bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of axitinib in combination with sintilimab as neoadjuvant therapy for patients with locally advanced renal cell carcinoma: A phase II clinical study.
Authors: Huang Yixin , Zhang Zhiling , Zou Xiangpeng ,   Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Published: June 2024

e16534

Background: NCCN, EAU and CUA guidelines recommend radical nephrectomy (RN) for patients with locally advanced renal cell carcinoma (RCC). However, some patients experience complex local invasion, resulting in the difficulty of operation and the high rate of postoperative recurrence. Preoperative neoadjuvant therapy has been shown to reduce tumor volume effectively, consequently increasing the success rate of RN. The objective of this study is to evaluate the effectiveness and safety of combining neoadjuvant Axitinib with sintilimab in these patients. Methods: This is a phase II study to assess the efficacy and safety of neoadjuvant Axitinib combined with sintilimab in RCC patients. Patients diagnosed with locally advanced RCC enrolled in this study received Axitinib (5 mg bid) plus sintilimab (200mg Q3W) until progressive disease or unacceptable toxicity, and then patients will withdraw from the study and explore the option of surgical resection or alternative targeted/immunotherapy. Surgical intervention will be conducted after patients complete four cycles of PD-1 therapy. Results: A total of 12 patients were enrolled in the study. All patients had computerized tomography at screening and after treatment. The median reduction rate of primary tumor volume and active volume in that study were 26.4% and 58.6%, respectively. Stable disease was observed in 10 patients, and partial response was observed in 2 patients and progressive disease was observed in 1 patient. All patients (100.0%) enrolled in the study experienced a treatment-related adverse event (TRAE) of any grade. TRAEs of any grade leading to discontinuation occurred in 2 patients. Only one patient experienced a Grade 3 TRAEs, manifested as increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Only one patient did not undergo RN due to cardiovascular disease. Conclusions: Most of the patients showed a certain degree of tolerance to the medication and underwent RN successfully. But, only a minority of patients can benefit from Axitinib in Combination with Sintilimab in neoadjuvant therapy for locally advanced RCC. The combination of AKI and PD-1 is still a potential choice for preoperative tumor reduction in locally advanced RCC. There is an urgent need to explore a more effective and safe neoadjuvant therapy for these patients.
Cabozantinib tolerability in metastatic renal cell carcinoma: A meta-analysis.
Authors: Farooq Hafsa , Andrzejczyk Anna , Farooq Amna , Wu Shenhong
Published: June 2024

e16546

Background: Cabozantinib, an oral multiple receptor-tyrosine kinase inhibitor, has been used as a single agent or in combination with immunotherapy in the treatment of metastatic renal cell carcinoma, and is associated with discontinuation due to adverse events. We conducted a meta-analysis of clinical trials to evaluate the tolerability of cabozantinib in this setting. Methods: A systematic literature search (from January 2014 to January 2024) was conducted to identify clinical trials of cabozantinib in metastatic renal cell carcinoma. Eligible studies included clinical trials with single‐agent cabozantinib or in combination with chemotherapy/immunotherapy in metastatic renal cell carcinoma reporting treatment discontinuation due to adverse events. Incidence, relative risk and 95% confidence intervals (CI) were calculated by a fixed or random effects model. Results: A total of 2,993 patients from 14 studies were included in the meta‐analysis (cabozantinib group n = 1532, control n = 1404). The summary discontinuation rate for cabozantinib due to adverse events was 13.3% (95% CI: 9.6-18.3%). There was no significant difference between cabozantinib as a single agent and in combination with other agents (P=0.52). No significant difference was identified between clear cell and non-clear cell RCC (P=0.25). When compared with controls, cabozantinib overall has similar discontinuation rate due to adverse events (RR: 0.79, 95% CI: 0.43-1.44, P=0.44). However, cabozantinib has significantly lower discontinuation rate as compared to sunitinib (OR: 0.57, 95% CI: 0.39-0.84, P=0.004). Conclusions: The tolerability of cabozantinib is comparable to other therapies overall, and it may be better tolerated than sunitinib in the treatment of advanced renal cell carcinoma.
Systematic literature review and network meta-analysis of first-line therapies for locally advanced/metastatic urothelial carcinoma.
Authors: Bloudek Lisa , Huang Shirley , Wright Phoebe , Shih Vanessa , Dillon Ryan , Martirosyan Anna , Pandey Rajshree , Williams Troy , Chang Nancy N.
Published: June 2024

e16547

Background: Platinum-based chemotherapy (PBC) has been the standard of care for first-line (1L) locally advanced/metastatic urothelial carcinoma (la/mUC). This systematic literature review (SLR) and network meta-analysis (NMA) analyzed the latest 1L clinical trial data to assess the comparative efficacy of the novel regimen enfortumab vedotin in combination with pembrolizumab (EV+P) against PBC and other approved and investigational 1L regimens for patients with la/mUC. Methods: English language publications (1/2000-10/2023) and congress presentations (1/2015-10/2023) of Phase 2 and 3 clinical trials assessing efficacy and safety of 1L therapies in la/mUC were identified in the SLR. Studies were categorized as: mixed eligibility (cisplatin [cis]-eligible and -ineligible), cis-eligible, and cis-ineligible. An NMA assessed comparative efficacy of EV+P to guideline-recommended therapies and emerging therapies with demonstrated survival benefit. 1L switch maintenance therapies were not included due to differences in study design. Comparative efficacy for overall survival (OS) was assessed under a Bayesian framework assuming constant hazard ratio (HR). Results: The SLR identified 69 unique studies, 2 of which demonstrated survival benefit over PBC (EV-302 and CheckMate-901 substudy). Across all mixed eligibility studies, median OS for PBC ranged from 12.1-16.1 months. Five studies were included in the NMA (3 mixed eligibility, 4 cis-eligible, 3 cis-ineligible). NMA results for the mixed eligibility network showed that EV+P improved OS over all comparator regimens (HR 0.47-0.51; Table). In the cis-eligible network, EV+P subgroup analysis showed improved OS over nivolumab+PBC (HR 0.68 [95% CI 0.47, 0.98]) and PBC (HR 0.53 [95% CI 0.39, 0.72]) and numerically improved OS over ddMVAC (HR 0.76 [95% CI 0.48, 1.20]). In the cis-ineligible network, EV+P subgroup analysis showed improved OS over all comparator regimens (HR range 0.43-0.52). Limitations include few studies contributing to the networks and heterogeneity in patient populations. Conclusions: EV+P is the only regimen shown to improve survival compared with PBC regardless of cisplatin eligibility. This indirect comparison suggests that EV+P has a favorable survival benefit compared with other approved and investigational 1L regimens in patients with previously untreated la/mUC. [Table: see text]
Tislelizumab combined with gemcitabine and cisplatin (GC) as adjuvant therapy in patients with high-risk upper urothelial carcinoma (UTUC) after surgery: A 2-year follow-up, real-world study.
Authors: Quan Penghe , Hou Haozhong , Yang Xiaojian
Published: June 2024

e16548

Background: In China, the prevalence of upper tract urothelial carcinoma (UTUC) among patients (pts) with urothelial carcinoma (UC) ranges from 9.3% to 19.9%, which is higher compared to the 5%-10% observed in Caucasoid populations. Following radical nephroureterectomy (RNU), UTUC pts with high-risk factors (e.g., local , pT3-4a, ypT2-4a, or N+) still have a poor prognosis and require adjuvant therapy. Immune checkpoint inhibitor as adjuvant therapy has been previously demonstrated improved disease-free survival (DFS) for UC pts, but the data from UTUC studies is limited.This real-world study aimed to evaluate the efficacy and safety of tislelizumab (Tisle) plus gemcitabine and cisplatin (GC) in high-risk UTUC pts. Methods: Pts who were diagnosed with T1N1 or T2-T4aN0-1M0 UTUC, tolerated surgery, and had adequate renal function reserve after surgery and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 were retrospectively enrolled from the Department of Urology, Xijing Hospital of Air Force Military Medical University between January 2020 and March 2023. Within 90 days following the RNU surgery, pts received adjuvant therapy of 200 mg Tisle on day 1 every 3 weeks plus 0-6 cycle GC chemotherapy (1000 mg/m2 gemcitabine on days 1 and 8; 70 mg/m2 cisplatin on day 2). Tisle was continued until disease progression or intolerable toxicity. The primary endpoint was 3-year DFS rate. Secondary endpoints were 5-year DFS rate, overall survival (OS), cancer-specific survival (CSS), and safety. Results: A total of 53 pts were enrolled in this study for efficacy evaluation. As of the cut-off date , median follow-up time was 26 (5-46) months, and of the pts were followed up for >24 months. The 2-year DFS rate was 75.56% (95% confidence intervals [CI], 57.87%-86.63%), and the 2-year OS rate was 79.63% (95% CI, 61.50%-89.88%). Compared to GC < 3 cycles, GC ≥ 3 cycles significantly improved DFS (hazard ratio [HR], 0.125; 95% CI, 0.034-0.461; p=0.019) and OS (HR, 0.147; 95% CI, 0.037-0.589; p=0.037), indicating a long tail in survival with the addition of Tisle to GC. Conclusions: In this real-world setting, adjuvant therapy with Tisle plus GC demonstrated encouraging efficacy and well-tolerated safety among high-risk UTUC pts. The final results will reported in further studies.
Costs associated with novel first-line (1L) treatments in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) from a United States (US) Medicare and commercial payer perspective.
Authors: Ike Chiemeka , Kongnakorn Thitima , Tichy Eszter , Sanchez Alvarez Javier , Kearney Mairead
Published: June 2024

e16552

Background: Recent drug approvals in the 1L treatment (tx) setting have expanded options for pts with la/mUC. It is important to understand the economic burden of these novel therapies within the current tx landscape. This study estimated first-year cost of care in the US from a Medicare and commercial payer perspective for pts with la/mUC treated with the following 1L tx: enfortumab vedotin (EV) + pembrolizumab (PEM) in platinum-eligible pts, nivolumab (NIV) + platinum-based chemotherapy (PBC) in cisplatin-eligible pts, and 1L PBC with or without avelumab (AVE) 1L maintenance (1LM). Methods: A cost of care model was developed to estimate direct medical care costs in the first year of tx with EV + PEM, NIV + PBC, and PBC with and without AVE 1LM in pts with la/mUC who are eligible for 1L PBC; pts treated with NIV + PBC were eligible for cisplatin. The latest available costs (2023 USD)—including drug acquisition and administration, disease management, adverse event (AE) management, and subsequent therapy (second-line or later line) costs—were calculated based on tx duration, progression-free survival, overall survival, and AE incidence with various therapies. Efficacy and safety data were sourced from key published trials (EV-302, CheckMate-901, JAVELIN Bladder 100) and product prescribing information. Results: Estimated first-year costs per treated pt are shown in the Table. Cost per treated pt was estimated to range between $56,952 to $438,660 and $90,918 to $457,390 for Medicare and commercial payers, respectively, with the highest cost for EV+PEM and the lowest for PBC only. Drug acquisition costs in the 1L represented the majority of the costs except PBC, for which subsequent tx and administration costs represented the largest cost component. Conclusions: Costs per treated pt were lower for PBC with AVE 1LM than for EV+PEM and NIV+PBC. As value-based oncology care is becoming increasingly important in the US, comprehensive understanding of costs across different tx options and sequences can facilitate informed tx choice. [Table: see text]
Treatment and outcomes of bladder cancer in Armenia.
Authors: Bardakhchyan Samvel , Gharadaghyan Hovsep , Zohrabyan Davit , Safaryan Liana , Avagyan Armen , Harutyunyan Lilit , Sargsyan Amalya , Mailyan Mariam , Harutyunyan Martin , Rushanyan Marine , Mkrtchyan Gohar , Karapetyan Nune , Mkhitaryan Sergo , Arakelyan Jemma
Published: June 2024

e16574

Background: Bladder cancer is the fifth most common cancer by incidence in Armenia with around 450 new cases diagnosed every year. Methods: For this retrospective hospital-based study we have collected data from three main oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. Data of patients with bladder cancer who were treated at these three centers during 01/Jan/2010 - 01/Jan/2023 period was collected from the medical records. Statistical analysis was conducted by 01/Nov/2023. Results: Eighty-seven patients with bladder cancer treated during mentioned period in these three hospitals were included in the final analysis. Male to female ratio was 8.6:1. 70% of patients were smokers. Median age at diagnosis was 65 years (range 37-82 years). 5.7% of patients had stage I, 17.2% stage II, 47.1% stage III, 25.3% stage IV bladder cancer, and for 4.6% of patients' stage was unknown. 9.2% of patients had grade 1, 18.4% grade 2 and 60.9% grade 3 tumors. Among stage IV patients the most common metastasis sites were lungs (36.4%), followed by non-regional lymph nodes (31.8%). Median overall survival (OS) was 31 months for the entire cohort. Median OS was 31 months for stage I, 62 months for stage II, 40 months for stage III and 14 months for stage IV patients. While OS for non-metastatic bladder cancer was higher than for metastatic stage, this difference was not statistically significant (39 vs 14 months; p=0,088). About 61% of patients received 1st line chemotherapy with Cisplatin and 33.3% with Carboplatin. Only 9% of patients received immunotherapy during their course of treatment. In non-metastatic setting median OS was significantly better for those treated with Cisplatin containing regimens, compared with those treated with Carboplatin containing regimens (40 vs 23 months; p=0,021), while in stage IV this difference was not statistically significant (30 vs 14 months; p=0,269). Conclusions: Bladder cancer is one of the most common cancers in Armenia. Treatment with Cisplatin in non-metastatic patients was associated with better OS compared with Carboplatin. Patients diagnosed in metastatic setting have really poor prognosis with median OS slightly surpassing 1 year. While new treatment modalities with immunotherapy and targeted therapy are showing promising results worldwide, they are not widely available in Armenia.
Tumor immune microenvironment analysis and MRI results of a phase II trial investigating tislelizumab (T) in the neoadjuvant treatment of high-risk upper tract urothelial carcinoma (UTUC).
Authors: Huang Jiwei , Cai Xinyun , Ng Cheoklong , Luo Yuansheng , Wang Zaoyu , Kong Wen , Zhang Jin , Chen Yonghui , Wu Guangyu , Chen Haige , Xue Wei
Published: June 2024

e16582

Background: Although PD-1/L1 checkpoint inhibitors have shown promising efficacy results in the neoadjuvant treatment of urothelial carcinoma, part of patients may have disease progression during the treatment. Up to now, there is no definitive biomarker to predict the response of neoadjuvant immunotherapy. We have formerly reported the preliminary results of T, a PD-1 checkpoint inhibitor, in the neoadjuvant treatment of UTUC. Herein, we report the tumor immune microenvironment analysis and contrast-enhanced MRI results to explore possible pathological and radiological characteristics in correlation with treatment response. Methods: Patients were given T 200mg IV every 3 weeks for at most 4 cycles followed by surgery (radical nephroureterectomy, ureteral resection or endoscopic ablation). The primary endpoint was pCR rate (ypT0N0). The secondary endpoints included pathological response rate (≤ypT1N0), objective response rate and safety. Contrast-enhanced MRI examination was performed before the third dose and another before the surgery and the apparent diffusion coefficient(ADC) was calculated. The infiltrating immune cells pattern within tumor microenvironment was analyzed using multiplexed immunofluorescence (mIF) staining on pretreatment samples. Results: Between Mar 2021 and Sep 2022, 16 patients were enrolled. 4 patients (25%) patients achieved pCR and 7 patients (43.8%) were re-staged as ≤ypT1N0 at specimens. Best of response was cPR in 6 patients, cSD in 7 patients and cPD in 3 patients. The density of PD-L1+CD68+ cells in the stromal region was significantly higher in cPR patients compared to cSD or cPD patients before neoadjuvant treatment (p=0.002). Additionally, the density of PD-1+CD8+ cells in the stromal region of cPR patients was also higher, although the significance was borderline (p=0.065). The average value of ADC showed no statistically significant difference between cPR patients and cSD or cPD patients (p=0.997). However, a significant higher entropy of ADC was found in cPR patients compared with cSD or cPD patients (p=0.002). Conclusions: The elevated ADC entropy on MRI and the enrichment of PD-L1+CD68+ cells within tumor microenvironment before treatment were observed in cPR patients. Both characteristics might help to identify UTUC patients who can benefit from neoadjuvant immune therapy. Clinical trial information: NCT04672330 .
Nimotuzumab, a novel anti-EGFR with concurrent chemoradiotherapy in muscle invasive bladder cancer: A real-world experience from India.
Authors: Rawat Shyam , Jain Rajesh
Published: June 2024

e16592

Background: Muscle invasive bladder cancer (MIBC) shows 55-75% EGFR overexpression. Radical cystectomy (RC) with/without neoadjuvant chemotherapy is mainstay of treatment. Targeting with anti-EGFR therapy would be potential treatment option to preserve the organ in MIBC. Methods: Evaluation of medical records of patients with transitional cell carcinoma of urinary bladder who received concurrent cisplatin (40 mg/m2) and radiotherapy (60 Gy) (CRT) with Nimotuzumab (200 mg) between 2012 and 2020 was done with prior consent of patients. Results: Medical records of 21 patients were analyzed of which 86% of male with average age of 64.6 years. Tobacco addiction was reported in 76% patients. Eighty-six percent of patients had locally advanced disease, of which 71% with grade III lesions. Treatment with CRT + Nimotuzumab was completed by all patients. Objective response rate was 100% (complete response 95% and partial response 5%) at 6-months post treatment. At the of follow-up was 59 months median overall survival (OS) and disease-free survival (DFS) was not reached. OS and DFS rates at 3-years were 100% and 90.4% respectively. Only two RC were performed subjecting to 90% organ preservation rate. There were no grade 3 or 4 adverse events, however grade 1-2 AEs Included neutropenia (28%), loose motion (76%) and skin reactions (47%). Conclusions: Concurrent CRT with Nimotuzumab could be a possible treatment option for organ preservation with improved outcomes and tolerable safety profile in patients with MIBC, and it can be evaluated further. Keywords: bladder cancer, MIBC, organ preservation, nimotuzumab, chemoradiation. Acknowledgment: We thank you Dr. Amit Y Jadhav for editorial support for this research project.
Effect of patient-derived tumor-like cell clusters on personalized medicine of patients with non-muscle invasive bladder cancer.
Authors: Xi Jianzhong , Yin Shenyi , He Yang , Ye Buqing
Published: June 2024

e16610

Background: Non-muscle invasive bladder cancer (NMIBC) has a high recurrence and progression rate, and the intravesical instillation chemotherapy drugs is diverse. To optimize patient prognosis, patient-derived tumor-like cell clusters (PTC) for drug testing seeks to identify an effective drug for individual patient. Methods: A prospective, single-center, parallel-group, randomized phase II clinical trial was conducted from December 2020 to December 2023 in Department of Urology of the Second Hospital of Tianjin Medical University (ClinicalTrials.gov: ChiCTR2000040996). This study enrolled a total of 120 patients who had been diagnosed as NMIBC. Patients who met the inclusion and exclusion criteria were randomly assigned to either the control group or the PTC drug-screening group. In the control group, chemotherapy drugs (gemcitabine, pirarubicin, epirubicin and hydroxycamptothecin) were selected for intravesical instillation according to the doctor's experience. In the PTC group, chemotherapy drugs were administered according to PTC drug screening results. Results: The PTC group was associated with significantly lower 1-year Relapse-Free Survival (RFS) rate (10.0 %; 95% CI, 2.4%-17.6%,) compared with the control (31.7%; 95% CI, 19.9%-43.4%), (HR=0.2264; 95% CI, 0.0845-0.6068; p = 0.0013). Similarly, the PTC group was associated with significantly lower 2-year RFS rate (18.3%; 95% CI, 8.5%-28.1%) compared with the control (48.3%; 95% CI, 35.7%-61.0%), (HR=0.3730; 95% CI, 0.1756-0.792; p = 0.0075). Conclusions: PTC drug screening significantly reduced the recurrence rate of postoperative NMIBC. Clinical trial information: ChiCTR2000040996 .
Clinical characteristics, oncologic outcome, and survival in patients with urothelial cancer with pure and partial squamous cell differentiation.
Authors: Brandt Maximilian Peter Johannes Karl , Lache Nina , Duwe Gregor , Fischer Nikita , Frey Lisa Johanna , Haferkamp Axel
Published: June 2024

e16612

Background: In bladder cancer (BC) patients, pure (SCC) and partial (PSCC) squamous cell carcinomas belong to the most common histologic subtypes with approximately 5% of cases. They are highly aggressive and curative treatment in a local disease stage is typically radical cystectomy (RC). In case of tumor progression or metastatic disease, only limited data on the optimal treatment algorithm and its efficacy exists. In this study, we present clinical characteristics and oncologic outcome in a large patient cohort of SCC and PSCC. Methods: Between 2003 and 2021, we extracted data from patients with SCC and PSCC histology who received RC due to invasive bladder cancer. Clinical characteristics, treatment patterns, progression free- and overall survival were the primary outcome parameters. Kaplan-Meier curves were calculated for PFS and OS and a log rank test was applied to compare survival curves. Results: Overall, 770 patients were screened of which 26 men and 28 women with a mean age of 68.4 (SD 11.7) and 67.9 years (SD 14) years were identified. Twenty-three patients had SCC and 31 PSCC. No neo-adjuvant treatment was applied compared to 16 adjuvant chemotherapy regimens. Urinary diversion was ileal-conduit in 30 cases, Mainz-pouch in nine, ureterocutaneostomy in eleven, ileal neo-bladder in three and transverse conduit of the colon in one patient. The mean number of extirpated lymphnodes were 22.8 (SD 17.7) with a mean positivity of three (SD 8.3) lymphnodes. Mean follow-up was 11.5 months with a PFS of 5.9 and 8.7 mo. and OS of 13.3 mo. (SD 12.2) and 7.5 (SD 7.8) in men and women, respectively. There was no statistically significant survival difference for men and women as well as SCC and PSCC. Conclusions: This contemporary data demonstrated the aggressive nature of SCC of the bladder with IC being the most common urinary diversion. Compared to data from transitional cell carcinoma, PFS and OS was shorter and application of adjuvant Cx was overall low. Structured novel treatment modalities are urgently needed in this highly aggressive bladder cancer population.
Artificial intelligence and identifying prognostic patterns in upper tract urothelical carcinoma (UTUC).
Authors: Staehler Michael , Ivanova Troja , Blajan Iulia , Aydogdu Can , Graser Annabel , Hofmann Marina , Schulz Gerald Bastian
Published: June 2024

e16616

Background: Artificial intelligence tools (AI) are increasingly used in all scientific fields. UTUC is rare form of kidney cancer and prognostic factors seem unclear. We sought to understand if AI could help identify prognostic parameters for overall survival in UTUC and aid in the development of a prognostic score. Methods: n=231 consecutive patients who underwent surgery for UTUC between 2005 and 2020 were included. De-personalized data included were age, gender, ECOG performance status, smoking habits, baseline creatinine and platelets, histology, laterality, pathological and clinical T-stage, grading, cis, TNM stage, necrosis, lymphovascular invasion, vascular invasion, resection margin, tumor size, duration of surgery, surgeon, surgical approach, blood loss, complications (graded by Clavien-Dindo), complete removal of the ureter including bladder cuff, duration until recurrence and duration until death and reason of death. Several publicly accessible AI tools (chatGPT, Tableau, Julius AI, Microsoft Power BI, Polymer) were asked to first identify prognostic parameters and develop a prognostic score for RCC outcome. Statistical analysis was done using chi-square test, cox regression and Kaplan-Meier survival estimation. AI was asked to analyze the data set based on Kaplan-Meier survival analysis and cox proportional log rank testing was performed to estimate score accuracy. Results: Median age was 70.9 years (43.7-81.8). 61% (n=160) were male. ECOG performance stats was 0 in 42.1% (n=82), 1 in 27.2% (n=52). 53.6% (n=105) were non-smoker and 24.5% (n=48) smoker and 21.9% (n=43) were former smokers. 10.3% (n=12) had synchronous bladder cancer. 60.4% (n=131) suffered from gross hematuria and 19.7% (n=42) had flank pain. Median follow-up was 34.5 months (0-174). Median overall survival (OS) was 58.9 months (95% CI 46.2-71.5). Bellmunt risk factors, BMI and baseline creatine and CRP levels correlated significantly with adverse overall survival (p>0.001). Tumors localized in the ureter, larger than 5cm, carcinoma in situ and high grade had a significant worse OS. Resecting a bladder cuff improved OS to 86.7 months (95% CI 65-108.4) compared to 39.9 months (95% CI 27.9-51.9, p=0.012) without. AI revealed ECOG performance status, nodal status, grade, surgical expertise and resecting a bladder cuff to be prognostic factors and did not identify conventional prognostic factors to be relevant for a scoring system to predict OS and PFS. Conclusions: AI can help identify parameters to predict overall survival outcomes in patients with UTUC based on clinical factors. Human adjustment still is necessary. Interestingly, surgeon, complete resection of the ureter including a bladder cuff are factors that can be influenced and should be considered in future evaluations of prognostic models besides tumor characteristics like histology, grading and nodal status that can’t be medically influenced.
Racial and gender disparities in the incidence of bladder cancer: A nationwide analysis.
Authors: Li Vivian , Javaid Saad , Frasier Kelly , Vinagolu-Baur Julia , Ortega Yaguachi Nataly , Rodriguez Evadne , Del Castillo Olivia , Batista Raquel , Jonas Kenlee , Palma Laura
Published: June 2024

e16623

Background: Several studies have been conducted to examine racial and gender disparities in various common malignancies. However, there remains a notable lack of comprehensive data addressing ethnic and gender disparities, specifically in relation to patients with Bladder cancer. This study sought to evaluate these disparities and their potential impact on the risk of developing bladder cancer. Methods: Using the National Inpatient Sample 2020, we identified patients diagnosed with Bladder cancer as their primary condition (local/regional and advanced metastatic).We analyzed disparities in the baseline characteristics, including age, gender, insurance status, income, comorbidities, and the risk associated with Bladder cancer. We utilized a log Binomial regression model to determine the risk ratios after adjusting for any confounding variables. Results: A total of 6,471,165 patients were analyzed, and it was found that 24,400 of them (0.4%) had bladder cancer. Among these patients, 76% were male, and 23% were female, p<0.001.The mean age of patients with and without Bladder cancer was 72(SD +/- 11.39) vs. 49(SD+/- 27.18) years, respectively, p<0.001. Female patients demonstrated a lower risk of developing bladder cancer than males (RR=0.31(0.24-0.27); p<0.001). Compared to white females, white and black males exhibited an increased risk of bladder cancer (RR=3.45(3.20-3.73); p<0.001 and RR=1.71(1.48-1.98); p<0.001, respectively). Hispanic males also showed an increased risk (RR=2.20(1.88-2.58); p<0.001), while Hispanic females demonstrated a decreased risk (RR=0.72(0.56-0.94); p=0.016). Males of other races had a higher risk of bladder cancer (RR=2.95(2.36-3.70); p<0.001), and no significant difference was observed in the risk of bladder cancer in Asian males and females (RR=1.39(0.66-2.92); p=0.384 and RR=0.83(0.34-2.01); p=0.694, respectively). The risk of bladder cancer increased with age (36-45: RR=4.45(2.21-8.96),p<0.001,46-64: RR=10.94(5.67-21.12),p<0.001, >65: RR =21.02(10.87-40.63), p<0.001). Conclusions: Disparities in healthcare access and understanding of specific challenges faced by high-risk groups deeply impact patients with bladder cancer. Gaining a deeper knowledge of these disparities can better support this vulnerable patient population and illuminate effective preventive measures for reducing the incidence of bladder cancer among high-risk demographic segments.
Hospital related outcomes of acute kidney injury in patients with bladder cancer: A nationwide inpatient study.
Authors: Vinagolu-Baur Julia , Javaid Saad , Frasier Kelly , Li Vivian , Ortega Yaguachi Nataly , Rodriguez Evadne , Del Castillo Olivia , Batista Raquel , Jonas Kenlee , Palma Laura
Published: June 2024

e16624

Background: Bladder cancer is the most common urinary tract cancer and is associated with a high risk of acute kidney injury(AKI). However, there is a lack of Nationwide data on bladder cancer concerning acute kidney injury. We studied the impact of AKI on bladder cancer and the predictors of these adverse outcomes. Methods: The National Inpatient Sample for the years 2017-2020 was employed to identify patients with a primary diagnosis of bladder cancer (local/regional and advanced metastatic), and they were stratified into two cohorts with and without acute kidney injury (AKI). We calculated mortality as the primary outcome and other factors such as hospital stay, cost, sepsis, and respiratory failure as secondary outcomes using multivariate regression analysis after adjusting for confounding factors. Results: A total of 102485 patients had Bladder cancer, among which 30345 had AKI. The mean age of patients with and without AKI was 74.02 vs 71.36 years, respectively (p<0.004). After adjusting for confounding variables, patients with AKI had higher odds of mortality (OR=2.7(2.06-3.54); p<0.001). Length of stay and total hospitalization cost was also significantly increased in patients with concurrent AKI (+2.5 days(2.25-2.76) and + $ 25924(21831-30017); p<0.001, respectively). Similarly, bladder cancer patients with AKI had an increased likelihood of Fluid and electrolyte disorders (OR=3.99(3.70-4.30); p<0.001), Acute respiratory failure (OR=3.65(3.09-4.32); p<0.001), Cardiac arrest (OR=4.32(2.62-7.10);p<0.001), Sepsis (OR=6.52(5.38-7.92);p <0.001), Intensive care unit admission (OR=3.19(2.73-3.73);p<0.001), Invasive mechanical ventilation (OR=3.35(2.76-4.07); p<0.001), Vasopressor use (OR=2.83(2.07-3.86);p<0.001), Pneumonia (OR=2.04(1.61-2.57); p<0.001) and constipation (OR=1.91(1.70-2.15), p<0.001). Conclusions: Our study concluded that AKI in bladder cancer patients was associated with more than twofold increased odds of mortality. The presence of AKI also leads to increased length of stay in the hospitals and increased healthcare resource utilization. Careful evaluation and prompt intervention in acute kidney injury patients can significantly improve outcomes and reduce mortality rates in individuals with bladder cancer. These proactive measures enhance patient survival and improve the quality of life with treatment. [Table: see text]
Avoiding unnecessary biopsy: Development of a predictive calculator to identify non-prostate cancer in patients with Prostate Imaging Reporting and Data System category ≥ 4 lesions.
Authors: Zeng Hong , Chen Yuntian , Xie Yandong , Dai Jindong , Wang Minghao , Wang Qian , Xu Nanwei , Chen Junru , Sun Guangxi , Zhao Jinge , Zeng Hao , Shen Pengfei
Published: June 2024

e17094

Background: The application of the Prostate Imaging Reporting and Data System (PI-RADS) has accelerated the use and promotion of multi-parameter magnetic resonance imaging (mpMRI) in prostate cancer (PCa) detection. Despite the high PCa detection rate, a considerable proportion of PI-RADS category 4 and 5 lesions are benign. The primary goal of this study is to develop and validate a prediction model for non-prostate cancer (non-PCa) in biopsy-naive patients with PI-RADS category ≥ 4 lesions. Methods: We retrospectively collected patients with PI-RADS category 4 or 5 lesions who underwent transperineal biopsies at West China Hospital from January 2018 to December 2022. Cases with prostate-specific antigen (PSA) > 20 ng/ml, PCa away from the area of the index lesion, and > 3 months from mpMRI to prostate biopsy were excluded. The included patients were randomly divided into a training cohort (70%) and a validation cohort (30%) for building and validating the prediction model, respectively. Logistic regression was used to screen independent predictors of non-PCa, and a nomogram was drawn based on the regression coefficients of the prediction model. The discrimination and calibration were assessed by the C-index and the calibration plots, respectively, the latter being quantified by the Brier score. Decision curve analysis (DCA) and clinical impact curve (CIC) were applied to measure the clinical net benefit. Results: A total of 1580 patients were included and the prevalence of non-PCa was 40.1%. Five independent predictors of non-PCa were incorporated into the optimal model, including age, prostate volume (PV), prostate-specific antigen density (PSAD), apparent diffusion coefficient (ADC) values, and lesion zone. The C-index was 0.925 (95%CI, 0.910-0.939) and 0.931 (95%CI, 0.910-0.953) in the training cohort and validation cohort, respectively. Favorable agreement was exhibited from the calibration curve, with a Brier score of 0.104. The DCA demonstrated an increased net benefit of the nomogram over a wide range of threshold probabilities compared to biopsy-free-all or biopsy-free-none strategy. At biopsy-free thresholds of 60%, 70%, and 80%, the nomogram was able to avoid 74.0%, 65.8%, and 55.6% unnecessary biopsies against 9.0%, 5.0%, and 3.6% of missed PCa (or 35.9%, 30.2%, and 25.1% men forewent biopsies, respectively). Conclusions: We developed the first five-item predictive model based on quantitative ADC and PSAD in patients with PI-RADS category ≥ 4 lesions. In a risk-averse scenario, the strategy may safely identify non-PCa to support clinical decision-making and reduce unnecessary prostate biopsies. [Table: see text]
Management outcomes of localized low-risk prostate cancer: A population-based study.
Authors: Mao Shifeng S. , Yin Yue , Wegner Rodney E. , Sanguino Ramirez Angela M , Lyne John , Miller Ralph , Cohen Jeffrey , Samiei Arash
Published: June 2024

e17096

Background: Optimal management of patients with low-risk prostate cancer (LRPC) remains a topic of debate. While active surveillance (AS) is an increasingly popular option, definitive local treatments, including radical prostatectomy (RP), external beam radiotherapy (EBRT), and prostate seed implantation (PSI), are also commonly used. This study assessed the treatment outcomes of patients with LRPC using a large patient population from the National Cancer Database (NCDB). Methods: We analyzed data from 195,452 patients diagnosed with LRPC between 2004 and 2015 using NCDB. Patients were classified based on their treatment modalities, including RP, EBRT, PSI, or no local therapy (NLT). Only patients with Charlson-Deyo comorbidity scores of 0 or 1 were included. Propensity score analysis was used to balance the treatment groups, and the accelerated failure time model was used to analyze the survival rates of the treatment groups. Results: After a median follow-up of 70.8 months, 24,545 deaths occurred, resulting in an all-cause mortality rate of 13%. Compared to NLT, RP significantly improved overall survival by 47% (1.47, p < .0001), 34% (1.34, p < .0001), 27% (1.27, p < .0001), and 10% (1.10, p = .0002) in the age groups < 60, 60-64, 65-69, and 70-74, respectively. However, the benefit of RP decreased with advancing age, leading to an 11% decrease in survival (0.89, p < .0001) in men aged ≥ 75 years. In contrast, EBRT did not improve overall survival in younger age groups; rather, it decreased survival by 11% (0.89, p = .0020) and 9% (0.91, p = .0111) in patients aged < 60 and 60-64, respectively. However, EBRT significantly improved overall survival in older patients by 6% (1.06, p = .0160) and 27% (1.27, p < .0001) for those aged 70-74 and over 75 years, respectively. Similarly, PSI did not improve overall survival in age groups younger than 64 years but exhibited significant overall survival benefits of 6% (1.06, p = .0242), 11% (1.11, p <.0001), and 34% (1.34, p < .0001) compared to NLT in age groups of 65-69, 70-74, and over 75, respectively. Conclusions: RP improves overall survival in patients with LRPC, especially in younger patients. EBRT and PSI primarily benefit older patients. NLT is a reasonable choice, particularly in younger patients when RP is not chosen. The study is hypothesis-generating and limited by the non-randomized, retrospective, and inherited nature of the NCDB data, which does not provide information regarding patients’ symptoms, sexual function, and disease-specific survival.
Radical prostatectomy versus XRT for early-stage prostate cancer: A retrospective, propensity-matched cohort study of 29,970 patients.
Authors: Salimath Varada , Mackey James David , Miles Brittany , Mehta Ankit
Published: June 2024

e17099

Background: Both radical prostatectomy and external beam radiation therapy (XRT) are standard therapeutic options for definitive treatment of early-stage prostate cancer. While both modalities are generally viewed as comparable when matched for risk stratification, there is a paucity of literature directly comparing their outcomes. Slow-growing malignancies are generally regarded as less radiation-sensitive, but this has not been conclusively proven in prostate cancer. Aggressive variants of prostate cancer have, however, been shown to have higher rates of radiation-resistance. Here, we present a retrospective database analysis comparing rates of bone metastases and mortality among early-stage prostate cancer patients treated with radical prostatectomy versus XRT. Methods: The TriNetX research network was used for this study, with patient cohorts created by the use of International Classification of Disease 10 (ICD-10) codes and Current Procedural Terminology (CPT) codes. Both cohorts consisted of men over age 50 with a diagnosis of prostate cancer (C61) and PSA levels below 10 ng/mL. One cohort was treated with surgical prostatectomy (1014183 or 55866), while the other underwent Intensity Modulated Radiation Treatment (77385 or 77386). The cohorts were balanced for age, race, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm, resulting in 14,985 patients in each arm. The cohorts were then evaluated for the development of bone metastases (C79.51) and mortality at five years. Results: Patients treated with prostatectomy were less likely to develop bone metastases within five years (3.4% vs 7.6%, RR 0.45, 95% CI (0.41,0.50), P value <0.0001). Prostatectomy was also associated with lower five-year mortality (4.2% vs 7.9%, RR 0.53, 95% CI (0.48,0.58), P value <0.0001). Conclusions: These results indicate that in early-stage prostate cancer, radical prostatectomy is associated with decreased rates of mortality and bone metastases within a 5-year period compared to XRT. Additional studies are needed to determine which prostate cancer variants are at increased risk of radiation treatment failure. Shared decision making regarding both outcomes and side effects is crucial when choosing a modality of definitive treatment in early-stage prostate cancer.
Rectal spacer in radiotherapy for prostate cancer: Correlation of spacer symmetry to rectal dosimetry.
Authors: Charas Tomer , Ben Dor Yossi , Bakouche Veronique , Billan Salem
Published: June 2024

e17102

Background: Rectal spacers are used to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer, and to limit the exposure of the rectum to excessive radiation. These spacers use different insertion techniques and filling materials. Our study aims to compare and correlate the symmetry and rectal dosimetry in patients implanted with either the balloon spacer (BioProtect Balloon Implant System) or a gel spacer (SpaceOAR). Methods: A qualitative model utilizing measurements of prostate-rectal interspace from axial computed tomography scans was applied to assess 62 T1c-T4 prostate cancer patients (28 balloon, 34 gel spacer) undergoing SBRT (5/6 fractions, 36-40 Gy) or IMRT (20/28 fractions, 60-70 Gy). Spacer symmetry at midgland, 1 cm superior or inferior to midgland was scored as ‘S’. Asymmetrical placement (1 or 2cm lateral left or right) was scored as 1 or 2. Axial slices with no spacer was scored as 0. A total symmetry score (SYM) was evaluated by using a scoring of SYM-S indicating spacer symmetry in all 3 slices and scores ranging 1-to-4 representing increasing spacer asymmetry. SYM score was then evaluated relatively to rectal dosimetry at V60%-V100%. Results: For balloon and gel spacers, symmetrical distribution at midline, at 1 cm inferior and superior to midgland was observed in 16 (57.1%) and 18 (52.9%) patients, 16 (57.1%) and 15 (44.1%) patients, 10 (35.7%) and 12 (35.3%) patients, respectively. The balloon was not visible in 3 (10.7%) superior slices compared to 3 (8.8%) inferior and 6 (17.6%) superior gel spacer slices, receiving score 0. The mean rectal dose for the balloon spacer compared to the gel spacer was 9.8 and 12.9 for V60%, 5.6 and 7.9 for V70%, 3.1 and 4.5 for V80%, 1.5 and 2.0 for V90% and 0.12 and 0.17 for 100% respectively. The study results show that as the spacers became more asymmetric, the rectal dose-volume at V60%-V100% increased. Conclusions: The balloon provides a better symmetrical distribution and lower dose to the rectum compared to the gel. The potential advantages of the balloon should be further evaluated in a prospective setting.
In-hospital outcomes of patients with ovarian cancer and venous thromboembolism: A Nationwide Inpatient Sample analysis.
Authors: Gaddam Mrunanjali , Iqbal Rabia , Jayakumar Jayalekshmi , Ginjupalli Manasa , Sanghvi Ankushi , Nanavaty Dhairya , Sanka Sujana , Sekandlapuram Rohit , Thanneeru Priya , Hotwani Priya , Kumar Vikash , Koifman Michelle , Sinha Samridhi , Colon Ramos Ana , Clement Jincy
Published: June 2024

e17576

Background: Ovarian Cancer is one of the most common gynecological cancers. It has 5-year relative survival of 50.8 %. Around 12700 people die from this cancer each year, and it ranks fifth in cancer death among women. Studies have shown a strong association of ovarian cancer with venous thromboembolism (VTE) which includes deep venous thrombosis (DVT) and Pulmonary Embolism (PE). However, data surrounding outcomes associated with VTE in this population is limited. We aim to estimate the effect of VTE on mortality and healthcare utilization in this population. Methods: We queried the National Inpatient Sample (NIS) 2018-2020 to collect data for all adult hospitalizations >18 years with a diagnosis of ovarian cancer using appropriate ICD 10 codes. These hospitalizations were further classified into hospitalizations with and without DVT and PE. Multivariate regression analysis was performed to study the impact of DVT/PE taking mortality as the primary outcome and total cost and length of hospital stay (LOS) as secondary outcomes in the subpopulation of ovarian cancer hospitalizations. Results: There were a total of 298085 adult hospitalizations with a diagnosis of ovarian cancer with a mean age of 63 years. Among hospitalizations with ovarian cancer, acute DVT was found in 2.75% and acute PE was present in 4.5 %. In these hospitalizations, in-patient mortality was 9.3% in those with either DVT or PE. Multivariate regression analysis revealed that among adults, hospitalizations with ovarian cancer had higher odds of Acute DVT [OR 3.5, P<0.01] and Acute PE [OR 3.76, P<0.01] than those without. The odds of all-cause mortality from VTE [OR 2.18, P<0.01] were significantly higher in patients with ovarian cancer than those without. The total cost of hospital stay was 26211 $ ($22183 - $30238, p<0.01) higher and LOS was 1.67 times higher (1.2 - 2.32; P<0.01) when patients with ovarian cancer developed VTE (Table). Conclusions: Our study concludes that ovarian cancer patients who develop VTE tend to have worse outcomes in terms of mortality. Length of hospital stay and total hospital charge are also increased in patients developing VTE, thereby increasing healthcare utilization. This highlights the importance of having larger-scale studies in the future to assess outcomes in ovarian cancer patients with VTE and the need to formulate risk assessment models for the role of primary thromboprophylaxis. Adjusted analysis showing odds ratio of mortality, total hospital charge and LOS in ovarian cancer hospitalizations. [Table: see text]