tbuckley/cabot-search huggingface dataset:
Prostate Cancer Foundation (PCF) screening guidelines for prostate cancer in Black men in the United States.
Authors: Isla Garraway, Sigrid V. Carlsson, Yaw A. Nyame, Jason Vassey, Marina Chilov, Mark T. Fleming, Stanley K Frencher, Daniel J. George, Adam S. Kibel, Sherita A King, Rick Kittles, Brandon A Mahal, Curtis Alvin Pettaway, Timothy Rebbeck, Brent S. Rose, Randy Vince, Robert A. Winn, Kosj Yamoah, William K. Oh
Journal: Journal of Clinical Oncology (2024)

264 Background: Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer. Few guidelines have outlined specific recommendations for prostate-specific antigen (PSA)-based prostate cancer screening among Black men. We performed a comprehensive literature search and assembled a diverse, interdisciplinary panel of experts to establish practical consensus guidelines addressing PSA screening in Black men. Methods: A comprehensive literature search was conducted in April 2023 in PubMed and Embase. A total of 287 studies were reviewed utilizing Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Of these, 265 were relevant. The panel’s expertise included fields of primary care, urology, medical and radiation oncology, translational science, and patient advocates. Results: Six guideline statements were developed. Three randomized controlled trials provided Level 1 evidence that regular PSA screening of men aged 50-74 of average risk reduces metastasis and prostate cancer death at 16-22 years. The best available evidence for Black men, who are considered higher than average risk for prostate cancer metastasis and death, comes from observational (Level 3) and modeling (Level 4) studies that consider the age to obtain a baseline PSA, the frequency of testing, and the age when screening should end. Cohort studies suggest that discussions with health care providers about baseline PSA testing should begin by the time Black men are in their early 40s and modeling data suggests prostate cancer develops 3-9 years earlier in Black men compared to their peers. Lowering the age for baseline PSA testing from 50-55 years to 40-45, followed by regular screening intervals until the age of 70 (when to stop is determined by age, PSA values, and health factors) would reduce prostate cancer mortality in Black men (~30% relative reduction) without significantly increasing the rate of overdiagnosis. Conclusions: Black men should obtain information about PSA screening for prostate cancer. Among Black men who elect screening, baseline PSA testing should occur between ages 40-45. Depending on the PSA value and health status, annual screening should be strongly considered. Personalized prostate cancer surveillance and/or treatment can prevent potential harms from overdiagnosis.
Analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with carboplatin-paclitaxel after multiple lines of treatment.
Authors: Elisa María Fernández Pérez, Isabel Beltrán Guerra, Adrian Sánchez Vegas, Carlos Enrique Robles, Gloria Lourenzo Aguilera, Marta Fernández Carcaño, Carlos Ayala De Miguel, Sebastián Díaz López, Guillermo García González, Leonid Bachurin, Javier Rico López, Jose Fuentes Pradera, Jeronimo Jimenez Castro, María Rodríguez de la Borbolla, Pilar López Álvarez, María José Gómez Reina, Manuel Chaves Conde, Eva Fernández Parra
Journal: Journal of Clinical Oncology (2024)

144 Background: Metastatic castration-resistant prostate cancer (mCRPC) occurs in men with advanced disease progressing to androgen deprivation therapy, with serum testosterone &lt; 50 ng/dL. In this setting, several active therapies are available, such as chemotherapy and androgen receptor-targeted agents. We analyzed the efficacy of the carboplatin - paclitaxel (C-P) combination in mCRPC patients after several lines of treatment. Methods: In this retrospective observational study, we analyzed the clinical data of 43 patients with mCRPC who received treatment with biweekly C-P between 2015-2022 at the Hospital Universitario Virgen de Valme. The data collected refer to the baseline characteristics of the patients at the start of treatment (age, functional status), stage at diagnosis and treatments received in first and successive lines, among others. The response variables analyzed were both overall survival (OS) and progression-free survival (PFS). Treatment-derived toxicity was collected. The data were processed with IBM-SPSS Statistics v. 25. The information was collected from Diraya Estación Clínica v 4.0.80 and Farmis-Oncofarm. Results: As of September 2022, data had been collected for 43 men with mCRPC. Histology was adenocarcinoma in all cases. At the start of C-P treatment: 48.9% of patients were in good functional status (ECOG ≤ 1), median age was 71 years and 62.8% had received at least 3 lines of treatment. Patients received C-P for a median of 12 weeks: 76.7% showed clinical improvement and 44.2% had PSA decline, with PSA decline ≥ 30% in 27.5% of patients. The median OS (mOS) was 8 months (95% CI 6.46-9.54) and the median PFS was 14 weeks. By Kaplan-Meier survival analysis, we compared mOS as a function of PSA: response/non-response, the differences being statistically significant: 11 (95% CI=6.22-15.78) vs. 6 (95% CI=4.21-7.79) months, respectively (Log Rank 0.001). The main toxicity was hematological. Conclusions: The C-P combination may be an effective treatment option in patients with mCRPC refractory to various lines of therapy, with PSA being a good marker of response to treatment.
Patient-provider rurality and outcomes in older men with prostate cancer.
Authors: Nickolas Stabellini, Stephanie Jiang, Vraj Patel, Biplab Datta, Priyanshu Nain, Lakshya Seth, Harikrishnan Hyma Kunhiraman, Sarah Malik, Sagar A. Patel, Manali Rupji, Kevin C Ward, Jeffrey M. Switchenko, Justin Moore, Neal L Weintraub, Avirup Guha
Journal: Journal of Clinical Oncology (2024)

265 Background: The impact of rural residence status as a social determinant of health on prostate cancer (PC) outcomes, considering both patient and provider location, remains unexplored. Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database to identify males aged ≥66 with new primary PC diagnoses (2009-2017). Patients' rurality was defined using the 2013 SEER Rural Urban Continuum Code. Provider rurality was defined by matching the provider to Core Based Statistical Area Codes with the 2013 National Center for Health Statistics Urban–Rural Classification scheme for counties. The primary outcome was All-cause mortality. Given proportional hazard violation, adjusted extended Cox models were performed for the primary outcome. Secondary outcomes were PC-specific mortality (PCSM) and cardiovascular mortality (CVDm). Adjusted Fine-Gray models, accounting for competing risks (other causes of mortality), were applied to assess PCSM and CVDm. Results: We included 75,291 PC patients, with a median age of 72 years (interquartile range 69-76), of whom 8.9% received androgen deprivation therapy (ADT). Among them, 91.7% originated from and received treatment in metropolitan areas, 7% were from urban areas but were served by metropolitan providers, 0.8% lived in rural areas and were served by metropolitan providers, and 0.5% resided in rural areas and were served by non-metropolitan providers. All-cause mortality risk was 44% higher in patients who hailed from rural areas and had a provider from a non-metropolitan area [adjusted hazards ratio = 1.44 (95% confidence interval = 1.15-1.79); Table]. Conclusions: Patients from rural areas with non-metropolitan providers face a higher risk of all-cause mortality, underscoring the role of rurality as a contributing factor to disparities in this PC outcome.[Table: see text]
Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial.
Authors: Nizar M. Tannir, Bernard Escudier, David F. McDermott, Mauricio Burotto, Toni K. Choueiri, Hans J. Hammers, Elizabeth R. Plimack, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Michael B. Atkins, Christian K. Kollmannsberger, Marc-Oliver Grimm, Yoshihiko Tomita, Brian I. Rini, Ruiyun Jiang, Heshani Desilva, Chung-Wei Lee, Robert J. Motzer
Journal: Journal of Clinical Oncology (2024)

363 Background: First-line NIVO+IPI has provided substantial long-term survival benefits over SUN in patients (pts) with aRCC in CheckMate 214. We report survival, response per independent radiology review committee (IRRC) and safety after 6 y minimum (80 mo median) follow-up in all randomized pts, by IMDC risk and in pts with overall survival (OS) ≥ 6 y (long-term survivors; LTS). Longer follow-up data (minimum, 7.5 y) will be presented. Methods: Pts with clear cell aRCC were randomized 1:1 to NIVO 3 mg/kg + IPI 1 mg/kg Q3W×4 then NIVO 3 mg/kg Q2W vs SUN 50 mg QD for 4 wk on, 2 wk off. Endpoints: OS, progression-free survival (PFS) and objective response rate (ORR; both per IRRC using RECIST v1.1) in IMDC intermediate/poor risk (IP; primary), intent-to-treat (ITT; secondary) and favorable risk (FAV; exploratory) pts. Exploratory outcomes in LTS pts were assessed post hoc. Results: OS with NIVO+IPI vs SUN remained superior in ITT (HR 0.72) and IP (HR 0.68) pts; OS benefits were similar between arms in FAV pts (HR 0.87; Table). Median PFS was consistent with previous reports. ORR per IRRC was higher with NIVO+IPI vs SUN, with more ongoing responses in ITT (60% vs 50%) and IP (60% vs 50%) pts. In FAV pts, ORR was lower with NIVO+IPI vs SUN, yet more responses were ongoing (59% vs 52%, respectively). Median duration of response (DOR) was longer and complete response (CR) rate was higher with NIVO+IPI vs SUN regardless of IMDC risk. Incidence of any and grade 3-4 treatment-related adverse events remained largely unchanged. No new drug-related deaths occurred in either arm since the previous database lock. In the LTS subgroup (NIVO+IPI, n = 208; SUN, n = 151), ORR was higher (66% vs 53%), more pts had a CR (27% vs 9%) and fewer progressed (4% vs 11%) with NIVO+IPI vs SUN. Median DOR was longer with NIVO+IPI (n = 137) vs SUN (n = 80) among LTS with confirmed response (76 vs 40 mo). Updated survival, response and safety data with 7.5 y minimum follow-up, along with additional subgroup analyses, will be presented. Conclusions: NIVO+IPI demonstrated long-term survival and more durable response benefits vs SUN in ITT and IP pts. CR rates were higher and median DOR was longer with NIVO+IPI vs SUN regardless of IMDC risk group, and in LTS pts. No new safety signals emerged. Clinical trial information: NCT02231749 . [Table: see text]
Development of a patient-centered health-related quality of life (HRQOL) measure for metastatic renal cell carcinoma (mRCC): A three-phase study.
Authors: Cristiane Decat Bergerot, Daniela V. Castro, Paulo Gustavo Bergerot, Benjamin D. Mercier, Elizabeth Nally, Adil A. Ali, Errol James Philip, Murilo Buso, Thomas E. Hutson, Viktor Grünwald, Axel Bex, Sarah P. Psutka, Brian I. Rini, Elizabeth R. Plimack, Viraj A. Master, Laurence Albiges, Toni K. Choueiri, Sumanta Kumar Pal, Thomas Powles
Journal: Journal of Clinical Oncology (2024)

365 Background: Patients (pts) with mRCC require a tailored HRQOL assessment. Previous research (Bergerot et al. Oncologist 2023; Bergerot et al. J Clin Oncol 2023) explored FKSI-19, EORTC QLQ-C30, and EQ-5D item relevance. We aimed to develop a tailored HRQOL measure for pts with mRCC through a three-phase approach involving patient engagement, expert input, and advocacy. Methods: In Phase 1, 117 pts with mRCC (83:34 M:F, median age=64) from the US, Europe and Brazil participated in a survey study to assess the relevance of items from established measures (FKSI-19, EORTC QLQ-C30, EQ-5D). In this cohort, 88% of pts had clear cell histology and 35%, 30% and 19% received immunotherapy alone, targeted therapy alone or combination therapy, respectively. Questions identified as relevant (base on ≥66% consensus) were selected for inclusion in a preliminary survey. Phase 2 involved assembling a panel of 11 experts who rigorously reviewed and refined survey questions. In Phase 3, preliminary version were presented to 8 patient advocates (5:3 F:M; 6:2 pts:caregivers) to ensure alignment with pts' needs and experiences. Results: Phase 1 analysis identified 10 items. Pts requested the inclusion of a question about social/family issues and better coverage of emotional symptoms. An 12-item questionnaire was created, and the expert committee refined three items to incorporate patient suggestions and added one item related to functional status (Table). This questionnaire included 1 cancer-specific item, 3 cancer or treatment-specific items, 3 non-specific emotional items, and 4 non-specific physical items. Patient advocates provided feedback, agreeing with the items excluded from previous questionnaires and those included. They suggested minor edits to item wording. Conclusions: The novel approach holds the potential to replace traditional HRQOL measures that may lack relevance to specific clinical circumstances. Further validation is planned in a phase 3 trial, ensuring its applicability in clinical practice. [Table: see text]
Real-world (RW) survival and outcomes with androgen receptor pathway inhibitor (ARPI) –doublet therapy in patients (pts) with de novo metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Joshua Parrish, Thomas J. Polascik, Agnes Hong, Nader N. El-Chaar, Amanda Marie De Hoedt, Janet Kim, Claire Trustram Eve, Maelys Touya, Krishnan Ramaswamy, Lin Gu, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2024)

145 Background: With multiple phase 3 trials showing improved overall survival (OS) with doublet therapy (androgen-deprivation therapy [ADT]+ARPI), it has become the standard of care for pts with mCSPC. However, data on RW effectiveness of ARPI doublets are limited. This study assessed OS, time to progression to metastatic castration-resistant prostate cancer (mCRPC), and PSA decline to &lt;0.2 ng/mL in pts with de novo mCSPC on ADT alone vs ADT+ARPI doublets or ADT+first-generation nonsteroidal antiandrogens (NSAAs). Methods: Men in the Veteran’s Health Administration with ≥1 ICD code for PC and de novo mCSPC diagnosis confirmed by clinical chart review were identified and categorized into first-line (1L) ADT alone, ADT+NSAA, or ADT+ARPI cohorts (study period: Feb 2018−Mar 2023). Target recruitment quotas ensured representation of each treatment (Tx) regimen. Index date was the ADT initiation date. OS and time to mCRPC were calculated using inverse probability of Tx weighting (IPTW)-adjusted Cox regression. IPTW-adjusted incidence rate ratios (IRR) of the proportion of pts with PSA decline to &lt;0.2 ng/mL at any time during 1L Tx were estimated using Poisson regression. Results: 384 men with de novo mCSPC were identified (Table). Median follow-up range was 34.8–38.1 mo. 1L Tx duration for ADT+ARPI was over twice as long as ADT alone (Table). Importantly, pts on ADT+ARPI had a 39% lower risk of death vs ADT alone (HR: 0.61, 95% CI: 0.43–0.87); while OS was similar between ADT+NSAA vs. ADT alone (HR: 1.09, 95% CI: 0.79–1.49). Consistent with the improved OS, ADT+ARPI showed a 54% lower risk of progression to mCRPC (HR: 0.46, 95% CI: 0.33–0.66) and significant superiority in achieving PSA &lt;0.2 ng/mL (57% vs 17%; Table) than ADT alone. Conclusions: This is one of the first RW studies to validate clinical trial findings of the effectiveness of ARPI-doublets for de novo mCSPC as evidenced by significantly improved OS, time to mCRPC, and PSA response. ADT+NSAA may have limited value vs ADT alone, and ARPI-doublet is an effective Tx for de novo mCSPC. [Table: see text]
A meta-analysis assessing objective response rates with first-line systemic treatment options in locally advanced/metastatic urothelial carcinoma.
Authors: Akshat Saxena, Syed Arsalan Ahmed Naqvi, Nikita Tripathi, Muhammad Ali Khan, Arifa Bibi, Tara Ballouz, Haidar Abdul-Muhsin, Mark Tyson, Irbaz Bin Riaz, Alan Haruo Bryce, Parminder Singh
Journal: Journal of Clinical Oncology (2024)

639 Background: Immunotherapy combined with chemotherapy (IO/C) as the first-line management of locally advanced or metastatic urothelial carcinoma (LA/mUC) has been investigated in multiple trials with conflicting outcomes. Therefore, we conducted a meta-analysis of available trials to compare objective response rates (ORR) of this combination regimen, both in overall and in cisplatin-ineligible populations. Methods: EMABSE and MEDLINE were searched from 2000 through July 20 th , 2023, to identify phase II and III clinical trials assessing IO, C or both in LA/mUC. Main outcome of interest was objective response rates (ORR) as defined in the included trials. An inverse variance random-effects meta-analysis was performed to estimate pooled ORR using the restricted maximum likelihood estimation method. Subgroup differences were assessed among IO/C, IO alone, and C alone. The threshold for statistical significance was established at 0.1. Results: Of 5975 citations identified, a total of 26 trials with a total of 4,628 participants were included in this systematic review. In the overall group, the ORR in IO/C trials (5 trials, 1,236 patients) was 44.70% (95% CI: 21.88%- 70.0%). In IO trials (7 trials, 2,189 patients), ORR was 23.68% (19.55%- 28.36%) and in C trials (26 trials, 4,628 patients) was 43.46% (37.43%-49.68%]). In the cisplatin-ineligible group, the ORR in IO/C trials (2 trials, 240 patients) was 60.06% (33.38%-81.86%), in IO trials (6 trials, 1,103 patients) was 26.15% (23.01%; 29.56%), and in C trials (8 trials, 767 patients) was 42.45% (35.67%-49.52%). In terms of subgroup differences, the difference in ORR was statistically significant between IO/C and IO trials (p= 0.0844) and between IO and chemotherapy trials (p&lt; 0.0001) in the overall population. Similarly, we found a statistically significant difference in ORR between IO/C and IO (p= 0.0108) and between IO and chemotherapy trials (p&lt; 0.0001) in the cisplatin-ineligible population. No statistically significant differences were observed between IO/C and C alone. Conclusions: First-line IO/C may achieve a better objective response compared to IO alone in patients diagnosed with locally advanced/metastatic UC. Although, there appears to be a trend of greater benefit with IO/C compared to C alone, the difference was not statistically significant. The results will be updated as soon data from new trials (CheckMate 901 and EV 302) becomes available which could offer new insights. [Table: see text]
Patterns of early 18F-FDG PET response to nivolumab (NIVO) and ipilimumab nivolumab (IPINIVO) in patients with metastatic renal cancer (MRC).
Authors: Natalie Charnley, Diana Rosof-Wiliams, Mike Dobson, Susan Cox, Nisreen Amin, Omi Parikh, Catherine Thompson, Falalu Dahiru Danwata, John Cain
Journal: Journal of Clinical Oncology (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 &gt;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 &gt;20% decrease in SUV. (Mean 41.2 Range -21.2% to -55.3%) For IPINIVO in 4/8 patients there was a &gt;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 &gt;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.