There is a strong need for studies to assess the association with the clinical outcome in CRPC. Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC pts were recruited in 16 institutions. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma AR (Grande E, ASC0 2017 #) and CTC characterization (Grande E, ESMO 2016). Outcome measures included PSA-PFS (sPFS), radiographic PFS (rPFS) and OS. Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-eight patients had CTC blood samples available. CTCs were detected at baseline, 12 weeks and progression in 36% (35/98), 27% (26/95) and 78% (32/41), respectively. The CTC conversion rate (positive to negative after 12 w) was 43% (15/35). All CTC conversions had ≥50% decline in PSA (15/15) whereas only 35% (7/20) of pts with persistent CTCs. At first interim analysis, with a median follow-up of 10.6 months, detection of CTCs at baseline was associated with worse sPFS (median, 7.59 m versus NR, HR, 3.67; 95% CI 1.90-7.10; P < 0.001), rPFS (median, 12.9 m versus NR; HR, 7.61; 95% CI, 2.80-20.64; P < 0.001) and OS (medians NR, HR, 9.51; 95% CI, 1.11-81.52; P = 0.0398). CTC positive pts were less likely to have a ≥90% decline in PSA (OR, 2.88; 95% CI, 1.13-7.72; P = 0.02). Conclusions: CTC detection using AdnaTest is associated with an adverse outcome in chemotherapy-naïve asymptomatic or oligo-symptomatic mCRPC pts. Clinical trial information: NCT02288936.