bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States.
Authors: George Daniel J. , Kariburyo-Yay Furaha , Aggarwal Himani , Tepsick Jon G. , Yu Rebekah , Li Weiyan , McLaurin Kimmie K. , Orji Chinelo , Lal Lincy S. , Ghate Sameer R.
Published: January 2024

332

Background: Olaparib is one of the first targeted therapies for patients (pts) with mCRPC. This study focused on assessing treatment patterns and results of genetic testing for HRRm in mCRPC pts treated with olaparib monotherapy. Methods: This retrospective study used data abstracted from electronic medical records in the ConcertAI Oncology Dataset with PC diagnosis between 1990 and 2023. Pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. HRRm was defined as a mutation in at least 1 of 14 genes of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L) regardless of test type. Pt demographic and clinical characteristics, patterns of individual HRRm, testing type, and timing of biomarker testing were summarized. The index date was the start date of the earliest olaparib monotherapy treatment. Results: A total of 192 mCRPC olaparib treated pts with at least one HRRm were identified. The median age was 73 years at index date. More than half of pts (56.3%) had an ECOG score of 0 or 1, and 51.0% of pts had a Gleason Score of ≥8 at index. Most pts (87.0%) had bone metastasis at index, and 20.3% had 3 or more sites of distant metastasis. Nearly one-third of pts (31.7%) had documentation of opioid use at index. Over half of the pts (56.2%) had any BRCA mutation ( BRCA2 33.3%, BRCA1 4.7%, co-occurring HRRm 18.2%) and 43.8% had non- BRCA mutation ( ATM 20.8%, CDK12 4.2%, co-occurring HRRm 11.5%, other non- BRCA 7.3%) Over 40% of pts had somatic only testing (40.6%), while 15.1% had germline only testing, 27.6% of the pts had both germline and somatic testing, and 16.7% had other testing. Most pts were tested on or after mCRPC diagnosis (142 pts; 74.0%) and the median time from mCRPC diagnosis to the first biomarker test was 16.9 (IQR 23.3) months. Conclusions: This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course. [Table: see text]
Exploring the utility of prostate-derived extracellular vesicles as a urine biomarker for clinically significant prostate cancer.
Authors: Deol Ekamjit Singh , Britton Cameron J , Andrews Jack R. , Horjeti Edlira , Kim Yohan J , Joshi Vidhu B. , Ahmed Mohamed E. , Karnes R. Jeffrey , Lucien Fabrice
Published: January 2024

334

Background: Prostate cancer (PCa) screening has relied on prostate-specific antigen (PSA) levels to screen patients for biopsy. However, the limited specificity of serum PSA leads to high rates of negative biopsies and detection of clinically insignificant cancers. Tumor-derived extracellular vesicles, microscopic particles released by tumor cells and ubiquitously found in all bodily fluids, have emerged as novel biomarkers for a diverse set of malignancies. This study explored the utility of urine prostate-specific extracellular vesicles (ProsEVs) identified by unique surface protein markers with novel flow cytometry-based techniques as biomarkers for PCa screening. Methods: This prospective study recruited at a tertiary care center between Oct 2019 and Mar 2022. Patients with PSA≥2 ng/ml underwent prebiopsy mpMRI followed by transperineal prostate biopsy (PI-RADS 1-2) or combined MRI-guided biopsy (PI-RADS ≥ 3). Patients with metastatic PCa or prior systemic therapy were excluded. Urine samples were collected at MRI using Colli-Pee. ProsEVs were labeled using monoclonal antibodies for PSMA and STEAP1 and ProsEV concentrations were determined using nanoscale flow cytometry. EV densities were calculated by normalizing EV counts to prostate volume. Multivariable logistic regression models were constructed and model performance was compared used ROC curve analysis. Results: This study had a total of 179 patients prospectively recruited, 95 were diagnosed with Gleason score (GS) ≥ 7 prostate cancer (csPCa), while the remaining had GS <7 or benign disease. Analysis of urinary ProsEV densities revealed a significant dose-response relationship between benign, GS <7 PCa and GS ≥ 7 PCa groups and ProsEV densities (p=0.01 for PSMA, and <0.001 for STEAP1). The log sum of the PSMA and STEAP1 EV densities exhibited the strongest correlation with other ProsEV variables and was selected for model development. ROC curve analysis showed that the final model including Log Sum ProsEVs, PSA, and PI-RADS outperformed one including PSA and PI-RADS (0.733 vs 0.651, p=0.02). Specificity for detecting csPCa at a sensitivity of 90% was 39.5% in the final model compared to 37% for PSA and PI-RADS (Table). Conclusions: This study highlights the potential of urine ProsEVs as novel biomarkers for improving screening specificity for csPCa detection. Future works should explore analysis of intra-ProsEV content to further improve specificity and advance liquid biopsy techniques. [Table: see text]
Comparison of pathologist and deep learning–based prostate cancer grading for prediction of metastatic outcomes in primary prostate cancer.
Authors: DePaula Oliveira Lia , Lu Jiayun , Erak Eric , Mendes Adrianna , Bonthu Saikiran , Joshi Uttara , Kondragunta Chaith , Joshu Corinne E , Singhal Nitin , De Marzo Angelo M , Lotan Tamara L.
Published: January 2024

345

Background: Gleason grading is the most potent prognostic variable in primary prostate cancer, however inter-observer variability remains a major issue, particularly where subspecialty-trained pathologists are not available. Artificial intelligence algorithms for prostate cancer grading may improve health care equity by ensuring widespread access to standardized, high quality grading, however most algorithms have not been tested for performance with respect to oncologic outcomes. Here, we compared deep learning-based and pathologist-based Gleason grading for prediction of metastatic outcome in three large radical prostatectomy cohorts. Methods: Three previously published radical prostatectomy cohorts from Johns Hopkins were utilized for this study. The Natural History Cohort (n=318, PMID: 26058959) and Case-Cohort (n=231, PMID: 36006048) both utilized a case-cohort design on the outcome of metastasis, while the Race Cohort (n=335, PMID: 30851334) was designed for a grade-matched comparison of self-identified White and Black patients. For each cohort, a single representative H&E-stained slide from the dominant tumor nodule was scanned and Gleason Grade Group (GG) assessed by a modified deep learning-based grading algorithm (PMID: 35233002), or by a subspecialty-trained pathologist. Harrell’s C-indices based on unadjusted Cox models for time to metastasis were compared for the pathologist- and deep learning-assigned GG in each cohort. Results: The C-index for deep learning-assigned GG in the Natural History Cohort was 0.757 (95% confidence interval [CI]: 0.703-0.811) compared to 0.748 (95% CI: 0.692-0.804) for the pathologist-assigned GG. The C-index for deep learning-assigned GG in the Case-Cohort was 0.848 (95% CI: 0.727-0.969) compared to 0.843 (95% CI: 0.722-0.964) for the pathologist-assigned GG. The C-index for deep learning-assigned GG in the Race Cohort was 0.754 (95% CI: 0.697-0.810) compared to 0.780 (95% CI: 0.717-0.844) for the pathologist-assigned GG. In a combined analysis of all three cohorts, the C-index for the deep learning-assigned GG was 0.765 (95% CI: 0.725-0.805) compared to 0.772 (95% CI: 0.730-0.814) for the pathologist-assigned grade group. In the combined cohorts, the historical pathologist-assigned GG for the entire case had a C-index of 0.796 (95% CI: 0.757-0.836). Conclusions: Deep learning and subspecialty-trained pathologist grading were highly comparable for association with metastatic outcome across three large radical prostatectomy cohorts.
PSMA PET imaging for evaluation of recurrent or persistent prostate cancer after primary prostate radiation.
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

35

Background: PSMA PET is increasingly utilized for the evaluation of disease stage at biochemical recurrence. Here we evaluate the association of clinico-pathologic features with PSMA findings in biochemically recurrent patients after primary prostate radiation therapy (RT). Methods: We queried the Northwestern Medical System Electronic Data Warehouse between July 2021 and March 2023 to identify 122 men treated with primary RT for presumptive localized prostate cancer who subsequently underwent Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT for staging. Patient characteristics, including demographic, clinical, pathological, and imaging variables were obtained. PSMA positivity for suspicious nodal or metastatic disease was determined based on radiology interpretation, with equivocal or likely benign lesions considered as negative findings. Patients with incomplete clinical history (n=3) were excluded. Clinical variables were compared using a Wilcoxon rank-sum and Fisher’s exact tests. Regression analysis was performed to determine variables associated with PSMA positivity in biochemically recurrent patients. Statistical significance was determined if the p-value was less than 0.05. Results: Among the 119 men staged with PET PSMA after RT, median PSA was 3.18 (IQR 1.35, 5.55 ng/mL). 78% (93/119) were found to have suspicious PSMA positive disease. 39% had PSMA positivity in the prostate only (46/119), 6.7% had pelvic nodal disease (8/119), and 33% had extrapelvic disease (39/119). On univariable regression analysis, PSA at the time of PSMA was the only factor associated with PSMA positivity (OR 1.32 per 1 point increase, 95% CI 1.10, 1.67, p=0.01; Table). Higher PSAs at the time of scan were additionally associated with distant recurrence (73.3% of men with distant recurrence if scanned at PSA >10ng/mL versus 31.9% if scanned at PSA <4ng/mL p=0.029). 20% (9/46) of men with PSMA positivity within the prostate were biopsied identifying 78% (7/9) positivity, of which 67% (4/6) receiving treatment selected management with salvage treatments. Conclusions: Patients with prostate cancer initially treated with RT showed significant rates of PSMA positive disease even when scanned at low PSAs (including many below the nadir+2ng/mL definition). Evaluation at low PSAs favors the identification of localized disease only which can be cured by salvage therapy if confirmed by biopsy (i.e. prostatectomy, cryoablation, HIFU). [Table: see text]
Belzutifan versus everolimus in participants (pts) with previously treated advanced renal cell carcinoma (RCC): Patient-reported outcomes (PROs) in the phase 3 LITESPARK-005 study.
Authors: Powles Thomas , Albiges Laurence , Jalkanen Katriina Johanna , De Velasco Guillermo , Burotto Mauricio , Ghatalia Pooja , Suárez Cristina , Lam Elaine T. , Iacovelli Roberto , Gumus Mahmut , Verzoni Elena , Kollmannsberger Christian K. , Stadler Walter Michael , Venugopal Balaji , Shinde Reshma , Saretsky Todd L. , He Li , Vickery Donna , Choueiri Toni K. , Rini Brian I.
Published: January 2024

361

Background: In the randomized, open-label, phase 3 LITESPARK-005 (NCT04195750) study, belzutifan treatment showed superior PFS (primary endpoint; HR 0.75 [95% CI 0.63–0.90]; P<.001) and ORR (key secondary endpoint; estimated percentage-point difference 18.4 [95% CI 14.0–23.2]; P<.00001) vs everolimus in pts with advanced/metastatic clear cell RCC that progressed after prior immune checkpoint and anti-angiogenic therapies. We present PRO findings for belzutifan vs everolimus in LITESPARK-005. Methods: PROs were evaluated by FKSI-DRS and EORTC QLQ-C30 questionnaires in all randomized pts with ≥1 dose study treatment and ≥1 completed PROs assessment, administered electronically on d 1 of wk 1, 3, 5, and 9, Q4W thereafter, at treatment discontinuation, and d 30 after last dose. Time to deterioration (TTD) and least square (LS) mean change from baseline as measured by FKSI-DRS and QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) scales were prespecified as secondary endpoints. PROs were not formally statistically tested and 95% CI and P-values were nominal and descriptive. Results: As of June 13, 2023 (data cutoff date at second prespecified interim analysis), median (range) follow-up was 25.7 mo (16.8–39.1). Median (range) duration of treatment was 7.6 mo (0.1–35.8) with belzutifan vs 3.9 mo (0.0–33.2) with everolimus; 84 (22.6%) vs 18 (5.0%) pts remained on treatment. 366 of 374 pts randomized to belzutifan and 354 of 372 pts randomized to everolimus were included in the PRO analysis population. Completion rates for FKSI-DRS and QLQ-C30 were >90% at baseline and >55% at wk 17 (~4 mo) in each arm. Meaningfully longer TTD in FKSI-DRS and QLQ-C30 GHS/QoL scores were observed for belzutifan vs everolimus (Table). LS mean changes in FKSI-DRS and QLQ-C30 GHS/QoL scores suggested stability from baseline to wk 17 with belzutifan vs worsening with everolimus, and a potential greater worsening in PF scores with everolimus vs belzutifan. Conclusions: Belzutifan was associated with prolonged TTD in FKSI-DRS and EORTC QLQ-C30. Score changes from baseline to wk 17 also favored belzutifan over everolimus. Overall, PRO results indicate better disease-specific symptoms and quality of life among pts treated with belzutifan compared with everolimus. Clinical trial information: NCT04195750 .[Table: see text]
Assessing tobacco-related mortality trends in genitourinary cancers: A 1990-2019 analysis.
Authors: Jani Chinmay , Kareff Samuel A. , Salazar Ana S. , Sharma Janaki Neela
Published: January 2024

368

Background: Tobacco consumption is a well-established risk factor for genitourinary cancers like urothelial and renal cell. This study aims to examine mortality trends associated with tobacco use in these cancer types, both globally and within the U.S., over the period of 1990 to 2019. Methods: Data from the Global Burden of Disease database, based on the International Classification of Diseases versions 10 and 9, were utilized to extract mortality statistics for bladder cancer (BC) and kidney cancer (KC). Age-standardized death rates (ASDRs) for the overall population, as well as Tobacco Attributable Mortality (TAM) were collected by sex and year. TAM was calculated by applying population attributable fraction to cause-specific deaths and disability-adjusted life years by year, location, age group and sex. The database also provided Annual Percentage Change (APC) data. Trends were analyzed using Joinpoint regression. Results: Smoking rates as well as mortality due to tobacco consumption have steadily decreased for both cancers in both sexes globally as well as in the U.S. during the study period. Globally, ASDRs exhibited a decreasing trend for BC and KC, and for both sexes, excluding an increase in ASDR for KC in males (+0.2). In the U.S. ASDR decreased for KC but not for BC in males (Table 1). BC demonstrated the highest proportion of tobacco-induced mortality among the three cancer types, with a nearly 50% contribution globally among males in 1990 that reduced to 39% in 2019. Overall, the tobacco-induced ASDR for kidney cancer in males remained relatively constant globally. Despite reductions over three decades, BC still exhibited a high proportion of mortality attributed to tobacco, particularly among males (39% globally; 31% in the U.S.). In 2019, the U.S. continued to experience higher tobacco-induced mortality rates among females for both KC (17.1 vs. 8.8%) and BC (26.9 vs. 14.3%) compared to the global average. Conclusions: Despite the multiple advances in cancer treatment in the last decades, TAM remains minimally unchanged. While there has been a general reduction in smoking rates overall, a substantial burden persists for tobacco-related malignancies—particularly for BC and KC. These findings underscore the need for heightened awareness and more robust tobacco control policies both globally and within the U.S. [Table: see text]
Germline pathogenic variants in universal screening of genitourinary malignancies: A multisite single institution prospective study.
Authors: Choudry Mouneeb , Durant Adri , Edmonds Victoria , Warren Christoper , Kunze Katie , Golafshar Michael A. , Nielsen Sarah M. , Heald Brandie , Andrews Jack R. , Samadder N. Jewel , Tyson Mark
Published: January 2024

376

Background: Germline genetic testing (GGT) is becoming increasingly important in the management of genitourinary (GU) malignancies as novel targeted drug therapies emerge. Selection for genetic studies and testing has historically been highly selective and based on pathologic characteristics, family history, and age of diagnosis. The aim of our study was to investigate the prevalence of pathogenic variants (PGVs) in inherited cancer susceptibility genes utilizing a universal testing approach and to characterize the rate of PGVs that would have been missed based on current NCCN guidelines. Methods: A multisite single-institutional prospective study (INTERCEPT) offered GGT to all patients with new or active diagnoses of GU malignancies (bladder, prostate, and renal cancers) from April 1, 2018 to March 31, 2020 at Mayo Clinic Arizona, Mayo Clinic Florida and Mayo Clinic Rochester. Participants were offered GGT with a panel of >80 genes through Invitae Corp. Demographic, tumor characteristics and genetic results were evaluated. PGVs were classified as high-, intermediate-, or low- penetrance variants based on published literature. Respective NCCN GU GGT guidelines were used to determine if the PGVs discovered using our universal testing approach would have been missed with guideline-directed GGT. Results: A total of 3095 pan-cancer patients were enrolled in the study; 601 of which had a GU malignancy including: prostate cancer (358 patients), renal cancer (137), and bladder cancer (106). The mean age of enrollment was 66.8 years (SD 9.1), 89% were male, and 85.9% of patients were Non-Hispanic white. PGVs were identified in 82 of all GU patients (13.6%) and variants of undetermined significance (VUS) in 289 (48.1%) patients. PGV prevalence breakdown by cancer type was: 13.7% of prostate, 13.1% renal, and 14.2% bladder cancer patients. The proportion of high penetrance PGVs varied by malignancy type. Of all patients, 326 (54.2%) had advanced (stage III/IV) disease and 377 (64.4%) of these were metastatic upon initial evaluation. The majority of all PGVs identified were incremental, defined as PGVs that would not have been identified based on guideline-concordant GGT: 100% (15/15 patients) with bladder, 77.8% (14/18) with renal, and 57.1% (28/49) with prostate cancer. Conclusions: Universal GGT for prostate, renal and bladder cancer revealed that over 1 in 10 patients harbored potentially actionable PGVs, most of which would not have been identified with guidelines-based GGT. Utilization of GGT can impact our understanding of GU cancer pathogenesis, aid in familial cascade testing, and influence treatment decisions.
Prostate-specific membrane antigen expression in endothelial cells of renal tumor-associated neovasculature and risk of recurrence for renal cell carcinoma.
Authors: Kikugawa Tadahiko , Kagimoto Keito , Watanabe Ryuta , Miura Noriyoshi , Saika Takashi
Published: January 2024

377

Background: PSMA is highly expressed in prostate epithelial cancer cells and used not only for diagnostic but also for therapeutic purposes. Despite its name, PSMA is not specific in prostate cells and is also expressed endothelial cells within the neovasculature of other tumors including renal cell carcinoma. PSMA is particularly the correlation of increased PSMA expression with prostate cancer aggressiveness, but is unknown in renal cell carcinoma patients. Here we estimate whether PSMA expression in endothelial cells of renal tumor-associated neovasculature is associated with pathological venous invasion and prognosis for patients after renal tumor surgery. Methods: A total of 45 patients who underwent radical or partial nephrectomies performed at our institution were included in this study. We investigated pathological venous invasion and PSMA expression in tumor-associated vessels around renal cell carcinoma by immunostaining using removed tumor tissue. The PSMA immunostain was evaluated in tumor-associated vessels according to the staining intensity and divided into three groups: weak, moderate, and strong, respectively. Results: Higher PSMA expression group is increased the percentage of patients with histologically observed venous invasion. The level of PSMA immnostain were detected in 18 cases at weak, 11 at moderate, 16 at strong. Ten patients after surgery had recurrence during the observation period, and the prognosis was worse in the group with strong PSMA expression in tumor-associated vessels around renal cell carcinoma. Conclusions: PSMA expression in endothelial cells of renal tumor-associated neovasculature may be a novel prognostic factor for renal cell carcinoma.
Fluorescence in situ hybridization utility in the care management of renal cell carcinoma (prospective study, 30 cases).
Authors: Ben Tayeb Rafik , Mziyene Mohamed , Tahiri Layla , Bouguenouch Laila , El Fatemi Hinde
Published: January 2024

378

Background: In Morocco, Kidney cancer is the 18th most common tumour and the 19th lethal cancer in 2020. The average age of diagnosis is 65 years and men are more affected. Molecular studies of renal cell carcinoma (RCC) allowed the detection of several genetic abnormalities in each histological subtype. These aberrations got different diagnostic value depending on their specificity, prognostic implication and for some a therapeutic utility since the development of targeted therapies. The aim of our study is to evaluate the utility of fluorescence in-situ hybridization (FISH) in the diagnostic and the prognostic categorization of patients with renal cell carcinoma. Methods: We included prospectively cases of RCC diagnosed after histological examination and immunohistochemistry analysis for some cases. The methodology consisted in highlighting by FISH molecular abnormalities for each histological subtypes using Zytolight probes. Probes were chosen depending on the histological diagnosis and their corresponding molecular abnormalities. Results: A total of 30 cases of RCC were included. Clear cell carcinoma (ccRCC) represented 56,6%(17 cases) followed by papillary RCC (pRCC) with 20% (6 cases), chromophobe RCC (chRCC) with 10% (3 cases), 2 cases (6,6%) with uncertain diagnosis clear cell carcinoma or papillary carcinoma and one case of renal oncocytoma (RO) (3,3%), tubulo-cystic RCC tcRCC (3,3%). The FISH method supported the morphological diagnosis in all cases except in one biopsy diagnosed histologically as a ccRCC and this method allowed the diagnosis correction to a pRCC by the detection of a polysomy of chromosome 17 described in this histological subtype. The FISH method can also be used in prognostic categorisation of patients by the detection of some genetic aberrations with a prognostic implication like the loss of CDKN2a located in the long arm of chromosome 9 which predict a worse diagnosis. Conclusions: FISH method got an good performance in the diagnostic approach of RCC especially in cases with non-conclusive histology and immunohistochemistry. It can also be used in the prognosis of this tumour in addition to other histo-prognostic factors. This method will lead to more precision in diagnosis and better care management personalisation in RCC.
Criteria and indicators to evaluate quality of care in genitourinary tumor boards.
Authors: Puente Javier , Algaba Arrea Ferran , Buisán Oscar , Castellano Daniel , Duran Ignacio , Fernández Ávila Juan José , Gómez-Iturriaga Alfonso , Parada Blázquez Mariano Jose , Pérez Fentes Daniel , Sancho Gemma , Vallejo Casas Juan Antonio , Gratal Paula , Pardo Maria Teresa , Guillem Vicente
Published: January 2024

388

Background: Multidisciplinary Tumor Boards are an essential component of patient management, as they integrate input from various healthcare professionals to make comprehensive decisions about patient care. Management of patients with genitourinary (GU) tumors particularly relies on these multidisciplinary Tumor Boards. However, there are no guidelines on how these groups should operate. Methods: A systematic literature review was conducted to identify criteria useful to evaluate quality in GU Tumor Boards (GUTB); publication dates were January 2016 to December 2021. A scientific committee—comprising 12 GU specialists from several disciplines—reviewed the literature findings, proposed a list of criteria, and developed and selected indicators using the Delphi method in a first round. Thirty-nine experts from various disciplines (urology, radiation oncology, radiology, medical oncology, nuclear medicine, hospital pharmacy, and pathology) participated in the second round of the Delphi method to evaluate the indicators. In both rounds the appropriateness and utility of the criteria and/or indicators were scored using a 9-point Likert scale (1, extremely inappropriate or not useful; 9, extremely appropriate or useful). Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category (1–3, 4–6, or 7–9) that encompassed the median score of the group. Results: Forty-eight articles were selected from the literature review and were used to develop a list of 67 initial criteria. The scientific committee narrowed these criteria down to 45 to evaluate the quality of GUTB, covering five dimensions: organization (11 criteria), personnel (5 criteria), protocol and registry (21 criteria), resources (6 criteria), and interaction with patients (2 criteria). Then, 33 indicators were developed and evaluated in the first round of Delphi, which led to a selection of 26 indicators. In the second round the group of experts reached consensus on the appropriateness of all 26 indicators and on the utility of 24 of them. Finally, indicators were compiled into a list, including how they should be measured, so that they can be easily used in clinical practice. Conclusions: Criteria and indicators were developed by this working group to evaluate the quality of GUTB, aiming to serve as a guide to improve quality of care and achieve better outcomes in patients with GU.
Management, outcomes and predictors of recurrence in chromophobe renal cell carcinoma: Results from the Canadian Kidney Cancer information system (CKCis).
Authors: Arenovich Erica , Breau Rodney H. , Mallick Ranjeeta , Rendon Ricardo A. , Feifer Andrew , Pouliot Frederic , Tanguay Simon , Lavallee Luke , Lattouf Jean-Baptiste , Nayak Jasmir G. , Bhindi Bimal , Bansal Rahul K. , Finelli Antonio , Mannas Miles , Richard Patrick O. , Lalani Aly-Khan A. , Heng Daniel Yick Chin , Bjarnason Georg A. , Basappa Naveen S. , Wood Lori
Published: January 2024

389

Background: Chromophobe RCC (chRCC) make up 5% of all RCC however data regarding baseline demographics, management, outcomes, and predictors of recurrence and survival is lacking. Methods: The Canadian Kidney Cancer Information System (CKCis) is a multi-institutional prospective cohort. Patients (pts) with clinically localized chRCC between Jan 2011-Aug 2023 were included. Descriptive statistics were used, time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. Results: chRCC made up 5.3% of all RCC pts in CKCis and only 2.4% presented with metastatic disease. This study cohort includes 797 pts who presented with localized disease. Median follow up 4.1 yrs, mean age 58.4 yrs and male in 58.5%. Management included: surgery 90.2%, surveillance 5.5%, or other local modalities 3.3%. Recurrence occurred in 59 pts (7.4%): 50 (85%) with metastases, 7 (12%) with local recurrence, and 2 (3.4%) with contralateral tumors. Median time to recurrence was 2 yrs. Management of recurrences included: systemic therapy in 46%, radiation in 29%, metastasectomy in 25%, surveillance in 8%. 5 and 10 year overall survival was 95% and 83% in all pts, 97% and 90% if no recurrence and 75% and 44% if recurrence. In the 90.2% (718 pts) treated with curative surgery, predictors of recurrence on multivariate analysis include: higher T stage, necrosis, and sarcomatoid features. Predictors of worse survival include: sarcomatoid features, larger tumor size, higher T stage, and higher number of comorbidities. Conclusions: In this large Canadian cohort, patients with chRCC usually present with localized disease and have relatively favorable oncologic outcomes, even when they recur. Larger tumors with sarcomatoid features have a worse survival and more intensive follow up may be beneficial. The favorable 5 and 10 year outcomes in chRCC are a reminder that studies must be conducted and reported for individual histologies and not as a large cohort of non clear cell RCC. [Table: see text]
Impact of standard-of-truth method on evaluation of a diagnostic PET radiopharmaceutical: Learnings from the phase 3 SPOTLIGHT study.
Authors: Lowentritt Benjamin H. , Chau Albert , Davis Phillip
Published: January 2024

39

Background: SPOTLIGHT (NCT04186845) evaluated newly approved diagnostic PET radiopharmaceutical 18F-flotufolastat (18F-rhPSMA-7.3) in patients (pts) with recurrent prostate cancer (PCa). In the absence of the gold standard histopathology, it can be challenging to verify positive findings from a diagnostic agent under investigation, particularly in recurrent PCa where it is neither feasible nor ethical to obtain multiple biopsies from the same patient. Consequently, conventional imaging is often used as a standard of truth (SoT) despite potential for it to be less sensitive than the investigational agent. Here, we explore the impact of SoT methods used in SPOTLIGHT on the study endpoints. Methods: The SPOTLIGHT coprimary endpoints were patient-level verified detection rate (VDR) and combined region-level positive predictive value (crPPV). Patient-level PPV was an exploratory endpoint. Pts with recurrent PCa underwent PET 50–70 min after IV administration of 296 MBq 18F-flotufolastat. For SoT assessment, the protocol required either histopathology or confirmatory imaging (≤60 and ≤90 days post-PET, respectively). Three blinded readers evaluated the scans, with majority read representing agreement between ≥2 readers. A separate Truth Panel established SoT for all pts. Post-study analysis revealed that, likely due to the study occurring during COVID, some pts had neither histopathology nor post-scan confirmatory imaging. These pts had only baseline/historic imaging as SoT. The present analysis stratified endpoint data according to the SoT method the panel used to verify PET-positive lesions. Results: Of 366 evaluable pts, 69 had histopathology and 297 had only confirmatory imaging for SoT. Of those with an imaging SoT, 90 (30%) had baseline/historic imaging only. As the Table shows, for each endpoint the highest value was obtained when using histopathology as SoT. VDR was ~4-fold higher with histopathology vs baseline/historic imaging, crPPV was 2-fold higher and PPV 2.5-fold. Conclusions: These data illustrate the substantial impact SoT methods can have on clinical trial endpoints and highlight a limitation of evaluating SPOTLIGHT endpoints in a cohort with various SoT methods (Table, column 1).1 Notably lower endpoint values are achieved when including pts with baseline/historic imaging SoT vs gold standard histopathology. 1. J Urol. 2023; 210:299-311. Clinical trial information: NCT04186845 . [Table: see text]
Treatment-free survival after first-line therapies for metastatic renal cell carcinoma: An International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) analysis.
Authors: Gupta Mehul , Wells Connor , Regan Meredith M. , Xie Wanling , Navani Vishal , Saliby Renee Maria , Basappa Naveen S. , Donskov Frede , Yuasa Takeshi , Takemura Kosuke null , Kollmannsberger Christian K. , Crumbaker Megan , Lalani Aly-Khan A. , Powles Thomas , Pal Sumanta Kumar , McKay Rana R. , Lee Jae-Lyun , Kanesvaran Ravindran , Choueiri Toni K. , Heng Daniel Yick Chin
Published: January 2024

390

Background: Patients treated with immune checkpoint blockade (ICB) may experience disease control without need for ongoing systemic therapy, a period not well described by conventional time-to-event endpoints. Treatment-free survival (TFS) represents a novel endpoint to quantify this period. Methods: We identified patients with mRCC from the IMDC dataset initiating first-line systemic therapy with VEGFR monotherapy (sunitinib, pazopanib), combination ICB-VEGFR therapy ([axitinib or envatinib]-pembrolizumab, cabozantinib-nivolumab, axitinib-avelumab), or ICB doublet therapy (ipilimumab-nivolumab) between February 1, 2014, and February 1, 2023. Overall survival from treatment initiation was partitioned into periods including TFS, time on first-line therapy, and survival after subsequent therapy initiation utilizing differences in restricted mean survival time (RMST) over 36-months. TFS was defined as the difference between the 36-month RMST between: (1) time from treatment initiation to discontinuation of first-line therapy, death, or censor at last follow-up and (2) time from treatment initiation to subsequent therapy initiation, death, or censor at last follow-up. Results: 3,758 patients with mRCC initiated first-line VEGFR monotherapy (n=2,635; median age 62 years; 19.1% IMDC favourable risk), ICB-VEGFR regimens (n=354; median age 60 years; 33.3% IMDC favourable risk), or doublet ICB (n=769; median age 62 years; 0% IMDC favourable risk). Patients with favourable IMDC risk initiating VEGFR monotherapy and ICB-VEGFR regimens experienced a TFS duration of 8.5% (3.1 mos 95% CI 1.5 - 4.6) and 10.1% (3.7 mos 95% CI 0.2-7.2) of the 36-month period respectively. Among intermediate/poor risk patients, those treated with VEGFR monotherapy, ICB-VEGFR regimens, and ICB doublet therapy experienced 5.9% (2.1 mos 95% CI 1.4 - 2.8), 10.3% (4.7 mos 95% CI 1.0-6.4), and 14.6% (5.3 mos 95% CI 3.8-6.8) of the 36-month period alive and treatment free respectively. Conclusions: Patients receiving VEGFR monotherapy or ICB-VEGFR combination therapies spent at most 10% of the 36-month period surviving treatment free, while IMDC intermediate/poor risk patients treated with ICB doublet therapy experienced a TFS period of 15% of the 36-month period.[Table: see text]
Ipilimumab/nivolumab (I/N) compared to axitinib/pembrolizumab (A/P) in metastatic renal cell carcinoma (mRCC): Insights from a Canadian population.
Authors: Ohm Hyejee , Ghosh Sunita , Gupta Mehul , Wood Lori , Castonguay Vincent , Graham Jeffrey , Kollmannsberger Christian K. , Bosse Dominick , Soulieres Denis , Heng Daniel Yick Chin , Fallah-Rad Nazanin , Finelli Antonio , Tanguay Simon , Lalani Aly-Khan A. , Bhindi Bimal , Bjarnason Georg A. , Breau Rodney H. , Pouliot Frederic , Basappa Naveen S.
Published: January 2024

393

Background: First-line treatment for mRCC includes I/N and A/P. These two regimens have not been compared in a randomized clinical trial as both CM-214 and KN-426 used single-agent tyrosine kinase inhibitors (TKIs) as the comparator. Meta-analyses suggest improved efficacy outcomes with A/P, but increased likelihood of complete response with I/N. We compared these treatments in the real-world. Methods: Data of consented mRCC patients with clear cell histology from the Canadian Kidney Cancer information system (CKCis) was obtained from January 2013 to December 2021. Treatment outcomes adjusting for age including overall survival (OS), progression free survival (PFS), and response rate (RR) for all patients and intermediate-poor risk patients were completed. Chi-square tests compared the frequency of side effects. Results: Among 547 patients, 360 received I/N and 187 received A/P. Median follow-up was 30.0 (0.1-112.1) months. Median duration of treatment was 6.9 (0.0-68.4) months for I/N and 20.2 (0.1-72.4) months for A/P. Intermediate-poor risk patients were higher in the I/N compared to A/P cohort (91.9% vs. 66.2%; p<0.0001). Cox regression for OS showed no difference between I/N compared to A/P (aHR 1.1, 95% CI [0.77-1.58], p=0.61). PFS showed no statistical difference but a trend for worse with I/N at 12.1 months compared to 22.3 months for A/P (aHR=1.2, 95% CI [0.95-1.62], p=0.11). RR was 40.9% with I/N compared to 56.0% in A/P (aOR 0.52, 95%CI [0.33-0.83], p=0.005). Subgroup analyses for the intermediate-poor risk mRCC patients showed no differences in OS (aHR 0.95, 95%CI [0.65-1.38], p=0.79) and PFS (aHR 1.21, 95%CI [0.90-1.62], p=0.21) between treatment groups but improved RR (aOR 0.58, 95%CI [0.35-0.96], p=0.06) with A/P. 61.7% of I/N patients compared to 79.1% of A/P suffered adverse events that led to a dose or schedule change (p<0.001). Most common toxicities for both groups include diarrhea, fatigue, transaminitis, rash, and anorexia. Conclusions: There was no difference in OS between mRCC patients treated with I/N compared to A/P. A/P demonstrates improved RR and a trend towards longer PFS at the expense of increased frequency of side effects. Despite a median follow-up of 30 months, the data is limited by a high amount of censoring.[Table: see text]
Treatment patterns and costs among patients with metastatic renal cell carcinoma (mRCC) in the United States: A real-world study using integrated claims and clinical data.
Authors: Geynisman Daniel M. , Hill Nathan , Rosenblatt Lisa , Yin Xin , Haley Valerie , Nguyen Chi , Barron John , Vilanova David , George Saby
Published: January 2024

398

Background: The treatment landscape for mRCC has evolved in recent years with the use of tyrosine kinase inhibitors (TKI) and immuno-oncology (IO) therapies. This study examined patient characteristics, treatment patterns, costs, and survival for individuals with mRCC who received either IO-IO or IO+TKI as first-line (1L) regimens. Methods: This retrospective cohort study used an administrative claims dataset from a commercial health plan integrated with clinical data from a cancer care quality program (CCQP) and socioeconomic data from national surveys. Eligible patients began treatment for mRCC between 04/01/2018 and 1/31/2023, were aged ≥ 18 years old, and had ≥ 6 months of health plan enrollment prior to and ≥ 1 month after their 1L treatment. Patient characteristics and 1L and second-line (2L) regimens were described. Costs were summarized per patient per month (PPPM) within time intervals. The Kaplan-Meier method was used to estimate treatment-free interval (TFI) and survival times. Results: The study identified 824 eligible mRCC patients; mean age was 60, 77% were male, and 85% White/6% Black race. Patients receiving 1L IO-IO (n = 471; nivolumab plus ipilimumab) or IO+TKI regimens (n = 353; pembrolizumab plus axitinib [63.7%], nivolumab plus cabozantinib [21.8%], pembrolizumab plus lenvantinib [14.4%]) had similar baseline characteristics with the exception of health plan type, body mass index, and risk score (Table 1). As 2L therapy, patients most often received TKI monotherapy (56%) or IO+TKI (26%). Treatment costs were higher for IO-IO in the first 3 months but lower in subsequent time intervals compared with IO+TKI. Medication costs represented 80% of total costs on average. Between IO-IO and IO+TKI arms, median TFI (1.1 and 1.2 months, respectively) and cumulative survival time (75.1% and 78.3% at 12 months, respectively) were similar. Conclusions: The study described treatment patterns for mRCC and found patients receiving 1L IO-IO and IO+TKI regimens were similar demographically, though IO-IO patients started with poorer risk scores. Although IO-IO was associated with higher treatment costs in the first 3 months, the subsequent monthly costs were lower vs IO+TKI. Results also indicated that retreatment with IO in the 2L setting is occurring in real-world practice.[Table: see text]
A meta-analysis of overall survival and response in metastatic adrenocortical carcinoma: A review of 23 prospective trials of 880 patients.
Authors: Hall Angus , Crumbaker Megan , Pham James , Liu Jia (Jenny) , Sim Hao-Wen , Joshua Anthony M.
Published: January 2024

4

Background: Metastatic adrenocortical carcinoma (mACC) is a rare, aggressive tumour of the adrenal gland, with historically poor survival and limited established treatment modalities. The aim of this study was to systematically search for and analyse all prospective trials for mACC to establish benchmark response and survival outcomes. The study was registered on PROSPERO CRD42023430557. Methods: A systematic review and meta-analysis of five databases was performed between June 2023- July 2023. Key outcomes extracted included patient demographics, overall survival (OS), progression-free survival (PFS) and objective response rates (ORR). ORR was calculated using a random effects model and inverse variance methods. Time-to-event outcomes including PFS and OS, were extracted digitally from available Kaplan- Meier curves using the IPDfromKM tool and individual patient data (IPD) was generated as per Guyot et al. The PFS and OS data from individual studies were then pooled using a multivariate extension of the DerSimonian–Laird method to generate summary survival curves. Results: The final 23 trials (5 Phase 1b, 16 Phase II and 3 Phase 3) encompassed 880 patients were retrieved. Pooled ORR was 9.0% overall (2.9% for targeted therapy, 12.3% for chemotherapy and 15.3% for immunotherapy). Median OS was 9.9 months (7.4 months for targeted therapy, 11.2 months for chemotherapy and 10.6 months for immunotherapy). Median PFS was 2.6 months (2.7 months for targeted therapy, 3.0 months for chemotherapy and 2.1 months for immunotherapy). Kaplan-Meier curves for OS were available for 10 treatment lines (n = 605), with a pooled median OS of 9.9 months (95% CI 7.7-11.9) and 12-month OS of 41.6% (95CI 33.1-51.2). Median OS was 7.4 months for patients receiving targeted therapy (95% CI 4.7–12.0), 11.2 months for patients receiving chemotherapy (95% CI 6.9–14.7) and 10.6 months for patients receiving immunotherapy (95% CI 4.4–13.2]. 12-month OS was 30.4% (95% CI 15.9-58.3) for patients receiving targeted therapy, 45.4% (95% CI 33.7-61.2) for patients receiving chemotherapy and 45.3% (95% CI 36.2-56.6) for patients receiving immunotherapy. Conclusions: This study found that current treatments strategies confer limited survival and response benefit in mACC and highlight the need for research into the pathogenesis and novel strategies in the disease. Immunotherapy and chemotherapy demonstrate modest benefits for patients and future trials should attempt to surpass the survival benchmarks set in this study.
CRP kinetics to predict long-term efficacy of first-line immune-checkpoint inhibition combination therapies in metastatic renal cell carcinoma: An updated multicenter real-world experience applying different CRP kinetics definitions.
Authors: Hoeh Benedikt , Cano Garcia Cristina , Banek Severine , Klümper Niklas , Cox Alexander , Ellinger Joerg , Schmucker Philipp , Hahn Oliver , Mattigk Angelika , Zengerling Friedemann , Becker Philippe , Erdmann Kati , Buerk Bjoern , Flegar Luka , Huber Johannes , Kalogirou Charis , Zeuschner Philip
Published: January 2024

405

Background: Although biomarkers predicting therapy response in 1st line metastatic renal carcinoma (mRCC) therapy remain to be defined, C-reactive protein (CRP) kinetics have recently been associated with immunotherapy (IO) response. To assess the predictive and prognostic power of two contemporary CRP kinetics definitions in a large, real-world 1st line mRCC cohort. Methods: mRCC patients treated with IO-based 1st line therapy within 5 years were retrospectively included in this multi-center study. According to Fukuda et al., patients were defined as ‘CRP flare-responder’, ’CRP responder’ and ‘non-CRP responder’; according to Ishihara et al., as ‘normal’, ‘normalized’ and ‘non-normalized’ based on their early CRP kinetics. Patient and tumor characteristics were compared, and treatment outcome was measured by overall (OS) and progression-free survival (PFS), including multivariable Cox regression analyses. Results: Out of 316 mRCC patients, 227 (72%) were assigned to CRP groups according to Fukuda. Both CRP flare- (HR [Hazard ratio]: 0.59) and CRP responders (HR: 0.52) had a longer PFS, but not OS, than non-CRP responders. According to Ishihara, 276 (87%) patients were assigned to the respective groups, and both normal and normalized patients had a significantly longer PFS and OS, compared to non-normalized group. Conclusions: Different early CRP kinetics may predict therapy response in 1st line mRCC therapy in a large real-world cohort. However, further research regarding the optimal timing and frequency of measurement is needed.
Comparison of financial toxicity among patients with non-metastatic versus metastatic renal cell carcinoma.
Authors: Staehler Michael D. , Vaishampayan Ulka N. , Pal Sumanta Kumar , Msaouel Pavlos , Derweesh Ithaar , Battle Dena
Published: January 2024

408

Background: Little is known about the financial impact of renal cell carcinoma (RCC). We sought to ascertain real world data on financial implications and how financial toxicity (FT) impacts quality of life in patients with localized RCC versus patients with metastatic RCC. Methods: An online survey was conducted by the Kidney Cancer Research Alliance (KCCure), a non-profit patient advocacy organization, from 7/22 to 9/22. The survey included questions about costs and financial concerns and the COST questionnaire. Pearson’s correlation (r) and Kendal’s tau test were used to analyze the COST questionnaire, financial burden and hardship. Results: Out of 1062 responders 623 had localized RCC. Out of these patients 395 did not recur and 204 were willing to answer questions related to cost and financial hardship. 289 responders had metastatic disease and were on systemic therapy and 177 pts answered the COST questionnaire. In localized disease 28% reported that their diagnosis has not reduced their income, in 26% the diagnosis had reduced their income very much.31% experienced insurance denials for imaging, 30% faced delays in care due to pre-approval requirements, 45% faced high out-of-pocket costs for medical care. 24% of patients reported taking a hardship withdrawal from a retirement account, 28% stopped funding or lowered contributions to an existing retirement account, 20% borrowed from friends or family. In metastatic patients 14% reported difficulties to pay their premiums. 28% reported that their medical situation has not reduced their income and 26% claimed that their disease reduced their income very much. 36% reported high out of pocket costs are a barrier to care. 44% have received financial support through a manufacturer or a foundation. Median COST score in non-metastatic RCC was 32 (range 19-44)) and was significantly correlated to age, NCCN distress score, risk of recurrence and supplement intake (p < 0.05). Metastatic patients had a significantly higher median COST score of 22 (range 4-36)) that was also correlated to age, NCCN distress score, time since diagnosis and supplement intake (p < 0.05). Conclusions: RCC imposes financial hardship on patients. Younger patients with a higher NCCN distress score and a shorter time since diagnosis are more likely to suffer financial hardships. Patients are willing to pay for supplements. Financial counseling should be considered in these patient subgroups regardless of stage. [Table: see text]