bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inconsistency in the assessment of retroperitoneal lymph node metastasis in patients with testicular cancer: Influence on clinical stage, therapy and relapse rate.
Authors: Nestler Tim , Strauch Angelina , Nestler Kai , Schoch Justine , Kubitscheck Laura , Waldeck Stephan , Schmelz Hans 
Published: January 2024

506 Background: In testicular germ cell tumor (GCT) staging, current guidelines lack consensus in the measurement of retroperitoneal lymph node metastasis, including the recommended plane and dimension. Therefore, our objective was to investigate current guideline recommendations for staging of retroperitoneal lymph nodes and their influence on clinical stage (cS), relapse rate and therapy. Methods: In this explorative study we retrospectively analyzed 154 cSI GCT patients who underwent orchiectomy without any adjuvant therapy and had a follow-up of ≥ 24 months. Here, cSI was defined as retroperitoneal lymph nodes <10mm in axial short-axis diameter (SAD). In initial staging imaging the largest retroperitoneal lymph node was measured considering the different dimensions (SAD and long-axis diameter (LAD)) in the three different radiological planes: axial, sagittal and coronal. Results: In the studied cohort overall survival (OS) was 100% and relapse free survival was 82% with a mean follow-up of 95 months. By using axial SAD (RECIST 1.1) all patients were classified as cSI. Based on axial LAD (German S3 guideline) or LAD in any plane (EAU, ESMO, onkopedia and AJCC), significantly more patients would be classified as cSIIA (0% vs. 38% vs. 52%) or even cSIIB (0% vs. 1% vs. 25%; p<0.001). Overtreatment would occur in 0%, 31%, and 61% ( p<0.001) for axial SAD, axial LAD and LAD in any plane, while undertreatment would affect 18%, 10%, and 2% ( p<0.001), respectively. A stage-appropriate therapy would hypothetically require the following number of chemotherapy cycles (BEP or Carboplatin): optionally 34 for axial SAD vs. up to 361 for LAD in any plane. Conclusions: We found a huge variety of clinical stages according to different lymph node staging recommendations in current guidelines. With a 100% OS rate in the entire cohort and considering the balance between the risks of overtreatment and undertreatment, with stage-adapted treatment at relapse, we strongly recommend adopting axial SAD in accordance with RECIST 1.1. Prospective validation is warranted to standardize guideline recommendations.
Real-world comparison of prostate-specific antigen (PSA) response in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or enzalutamide (ENZ).
Authors: Lowentritt Benjamin H. , Du Shawn , Pilon Dominic , Khilfeh Ibrahim , Muser Erik , Rossi Carmine , Kinkead Frederic , Diaz Lilian , Korsiak Jill , Ellis Lorie , Lefebvre Patrick , Brown Gordon Andrew 
Published: January 2024

51 Background: APA and ENZ, two androgen receptor synthesis inhibitors (ARSIs), used in combination with androgen deprivation therapy (ADT) are among the recommended treatments for patients with mCSPC. Deep PSA response, evaluated as ≥90% PSA decline (PSA90), is an important outcome after ARSI initiation, with early, deep response associated with longer survival. The primary objective of this study was to compare PSA90 response in ARSI-naïve patients with mCSPC by 6 months after initiating APA or ENZ in real-world clinical practice. Methods: Linked electronic medical record (EMR) data of US community urology practices in the from PPS Analytics and administrative health data from Komodo Health Solutions Research Database were evaluated. Patients with mCSPC were selected into two cohorts, based on the index date, defined as the first paid pharmacy claim or in-office dispensation for APA or ENZ on or after 16 Dec 2019. Patients were required to have ≥12 months of pre-index EMR clinical activity. Pre-index characteristics (i.e., age, race, geographic region, payer type, index year, time from metastasis, time from first prostate cancer [PC] diagnosis, de novo PC, ADT use, first-generation antiandrogen use, chemotherapy use, metastasis locations, most recent PSA level, testosterone level, and Gleason score) were balanced between cohorts with inverse-probability treatment weighting (IPTW). Patients were followed from index date until the earliest of index ARSI discontinuation or switch, radiopharmaceutical initiation, end of open administrative claim or EMR clinical activity, or end of data availability (30 Sep 2022). PSA90 was defined as the earliest ≥90% decline in PSA relative to most recent pre-index PSA. The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: In total 860 APA and 869 ENZ patients were identified. Patient pre-index characteristics were balanced with IPTW (Table). By 6 months post-index, 80.3% of APA and 75.0% of ENZ patients had ≥1 PSA test result. By 6 months, significantly more APA patients attained a PSA90 response, as compared to ENZ patients (p=0.005; Table). The median time to PSA90 response was 3.5 months for APA and 4.9 months for ENZ. Conclusions: This US real-world study of patients with mCSPC demonstrated that treatment with APA produces a deep, early PSA response by 6 months in a greater percentage of patients than treatment with ENZ. [Table: see text]
Survivorship issues beyond 2 years after treatment in testicular germ cell tumors: Experience from a large centre in the United Kingdom.
Authors: Flanders Lucy , Ansell Wendy , Richardson Daniel , Wilson Peter , Ng Kenrick , Shamash Jonathan 
Published: January 2024

512 Background: Testicular germ cell tumors (tGCTs) are rare but are highly curable, resulting in a large cohort of long-term survivors. The primary aim of most follow-up programs after initial treatment is to detect recurrence, which emphasizes regular imaging and measurement of serum tumor markers. Most relapses occur in the first two years after treatment. However, many of these patients also experience survivorship issues beyond the two-year timepoint which are underrecognized in the clinical setting and underreported in clinical literature. Methods: We retrospectively reviewed clinical documentation across a cohort of tGCT patients in St Bartholomew’s Hospital who received adjuvant treatment (n=171), treatment for metastatic cancer (n=325) and those who underwent surveillance only (n=225) from 2011 and 2021. Only patients with a minimum follow-up of 5 years were included. Data was collected between Year 3 to Year 10 after initial treatment, ie only after two years of surveillance were completed. The frequency in which the following terminology/symptoms appeared in clinical documentation was recorded: relapse, endocrinology (a hormone problem including, but not included to hypogonadism/diabetes/thyroid dysfunction), lifestyle advice (eg weight management), blood pressure, cholesterol, psychology, fertility and other problems. Each reported issue was only recorded once per patient for this study. Results: Relapse rates were 0-0.75% annually (0% adjuvant, 0.7% metastatic, 0.75% surveillance). Total relapse rates beyond the two year time point, per group, were 0% in the adjuvant group, 5.8% in the metastatic group, and 6.0% in the surveillance group. Of the patient group who received treatment, significantly more reported endocrinological issues (7.0% average annually in the adjuvant group vs 4.2% metastatic vs 0.1% surveillance). Issues relating to blood pressure were equally reported (5.5% average annually in adjuvant vs 2.95% in metastatic vs 2.60% in surveillance) as were cholesterol (4.7% average annually in adjuvant vs 2.2% in metastatic vs 2.2% in surveillance). Fertility issues were more commonly reported in the group of patients who received treatment for metastatic cancer (2.4%) as opposed to those who received adjuvant treatment(0.5%) and surveillance only (0.7%). Conclusions: Relapse rates in our cohort of patients are low and consistent with previous studies. However, we highlight multiple survivorship issues for patients who have received treatment – particularly issues pertaining to endocrinological issues and fertility. These results suggest the need to incorporate monitoring of survivorship issues into our routine follow-up to improve patient experiences and outcomes. We suggest that a specialist clinic focused on long-term survivorship issues be established to better address the needs of this patient population.
Outcomes after primary retroperitoneal lymph node dissection in men with stage 2 non-seminomatous germ cell tumour: A multicenter retrospective cohort study.
Authors: Antonelli Luca , Heidenreich Axel , Bagrodia Aditya , Branger Nicolas , Clinton Timothy , Daneshmand Siamak , Djaladat Hooman , Hamilton Robert James , Ho Matthew , Sexton Wade J. , Nicol David , Nicolai Nicola , Olson Kathleen , Porter James , Singla Nirmish , Stroup Sean P. , Terbuch Angelika , Cary Clint , Fankhauser Christian Daniel 
Published: January 2024

516 Background: Based on only smaller retrospective cohort studies, current guidelines recommend primary retroperitoneal lymph node dissection (RPLND) for men with marker-negative stage 2a non-seminomatous germ cell tumor (NSGCT). We aimed to reassess the role of primary RPLND in marker negative stage 2a, explore results in stages 2b/c and/or marker-positive disease, and evaluate surgical methods, recurrence, and adjuvant chemotherapy indications. Methods: Data from 17 institutions were collected, comprising 305 men who underwent primary RPLND for stage 2 NSGCT. Regression analyses were conducted to predict histology in the RPLND specimen and progression-free survival (PFS). Results: A larger retroperitoneal lymph node diameter was associated with pure teratoma in the RPLND specimen (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.09, p-value = 0.02), but it did not correlate with PFS. The 5-year PFS rates were 85% for men with pure teratoma, 94% for men with viable cancer who received adjuvant chemotherapy, and 72% for men with viable cancer who did not receive adjuvant chemotherapy. The number of adjuvant chemotherapy cycles did not significantly affect PFS. Conclusions: Our study suggests considering primary RPLND not only in marker negative clinical stage 2a but also marker negative clinical stage 2b. Further research should identify the efficacy in men in other stages (2C or marker positive) and which patients may benefit from adjuvant chemotherapy and the optimal cycle number.
FGFR3 mutated (FGFR3mut+) urothelial carcinoma of bladder (UCB) or upper tract (UTUC): A comparative genomic landscape study.
Authors: Basin Michael , Sager Rebecca A , Pavlick Dean C. , Necchi Andrea , Spiess Philippe E. , Li Roger , Kamat Ashish M. , Grivas Petros , Cheng Liang , Lin Douglas I. , Ross Jeffrey S. , Basnet Alina , Bratslavsky Gennady , Jacob Joseph M 
Published: January 2024

540 Background: Activating DNA sequence genomic alterations (GA) in the FGFR3 gene including short variant (SV) mutations and kinase domain activating gene rearrangements/fusions (RE-FUS) are known drivers and relevant precision treatment targets for pts with UC. THOR trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs (taxane or vinflunine) in patients (pts) with advanced UCB or UTUC. PROOF-302 trial showed higher frequency of FGFR3 GA in UTUC (30%) vs UCB (13%). We sought to explore differences in frequency of FGFR3 alterations and the genomic landscapes of FGFR3-altered UCB and UTUC. Methods: 10,402 UCB and 2,325 UTUC (combined ureter and renal pelvis) underwent hybrid capture-based comprehensive genomic profiling (CGP) using a hybrid capture-based to assess all classes of GA and measure MSI status, TMB level, genomic ancestry, genomic signature, germline mutations and HRD score. PD-L1 was determined by IHC (Dako 22C3 using the TPS system. Results were compared using the Fisher Exact method with the Benjamini-Hochberg adjustment. Results: FGFR3mut+ status was significantly more frequent in UTUC than in UBC (24.9% vs 17.7%; p<.0001) (Table). UCB pts were more often male than UTUC (P=.0003). Age (71-72 yrs), EUR ancestry (85%) and GA/tumor (8.9-9.0) were similar. The number of GA/case and the frequency of EUR ancestry were similar. Targetable GA in ERBB2 and PIK3CA were more frequent in FGFR3mut+ UBC vs FGFR3mut+ UTUC. GA in PTEN, TSC1 and MTAP currently associated with clinical trials were similar in UBC and UTUC. The KEGG ERBB and VEGF signaling pathways were more frequently identified in UCB (p=0.036) and the MMR pathway more frequently identified in UTUC (p=0.014). The HRD signature was similar in both groups (2.3-3.1%). Anti-PD(L)1 putative biomarkers included a significantly higher frequency of MSI-high status in UTUC vs UCB but no significant difference in TMB or PD-L1 expression levels. Conclusions: Although histologically similar, the genomic landscape of FGFR3mut+ UTUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation. The findings may impact of clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents. [Table: see text]
Real-world treatment (Tx) sequences and time to discontinuation (rwTTD) in the first-line (1L) metastatic castration-resistant prostate cancer (mCRPC) setting.
Authors: Nash Smyth Emily , Whipple Samuel , Guinter Mark , Haddad Nadine , Piao Wenxian , Cui Zhanglin Lin , Balar Arjun Vasant 
Published: January 2024

55 Background: There is limited real-world data on tx sequencing in metastatic prostate cancer. Additionally, while guidelines support adding novel hormonal agents (NHA) to androgen deprivation tx (ADT) for metastatic hormone-sensitive prostate cancer, use is limited because of clinical and/or pt-driven factors. We evaluated tx patterns, rwTTD, and time-to-chemotherapy (rwTTC) for 1L mCRPC pts, including Black/African Americans (BAA) treated predominantly in a community oncology setting. Additionally, we analyzed systemic treatments prior to 1L mCRPC as well as progression to 2L mCRPC. Methods: This retrospective study included pts with mCRPC from the nationwide Flatiron Health EHR-derived, deidentified database who initiated 1L tx between 1/2013 and 1/2023. Study end was 4/2023. Tx patterns were described by time period (TP) of 1L initiation: TP1 - 01/2013–12/2017 and TP2 - 01/2018–01/2023; Kaplan-Meier analyses were conducted for rwTTD/TTC and a Cox proportional hazards regression model was used to determine the association between pt characteristics and rwTTD/TTC for 1L mCRPC. Subgroup analyses were performed for BAAs. Results: Of the 8915 1L-tx pts (median age 74 yrs), 871 (10%) were BAA (median age 70 yrs) and 5870 (66%) were NHA-naïve at 1L mCRPC. Overall, the percent of pts who were NHA-naïve decreased from 2018 (72%) to 2023 (39%) and a similar trend was observed for BAA (74% [2018] to 25% [2023]). 1L NHA use in mCRPC increased from TP1 to TP2 (overall: 70% to 80%; BAA: 73% to 83%), primarily driven by enzalutamide (Enz) (overall: 30% to 39%; BAA: 33% to 38%) and decrease in chemotherapy (overall: 16% to 12%; BAA: 17% to 13%). The top 3 1L mCRPC regimens for the overall population and BAA were abiraterone (Abi) (35%; 38%), Enz (32%; 33%), and docetaxel (10%; 11%). Among pts who progressed to 2L mCRPC, the most common sequences for patients tx with Abi or Enz for 1L mCRPC were ADT monotherapy in the prior line of tx and a switch to Abi (19%) or Enz (24%) upon progression from 1L to 2L. 1L rwTTD for the overall cohort is in the Table. Age ≥80 years, ECOG PS ≥1, socioeconomic status = 5 (highest), and median time ≤39.8 months from initial dx to mCRPC were associated with a higher hazard of discontinuation (all p ≤0.05). Conclusions: Overall, most pts received their first NHA in 1L mCRPC; NHA use increased and chemotherapy use decreased from TP1 to TP2. There was heterogeneity in tx sequences in patients treated with an NHA in 1L mCRPC; some pts were rechallenged with a different NHA in 2L despite lack of robust prospective data to support use. Overall, 1L rwTTD was short with a small numerical increase in TP2. Factors contributing to discontinuation, such as treatment resistance, need to be better understood to further improve real-world outcomes. [Table: see text]
Real-world treatment (tx) patterns and clinical outcomes in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) in Germany: Results of a retrospective observational study (CONVINCE).
Authors: Machtens Stefan , Schlack Katrin , Kubin Thomas , Ruhnke Markus , Schulte Clemens , Eisen Anna , Osowski Ulrike , Guenther Silke , Kearney Mairead , Lipp Rainer , Schmitz Stephan H. 
Published: January 2024

551 Background: Platinum-based chemotherapy (PBC) is the standard-of-care first-line (1L) tx for pts with la/mUC (followed by avelumab 1L maintenance in pts without progressive disease since its approval in Germany in Jan 2021). This study describes demographics, tx patterns, and clinical outcomes for pts with la/mUC treated in routine clinical practice in Germany between 2019 and 2021. Methods: CONVINCE, a retrospective, multicenter medical chart review study, was initiated in Dec 2021 and included adult pts who received 1L tx for la/mUC between 2019 and 2021. All pts were required to have ≥6 months of follow-up data available after end/start of 1L, depending on the type of tx received. Fully anonymized data were obtained from 27 oncology or urology institutions (8 hospitals and 19 office-based practices) across Germany. Descriptive statistics were used to analyze the results, and Kaplan-Meier methods were used to compute time-to-event outcomes. Pts were classified into 3 groups: (A) PBC with end of tx between Jan 2019 and Sep 2021 and (B) immuno-oncology (IO) therapy and (C) other non-PBC tx, both with start of tx between Jan 2019 and Sep 2021. Results: Of 188 pts included, median age at start of 1L was 70 years, 72.3% were male, most had ECOG PS 0/1 (92.5%), and the majority (60.1%) were treated by medical oncologists. A total of 143 pts (group A) received PBC (PBC + gemcitabine, 88.1%; PBC + non-gemcitabine agents, 8.4%; and cisplatin monotherapy, 3.5%). Cisplatin + gemcitabine (82.5%) was used more often than carboplatin + gemcitabine (17.5%). Six pts were treated with avelumab 1L maintenance following PBC. In group B, 36 pts (19.1%) received IO monotherapy (atezolizumab, 44.4%; pembrolizumab, 41.7%). In group C, 9 pts (4.8%) received non-PBC tx. Clinical outcomes in groups A and B are shown in the Table. Results for group C are not shown due to small sample size. Conclusions: CONVINCE describes characteristics, tx patterns, and outcomes in pts with la/mUC in routine clinical practice in Germany. In adherence with tx guidelines, most pts received PBC in 1L. New IO approvals, including avelumab 1L maintenance and other novel agents, could improve outcomes in pts with la/mUC. Further real-world studies should be performed to evaluate the uptake of these options within routine care. [Table: see text]
Safety and efficacy of enfortumab vedotin in patients with metastatic/locally advanced urothelial cancer: Real-world evidence from a European database.
Authors: Zschaebitz Stefanie , Klümper Niklas , Büttner Thomas , Holzwarth Nina , Biernath Nadine , Höllein Alexander , Niegisch Guenter , Seidl Daniel , Aydogdu Can , Handke Analena , Paffenholz Pia , Schlack Katrin , Cathomas Richard , Erne Eva , Banek Severine , Tauber Robert , Casuscelli Jozefina , Seitz Anna Katharina , Grünwald Viktor , Darr Christopher ,   GUARDIAN Study Group
Published: January 2024

553 Background: Enfortumab vedotin (EV) is an antibody drug conjugate targeting Nectin-4. It was approved by EMA/FDA in patients (pts) with metastatic/ locally advanced urothelial cancer post platinum and immune check point inhibitors following the results of the EV-301 trial. We report updated efficacy and safety data of EV in a large European cohort of real-world pts (GUARDIANS consortium) treated in hospitals and private practices. Methods: Retrospective data were collected from 25 German and Swiss hospitals and private practices for pts who received EV. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated by local investigators according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Weidentified 188 pts (32.4% female) with a median age of 66 yrs (range 31-89; 22.3% >/= 75 yrs). Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2/3-4/unknown in 36/39/11/3/11%. EV was administered in the fourth or later line in 43% of pts. Overall response rate (ORR) was 46.3% (partial remission: 42.0%, complete response 4.3%), disease control rate was 58.0%. Median OS (mOS) was 12.0 months (mo) (95% confidence interval 9.65-14.35) and median PFS (mPFS) was 7.0 mo (95% confidence interval 5.43-8.57). Any-grade AEs were observed in 71% and CTCAE grade ≥3 AEs in 32% of pts. Most common AEs were peripheral sensory neuropathy (33.5% any grade), skin toxicity (24.5%) and fatigue (22.9%). In pts >/= 75 yrs, females, and pts treated in >/=4th line mOS, mPFS, ORR, and toxicities were comparable to younger and male counterparts and pts treated in <4th line, respectively. Limitations are retrospective design and short follow-up. Conclusions: Anti-tumor activity of EV in real-world pts including difficult-to-treat subgroups is comparable to the results of the pivotal EV-301 trial. No new safety signals were observed.