bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of lymph node dissection in pT2-3 renal cell carcinoma: Analysis of the National Cancer Database.
Authors: Ghali Fady , Patel Devin , Meagher Margaret , Bradshaw Aaron , Patel Sunil , Dutt Raksha , Murphy James Don , Derweesh Ithaar 
Published: February 2020

756 Background: We sought to assess the impact of LND in non metastatic pT2-3 patients utilizing a large population-based dataset. Methods: The National Cancer Database was queried for patients with cN0pT2-3 RCC that underwent radical nephrectomy (RN) +/- LND from 2004-2015. Descriptive analyses and Multivariable cox regression (MVA) were performed to elucidate factors associated with all-cause mortality (ACM) on a per stage basis (pT2 and pT3 RCC). Kaplan-Meier analyses (KMA) were used to determine the impact of LND on ACM. Results: 43,143 patients were analyzed, 9,491 (22.0%) underwent LND, 6.7% were positive (pN+). MVA demonstrated increasing age (HR 1.04, p<0.001), pN+ (HR 2.90, p<0.001), increasing Charlson score (CCI, HR 2.92, p<0.001), and high grade (HR 1.11, p<0.001), were associated with worsened ACM in pT2. MVA in pT3 revealed increasing age (HR 1.03, p<0.001), pN0 with 0-4 nodes removed (HR 1.24, p<0.001), pN+ (HR 3.06, p<0.001), papillary and non-specific histology (HR 1.17 p=0.002, HR 1.14 p<0.001 respectively), increasing CCI (HR 2.09, p<0.001), high grade (HR1.19, p<0.001), black race (HR 1.12, p=0.028), and increasing tumor size (HR 1.00, p<0.001) were associated with worsened ACM. MVA for increased likelihood of pN+ found high grade (HR1.23, p<0.001), Academic facility and integrated network cancer center (HR 2.13 and 1.17, p<0.001 and p=0.013 respectively), >10cm tumor (HR 1.67 p<0.001), clear cell histology (p<0.001), Caucasian race (p<0.001)and male sex (HR 1.06 P=0.026) were associated. KMA of pT2 patients demonstrates no significant difference in 5-year OS for LND compared to no LND (60.8% vs. 55.9%, p=0.21), and worsened OS for pN+ compared to pN0 and pNx (p<0.001). KMA of pT3 patients showed worsened 5-year OS for patients undergoing LND (p<0.001), and pN+ had worsened OS compared to pN0 and pNx (p<0.001). Conclusions: LND conveyed no ACM benefit in cN0 pT2 or pT3 RCC. pN+ was associated with decreased survival, with risk factors including Caucasian race, clear cell histology, high grade disease, tumors >10cm. LND in patients with cN0pT2-T3 disease may identify higher risk cohorts.
Exenterative surgery to improve quality of life on men with locally advanced, symptomatic castration-resistant prostate cancer.
Authors: Haidl Friederike , Hartmann Florian , Pfister David A. , Heidenreich Axel 
Published: February 2020

77 Background: Invasion of the urinary bladder and/or the rectum by locally advanced castration sensitive (CSPC) or castration resistant PCA (CRPC) can result in debilitating symptoms with a significant negative impact on the patient’s well-being. Local progression might develop despite the application of new life prolonging agents. It was the purpose to retrospectively review the surgical and oncological outcome following pelvic exenteration surgery (PES) for locally advanced and symptomatic CRPC. Methods: Retrospective, single-centre, dual surgeon study of 103 men with symptomatic locally progressive and symptomatic CS- and CRPC treated between 2008 and 2019. Primary endpoint was symptomatic free survival (SFS) and the secondary endpoint were overall survival (OS) and complications defined by Clavien-Dindo criteria. Statistical tests were two-tailed with a p-value <0.05 considered to indicate significance. Symptom-free survival and cancer specific survival were calculated using Kaplan-Meier analysis. Results: 9 (8.7%), 71 (68.8%) and 21 (22.4%) patients underwent radical prostatectomy, radical cystoprostatectomy or anterior and posterior exenteration, resp. After a median follow-up of 36.5 (3 – 123) months, the SFS at 1 and 3 years was 89.2% (n=89) and 64.1% (n=66). The median SFS was 27.9 months. 78.6% of the patients were symptom-free during their remaining lifetime. OS at 1 and 3 years was 92.2% and 43.7%, respectively, and the median OS was 33.6 months. Clavien-Dindo grade 2, 3 and 4 complications developed in 31 (30.6%), 12 (12%) and 8 (8.1%), respectively. Conclusions: PES is a technically feasible approach in well-selected patients resulting in symptom relief of > 90% of patients which covered almost 80% of the remaining life time. Adequate preoperative imaging studies, endoscopic evaluation and extensive surgical experience is mandatory to achieving a benefit for the individual patient with improvement of quality of life.
Treatment outcomes for metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) following docetaxel (D) for hormone sensitive disease.
Authors: Schmidt Andrew Lachlan , Anton Angelyn , Wong Shirley S. , Azad Arun , Kwan Edmond Michael , Spain Lavinia Anne , Torres Javier , Muthusamy Arunbalaji , Parente Phillip , Parnis Francis , Goh Jeffrey C. , Joshua Anthony M. , Pook David William , Gibbs Peter , Tran Ben , Weickhardt Andrew James 
Published: February 2020

78 Background: There is no prospective data to guide optimal selection of treatment for first line (1L) mCRPC after D and androgen deprivation therapy (ADT) is given in the hormone sensitive setting. We explored efficacy of 1L treatment in this group. Methods: Pts with mCRPC treated with D for hormone sensitive disease were identified from a prospectively maintained multi-site mCRPC database (ePAD) of patients treated in a community and academic setting in Australia. 1L treatment, clinicopathologic and outcome data were extracted. Results: We identified 93 pts, median age 65y (range 43–85), who received median 6 cycles of D-ADT and developed mCRPC between May 2013 and Jun 2019. 58% had Gleason ≥ 8, median PSA at diagnosis was 53 ng/mL (range 0.67–7086), 65% had de-novo metastatic disease. Median time to mCRPC was 14.8mo (range 1.3 to 56.9) with median time to 1L 16.3mo (range 2.1–57.2). Eighty-five patients (91%) received at least one further active treatment for mCRPC with outcomes below. Conclusions: Abiraterone, enzalutamide, and cabazitaxel all demonstrate activity for 1L mCRPC following progression on D-ADT. Compared to historical controls, PSA responses appear less than pre-docetaxel, but greater than the post-docetaxel setting.[Table: see text]
Time to second progression (PFS2) in patients (pts) from TITAN with metastatic castration-sensitive prostate cancer (mCSPC) by first subsequent therapy (hormonal vs. taxane).
Authors: Agarwal Neeraj , Chowdhury Simon , Bjartell Anders , Chung Byung Ha , Pereira de Santana Gomes Andrea Juliana , Given Robert W. , Juárez Soto Álvaro , Merseburger Axel Stuart , Ozguroglu Mustafa , Uemura Hirotsugu , Ye Dingwei , Londhe Anil , Lopez-Gitlitz Angela , McCarthy Sharon Anne , Mundle Suneel , Chi Kim N. 
Published: February 2020

82 Background: TITAN, a phase 3, randomized, double-blind study of apalutamide (APA) vs placebo (PBO) added to androgen deprivation therapy (ADT), demonstrated significant improvement in radiographic progression-free survival and overall survival in a broad pt population with mCSPC who received APA (Chi KN et al. NEJM 2019). This post hoc analysis evaluates whether type of 1st life-prolonging subsequent therapy (hormonal vs taxane) has an effect on PFS2 benefit shown with APA + ADT. Methods: PFS2 (the time from randomization to disease progression on 1st subsequent therapy for prostate cancer or death, whichever occurs first) was evaluated for pts from TITAN based on 1st subsequent life-prolonging therapy (hormonal vs taxane) after study treatment. Analysis censored all other 1st subsequent systemic therapies after start of treatment. Results: 277 pts (APA, 87; PBO, 190) received subsequent systemic therapy for prostate cancer; 86 pts (APA, 24; PBO, 62) received hormonal therapy (abiraterone acetate + prednisone or enzalutamide) and 99 (APA, 30; PBO, 69) received taxane (docetaxel or cabazitaxel) as 1st subsequent therapy. Baseline demographic and disease characteristics were generally similar between groups. The taxane group had a higher proportion of pts with high volume and pts with > 10 bone metastases, and a lower proportion with prior docetaxel exposure when compared with the hormonal group. Median treatment duration with APA and PBO was 11.9 and 11.1 mos in the hormonal group and 11.0 and 11.3 mos in the taxane group. Regardless of subsequent therapy, PFS2 was significantly longer for APA vs PBO (HR 0.66 [95% CI 0.50-0.87], p = 0.0026). Pts in both groups who received APA had a significant reduction in risk of 2nd progression compared with PBO (hormonal: HR 0.68 [0.48-0.97], p = 0.0326; taxane: HR 0.67 [0.48-0.94], p = 0.0189; medians not reached). Safety analyses were not conducted; all pts had discontinued therapy, most due to disease progression. Conclusions: The addition of APA to ADT for treatment of mCSPC results in risk reduction of 2nd progression regardless of choice of hormonal or taxane as the 1st life-prolonging subsequent therapy. Clinical trial information: NCT02489318.
Phase II study of cabazitaxel (CAB) plus enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Graff Julie Nicole , Cheng Heather H. , Vuky Jacqueline , Alumkal Joshi J. , Kreitner Dustin , Petreaca Delia , Grivas Petros , Schweizer Michael Thomas , Higano Celestia S. , Chen Yiyi , Yu Evan Y. , Beer Tomasz M. 
Published: February 2020

86 Background: There are six agents that improve survival in mCRPC, each administered as a single agent. Combinations of agents with distinct mechanisms of action have the potential to improve outcomes. Methods: We performed a multi-institution phase I/II study to examine safety and efficacy of CAB plus ENZ with mandatory granulocyte-colony stimulating factor support in mCRPC. Results: A sample size of 3 to 12 subjects for the phase I portion and 33 for the phase II portion provided 82% power to detect PSA response rate (decrease ≥90%) of 50% compared to the null hypothesis of 24%. The main eligibility criteria allowed prior abiraterone/prednisone (AAP) and docetaxel (in the metastatic hormone sensitive setting). Baseline characteristics: median age 69 years (47 - 82), median PSA 20.2 ng/dl (0.2 - 966.3); 7 subjects had visceral disease, 10 received prior AAP, and 8 received prior docetaxel. In the phase I portion, there were no dose limiting toxicities using CAB 25 mg/m2 IV Q3wks up to 10 cycles and ENZ 160 mg PO QD, hence this dosing was used for the phase II portion. 33 men with mCRPC were treated with CAB plus ENZ in the phase II arm. PSA response rates are listed in Table. Prior exposure to AAP decreased PSA response, but subjects who had prior AAP also had higher pre-treatment PSA. There were no treatment related deaths. Dose reduction of CAB to 20 mg/m2 was needed in 7 subjects. Over the course of the study, 14 Grade 3 adverse events occurred that were deemed possibly related to treatment: fatigue (n=2, 6%), febrile neutropenia (n=2, 6%), leukopenia (n=2, 6%), thrombocytopenia (n=2, 6%), anemia (n=1, 3%), hypertension (n=1, 3%), leukocytosis (n=2, 6%), fracture (n=1, 3%), failure to thrive (n=1, 3%). Conclusions: CAB plus ENZ was tolerable and associated with promising anti-tumor activity, particularly in abiraterone-naïve subjects. Further evaluation of this regimen is warranted. This project was managed by the Prostate Cancer Clinical Trials Consortium and funded by Astellas Inc. and Sanofi. Clinical trial information: NCT02522715. [Table: see text]
Impact of upstream use of novel hormonal therapy on progression of patients (pts) to metastatic castration-resistant prostate cancer (mCRPC) in the United States (US).
Authors: Scher Howard I. , Saad Fred , Mehra Maneesha , Nair Sandhya , Dearden Lindsay , Potluri Ravi C. 
Published: February 2020

92 Background: Novel hormonal therapies (nHTs) provide significant delay in disease progression in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic (nm)CRPC. The impact of earlier use of these agents on the epidemiological burden of PC in the US was assessed. Methods: A disease stage transition model capturing pt flow through eight clinical states and tracking pt treatment history was used, with each nHT being used once. Progression-free survival (PFS) and overall survival (OS) data for each drug/regimen were derived from published sources where available. We analyzed scenarios 1) no nHTs and 2) with nHTs: (abiraterone acetate + prednisone [AAP], apalutamide [APA] and enzalutamide [ENZA] in high-risk mCSPC, and APA and ENZA in low-risk mCSPC and in high-risk nmCRPC). Resultant state progression parameters were compared, evaluating the impact of nHTs. The assumed nHT utilization was 17.2% in high-risk mCSPC, 7.1% in low-risk mCSPC, and 60.0% in high-risk nmCRPC. Results: For 2018, the model resulted in PC incidence of 240,150 and prevalence of 2,445,173; 49,450 pts progressed to mCRPC, 42% from PSA biochemical recurrence, 31% from mCSPC, and 27% from nmCRPC states. Longer PFS and OS afforded by novel treatments extended the mean time spent from 4.4 to 4.7 yrs in mCSPC and from 2.4 to 3.0 yrs in nmCRPC. This further resulted in reduction in inflow to mCRPC over 2019 – 2025 (table). Conclusions: Novel hormonal therapies are currently used earlier in PC, a trend anticipated to intensify. The disease model shows this change in the treatment paradigm to result in delaying progression to mCRPC and increasing OS in PC.[Table: see text]
A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).
Authors: Yu Evan Y. , Laidley David , Pouliot Frederic , Probst Stephan , Saad Fred , Sabbagh Robert , Sartor A. Oliver 
Published: February 2020

TPS260 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689.
A phase II, open-label study of durvalumab in combination with stereotactic body radiotherapy in androgen-intact patients with oligometastatic prostate cancer.
Authors: Porter Isobel , Eade Thomas , Kneebone Andrew , Hruby George , Mascall Sophie , Davis Alexander P. , Guminski Alexander David 
Published: February 2020

TPS263 Background: With the introduction of Ga68-PSMA PET, a new cohort of androgen-intact men with oligometastatic prostate cancer (PCa) recurrence has been identified. These men have normal traditional imaging and a disease-free interval usually measured in years from their definitive treatment. Recent data supports the use of metastasis-directed stereotactic body radiotherapy (SBRT) in oligometastatic PCa. Based on our institutional data in 57 patients treated with SBRT alone in the PSMA era, the median PSA progression free survival (PFS) is 11 months. Despite 100% local control, 80% relapsed by 18 months. Improving the PFS for these men is an important clinical need. Achieving this without the introduction of androgen deprivation therapy (ADT) will likely improve quality of life and minimise the adverse consequences of androgen deprivation. Radiotherapy results in cell stress and release of damage associated molecular patterns (DAMPs) with activation of antigen presenting cells. This stimulates a tumour antigen specific T-cell response and abscopal effect which can be heightened with PD-(L)1 inhibition. Most PD-(L)1 inhibition trials in PCa are in men with a high burden of castrate resistant disease. However, data suggests the castrate state can impair host anti-tumour immune response. PD-(L)1 inhibition combined with SBRT in androgen-intact men may result in improved PFS compared with our historical cohort treated with SBRT alone. Methods: This is a non-randomized, open label, phase II study of durvalumab (1500 mg IV every 4 weeks) starting 1 month prior to SBRT in men with recurrent PCa not immediately requiring ADT and with Ga68-PSMA PET detected oligometastasis. SBRT will be delivered with 30Gy/3# to lymph nodes or 24Gy/2# to bone metastasis. Durvalumab will be continued to a maximum of 12 months. Primary outcomes will be freedom from biochemical failure and toxicity. Secondary objectives include biochemical response rate, magnitude of response, overall survival, time and response to subsequent treatments and quality of life. The study is recruiting at Royal North Shore Hospital in Sydney with 18 of the planned 30 patients enrolled. Clinical trial information: ACTRN12619000097145.
Dosimetry of 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer: A sub-study of the VISION trial.
Authors: Kurth Jens , Herrmann Ken , Eiber Matthias , Rahbar Kambiz , Heuschkel Martin , Lassmann Michael , Jentzen Walter , Chicco Daniela , Messmann Richard , Sartor A. Oliver , Morris Michael J. , Krause Bernd J. 
Published: February 2020

TPS265 Background: Prostate-specific membrane antigen-617 labelled with lutetium-177 (177Lu-PSMA-617) is a promising treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) after treatment with taxane chemotherapy and a novel androgen axis inhibitor. The radiotherapeutic molecule has high PSMA binding affinity, prolonged tumor retention with a rapid kidney clearance, and high tumor-to-background ratio, delivering therapeutically relevant doses of radiation to prostate cancer lesions. A randomized, prospective phase 3 trial to assess the efficacy of 177Lu-PSMA-617 in patients with progressive PSMA-positive mCRPC is ongoing (VISION trial, NCT03511664). However, as with other targeted radionuclide treatment modalities, there may be a risk of radiotoxicity to normal organs. Therefore, estimation of absorbed doses in these organs in a representative manner within the framework of such a study is essential. Methods: As a substudy of the VISION trial, extensive intratherapeutic dosimetry will be performed in a group of 30 patients at four participating German sites. Patients will undergo planar whole-body scintigraphy scans and single-photon emission computed tomography/computerized tomography (SPECT/CT) scans of the upper and lower abdomen at approximately 2, 24, and 48 hours, and 7 days after administration, along with blood sampling and urine collection. SPECT/CT data will be quantitatively reconstructed and a standardized calibration procedure of the imaging and measurement equipment used (SPECT/CT, dose calibrator, well counter) will be performed at all sites according to European Association of Nuclear Medicine (EANM) and Medical International Radiation Dose (MIRD) guidelines [1]. Organ masses will be measured for each patient using CT imaging, if accessible. Absorbed doses for kidneys, liver, spleen, salivary and lacrimal glands, and bone marrow, as well as prostate cancer lesions, will be calculated for each patient following international guidelines [2,3]. References: [1] Ljungberg M et al. J Nucl Med 2016;57:151–62. [2] Siegel JA et al. J Nucl Med 1999;40:37S–61S. [3] Hindorf C et al. Eur J Nucl Med Mol Imaging 2010;37:1238–50. Clinical trial information: NCT03511664.
MRI-targeted biopsies in prostate cancer screening and the value of its combination with blood-based risk-prediction: The randomized, diagnostic study STHLM3MRI.
Authors: Nordström Tobias , Discacciati Andrea , Jäderling Fredrik , Karlsson Stefan Gosta , Aly Markus , Gronberg Henrik , Eklund Martin 
Published: February 2020

TPS378 Background: Blood-based biomarkers and magnetic resonance imaging followed by targeted biopsies have been suggested to improve detection of prostate cancer by increasing sensitivity to detect significant disease, decrease over-detection of low-risk cancers and avoid benign biopsies. The STHLM3-MRI projects aims to assess the value of combining blood-based risk prediction with bi-parametric MRI (bpMRI) in the prostate cancer diagnostic chain. Methods: The STHLM3MRI Main Study is a randomized, diagnostic study recruiting ≈10,000 Swedish men aged 50-74 for prostate cancer testing in a screen-by-invitation setting. The study design includes a first paired step (blood-test) followed by a randomized step (biopsy technique). Participants with elevated blood-test levels (PSA≥3ng/ml or Stockholm3 test≥11% risk of GG≥2 cancer) are recommended further work-up and randomized 2:3 to 12-core systematic biopsies (standard arm) or to bpMRI followed by MRI-targeted biopsies and systematic biopsies in men with PI-RADSv2 ≥3 lesions (experimental arm). Endpoints include number of detected prostate cancers, number of performed biopsy procedures and number of performed MRIs. The study is centralized to three biopsy sites, one radiology department and one pathology department. A data safety and monitoring board monitors study progress and participant safety. There are two pre-planned main analyses. First, we will report the first large randomized evidence comparing MRI-targeted biopsies and systematic biopsies for prostate cancer detection in a screen-by-invitation setting. Second, we will report a comparison of a diagnostic strategy including the Stockholm3 blood-test and MRI-targeted biopsies with standard practice using PSA and systematic biopsies. A third analysis will compare the use of the bloodtests PSA and Stockholm3 for risk-stratification of men undergoing MRI-targeted biopsy. 9 Oct 2019 the study had included 47% of planned participants (n = 4,701), aiming to close inclusion by March 2020 with first report during 2020. The study is registered at ClinicalTrials.gov: NCT03377881 and has regional ethical approval (2017-1280/31). Clinical trial information: NCT03377881.