bluuebunny/crossref_metadata_2025 huggingface dataset:
HER2 and PD-L1 immunohistochemistry (IHC) expression, and HER2 genomic alterations: Associations and clinical outcomes for advanced bladder cancer.
Authors: Aggen David H , Shah Neil J. , Zheng Junting , Alam Syed Muneeb , Balar Om , Niederhausern Andrew , Regazzi Ashley M. , Ratna Neha , Funt Samuel A , Teo Min Yuen , Pietzak Eugene J. , Solit David B. , Bajorin Dean F. , Ostrovnaya Irina , Rosenberg Jonathan E. , Al-Ahmadie Hikmat A. , Iyer Gopa
Published: January 2024

538

Background: Bladder cancer (BC) has a relatively high rate of human epidermal growth factor receptor 2 (HER2) alterations. The association between HER2 mutation/amplification, HER2, and PD-L1 immunohistochemistry (IHC) expression and associations with clinical outcomes for advanced bladder cancer (BC) has not been studied. Methods: We retrospectively analyzed BC samples for PD-L1 and HER2 IHC expression and compared HER2 alterations from genomic profiling with the MSK IMPACT platform. HER2 IHC expression was defined as 0, 1+, 2+, 3+, and PD-L1 IHC was the combined tumor and immune cell PD-L1 expression score (CPS). HER2 alteration was defined as either pathogenic mutation and/or amplification. We studied pairwise associations between HER2 alteration, PD-L1, and HER2 IHC expression in all patients and their associations with progression-free survival (PFS) and overall survival (OS) for muscle-invasive bladder cancer (MIBC) pts. Association analyses were performed using the Wilcoxon rank-sum test or Fisher’s exact test. Kaplan-Meier method and Cox proportional hazard models were used for time-to-event analyses. Results: Among 202 pts with HER2 IHC, 188 had MSK IMPACT, and 168 had PD-L1 CPS. The overall incidence of HER2 alteration was 22.3%; 48.2% had CPS ³10, and HER2 IHC distribution was 0:18.8%, 1+:29.7%, 2+:33.7%, and 3+:17.8%. The CPS score was inversely associated with HER2 IHC expression (p<0.001). No association was noted between CPS score and HER2 alteration (p=0.735). HER2 altered tumors were strongly correlated with high-level HER2 IHC expression (p<0.001). However, 41% (n=14/34) of HER2 IHC 3+ samples did not have HER2 alterations, and 17% (n=7/36) of HER2 altered samples had HER2 IHC expression of 0. In patients with MIBC, HER2 alteration and HER2 IHC expression (0/1+ vs. 2+/3+) were not associated with PFS (p=0.5 and p=0.4, respectively) or OS for MIBC pts (p=0.84 and p=0.94, respectively). A higher PD-L1 CPS score (>=10 vs <10) was associated with improved PFS for MIBC pts (p=0.03). Conclusions: Our study is the first to describe an inverse correlation between HER2 IHC expression and PD-L1 CPS score. Furthermore, HER2 IHC overexpression is strongly associated with HER2 amplification, but a subset of patients with high HER2 protein expression are potentially missed by genomic profiling alone. HER2 expression by IHC or HER2 genomic alteration is not a prognostic marker for MIBC pts in this cohort. This data provides the foundation for further HER2-directed advanced BC studies. [Table: see text]
A safety net for safety net hospitals: Affiliation with cancer centers and survival outcomes in patients with metastatic genitourinary cancers.
Authors: Bhanvadia Raj Ramnik , Taylor Jacob , Gaston Kris , Woldu Solomon L. , Lotan Yair , Margulis Vitaly
Published: January 2024

543

Background: Safety net hospitals (SNH) care for a substantial proportion of medically vulnerable populations (MVP). Addressing health disparities at a hospital level through partnerships with cancer centers is a potential strategy to improve outcomes of MVPs. We thus compared outcomes for metastatic prostate (mPCa), kidney (mKCa), and urothelial cancer (mUCC) among National Cancer Institute centers (NCI), NCI affiliated SNH (NCI-SNH), and non-affiliated SNH using the Texas Cancer Registry (TCR). Methods: The TCR has 98% case ascertainment of all cancers diagnosed in Texas. The TCR can identify each facility where a patient was diagnosed and treated, allowing detailed hospital level comparisons of outcomes. The TCR was queried from 2004-2017 for mPCa, mKCa, and mUCC. Publicly available data identified Texas NCIs. The top quartile of Disproportionate Share Hospital Index values identified SNH. SNH with established relationships to NCI were designated NCI-SNH and remainder were SNH. Non-SNH were hospitals not affiliated with NCI nor SNH. MVPs were defined as age > 75, non-US natives, non-whites, and uninsured or Medicaid patients. Cox multivariable regression was used to assess overall mortality (OM). Results: Of the 1,048,464 patients in TCR, MVPs accounted for 44.7% of cases. The SNHs and NCI-SNHs accounted for 53.1% of all MVP cancer care statewide. MVPs were the majority of cases within NCI-SNH compared to other SNH or NCI (80% vs 45% vs 37.1%, p<0.01). TCR identified 20,503 metastatic genitourinary (GU) cancers. For mPCa, rates of hormone therapy were similar between NCI-SNH (76.7%) and NCI (76.2%), but greater than SNH (51.5%) or non-SNH (49.7%) ( p<0.01). Receipt of chemotherapy or immunotherapy was greater at NCI-SNH compared to other SNH or non-SNH for both mKCa (36.1% vs 31.1% vs 27.1%, p<0.01) and mUCC (44.0% vs 36.7% vs 33.2%, p<0.01). On multivariable cox analysis, equivalent OM between NCI and NCI-SNH for any metastatic GU cancer (Table). OM was worse at other SNH and non-SNH compared to NCI (Table). Conclusions: Medically vulnerable patients made up almost half of cancer care in Texas and majority were cared for at SNH. NCI-SNHs had equivalent OM to NCI and superior OM compared to other SNH. Future initiatives to improve cancer care should focus on strengthening existing relationships between NCI and SNH, and examine mechanisms to centralize care of MVPs to these facilities.[Table: see text]
Exploration of enfortumab vedotin (EV)–related cutaneous events by race in two real-world cohorts.
Authors: Vlachou Evangelia , Mamtani Ronac , Hahn Noah M. , Johnson Burles Avner , Hoffman-Censits Jean H. , Nimgaonkar Vivek
Published: January 2024

544

Background: EV is an antibody drug conjugate, approved in advanced urothelial cancer (UC). The Nectin-4 target of EV is present in tumor and normal skin, and EV-related cutaneous events (EVCEs) are common. EVCEs often appear early with variable grade presentation. Continuation of EV is typically safe with supportive management, but rare life-threatening manifestations have occurred. Dermatologic conditions, including medication-related skin events are often underdiagnosed or under-staged in Black patients (pts). Black pts are also frequently under-represented in UC trials, and it is unknown whether EVCE incidence varies by skin tone. We explored whether EVCE frequency varies between Black and White pts in an urban cohort and a large community-based national dataset. Methods: This retrospective cohort analysis used data from Johns Hopkins Hospital (JH) and Flatiron Health (FH), a de-identified electronic health record (EHR)-derived database of community-based oncology clinics across the U.S. Pts treated with EV monotherapy at JH and in the FH database who self-identified as Black or White race were included. In the JH cohort, chart review was used to extract demographics, treatment details, and EVCEs. EVCEs were defined as any grade, new or exacerbated dermatologic event after EV initiation, not attributed to other cause. In the FH cohort, EVCEs were identified through pre-defined skin-related ICD-10 codes identified by the study authors. Odds ratios (OR) with 95% confidence intervals of EVCE incidence between Black and White pts were calculated separately for each cohort. Results: 78 toxicity-evaluable pts were identified in the JH cohort and 316 in the FH cohort. 12 were Black (15.4%) in the JH Cohort vs. 24 Black (7.6%) in the FH cohort. Median age was 71 years (IQR: 64-78), 20 (25.6%) were female, 50 (64.1%) pts had a primary site in the bladder, and 13 (16.7%) had EV as second-line and 49 (62.8%) as third-line treatment in the JH cohort, vs. 71 years (IQR: 65-77), 84 females (26.6%), 226 (71.5%) with bladder primary site, and 122 (38.6%) and 108 (34.2%) receiving EV as second-and-third-line treatment respectively in the FH Cohort. In the JH Cohort 8 of 12 Black pts (66.7%) as compared to 32 of 58 (55.2%) White pts experienced an EVCE (Table, OR 1.63, 95% CI [0.44, 6.0]). In the FH cohort, 6/24 Black pts (25%) compared to 46 /292 White pts (15.8%) experienced an EVCE (Table, OR 1.78, 95% CI [0.67, 4.73]). Conclusions: In this hypothesis-generating analysis of EV treated pts, the largest reported cohort of Black EV treated pts to date, we observed an increased EVCE frequency in Black pts relative to White, though statistical significance was not demonstrated. Future prospective EV studies should aim to recruit Black patients to better characterize this finding. [Table: see text]
Patterns of concurrent chemotherapy selection in US patients undergoing trimodality therapy for muscle-invasive bladder cancer.
Authors: Callihan Eryn , Molina Kuna Elizabeth , Robin Tyler P. , Eule Corbin J. , Kim Simon P. , Flaig Thomas W.
Published: January 2024

554

Background: Trimodality therapy (TMT) consists of concurrent chemoradiation following maximal transurethral resection of the bladder tumor for muscle-invasive bladder cancer (MIBC). Current TMT treatment guidelines allow for several different radiosensitizing chemotherapy regimens, however there is limited data on existing use patterns. Methods: Using data from CancerLinQ Discovery, 71,499 patients with a bladder tumor diagnosed between 2000-2022 were included. Patients with documented radiation to “bladder” or “pelvis” with no known metastatic disease and a documented chemotherapy regimen started within a 30-day window of radiation, were included in the final analyses (n=233). Chemotherapy regimens included cisplatin, gemcitabine, 5FU+ mitomycin, taxanes, and other. Through bivariate analyses, patient characteristics and TMT treatment patterns were characterized. Results: The most commonly utilized TMT chemotherapy regimen was cisplatin alone (42.5%) followed by gemcitabine (19.3%), 5FU+ mitomycin (15.8%), taxanes (12.5%) and other (9.9%). These data demonstrated a significant relationship between age at diagnosis and chosen TMT regimen (p=0.017). Patients <65 were more likely to receive cisplatin (27.3%), 5FU mitomycin (29.7%) or other (30.4%) while patients 85+ were more likely to receive gemcitabine (28.9%). Patients more frequently received cisplatin alone prior to 2017 (before 2011: 28.3% vs. 2011-2016: 53.5% vs. 2017-2022:18.2%, p-value <.001), with a trend towards more gemcitabine use in the most recent period between 2017-2022 (51.1% vs. before 2011: 20.0% vs 2011-2016: 28.9%, p-value <.001). Additionally, there was less taxane use over time (before 2011: 37.9% vs. 2011-2016: 55.2% vs 2017-2022: 6.9%, p-value <.001). Finally, the association between TMT regimen and Charlson Comorbidity Index (CCI) trended toward significance—those treated with cisplatin alone were most likely to have a CCI of 0 (62.6%, p-value = 0.081) while patients receiving gemcitabine alone or 5FU + mitomycin were more likely to have a CCI of 1+ (gemcitabine alone: 51.1%, 5FU + mitomycin 51.4%, p-value = 0.081). Conclusions: There remains wide variation in the use of chemotherapy regimens in TMT with cisplatin monotherapy as the most utilized radiosensitizing agent overall. Since 2000, there has been a shift away from taxane therapy and increased gemcitabine use. Patients with lower CCI had a trend to more frequently receive cisplatin and older patients more frequently received gemcitabine. Further investigations are needed to better characterize patient characteristics as well as toxicity and survival by drug regimen to better help inform treatment guidelines.
Geriatric assessment (GA) in elderly patients with urothelial cancer (UC): Can GA select frail patients and avoid toxic treatment? Multidisciplinary single center experience.
Authors: Girones Sarrio Maria Regina , Arnal Rondán Maria , Berenguer Francés Miguel Angel , Torres Martínez Alba Girones , Conde Moreno Antonio Jose , Pontones José Luis , Delgado Francisco , Bonastre Cristina , Ramos David , Gómez Sepúlveda Nuria , Lorente Estelles David , Forcano Silvia
Published: January 2024

564

Background: UC is a disease of the elderly. Median age at UC diagnosis is olderthan for other major tumours (73 years old). The correct management of UC in the elderly remains controversial. Treatment-decisions should be based on biological age, not in chronological one. The role of geriatric assessment (GA) evolution is potentially beneficial. It has been detected between 10% to 25% frailty patients aged over 65 years are characterised as frail on GA on other tumors. GA has not been studied prospectively in UC patients. Objective: to assess the paper of GA in elderly patients with UC patients attended in an outpatient medical oncology consultation. To confirm that GA can detect at least 25% of frailty patients unsuitable for active treatment. Methods: Prospective interventional study. GA was done by a Geriatrician at patient’s home. Treatment-decisions were based on GA results, physician choice and patients/caregivers goals. Population: patients ≥ 70 years old sent from January 2019 to September 2023 diagnosed with UC. Patients unsuitable to be ambulatory (Performance status PS ≥ 3) were excluded. Ethics review board approved the analysis. All participants signed informed consent. Results: 82 patients were aged ≥ 70 years old (57% of all patients attended). Table shows patient’s information. GA detected 24 (30%) of frailty patients. They were elder, former smokers, had worse PS and worse overall survival in all stages. Non frail patient received active treatment. Comorbid and polypharmacy population was found in all three GA groups. More fit and vulnerable patients were treated with cisplatin by GA assessment than if we have applied Galsky criteria. This suggests than the strict use of a CrcL < 60 ml/min is still controversial. Conclusions: In a very selected population, GA can still find 30% of frail patients unsuitable for treatment. Frailty seems to be a predictive and prognostic factor in elderly patients with UC. Treatment selection based on GA increase the number of patients suitable for platinum treatment. Defining “platinum-ineligible” patients with metastatic urothelial cancer should be reviewed. Selection bias cannot be excluded from our analysis.
Characteristics of patients (pts) with muscle-invasive urothelial carcinoma (MIUC) who received adjuvant nivolumab (NIVO) or adjuvant platinum-based chemotherapy (CHEMO) in the real-world (RW) setting.
Authors: Chehrazi-Raffle Alex , Feinberg Bruce A. , John William S. , Miller Taavy A. , Bland Emily , Gordon Sarah , Laney Jalyna R. , Klink Andrew J. , Ebrahimi Hedyeh , Patel Miraj Y. , Rosenblatt Lisa , Alonso Carmelo , Singh Nisha , Yin Xin
Published: January 2024

565

Background: NIVO has shown promise as an adjuvant treatment for MIUC. In the CheckMate 274 trial, NIVO achieved a significant improvement in disease-free survival compared to placebo in MIUC pts at high risk of recurrence following radical surgery. However, it is unclear how treatment decisions are made in the RW setting and what factors drive providers in selecting either NIVO or CHEMO as adjuvant treatment. We compared the baseline demographic and clinical characteristics of pts with MIUC who received adjuvant NIVO to those who received adjuvant platinum-based CHEMO in the RW setting. Methods: This retrospective medical chart review included pts diagnosed with stage II-IIIB MIUC who initiated treatment with NIVO or CHEMO within 120 days of radical resection between 9/1/2021 and 11/25/2022. Treating oncologists from a US nationally representative network abstracted pts’ data from electronic medical charts. Pts’ demographic and clinical characteristics were assessed. Results: Age, sex, and race were similar across cohorts (Table). Pts who received adjuvant NIVO (n = 158) vs CHEMO (n = 88) were more likely to have ECOG-PS≥ 2 at treatment initiation (24.1% vs 17.1%; P = 0.02), and more likely to receive PD-L1 testing (Not tested: 36.1% vs. 47.7%; P < 0.0001) and have PD-L1 expression levels ≥ 50% (13.9% vs 1.1%; P < 0.0001). A higher proportion of pts who received NIVO vs CHEMO had diabetes with chronic complications (15.8% vs 5.7%; P = 0.02) and hypertension (20.9% vs 6.8%; P = 0.004), and were determined to be cisplatin-ineligible (41.8% vs 25%; P = 0.007), predominately based on creatinine clearance (< 60 mL/min: 48.7% vs. 34.1%; P = 0.002) and poor PS (13.9% vs. 4.6%; P = 0.07); rheumatologic disease was less common among the NIVO cohort (1.9% vs 11.4%; P = 0.002). Conclusions: This RW analysis demonstrated that pts with MIUC who received adjuvant NIVO had greater baseline disease severity and comorbidities than those who received adjuvant CHEMO. These findings suggest that patient characteristics influence treatment selection of adjuvant therapy in this patient population, highlighting the need to adjust for baseline characteristics in future comparative analyses.[Table: see text]
Pathologic and survival outcomes following radical cystectomy for “progressive” and “de novo” muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status.
Authors: Xia Leilei , Dadabhoy Anosh , Wood Erika L. , Roberson Daniel , Guzzo Thomas J. , Bivalacqua Trinity , Daneshmand Siamak
Published: January 2024

566

Background: Muscle-invasive bladder cancer (MIBC) can present as de novo MIBC (dnMIBC) or progressive MIBC (pgMIBC), the latter occurring in patients with a history of non-muscle-invasive bladder cancer (NMIBC). Retrospective cohort studies have reported varied survival outcomes following RC for pgMIBC versus dnMIBC.Here we aim to pool previous studies and compare survival and pathologic outcomes in patients with pgMIBC and dnMIBC following radical cystectomy (RC), with an investigation of the impact of neoadjuvant chemotherapy (NAC). Methods: A comprehensive literature search was conducted on PubMed and EMBASE databases to identify studies comparing pgMIBC to dnMIBC. Survival outcomes, including cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS), as well as pathologic outcomes following surgery (rates of ≤pT1, pT0, pT3/T4, and pN+ disease) were compared between pgMIBC and dnMIBC. Results: The analysis included 19 cohorts from 16 studies, categorized into three groups based on NAC status: 1. patients who underwent RC following completion of NAC (RC + NAC only group); 2. patients who underwent RC, with or without NAC (RC +/- NAC group); 3. patients who only underwent RC without NAC (RC only group). Compared to dnMIBC, pgMIBC demonstrated worse outcomes for CSS, OS, and RFS. In the RC + NAC only group (3 cohorts), the hazard ratio (HR) for CSS was 1.52 (95% confidence interval [CI] = 1.05-2.2), the HR for OS was 1.46 (95%CI = 1.05-2.02). Similarly, in the RC +/- NAC group (6 cohorts for CSS and 3 cohorts for OS), the HR for CSS was 1.27 (95%CI = 1.05-1.55), and the HR for OS was 1.27 (95%CI = 1.08-1.51). There were no significant differences observed in pathologic outcomes, including rates of ≤pT1, pT0, and pT3/T4 disease, across all subgroups. However, pgMIBC was associated with a higher risk of nodal metastatic (pN+) disease in the RC + NAC only group (4 cohorts, relative risk [RR] = 1.43, 95%CI = 1.12-1.84). Conclusions: The findings highlight the potentially worse prognosis in patients with pgMIBC compared to dnMIBC, even with the modern use of NAC. The study emphasizes the importance of careful patient counseling, further classification of patients for treatment selection, and the consideration of additional or innovative systemic therapies for pgMIBC.
Clinical efficacy of lurbinectedin in metastatic neuroendocrine carcinomas of the genitourinary tract: Multi-institutional real-world experience.
Authors: Moussa Mohammad Jad , Naqvi Syed Arsalan Ahmed , Khandelwal Jaanki , Campbell Matthew T , Aparicio Ana , Siddiqui Bilal Ahmed , Bryce Alan Haruo , Singh Parminder , Alhalabi Omar
Published: January 2024

601

Background: Neuroendocrine carcinomas (NEC) of the genitourinary (GU) tract, including small cell (SC) NEC and large cell (LC) NEC, are rare aggressive malignancies. Although highly sensitive to cisplatin-based chemotherapy, GU metastatic NEC (mNEC) have limited data to support next therapies. Lurbinectedin, a marine-derived alkylating drug and a selective inhibitor of oncogenic transcription and DNA repair pathways, is FDA-approved for small cell lung cancer (SCLC) after progression on frontline platinum-based therapy, with a disease control rate (DCR) of 68.6%. It is unknown whether DCR is similar in SCLC and GU mNEC. Methods: We report the first multi-institutional series (n=14) of lurbinectedin in GU mNEC. Imaging-based best overall responses (BOR) were noted as complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). DCR includes CR, PR, and SD. We use the Kaplan-Meier method for overall survival (OS) and progression-free survival (PFS) from lurbinectedin start date. We define duration of response (DoR) from response date to progression or last contact date for patients (pts) with CR or PR. Results: Most pts had a median age at metastasis of 70.5 years (ICR: 64-74.5) [Table]. Primary locations were bladder (7/14, 50%), prostate (5/14, 35.7%) and ureter (2/14, 12.3%). Histology at diagnosis mostly consisted of mixed or pure SCNEC, with one exception of LCNEC. Most pts had visceral disease, prior immunotherapy and at least 2 prior lines of therapy for mNEC before lurbinectedin (8/14, 57.1%). DCR was 6/14 (42.8%), including 5 bladder pts and 1 prostate pt. Among bladder pts, BOR included one CR (1/7, 14.3%) for the LCNEC case, 2 PR (2/7, 28.6%), 2 SD (2/7, 28.6%) and 2 PD (2/7, 28.6%). Most prostate and ureteral pts either progressed on lurbinectedin or were NE (Prostate: 1 PR, 2 PD, and 2 NE; Ureteral: 1 PD and 1 NE). For all 14 pts, median OS was 11.47 months (95% CI: 2.17-13.63) and median PFS was 2.8 mo (1.4-10.9). Median DoR was 7.38 mo (2.3-9.53) for 4 responding pts (CR or PR). Treatment was stopped due to progression (9/14, 64.3%), three adverse events [thrombocytopenia, electrolyte abnormalities, cerebrovascular accident] (3/14, 21.4%), and pt preference (1/14, 7.1%). Conclusions: Lurbinectedin offers encouraging responses (DCR: 5/7, 71.4%) close to those in SCLC, in previously treated bladder mNEC. One CR was noted for a bladder pt with LCNEC. Responses were less appreciated in prostate and ureteral mNEC due to NE responses and limited number. Larger cohorts are needed to confirm survival benefit and genetic analyses are warranted to identify characteristics of responders. [Table: see text]
Tislelizumab in combination with gemcitabine plus cisplatin as neoadjuvant therapy for lymph node‐positive bladder cancer: Results of a prospective study.
Authors: Yang Xiao , Zhuang Juntao , Cao Qiang , Cai Lingkai , Wu Qikai , Lu Qiang
Published: January 2024

619

Background: Although multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs combined with gemcitabine plus cisplatin in MIBC, lymph node‐positive bladder cancer is generally excluded. In this study, our specific aim was to compare the efficacy and prognosis of neoadjuvant tislelizumab combined with gemcitabine plus cisplatin in patients with lymph node‐positive bladder cancer. Methods: In this investigator-initiated study, eligible patients had cT2-T4 N+ M0 MIBC, cisplatin-eligible, and to be planned radical cystectomy (RC). Patients received tislelizumab 200 mg in day 8 (D8), cisplatin 70 mg/m2 D2-4, and gemcitabine 1000 mg/m2 D1 and D8 every 21 days for 3 or 4 cycles. RC was performed within 6 weeks after last dose treatment. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (<ypT2), EFS, OS and safety. Results: A total of 15 pts were enrolled,14 pts (2 cT2, 7 cT3, 5 cT4) have completed neoadjuvant therapy and underwent RC. One patient declined surgery for personal reasons and received further systemic therapy. In 14 pts evaluable for efficacy, the investigator-assessed confirmed clinical complete response was 21.4% (3/14). Final pathologic results showed that 5 pts (50%) achieved pCR (ypT0N0), 4 ypT1, and 5 ypT2/T3, and 9 patients (<ypT2N0,64.2%) had staging downgrades, with no patients experiencing progression. A complete nodal response (pN0) occurred in 11 (78.5%) pts after tislelizumab +chemotherapy. The median follow-up was 8.9 months, with one death due to multiple metastases and the remaining patients showing no signs of recurrence or metastasis. Median EFS and OS was not reached. Most common neoadjuvant therapy-related AEs of any grade were hematologic toxicities (11/14,78.5%), nausea (9/14,64.2%), vomiting (8/14,57.1%). Grade ≥3 neoadjuvant therapy-related AEs were neutropenia (n = 3), thrombocytopenia (n = 2), anemia (n = 2). One patient discontinued tislelizumab due to AEs. Conclusions: The combination of tislelizumab and gemcitabine/cisplatin is clinically active with a manageable safety profile as a neoadjuvant therapy for lymph node‐positive bladder cancer. Clinical trial information: NCT04570410 .
Time to next systemic therapy after stereotactic body radiation therapy for oligoprogressive metastatic castrate-resistant prostate cancer.
Authors: Eule Corbin J. , Candelario Nellowe , Robin Tyler P.
Published: January 2024

62

Background: Patients with castrate-resistant prostate cancer (CRPC) with progressive disease are generally require a change/escalation in systemic therapy. For patients with limited ( ≤3) sites of progressive disease (oligoprogression), metastasis-directed therapy with stereotactic body radiation therapy (SBRT) may allow a longer interval before next line systemic therapy, but there is limited data describing this approach. Methods: This is a retrospective study of patients with oligoprogressive metastatic CRPC (omCRPC) treated with SBRT at a single center between 2011-2022. The primary endpoint was time to next systemic therapy (TTNST) after SBRT. Secondary endpoints included overall survival (OS) after SBRT and TTNST stratified by presence of untreated non-progressing metastases. Results: Thirty-two patients with omCRPC received SBRT to 38 metastases. Patients had a median age of 72.5 years (range 50.6-84.3) and median PSA 6.85 ng/mL (range 0.39-922.0) at time of SBRT. The majority had an ECOG of 1-2 (29 patients, 90.6%) and metastases detected on conventional CT and/or bone scans (26 patients, 81.3%). The most commonly utilized SBRT regimen was 3000 cGy in 5 fractions (18 metastases, 47.4%) (Table). Sixteen patients were treated to all known sites of disease, whereas 16 patients received SBRT to oligoprogressive metastases but had at least one untreated non-progressing metastasis at the time of SBRT. Of 32 patients, 23 (65.7%) received SBRT to bone only, 3 (9.4%) to lymph node (LN) only, and 6 (18.8%) to other sites (pelvic tumor, n=2; pelvic tumor + LN, n =1; LN + bone, n=1; dura + bone, n=1; liver, n=1). Patients had received a median of 1.0 prior line of androgen receptor signaling inhibitors and were predominantly (26 patients, 81.3%) chemotherapy naïve. Following SBRT, the median TTNST was 10.1 months and median OS was 41.3 months. For patients with 0 versus ≥1 untreated non-progressing metastasis, TTNST was 11.3 versus 8.7 months, respectively (HR 0.67, 95% CI 0.33-1.36, logrank p=0.24). There were no grade ≥3 toxicities due to SBRT. Conclusions: In this cohort, patients with omCRPC treated with SBRT delayed the next line of systemic therapy for a median of 10.1 months. SBRT in patients with omCRPC may delay initiation of next line systemic therapy in well selected patients, including those with ≥1 untreated non-progressing metastases. [Table: see text]
The pretreatment neutrophil-to-lymphocyte ratio to predict clinical response to maintenance avelumab therapy in patients with metastatic urothelial cancer.
Authors: Inoue Satoshi , Sai Hiroki , Hayakawa Akira , Morishita Koya , Yuguchi Yuri , Suzuki Tomohide , Matsui Hirotaka , Maeda Motohiro , Asano Akiyuki , Tochigi Kosuke , Akamatsu Shusuke
Published: January 2024

620

Background: It has not been elucidated how preceding first-line chemotherapy affects neutrophil-to-lymphocyte ratio (NLR) and maintenance avelumab therapy. We investigated the relationship between NLR levels just before the initiation of treatment with maintenance avelumab therapy and clinical outcomes in metastatic urothelial cancer (mUC) patients. Methods: This retrospective study was analyzed for patients with mUC who received maintenance avelumab therapy between February 2021 and July 2023 at Nagoya University and several affiliated hospitals in Japan. We investigated the relationship between NLR levels just before avelumab therapy and clinical outcomes. All patients were divided into two groups according to NLR levels just before avelumab therapy. A NLR level of ≥3.00 was defined as elevated according to a calculation by a receiver-operation curve analysis. Progression-free survival (PFS) and overall survival (OS) rates were estimated using Kaplan–Meier curves and Cox proportional hazards models. Results: The median age and follow-up duration were 73 years (range 49-83 years) and 11.6 months (range 2.4-26.5 months), respectively. The high NLR group consisted of 29 patients (45.3%). Patients in the high NLR group had significantly shorter PFS and OS than those in the low NLR group (p=0.018 and p=0.027, respectively). Similarly, PFS and OS was significantly shortened in patients with NLR levels that had increased during first-line chemotherapy than their counterparts (p=0.018 and p=0.008, respectively). Furthermore, patients in the high NLR group had a significantly lower disease control rate than those in the low NLR group (58.6% vs 91.4%, p=0.003). While there was not a significant association between OS and NLR at the start of first-line chemotherapy (p = 0.763). Multivariate analyses revealed that stable disease as best response to first-line chemotherapy was significantly associated with PFS [hazard ratio (HR), 4.55; p=0.001] and OS (HR, 21.58; p=0.001). Conclusions: High NLR levels just before avelumab therapy might be a prognostic factor for mUC patients undergoing maintenance avelumab therapy.
Clinical impact of C-reactive protein flare response in patients with advanced urothelial carcinoma who received pembrolizumab.
Authors: Tomisaki Ikko , Harada Mirii , Minato Akinori , Higashijima Katsuyoshi , Takaba Tomohisa , Nagata Yujiro , Harada Kenichi , Fujimoto Naohiro
Published: January 2024

634

Background: C-reactive protein (CRP) has been reported as one of the useful predictive markers in patients with advanced urothelial carcinoma (UC). Not only baseline revel, kinetics of CRP during medical treatment also has been demonstrated. However, there are extremely limited data on temporary elevated CRP levels followed by decreasing below baseline (CRP flare response) after administration of immune checkpoint inhibitors. The aim of this study was to clarify the clinical significance of CRP flare response after administering pembrolizumab in patients with advanced UC. Methods: We retrospectively reviewed patients with advanced UC who consecutively received pembrolizumab as second-line or later therapy between March 2018 and January 2023 at one academic center and six general hospitals. Patients were categorized into 3 groups according to early CRP kinetics: flare-responder (CRP levels had increased to more than double from baseline within 1 month after pembrolizumab administration (CRP flare) and decreasing to below-baseline levels within 3 months); responder (CRP levels decreased ≥30% from baseline within 3 months without CRP flare); non-responder (the remaining patients). Tumor responses, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared among the groups. Results: A total of 97 eligible patients, 15, 25, and 57 patients were classified into flare-responder, responder, and non-responder group, respectively. Objective response rates of flare-responder (43%) and responder (52%) were higher than that of non-responder groups (17%). Median follow-up was 7.8 months. Progression and death were observed in 83 and 70 patients during follow-up, respectively. Median OS was 19.8, 15.2, and 7.8 months in the flare-responder, responder, and non-responder group, respectively (P= 0.03). Furthermore, Median PFS was 8.1, 6.3, and 2.7 months in the flare-responder, responder, and non-responder group, respectively (P= 0.006). In multivariate analysis, CRP-flare response was a significant favorable predictive factor associated with OS. The patients who developed any grade AEs were 33, 40, 20.7% in the flare-responder, responder, and non-responder group, respectively (P= 0.16). Similarly there were no significant differences in occurrence of severe AEs (≥Grade 3). Conclusions: CRP flare response was observed in 15% of patients with advanced UC who received pembrolizumab and favorable oncological outcomes were observed in these patients. CRP-flare might be a promising predictive and prognostic marker in patients with advanced UC who underwent pembrolizumab therapy.
Safety of intraoperative tranexamic acid use on the risk of venous thromboembolism (VTE) in patients undergoing robotic assisted radical cystectomy (RARC).
Authors: Ahmed Mohamed E. , Andrews Jack R. , Mahmoud Ahmed M. , Thapa Prabin , Khanna Abhinav , Shah Paras , Sharma Vidit , Thompson R. Houston , Frank Igor , Karnes R. Jeffrey , Tollefson Matthew K.
Published: January 2024

641

Background: Perioperative blood transfusion is associated with an increased risk of adverse events and tranexamic acid (TXA) use has been proposed to decrease the need for perioperative blood transfusion. Herein, we seek to investigate the impact of intraoperative TXA on perioperative risk of VTE in a subset of patients who underwent robotic-assisted radical cystectomy (RARC) for bladder cancer. Methods: We queried the prospectively maintained Mayo Clinic Radical Cystectomy registry and identified patients who underwent RARC between 2004-2021 and received TXA intraoperatively. In univariable and multivariable analyses, we investigated factors associated with bleeding and VTE within 30 days post-operatively. Results: Of 2862 patients, we identified 94 patients who received TXA (IV) intraoperatively (Group A) and were propensity score matched 1:1 for age, neoadjuvant chemotherapy, pT stage, pN stage, and preoperative hemoglobin with a group who did not receive TXA; 38 patients (Group B). In univariable and multivariable models, use of TXA has no statistically significant impact on patient’s risk of bleeding or VTE. In a univariable model, number of positive lymph nodes and extent of lymph node dissection were associated with increased risk of VTE (Table 1). Conclusions: In our study, use of TXA in patient’s undergoing RARC was safe and was not associated with increased risk of VTE. [Table: see text]
Clinical efficacy of enfortumab-pembrolizumab combination therapy in locally advanced/metastatic urothelial carcinoma (UC): A real-world experience.
Authors: Tripathi Nikita , Naqvi Syed Arsalan Ahmed , Ballouz Tara , Saxena Akshat , Bibi Arifa , Khan Muhammad Ali , Channar Aneeta , Riaz Irbaz Bin , Tyson Mark , Bryce Alan Haruo , Singh Parminder
Published: January 2024

643

Background: The FDA approval of enfortumab (EV) and pembrolizumab (Pembro) combination therapy as a first-line treatment for cisplatin-ineligible patients with locally advanced/metastatic urothelial carcinoma (la/mUC) was based on the EV-103 trial. We aim to assess the clinical response rate of this combination therapy in our institution's patients with locally advanced and metastatic UC. Methods: This retrospective cohort study included 20 patients diagnosed with locally advanced/metastatic UC(la/mUC) who were treated with EV-Pembro combination for at least 2 cycles, from June 2022 to August 2023 at the Mayo Clinic. Patients who were treatment naïve or who progressed one or more lines of therapy were included in the study cohort. Main outcome of interest included imaging-based best overall response rate in terms of complete (CR) and partial (PR) response, stable disease (SD), and progressive disease (PD). Results: Out of 20 patients, the number of males and females were 16 (80%) and 4 (20%) respectively; the median age was 77 years (IQR: 51-92). 3 (15%) of patients had involvement of upper urinary tract disease along with bladder cancer. The common sites of visceral metastasis at the time of initial presentation include liver 2(10%), lung 6(30%) and lymph nodes12(60%). Common toxicities of this regimen included rash, pruritis, peripheral neuropathy, fatigue, transaminitis, dysgeusia, and diarrhea. The treatment was stopped in 10 (50%) patients due to completion of planned therapy (achieved CR or proceeded with resection of residual disease) (30%), 5 patients due to progression (50%), 1 patient due to therapy side effects (10%) and in 1 patient due to death (10%). The objective response was 45% (N =9); 5 (25%) had PR, and 4 (20%) had CR. A total of 2 (10%) had SD while 2 (10%) experienced PD. Histological correlation with clinical benefit is shown in the table. Conclusions: EV-Pembro combination therapy shows promising responses in patients who have progressed after previous lines of therapy, consistent with previously published data on EV 201 in small cohorts. However, ongoing expansion of this cohort and data from larger studies will help further elucidate survival benefits and their correlation with genetic testing. [Table: see text]
RC48-ADC versus BCG in adjuvant treatment of high-risk non-muscle-invasive bladder cancer with HER2 over-expression: A real-world retrospective study.
Authors: Liu Haoyang , Chen Junru , Liu Haolin , Zhu Qiyu , Liao Banghua , Liu Zhenhua , Shen Pengfei , Zeng Hao
Published: January 2024

644

Background: Bladder cancer ranks as the tenth most prevalent malignancy globally, with non-muscle invasive bladder cancer (NMIBC) accounting for approximately 75% of cases. Patients diagnosed with high-risk NMIBC (HR-NMIBC) face a grim prognosis, characterized by a 5-year disease progression rate of up to 40%. Currently, the standard treatment for HR-NMIBC involves transurethral resection of bladder tumor (TURBT) followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy. However, BCG infusion therapy is associated with prolonged duration, substantial costs, and a high frequency of toxic side effects. RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, has shown promising efficacy with a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma (mUC) in a Phase II clinical trial (NCT03507166). Therefore, investigating the therapeutic potential of RC48-ADC in HR-NMIBC patients holds significant clinical importance. Methods: We conducted a retrospective analysis on patients diagnosed with HR-NMIBC exhibiting HER2 overexpression (≥ HER2 2+) who underwent adjuvant therapy with either RC48-ADC, a HER2-targeting antibody-drug conjugate, or BCG, at West China Hospital of Sichuan University between 2019 and 2023. The primary study endpoint was the twelve-month recurrence-free survival (RFS) rate, with safety assessments as secondary endpoints. Results: A total of thirty patients diagnosed with HR-NMIBC displaying HER2 overexpression were included in the study. Following TURBT, eleven patients received adjuvant therapy with RC48-ADC, while nineteen received adjuvant therapy with BCG. The median follow-up duration for patients receiving RC48-ADC and BCG adjuvant therapy was 7.3 and 16.43 months, respectively. Among patients treated with RC48-ADC, the twelve-month RFS rate was 100%, with one out of the 11 patients experiencing relapse after 14.2 months of RC48-ADC adjuvant therapy. In the BCG-treated group, the twelve-month RFS rate was 57.6%. However, Kaplan-Meier analysis revealed no statistically significant difference between these two groups (P=0.22). In the RC48-treated group, the most commonly reported treatment-related adverse events (TRAEs) included alopecia (45.5%), arthralgia (18.2%), and nausea (18.2%). A total of 27.7% of patients experienced grade 3 TRAEs, including alopecia, rash, and hypoesthesia, with no observations of grade 4 or grade 5 TRAEs. Conclusions: RC48-ADC has demonstrated promising efficacy with a manageable safety profile as an adjuvant therapy in patients with HR-NMIBC. RC48 may be an alternative adjuvant therapy for BCG in terms of the 12-month recurrence-free survival rate.
A study of blood myeloid-derived suppressor cells for predicting pembrolizumab efficacy in patients with metastatic urothelial carcinoma.
Authors: Kato MInoru , Yamamoto Shoma , Azuma Yukari , Takeyama Yuji , Uchida Junji
Published: January 2024

658

Background: Immune checkpoint inhibitors (ICIs) are crucial for treating metastatic urothelial carcinoma (mUC) patients, yet current prognostic biomarkers fail to predict ICI efficacy. Previous preclinical models have suggested myeloid-derived suppressor cells (MDSCs) as a potential therapeutic target in bladder cancer. This study aims to evaluate the predictive value of blood MDSCs in mUC patients undergoing pembrolizumab treatment. Methods: Ninety-eight mUC patients who progressed with platinum-based chemotherapy at Osaka Metropolitan University received pembrolizumab. Among them, 30 patients were assessed for blood MDSCs. Peripheral blood samples were collected from healthy individuals (n = 6) and mUC patients (n = 30) before pembrolizumab initiation. The mononuclear cell layer was isolated using density gradient centrifugation for MDSC analysis through flow cytometry. Monocytic and polymorphonuclear MDSCs were defined as CD11b+ HLADR – CD33 high CD14 + CD15 – and CD11b+ HLADR – CD33 low CD14 – CD15 +, respectively. The neutrophil-lymphocyte ratio (NLR) in blood served as a control. Treatment response was assessed via CT images using RECICT v1.1. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method, with log-rank test for between-group comparison. Results: First, blood MDSCs were significantly elevated in mUC patients compared to healthy controls (p = 0.0024, Mann Whitney test). Secondly, patients with MDSClow (≤ median, n = 15) had significantly longer PFS than those with MDSChigh (> median, n = 15) (17.6 vs. 1.9 months, p = 0.0126). However, no significant difference was observed in OS. In contrast, when the NLR cutoff was set at 3.5, no significant association was found for PFS and OS. Conclusions: Blood MDSCs show promise as a predictive marker for pembrolizumab therapy efficacy.
Oncologic outcomes of neoadjuvant chemotherapy and lymph node dissection with partial cystectomy for muscle-invasive bladder cancer.
Authors: Antar Ryan Michael , Xu Vincent Eric , Gordon Olivia French , Farag Christian Mark , Azari Sarah , Whalen Michael Joseph
Published: January 2024

698

Background: Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymphadenectomy (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS). Methods: We identified patients with cT2-4N0M0 BCa who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS between PC patients who did and did not receive NAC. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy (≥10 LN yield), and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients. Results: Of 2,832 patients included, 231 (8.1%) patients received multi-agent NAC with PC and had improved median OS compared to those who did not (115.0 vs. 87.4 months, p<0.001). This finding persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10LN. Conversely, age >80, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND (OR=0.634, p<0.001), while NAC was more likely administered to PC patients diagnosed from 2015-2019 (OR=2.177, p=0.022). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR=2.189, p<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR=1.745, p=0.003; OR=2.465, p<0.001, respectively). Conclusions: Despite guidelines, there is an insufficient utilization of NAC and PLND when performing PC. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation. [Table: see text]
Survival and comorbid diabetes mellitus in metastatic hormone-sensitive prostate cancer.
Authors: Baxi Priya , Eaton Daniel B. , Puri Varun , Schoen Martin W.
Published: January 2024

74

Background: Diabetes is increasing in prevalence and management of comorbid disease in cancer is important for outcomes. Comorbid diabetes mellitus in patients with metastatic hormone sensitive prostate cancer (mHSPC) is important to consider as cancer treatments can adversely affect metabolic health and have added interactions with diabetes medicines. Little is known about the comparative effectiveness of diabetes management with insulin or oral medications. We aim to assess the survival of patients with comorbid diabetes based on insulin, oral, or no medication management. Methods: Patients diagnosed with mHSPC from 2000-2021 were identified within the Veterans Health Administration. Uncomplicated or complicated diabetes was determined using Charlson codes from the International Classification of Diseases. Treatment was determined by prescriptions of insulin, oral medication, or no use in VHA prescription records in the year prior, up to 14 days before diagnosis. Kaplan-Meier, ANOVA, and Cox proportional hazard models were used to analyze the data and covariates such as body-mass index, age, race, and baseline PSA. Results: Patients with mHSPC had significant differences in survival with diagnosis of diabetes, see table. Patients with complicated diabetes had a higher mean BMI than patients with uncomplicated diabetes (28.3 vs. 29.1, p <.001). In patients with diabetes (n = 4740), insulin was used in 1091, oral medication in 1833, or no medicines in 1816. Oral diabetes medication was associated with improved survival compared to insulin and no medication use had the lowest survival (26.6 months vs. 24.3 vs. 21.9, p <0.001). In an adjusted multivariable model, both insulin and oral medicine use were associated with increased risk of death with adjusted Hazard Ratio (aHR) for insulin 1.25 (95% CI 1.17-1.35), for oral medicine aHR 1.11 (95% CI 1.05-1.18). Conclusions: Among veterans with mHSPC, diabetes was associated with decreased survival. Within patients with a diagnosis of complicated or uncomplicated diabetes, the use of oral medication was associated with longer survival compared to insulin. Further assessment of the management of comorbid diabetes may help guide treatment and prevent adverse events. [Table: see text]