bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with carboplatin-paclitaxel after multiple lines of treatment.
Authors: Fernández Pérez Elisa María , Beltrán Guerra Isabel , Sánchez Vegas Adrian , Robles Carlos Enrique , Lourenzo Aguilera Gloria , Fernández Carcaño Marta , Ayala De Miguel Carlos , Díaz López Sebastián , García González Guillermo , Bachurin Leonid , Rico López Javier , Fuentes Pradera Jose , Jimenez Castro Jeronimo , Rodríguez de la Borbolla María , López Álvarez Pilar , Gómez Reina María José , Chaves Conde Manuel , Fernández Parra Eva 
Published: January 2024

144 Background: Metastatic castration-resistant prostate cancer (mCRPC) occurs in men with advanced disease progressing to androgen deprivation therapy, with serum testosterone < 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.
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: Parrish Joshua , Polascik Thomas J. , Hong Agnes , El-Chaar Nader N. , De Hoedt Amanda Marie , Kim Janet , Trustram Eve Claire , Touya Maelys , Ramaswamy Krishnan , Gu Lin , Freedland Stephen J. 
Published: January 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 <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 <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 <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]
Efficacy and safety between first-line therapies in metastatic castration-resistant prostate cancer in combination in the PARPi and ARSI era: A systematic review and network meta-analysis.
Authors: Guo Xuanjun , Li Yixin , Wang Mengying , Peng Hexiang , Guo Huangda , Hou Tianjiao , Zhang Hanyu , Jiang Jin , Sheng Tao , Fan Yu , Wu Tao , He Zhisong 
Published: January 2024

146 Background: The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has evolved tremendously, while little is known about the efficacy and safety comparison between current first-line mCRPC systemic therapies in the overall patient population and in the context of clinically relevant subgroups. Methods: We conducted a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs). Multiple databases (PubMed, Embase, and Cochrane Library), ClinicalTrials.gov, and major congress abstracts were searched in the first-line treatment of mCRPC. The primary efficacy outcomes were radiographic progression-free survival (rPFS) and overall survival (OS). The safety outcomes were adverse events (AEs), serious AEs (sAEs), and grade ≥3 AEs. Two separate pairwise meta-analyses were conducted since there were no common arms between therapies with and without docetaxel (Doc) when considering OS and safety outcomes, while only trials without Doc assessed rPFS. Moreover, we performed subgroup analyses according to treatment regimens and homologous recombination repair (HRR) gene alteration status. Results: The analysis included data from 35 clinical trials (38 references) published as of June 6, 2023, comprising a total of 24,400 patients. For the non-Doc group, analysis of treatment ranking revealed that PARPi doublet, especially talazoparib plus enzalutamide, had the highest likelihood of improving rPFS and OS compared with ARSI doublet, ARSI monotherapy, and immunotherapy, mainly in the HRR-deficient patients while raising some concerns about safety profiles. Regarding therapies based on Doc, most Doc doublet regimens demonstrated subtle improvement in OS compared to Doc monotherapy with tolerable toxicity. Conclusions: This systematic review and meta-analysis provided a comprehensive analysis of the therapeutic effects and safety profiles of various first-line mCRPC systemic therapies. Our findings may provide decision-making guidance to clinicians and help inform mCRPC patients-centered treatment regimens. In an era of PARPi combination with ARSI, unfortunately, because of the lack of common arm delivery of Doc, we cannot estimate the relative value of Doc versus non-Doc as first-line mCRPC therapies.
Final study analysis of PRINT: Prostate cancer intensive, non–cross-reactive therapy for CRPC.
Authors: Liaw Bobby Chi-Hung , Joshi Himanshu , Sheng Tianxiang , Tsao Che-Kai , Galsky Matt D. , Bakst Richard Lorne , Stewart Robert , Stock Richard , Oh William K. 
Published: January 2024

147 Background: The long-standing approach to mCRPC management has been to treat sequentially with one agent until resistance is met. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non–cross-reactive regimen as a way to more effectively treat an intrinsic heterogeneous disease, delay or prevent drug resistance, and minimize treatment toxicity. Methods: All patients receive treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks. Upon completion of regimen, patients are followed on ADT alone. Primary endpoint for the study is time to progression (TTP), either by PSA or imaging. Secondary endpoints are PSA response rate with each module, changes to alkaline phosphatase levels, and safety. Results: From 3/2017 to 11/2020, 40 men with mCRPC were enrolled, with 33 completing the 9-month study regimen and evaluable for endpoint analysis. With median follow up of 139 weeks, median TTP after regimen completion was 15.9 weeks (95% CI 10.6-25.0 weeks), which did not meet prespecified TTP of 20 weeks to be considered a significant improvement over standard management. PSA response rates showed successive improvement with each sequential treatment module (Table). 77.8% of patients with elevated baseline alkaline phosphatase levels had normalization post-treatment. Previously reported, the treatment regimen was well-tolerated, with few grade 3/4 AE’s attributable by the investigator to the study regimen. Five patients (15.2%) were able to remain on post-study surveillance with ADT alone without the addition of a mCRPC agent for over a year, with one patient subsequently discontinuing ADT with PSA remaining undetectable in setting of recovering testosterone levels. Conclusions: Treatment of mCRPC with a rapidly cycling non–cross-reactive regimen did not significantly improve time to disease progression as compared to standard management. However, it is associated with significant antitumor response, with potential for long-term suppression of disease. Additional analysis into clinicopathologic and genomic factors that may predict for prolonged disease control is ongoing. Clinical trial information: NCT02903160 . [Table: see text]
PSA flare in patients with metastatic castration-resistant prostate cancer undergoing 177Lu-PSMA treatment.
Authors: Li Haoran , Wulff-Burchfield Elizabeth Marie , Abbasi Saqib , Narang Arshit , Dal Emre , Donald Joseph , Yap Wendell Y , Shen Xinglei , Chen Ronald C. , Parikh Rahul Atul 
Published: January 2024

157 Background: 177Lu-PSMA (Lu-177) is an FDA-approved radiopharmaceutical agent for metastatic castration-resistant prostate cancer (mCRPC) progressed on prior chemotherapy and androgen receptor pathway inhibitor. The chronology, frequency and association PSA flare with Lu-177 on overall treatment outcome is unclear. Our retrospective study evaluates the association of PSA flare with clinical outcomes in mCRPC patients undergoing Lu-177 therapy. Methods: A retrospective study was conducted from 4/2022-8/2023 for patients treated with Lu-177 at the University of Kansas Cancer Center. PSA flare was defined as an initial rise in PSA levels that subsequently declined. A bone flare is defined as increased radiotracer uptake in bone scans. The primary outcome was progression-free survival (PFS). The secondary outcomes included overall survival (OS), PSA response, disease control rate (DCR) and safety. Results: A total of 46 patients were included in this study. The median age was 73 years (range: 52-100). Of these, 14 patients (30.4%) had completed 6 cycles of treatment. The median number Lu-177 cycles received was 3 (range: 1-6). PSA flare was observed in 7 patients (15.2%), and all of the PSA flare occurred in the first cycle. The median time from the start of treatment to the onset of PSA flare was 2 weeks (range: 1-4). The median change in PSA from baseline to flare increased by 41% (range: 22-1133%). The median time from PSA flare to PSA nadir was 12 weeks (range: 9-30). The median change in PSA from flare to nadir decreased by 73% (range: 57-95%). Bone flare was seen in 4 patients (13.8%) and the median onset time is 12 weeks (range: 10-17). There was no significant difference in PFS and OS between patients with or without PSA flare [median PFS: 7.1 vs. not reached (NR), p=0.11; median OS: NR vs. NR, p=0.27). A total of 22 patients (56.4%) exhibited a 50% PSA decrease (PSA 50). The proportion of patients with PSA 50 response was similar in both the PSA flare group (57.1%) and the non-PSA flare group (56.3%) (p=0.97). Among the patients who underwent radiographic assessment (n=29), the DCR was achieved in 66.7% vs. 60.9% of patients with or without PSA flare (p=0.79). The most common side effects in patients with or without flare included fatigue (71.4% vs. 66.7%, p=0.81), arthralgia (0% vs. 26.7, p=0.31), nausea (14.3% vs. 20%, p=0.73), diarrhea (28.6% vs. 10%, p=0.20), and anorexia (28.6% vs. 10%, p=0.20). Conclusions: PSA flare in patients treated with Lu-177 is not uncommon. Our study suggests the clinical response appears consistent regardless of the flare. Further studies and additional long-term follow-up are needed to validate our findings.
Characteristics and outcomes of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) showing a primary resistance (PR) to docetaxel (DOC): Results from a large real-world database.
Authors: Caffo Orazio , ButtIgliero Consuelo , Ermacora Paola , Sorarù Mariella , Di Girolamo Stefania , Sabbatini Roberto , Gori Stefania , Facchini Gaetano , Cattrini Carlo , Marchetti Andrea , Valcamonico Francesca , Vignani Francesca , Conteduca Vincenza , Sartori Donata , Barile Carmen , Naglieri Emanuele , Calvani Nicola , Cavo Alessia , Biasini Claudia , Bimbatti Davide ,   on behalf of ECHOS trial group
Published: January 2024

158 Background: ECHOS trial is a large real-world study, which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, > 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the characteristics and outcomes of mCSPC pts progressing within 6 mos from the start of DOC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. PR was defined as the onset of progressive disease within 6 mos from the DOC start. Results: Among 920 mCSPC pts treated with DOC, 122 (14.3%) were PR. Most of them (95.6%) presented a de novo (DN) disease, which showed mostly high volume (HV) features (82.3%). Compared to the pts without PR, those showing PR presented more frequently a visceral involvement (26.2% vs 18.2%; p = 0.038), had lower baseline levels of hemoglobin (12.8 g/dl vs 13.4 g/dl; p < 0.0001), and higher baseline levels of lactate dehydrogenase (266 U/L vs 220,5 U/L; p < 0.002). No other significant differences were observed in terms of baseline PSA and alkaline phosphatase levels, symptoms degree, disease volume and timing of mets presentation between PR e no-PR pts. The median number of life prolonging agents administered after DOC progression was 1 in pts with PR as well as in pts without PR. The median overall survival was 11.9 mos and 44.9 mos in PR and no-PR pts, respectively (p < 0.0001). Conclusions: Our data suggest that PR led a significant worsening of prognosis with a relevant shortening of life expectancy in pts who receive DOC for mCSPC.
Comparative survival in metastatic castration-sensitive prostate cancer (mCSPC) by prognostic subgroups: A living network meta-analysis.
Authors: Naqvi Syed Arsalan Ahmed , Riaz Irbaz Bin , Khakwani Kaneez Zahra Rubab , Bibi Arifa , Andrews Jack R. , Childs Daniel S , Ravi Praful , Orme Jacob , Singh Parminder , Sweeney Christopher , Bryce Alan Haruo 
Published: January 2024

171 Background: Treatment effects vary by volume of disease and timing of metastatic presentation in patients with mCSPC. Therefore, we updated the existing body of evidence to assess the comparative efficacy of systemic therapy in mCSPC by prognostic subgroups to inform clinical practice guidelines. Methods: This living systematic review was conducted using the living interactive evidence (LIvE) synthesis framework. Phase III clinical trials assessing contemporary systemic therapy in mCSPC and reporting overall survival (OS) by four prognostic subgroups were included. Prognostic subgroups included synchronous high volume (SHV), synchronous low volume (SLV), metachronous high volume (MHV), and metachronous low volume (MLV) disease. Mixed treatment comparisons were made using a network-meta-analytic approach in each subgroup. P-scores were used to assess relative treatment rankings in congruency with pairwise estimates. Higher scores indicated better efficacy. Results: This study included a total of nine trials with eight unique treatment options. In patients with SHV disease, darolutamide+docetaxel+ADT (DARO+D+ADT) significantly improved OS when compared to D+ADT (HR: 0.69; 0.57-0.85), enzalutamide (E)+ADT (HR: 0.67; 95% CI: 0.46-0.99), and apalutamide (APA)+ADT (HR: 0.65; 95% CI: 0.43-0.96). In patients with SLV disease, E+ADT (HR: 0.62; 95% CI: 0.42-0.91) and AAP+ADT (HR: 0.66; 95% CI: 0.49-0.89) significantly improved OS when compared to ADT. Although E+D+ADT trended toward improvement compared to other treatments, the results were not statistically significant. In patients withMHV disease, no statistically significant differences were observed among mixed treatment comparisons. However, OS with DARO+D+ADT trended toward improvement when compared to D+ADT (HR: 0.69; 95% CI: 0.39-1.23), APA+ADT (HR: 0.72; 95% CI: 0.23-2.33), E+ADT (HR: 0.67; 95% CI: 0.24-1.86), and E+D+ADT (HR: 0.59; 95% CI: 0.26-1.34). In patients with MLV disease, E+ADT significantly improved OS compared to ADT (HR: 0.51; 95% CI: 0.32-0.79), and D+ADT (HR: 0.48; 95% CI: 0.27-0.85). APA+ADT significant improved OS compared to ADT (HR: 0.22; 95% CI: 0.09-0.54), and D+ADT (HR: 0.21; 95% CI: 0.08-0.55). No other statistically significant differences were observed among mixed treatment comparisons. Conclusions: Current evidence suggests that triplet systemic therapy may be preferred in SHV, E systemic triplet and E hormonal doublet in SLV, DARO systemic triplet and APA hormonal doublet in MHV, and APA or E hormonal doublets in MLV mCSPC. [Table: see text]
The prognostic value of circulating miRNAs in patients with localized/locally advanced prostate cancer after radical prostatectomy and radiotherapy.
Authors: Zedan Ahmed H. , Hansen Torben , Madsen Jonna Skov , Osther Palle Jörn Sloth 
Published: January 2024

184 Background: The outcome after curative intended management of local prostate cancer (PC) is promising. However, there is still a risk of biochemical relapse (BR) after either radical prostatectomy (RP) or radiotherapy (RT). MicroRNAs (miRNAs) have showed encouraging results as alternative biomarkers in different settings of PCa. The aim of this study was to investigate the prognostic value of circulating miRNAs after management of local PCa. Methods: In total 107 newly diagnosed patients with local or locally advanced PCa were included in the study. The cohort was divided into an interventional group with 59 patients (RP (39 patients) or RT (20 patients)) and an observational group with 48 patients (active surveillance (AS)). Both baseline samples at time of diagnosis and follow-up samples six months after treatment were collected. The relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma using real-time polymerase chain reaction. Results: In the interventional cohort, the decrease in miRNA-125b after RT was significantly associated with a longer time to biochemical recurrence (BR) (HR= 0.17, p=0.03), and a higher level of miRNA-125b at baseline samples showed a tendency to higher risk for BR in the same population (HR= 2.82, p=0.09). On the other hand, lower levels of miRNA-221 at both baseline and follow-up samples tended to be associated with lower risk of BR in patients managed by RT (HR=0.14, p=0.07, and HR=0.13, p=0.07, respectively). None of these four miRNAs was associated with a significant risk of progression in patients managed by AS. Conclusions: Both baseline and the dynamics of miRNA-125b was informative as to the risk of BR in patients with PCa treated by RP. Validation in independent cohorts is called for.
Tumor suppressor genes (TSG), treatment, and survival in de novo metastatic hormone-sensitive prostate cancer.
Authors: Schoen Martin W. , Montgomery Robert Bruce , Knoche Eric Marshall 
Published: January 2024

187 Background: The standard of care for metastatic hormone sensitive prostate cancer (mHSPC) has changed substantially in less than a decade. For patients with suitable functional status, combination therapy is recommended. A diverse molecular landscape of mHSPC exists, however molecular findings have yet to inform treatment in mHSPC. Outcomes for patients vary according to baseline molecular features and patients with mutations of tumor suppressor genes (TSG) have worse survival. We sought to examine the impact of TSG alterations on overall survival (OS) for men with de novo mHSPC. Methods: We identified patients diagnosed with de-novo mHSPC from July 2017-December 2021 within the Veterans Health Affairs. Alterations in TSG including TP53, PTEN, and RB1 were determined from National Precision Oncology Program (NPOP) testing collected at any time and all alterations were included. Only patients who survived 4 months and treated within 4 months of diagnosis were included. Treatments included androgen deprivation therapy (ADT) alone, docetaxel, or androgen receptor pathway inhibitors (ARPI). Kaplan-Meier and Cox proportional hazard models to assess the association between TSG and age, BMI, weight change in the year prior to mHSPC, Charlson comorbidity index, PSA at diagnosis, Black race, treatments for mHSPC, and OS. Results: We identified 2808 veterans with de novo mHSPC and 915 (32.6%) had NPOP data available. Patients with NPOP data were younger (mean age 71.4 vs. 75.2 years, p<0.001) and had longer OS than veterans without testing (43.7 months vs. 31.0, p<0.001). TSG alterations were found in 475 of 915 veterans (51.9%) and included 344 TP53 (37.6%), 206 PTEN (22.5%) and 50 RB1 (5.5%). Veterans with TSG had shorter OS compared to no TSG, median OS 48.5 months without TSG vs 37.7 with 1 or more TSG (p<0.001). Each TSG alteration was associated with mortality, TP53 adjusted Hazard Ratio (aHR) and 95% confidence interval 1.68 (1.35-2.09), PTEN aHR 1.33 (1.02-1.73), RB1 aHR 1.51 (1.01-2.26). ADT alone was given in 354 veterans (38.7%), docetaxel in 139 (15.2%), and ARPI in 422 (46.1%). In veterans with one or more TSG neither docetaxel nor ARPI therapy was associated with OS in unadjusted or adjusted analyses compared to ADT alone (Table). Conclusions: TSG alterations were associated with shorter survival in de novo mHSPC in veterans with molecular testing. In this real-world observational study, treatment intensification with docetaxel or ARPI in veterans with TSG was not associated with improved overall survival. [Table: see text]