bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant darolutamide plus androgen deprivation therapy for high-risk/very high-risk localized prostate cancer: A multicenter, open-labeled, single-arm phase II trial.
Authors: Zhuang Junlong , Wang Yuwen , Zhang Shun , Qiu Xuefeng , Zhou Feng , Fu Yao , Wei Xuedong , Xu Linfeng , Guo Hongqian 
Published: January 2024

321 Background: Radical prostatectomy (RP) is associated with adverse surgical outcomes and an increased risk of disease progression in patients with high-risk/very high-risk localized prostate cancer (HRLPC/VHRLPC). This study aimed to evaluate the efficacy and safety of neoadjuvant darolutamide, a next-generation androgen receptor inhibitor, plus androgen deprivation therapy (ADT) for patients with HRLPC/VHRLPC undergoing RP. Methods: In this multicenter, single-arm phase II clinical trial, patients aged 18-75 year with HRLPC/VHRLPC (defined as Gleason ≥ 8 and/or cT3-4N0-1 and/or PSA ≥ 20 ng/mL). Patients with at least one of the following features were diagnosed with VHRLPC: cT3b-cT4, primary Gleason pattern 5, 2 or 3 high risk features, > 4 cores with Grade Group 4 or 5. Eligible patients received 6-month neoadjuvant darolutamide plus ADT followed by RP. The primary endpoint was pathological response rate (the proportion of patients with pathologic complete response [pCR] or minimal residual disease [MRD]). The secondary endpoints included safety, PSA progression-free survival, positive surgical margins rate, downstaging rate and PSA response rate. Results: Thirty patients were enrolled, and all patients had received robotic-assisted RP. The median age was 71.0 (interquartile range [IQR], 65.2-73.0) years, and the median PSA level was 37.8 (IQR, 21.0-94.7) ng/mL at baseline. A majority of the patients had VHRLPC (93.3%), while 6.7% had HRLPC, among whom N1 disease, cT3-4, Gleason 8-10, and PSA ≥ 20 ng/mL accounted for 26.7%, 86.7%, 90% and 77% of cases, respectively. The median prostate volume before RP was 19.4 mL (IQR, 15.6-28.4). Twenty-seven patients (90%) had undetectable PSA levels (＜0.01 ng/mL). The pCR rate was 6.7% and the MRD rate was 33.3%, resulting in a pathological response rate of 40.0%. Twenty patients (66.7%) achieved downstaging, and only four case (13.3%) had positive surgical margins. Eleven patients (36.6%) had extracapsular extension. The details of clinical and pathological outcome after neoadjuvant therapy are described in the Table. Conclusions: Darolutamide plus ADT for six months before RP improved clinical and pathological responses in men with HRLPC/VHRLPC, with favorable safety profile. Clinical trial information: NCT05249712 .[Table: see text]
Safety and clinical validity of tumor genomic testing for guiding active surveillance selection in men with NCCN intermediate-risk prostate cancer.
Authors: Lenz Lauren , Clegg Wyatt , Iliev Diana , Korman Howard , Morgan Todd Matthew , Hafron Jason , DeHaan Alexander , Tutrone Ronald F. , Richardson Timothy , Cline Kevin , Yonover Paul M. , Jasper Jeff , Gutin Alexander , Finch Robert , Slavin Thomas Paul , Cohen Todd 
Published: January 2024

336 Background: Clinicopathologic features are considered the gold standard for predicting prostate cancer (PCa) disease severity and guiding decisions on the use of active surveillance (AS) or definitive treatment (DT). However, tumor genomic testing has been shown to provide valuable information as an addition to clinical risk stratification measures, allowing for more accurate identification of AS candidates. This study evaluated the safety of genomic testing for guiding AS selection in patients with National Comprehensive Cancer Network (NCCN) intermediate-risk PCa. Methods: In this retrospective observational cohort study, patients with NCCN intermediate-risk PCa underwent Prolaris testing at diagnosis from 9/2015–12/2018. The Prolaris test combines a molecular cell cycle progression score with clinicopathologic features (USCF Cancer of the Prostate Risk Assessment [CAPRA] score, inclusive of Gleason score), generating a Combined Clinical Risk (CCR) score to identify patients as candidates for AS or DT. Patients with a CCR-based 10-year disease-specific mortality (DSM) risk ≤3.2% were recommended to AS. Clinical follow up data, including initial treatment selection and time to metastasis, were retrospectively collected from the treating clinics. Kaplan-Meier estimates were used to evaluate the safety of AS in patients who initially selected AS. Cox proportional hazards models were used to evaluate CCR as a predictor of metastasis in all patients. Results: In total, 3204 patients were included in this analysis, with 1468 (46%) recommended to AS and 1736 (54%) recommended to DT. Among the 973 (30%) patients who initially selected AS, 613 (63%) were recommended to AS and 360 (37%) were recommended to DT. In patients who were recommended to AS and initially selected AS, the observed risk of metastasis within 5 years of diagnosis was 0.37% (95% confidence interval [CI], 0.09%–1.47%). Patients who were recommended to AS had a significantly lower rate of metastasis than patients who were recommended to DT after accounting for initial treatment decision (AS vs DT) and CAPRA score (hazard ratio 4.20 [95% CI, 1.41–18.04], P-value = 0.03). Conclusions: For patients with NCCN intermediate-risk PCa who were identified by genomic testing as candidates for AS, AS is safe based on the very low observed metastasis risk. The CCR score is a strong predictor of metastasis beyond clinicopathologic factors.
Prostate extracellular vesicles and prediction of clinically significant prostate cancer: A prospective single-institution pilot study.
Authors: Britton Cameron J , Andrews Jack R. , Arafa Ali , Kim Yohan J , Rangel Laureano J , Schulte Phillip J. , Joshi Vidhu B. , Ahmed Mohamed E. , Karnes R. Jeffrey , Lucien Fabrice 
Published: January 2024

337 Background: Prostate cancer remains the most common solid organ malignancy among males in the United States. Commercial biomarkers and multiparametric MRI have been utilized to better triage men with elevated PSA and determine patients most likely to have clinically significant prostate cancer (csPCa) upon prostate biopsy. We studied the combination of MRI with PSA-based and novel extracellular vesicle (EV)-based biomarkers to determine the optimal pre-biopsy testing to reduce the number of unnecessary biopsies. Methods: Men presenting to our clinic with elevated PSA (≥ 2 ng/ml) were prospectively enrolled from October 2019 to March 2022. All men underwent multiparametric MRI and blood draws to determine prostate health index (PHI) scoring, EV density, and PSA density. MRI-fusion biopsy was performed with both systematic and targeted prostate sampling, with clinicians blinded to prior blood testing results. Blood concentrations of prostate EV (ProsEVs) were measured by nanoscale flow cytometry using antibodies against PSMA and STEAP1. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and receiver operator characteristic (ROC) curves were constructed separately for all patients, those without prior diagnosis of PCa, and biopsy-naïve patients. Bootstrapping analysis was performed to provide more accurate assessment of the predictive ability of all combinations. Results: Ultimately, 175 men enrolled and underwent MRI, blood testing, and prostate biopsy. Among the 175 patients included, 101 (58%) had never undergone biopsy, 38 (22%) had a previous negative biopsy, and 36 (21%) were on active surveillance (AS) for GS6 disease. AUC of mpMRI (PI-RADS≥3) to predict clinically significant PCa was 0.66 with a sensitivity, specificity, NPV and PPV of 95.2%, 37.6%, 76.0% and 79.26%. MRI combined with STEAP1-EV density had an AUC of 0.77 with a sensitivity, specificity, NPV and PPV of 90.1%, 46.7%, 64.4% and 80.9%. A multivariable model including MRI, STEAP1-EV density, PSA density and PHI density outperformed other combinations with an AUC, sensitivity, specificity, NPV and PPV of 0.90, 89.2%, 68.7%, 72.8% and 88.1%. Conclusions: Combination of mpMRI with ProsEV and PSA derivatives demonstrated better predictive ability for csPCa on biopsy compared to imaging or serum testing alone. Inclusion of prostate volume with biomarkers further increased predictive ability which could lead to a decrease in number of unnecessary biopsies for men with benign conditions and indolent cancer.
PSMA-based PET as an imaging biomarker of androgen receptor signaling in high-risk localized and locally advanced prostate cancer (PCa).
Authors: English Keara , Deville Curtiland , Anabaraonye Nancy 
Published: January 2024

341 Background: The purpose of this prospective, nonrandomized, pilot imaging study (NCT02420977) is to evaluate prostate-specific membrane antigen (PSMA), [18F]DCFPyL (DCFPyL), as a PET/CT imaging biomarker of androgen receptor (AR) signaling in newly diagnosed PCa. Methods: 23 men with treatment-naïve, newly diagnosed high-risk prostate cancer were enrolled. Patients underwent DCFPyL PET/CT imaging and MRI/ultrasound fusion-guided prostate biopsy before and after 2-3 months of nADT (LHRH agonist and anti-androgen), followed by definitive IMRT. We measured the total number of lesions, lesion location, maximum standardized tumor uptake value (SUVmax), PSA, and changes in those variables between baseline and follow-up scans. Concordance between biopsy pathology results and PSMA imaging parameters before and after ADT was evaluated. Results: 3 patients were excluded after baseline PET/CT due to high-burden metastases, small cell histology, and declining to proceed further. 20 patients remained for evaluation. At baseline, 19/20 and 8/20 had at least 1 avid intraprostatic and extraprostatic lesion, respectively, with a 50 total lesions (28 prostate, 19 nodal, 3 bone); median intraprostatic and extraprostatic SUVmax were respectively 9.6 (range: 3.3-56.8) and 7.0 (range: 2.3-61.9). Post-nADT scans revealed 32 lesions (19 prostate, 11 nodes, 2 bone); median intraprostatic and extraprostatic SUVmax decreased respectively to 4.1 (range 1.9-27.8) and 3.2 (range: 1.7-8.9). 3/19 (15.8%) of the patients demonstrated complete uptake resolution of the avid intraprostatic foci, 15/19 (78.9%) showed decreased uptake (58.3% median decrease in SUVmax), and 1/19 (5.26%) showed increased SUVmax. Of the 8 patients with extraprostatic lesions, 2/8 (25%) demonstrated complete uptake resolution, 5/8 (62.5%) showed partially decreased uptake (66.67% median decrease in SUVmax), and 1/8 (12.5%) showed increased SUVmax. One of the same patients still had 2 lesions, for a total of 13 intraprostatic target lesions. Regarding concordance between pathologic results and PSMA imaging response pre- and post-nADT, 14/19 (73%) had biopsies fully concordant with PSMA scan (i.e. residual tumor and residual PET avidity), 4/19 (21%) had biopsies mostly concordant with the scan (i.e. complete pathologic response with partial PET response or vice versa), and 1/19 (5%) had a biopsy discordant with the PSMA scan (i.e. no pathology response, but complete response on PSMA). Conclusions: Post-nADT PET detected fewer PSMA-positive lesions with overall decreased or resolved tumor uptake, except for 2 separate patients with increased intra- and extraprostatic uptake. 95% of post-nADT PSMA scans were fully or mostly concordant with post-nADT biopsies, suggesting that PSMA scans may be a clinically useful, prognostic imaging biomarker for disease status evaluation post-nADT. Clinical trial information: NCT02420977 .
Patterns of PSMA PET/CT scan usage for initial staging and recurrence in a multi-centered hospital system.
Authors: Bennett Richard , Li Eric , Ho Austin Y. , Aguiar Jonathan , Mahenthiran Ashorne Krithiesh , Kumar Sai , Suk-ouichai Chalairat , Neill Clayton , Patel Hiten Dilip , Schaeffer Edward M. , Savas Hatice , Ross Ashley 
Published: January 2024

36 Background: PET PSMA-based imaging for prostate cancer staging has been approved since late 2020 and was widely available in our medical system by July 2021. We sought to examine the patterns of use of PSMA PET/CT and conventional imaging for staging since this time. Methods: We retrospectively identified men who were diagnosed with presumptive NCCN unfavorable intermediate risk (UIR), high risk, or very high risk (VHR) and men who underwent staging work-up for biochemical recurrence (BCR) from July 2021 – June 2023. Patient clinical, pathological, and imaging variables were collected. Sufficient conventional imaging for initial staging was defined as the use of a bone scan and one or more of an MRI or CT scan. The date of staging was determined by the initiation of staging with conventional imaging or the date of PSMA scan if used. Results: In the study period, 899 men were diagnosed with presumptive NCCN UIR-VHR disease. Among these individuals 32% (290/899) underwent no or insufficient staging, 26% (230/899) underwent staging with conventional imaging only, and 42% (379/899) underwent initial staging evaluations that included PET PSMA. The frequency of PET PSMA used for initial staging increased from 24% (20/82) to 80% (167/208) over the 2-year study period. 1173 men with biochemical recurrence who underwent a staging work-up were identified. Median PSA of these men was 1.37 ng/mL (IQR 0.23, 6.59 ng/mL). The frequency of PET PSMA imaging increased in these men from 91% (225/246) to 98% (296/303) over the 2-year study period. When ordering both PSMA and conventional imaging for initial staging, providers tended to order PSMA scans after initial conventional imaging orders (72%) rather than before (18%) or on the same day (11%). Conclusions: The use of PSMA PET/CT imaging rose since its implementation in our system in July 2021 with PSMA PET being utilized in 80% of patients being initially staged and 98% of those staged at BCR. Conventional imaging and Axumin PET are rarely used in BCR. If both PET PSMA and conventional imaging were ordered for initial staging, PET PSMA was typically performed after conventional imaging. Growing data may inform best sequencing and use of conventional imaging in the PSMA-PET era.
Association between thymectomy and incidence of renal cell carcinoma (RCC).
Authors: Barragan-Carrillo Regina , Ebrahimi Hedyeh , Chawla Neal Shiv , Salgia Nicholas , Castro Daniela V. , Chehrazi-Raffle Alex , Dizman Nazli , Hsu Joann , Meza Luis A , Zengin Zeynep Busra , LeVee Alexis Ann , Tripathi Abhishek , Dorff Tanya B. , Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Eilber Karyn , Dallas Kai , Pal Sumanta Kumar 
Published: January 2024

371 Background: Recently, thymectomy in adults has been linked to a higher incidence of several malignancies (Kooshesh et al NEJM 2023). Accompanying translational studies suggest that depleted T-cell production (both CD4+ and C8+) and decreased clonality may selectively drive the pathogenesis of immunogenic cancers such as RCC. We sought to confirm this finding in a large population-based cohort. Methods: We interrogated the California Office of Statewide Health Planning and Development (OSHPD) database, which collects information from all inpatient admissions, emergency room visits, and inpatient/outpatient procedures in the state. Patients who underwent thymectomy and nephrectomy (specifically for RCC) were identified from Jan 1, 2012, to Dec 31, 2019, using CPT and ICD-9/10 codes. The frequency of nephrectomy following thymectomy was computed. The frequency of both surgical interventions in the general population was derived by comparing their respective incidence in the OSHPD database against age-matched California census data. Chi square test was used to determine differences among groups. Fisher’s exact test was used to determine if the incidence of nephrectomy following thymectomy was different from the incidence of nephrectomy overall. Results: During the study period, 1,969 pts (mean age 56) underwent thymectomy and 31,093 pts (mean age 57) underwent nephrectomy. Relative to patients who underwent thymectomy, a larger proportion of patients undergoing nephrectomy were male (57% vs 45%) and Hispanic (28% vs 18%) (p<0.01)., while a smaller proportion was Asian (7% vs 18%) (p<0.01). Expressed as a percentage of the underlying age-matched population (18,343,792 pts), 0.01% of pts received thymectomy, and 0.17% of pts underwent nephrectomy. A total of 11 pts underwent nephrectomy following thymectomy, suggesting an incidence of 0.56% in this cohort. This was significantly higher than the incidence of nephrectomy in the population at large (P=0.002). The median age of patients who had a nephrectomy for RCC with a prior thymectomy was considerably younger than the general population who underwent a nephrectomy (mean age 52 vs. 57 years). Conclusions: In a large population-based study, we observed a significantly higher rate of nephrectomy for RCC in patients who had received prior thymectomy. These results bolster previous studies done in smaller datasets. Further work is needed to define causality and clarify the mechanism of this association.
Patterns of early 18F-FDG PET response to nivolumab (NIVO) and ipilimumab nivolumab (IPINIVO) in patients with metastatic renal cancer (MRC).
Authors: Charnley Natalie , Rosof-Wiliams Diana , Dobson Mike , Cox Susan , Amin Nisreen , Parikh Omi , Thompson Catherine , Danwata Falalu Dahiru , Cain John 
Published: January 2024

374 Background: Immunotherapy with IPINIVO and NIVO is a standard treatment in MRC. This leads to recruitment and activation of immune cells. The ‘immune burst’ is seen at 1-4 weeks. Glycolysis leads to cellular 18F-FDG uptake. This can reflect malignancy. Sensitivity for renal tumours is poor, though high SUV suggests aggressive behaviour. Sensitivity for metastases can be 90% This study investigated 18F-FDG uptake in patients with MRC prior to treatment with immunotherapy. A scan was also performed at 2 weeks to assess a possible ‘flare’, due to glycolysis of the immune infiltrate, before significant standard radiological change was expected. Methods: Twenty six patients with MRC were enrolled. 8 patients had IPINIVO first line, and 18 had NIVO second line. Patients had a PET scan before and 2 weeks after treatment. Maximal standardised uptake values (SUV) were measured and corrected (COR) to the hepatic SUV. Results: All patients had some 18F-FDG avid metastases. SUVs varied within the same patient. For IPINIVO patients SUVmax was 17, mean 5.8 (3.7 and 2.5 COR respectively) and for NIVO patients SUV max was 25.1, mean 5.1. (7.6 and 2.3 COR respectively). There was no difference in mean SUV in the 2 groups (p=0.5). For NIVO patients there was a trend for patients who had a longer response to first line tyrosine kinase inhibitor, hence better prognosis, to have a lower SUV. (p=0.18) For NIVO there was a 12.4 % mean increase in SUV (p=0.06) In 8/16 patients there was a >20% increase in SUV in the measured metastases ( mean 50.4 % increase, range 22.2 – 142.9 ). Flare occurred at a range of tumour sites. Only metastases which were 18F-FDG avid had a flare. In 4 patients there was a >20% decrease in SUV. (Mean 41.2 Range -21.2% to -55.3%) For IPINIVO in 4/8 patients there was a >20% increase in SUV, mean 57.2 (Range 21- 134%) Flare only occurred in lymph nodes and an adrenal gland. In 2 patients there was a >20% decrease in SUV. (Mean - 50.7 Range -21.2% to -64%) Two patients had normal tissue flare: in thyroid, and mediastinal nodes. Conclusions: This is the first study to demonstrate tumour 18F-FDG flare in patients with MRC following immunotherapy, which may be due to influx and activation of glycolytic immune cells. There is a suggestion that tumour biology, and response to first line tyrosine kinase inhibitor is reflected in the SUV of metastases in patients having treatment with second line nivolumab.
Health-related quality of life (HRQoL) profile and clinical outcomes in first-line (1L) advanced renal cell carcinoma (aRCC): A modelling analysis based on CheckMate 9ER (CM9ER) trial.
Authors: Bedke Jens , Giles Rachel H. , Powles Thomas , Derosa Michael , Floden Lysbeth , Purnajo Intan , Lothgren Mickael , Ogareva Alessia , Cella David 
Published: January 2024

384 Background: Cabozantinib plus nivolumab (CN) is a 1L therapy for aRCC. In the CM9ER trial CN had superior efficacy to sunitinib (SUN) and showed HRQoL benefit. We investigated the relationship between clinical outcomes, treatment and early deterioration in HRQoL dimensions in the CM9ER population. Methods: Using the CM9ER intention-to-treat (ITT) population (median follow-up 32.9 months) we: (a) explored time-to-event outcomes for CN vs SUN (b) identified determinants of HRQoL benefit by performing ordinal regression using the 19-item Functional Assessment of Cancer Therapy – Kidney Symptom Index (FKSI-19) item scores at week 13 (c) investigated relationships between early (week 13) deterioration in FKSI-19 items and clinical outcomes using a cox proportional modeling framework. First, univariate Cox proportional hazard modeling assessed the predictiveness of early FKSI-19 item deterioration (sig. threshold p ≤ 0.20). Items with significant univariate associations with the outcome were included in multivariate regression modeling (sig. threshold p ≤ 0.10). Treatment and baseline stratification factors (geographic region, baseline IMDC score, PD-L1 status) remained in all models. Results: All CM9ER ITT patients (N = 651; CN, 323; SUN, 328) were included. Compared with SUN, CN patients had a longer median duration of treatment (94.6 wks vs 36.5 wks), time to disease progression (83.1 wks vs 42.1 wks) and time to first grade 3/4 adverse event (16.3 wks vs 12.0 wks). FKSI-19 items with early deterioration favoring CN vs SUN ( p ≤ 0.05) were: lack of energy; pain; fatigue; bone pain; weak all over; nausea; bothered by treatment side effects; able to work. The table reports variables significantly associated with clinical outcomes ( p ≤ 0.05). Conclusions: Early deterioration in bone pain and sleep were associated with increased risk of mortality, and early deterioration in pain with reduced risk of toxicity-related discontinuation. We found no association between early FKSI-19 item deterioration and risk of progression or tumor shrinkage. Controlling for other variables, CN (vs SUN) treatment was positively and significantly associated with increased chance of tumor shrinkage, survival and progression-free survival, independent of early HRQoL deterioration. Clinical trial information: NCT03141177 . [Table: see text]