Treatment Of Muscle-invasive Bladder Cancer Research Articles

Prognostic Impact of CD36 Immunohistochemical Expression in Patients with Muscle-Invasive Bladder Cancer Treated with Cystectomy and Adjuvant Chemotherapy.

Neoadjuvant chemotherapy followed by a cystectomy is the standard treatment in muscle-invasive bladder cancer (MIBC). However, the role of chemotherapy in the adjuvant setting remains controversial, and therefore new prognostic and predictive biomarkers are needed to improve the selection of MIBC patients. While lipid metabolism has been related to several biological processes in many tumours, including bladder cancer, no metabolic biomarkers have been identified as prognostic in routine clinical practice. In this multicentre, retrospective study of 198 patients treated with cystectomy followed by platinum-based adjuvant chemotherapy, we analysed the immunohistochemical expression of CD36 and correlated our findings with clinicopathological characteristics and survival. CD36 immunostaining was positive in 30 patients (15%) and associated with more advanced pathologic stages (pT3b-T4; p = 0.015). Moreover, a trend toward lymph node involvement in CD36-positive tumours, especially in earlier disease stages (pT1-T3; p = 0.101), was also observed. Among patients with tumour progression during the first 12 months after cystectomy, disease-free survival was shorter in CD36-positive tumours than in those CD36-negative (6.51 months (95% CI 5.05–7.96) vs. 8.74 months (95% CI 8.16–9.32); p = 0.049). Our results suggest an association between CD36 immunopositivity and more aggressive features of MIBC and lead us to suggest that CD36 could well be a useful prognostic marker in MIBC.

Frontiers in Non-metastatic, Muscle-invasive Bladder Cancer

The treatment landscape of bladder cancer is rapidly changing, with the introduction of novel therapies such as immune checkpoint inhibitors (ICIs), targeted therapies and antibody–drug conjugates. While most of the initial developments were in the treatment of metastatic disease, several recent advances have been made in the treatment of non-metastatic muscle-invasive disease. ICIs have demonstrated a role in the adjuvant treatment of muscle-invasive bladder cancer and on-going studies are poised to better elucidate that role. Multiple studies are also investigating a role for ICIs as monotherapy or in combination with other treatments in the neoadjuvant treatment of urothelial cancer. There are also on-going studies exploring novel approaches to bladder preservation in patients with muscle-invasive bladder cancer.

Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer

BackgroundPatients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC. ObjectiveTo investigate factors associated with the development of advanced CKD following radical cystectomy. Design, setting, and participantsUsing national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018. Outcome measurements and statistical analysisWe examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of <30 ml/min/1.73 m2) after radical cystectomy using multivariable logistic and proportional hazard regression, with and without consideration of competing risks. We examined survival using Kaplan-Meier product limit estimates and proportional hazard regression. Results and limitationsThe median age at surgery was 67 yr and the mean preoperative eGFR was 69.1 ± 20.3 ml/min/1.73 m2. Approximately three out of ten patients (n = 962, 29%) progressed to advanced CKD within 12 mo. Older age (hazard ratio [HR] per 5-yr increase 1.15, 95% confidence interval [CI] 1.10–1.20), preoperative hydronephrosis (HR 1.50, 95% CI 1.29–1.76), adjuvant chemotherapy (HR 1.19, 95% CI 1.00–1.41), higher comorbidity index (HR 1.13, 95% CI 1.11–1.16 per point), and lower baseline kidney function (HR 0.75, 95% CI 0.73–0.78) were associated with the development of advanced CKD. Baseline kidney function at the time of surgery was associated with survival. Generalizability is limited due to the predominantly male cohort. ConclusionsImpaired kidney function at baseline is associated with progression to advanced CKD and mortality after radical cystectomy. Preoperative kidney function should be incorporated into risk stratification algorithms for patients undergoing radical cystectomy. Patient summaryImpaired kidney function at baseline is associated with progression to advanced chronic kidney disease and mortality after radical cystectomy.

High ORAI3 expression correlates with good prognosis in human muscle-invasive bladder cancer

The involvement of store-operated calcium channels (SOCCs) in tumor initiation and metastatic dissemination has been extensively studied, but how its member ORAI3 influences tumor progression is still elusive. The present study aimed to evaluate the prognostic value of ORAI3 expression and examine the correlation between ORAI3 expression and immune cell infiltration within the tumor microenvironment (TME) in human muscle-invasive bladder cancer (MIBC). We examined the expression profile of ORAI3 in MIBC using data from two databases; analyzed the correlation between ORAI3 expression and patient survival; explored cellular pathways related to ORAI3 expression by Gene Set Enrichment Analysis (GSEA); and predicted potential drugs using Connectivity Map (CMap). ORAI3 was significantly lower expressed in tumor mass compared to normal samples in MIBC, with a higher level of methylation at the promoter region in tumor than in normal tissue, indicating that ORAI3 is suppressed during cancer progression. Survival analysis showed that higher expression of ORAI3 correlated with good prognosis in MIBC. GSEA demonstrated that ORAI3 expression inversely correlated with cell differentiation, development and gene silencing, with differential expression of genes involved in epidermal and keratinocyte differentiation pathways and inflammatory responses. RNA sequencing of an ORAI3-silenced human bladder cancer cell line (T24 cells) corroborated enhancement of pro-neoplastic pathways in absence of ORAI3. Western blottingMoreover, ORAI3 facilitated the recruitment of Th17 cells and natural killer cells, whereas hampered Th2 and macrophage infiltration. Our results revealed 4 molecules with potential to be beneficial as adjuvant drugs in MIBC treatment. We concluded that high ORAI3 expression correlates with increased survival in human MIBC.

Место робот-ассистированной цистэктомии в лечении мышечно-инвазивного рака мочевого пузыря

Bladder cancer occupies one of the leading positions in morbidity in the world and constitutes a serious problem for healthcare system. The muscle-invasive bladder cancer is the most aggressive and more difficult to treat with drug therapy. Radical cystectomy is the standard treatment for muscle-invasive bladder cancer, with the most commonly used open approach. Currently, there is an active introduction of minimally invasive procedures, which is due to their advantages in perioperative care. Laparoscopic procedures have been broadly adopted for the oncourological practice, but the real breakthrough in the field of minimally invasive surgery has occurred after implementing of robotic-assisted interventions. It should be noted that the extensive radical procedures are associated with significant intra- and postoperative complications, which directly affects the patients condition and quality of life postoperatively. In this regard, robotic-assisted radical cystectomy appears to be a promising treatment method for muscle-invasive bladder cancer. The aim of this review is to collect and analyze current information on the results of robotic-assisted radical cystectomy, with particular attention to the comparison with open and laparoscopic techniques for different surgical and oncological outcomes.

Explore the unexplored: Potential anti-tumor properties of Rhododendron against bladder cancer.

Explore the unexplored: Potential anti-tumor properties of Rhododendron against bladder cancer.

Curative Effect and Survival Assessment Comparing Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin and Cisplatin as Neoadjuvant Therapy for Bladder Cancer: A Systematic Review and Meta-Analysis

BackgroundNeoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes than radical cystectomy or a cisplatin-based regimen. In the present study, we aimed to compare the two most commonly used cisplatin-based neoadjuvant chemotherapies, gemcitabine plus cisplatin and methotrexate plus vinblastine plus doxorubicin plus cisplatin, by summarizing and analyzing clinical data and outcomes of published research.MethodsWe searched for qualified studies that compared these two types of neoadjuvant chemotherapy, including 4 randomized controlled trials and 14 retrospective studies. Data and information on pathological responses and long-term survival studies were extracted and analyzed separately.ResultsA total of 18 studies with 3116 patients were selected from 1188 studies, which contained data on pathological complete response, pathological partial response, and overall survival. In contrast to the results of previous studies, there was no significant difference in pathological complete response (odds ratio, 0.97; 95% confidence interval, 0.81-1.15), pathological partial response (odds ratio, 0.85; 95% confidence interval, 0.72-1.14), and overall survival (hazard ratio, 0.99; 95% confidence interval, 0.83-1.17) between GC and MVAC in this meta-analysis.ConclusionNo significant differences were observed between GC and MVAC in the muscle-invasive bladder cancer treatment due to the similar curative effect and parallel long survival outcomes due to the similar curative effect and parallel long survival outcomes. The priority selection of GC or MVAC in the clinic should be guided by further investigation, and the clinical standard strategy still counts on the results of more randomized controlled trials in the future.

Trimodal therapy vs. radical cystectomy for muscle-invasive bladder cancer: A Markov microsimulation model.

Radical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for select patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods. A two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT. A total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence. RC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.

Dramatic Impact of Centralization and a Multidisciplinary Bladder Cancer Program in Reducing Mortality: The CABEM Project.

PURPOSEMuscle-invasive bladder cancer (MIBC) is an aggressive disease with a complex treatment. In Brazil, as in most developing countries, data are scarce, but mortality seems exceedingly high. We have created a centralization program involving a multidisciplinary clinic in a region comprising seven municipalities. The aim of this study is to evaluate the impact of a multidisciplinary clinic and a centralization-of-care program (CABEM program) on MIBC treatment in Brazil.PATIENTS AND METHODSA total of 116 consecutive patients were evaluated. In group 1, 58 patients treated for MIBC before establishing a bladder cancer program from 2011 to 2017 were retrospectively evaluated. Group 2 represented 58 patients treated for MIBC after the implementation of the CABEM centralization program. Age, sex, staging, comorbidity indexes, mortality rates, type of treatment, and perioperative outcomes were compared.RESULTSPatients from group 2 versus 1 were older (68 v 64.2 years, P = .02) with a higher body mass index (25.5 v 22.6 kg/m2, P = .017) and had more comorbidities according to both age-adjusted Charlson Comorbidity Index (4.2 v 2.8, P = .0007) and Isbarn index (60.6 v 43.9, P = .0027). Radical cystectomy (RC) was the only treatment modality for patients in group 1, whereas in group 2, there were 31 (53%) RC; three (5%) partial cystectomies; seven (12%) trimodal therapies; 13 (22%) palliative chemotherapies; and three (5%) exclusive transurethral resections of the bladder tumor. No patient in group 1 received neoadjuvant chemotherapy, whereas it was offered to 69% of patients treated with RC. Ninety-day mortality rates were 34.5% versus 5% for groups 1 versus 2 (P < .002). One-year mortality was also lower in group 2.CONCLUSIONOur data support that a centralization program, a structured bladder clinic associated with protocols, a multidisciplinary team, and inclusion of chemotherapy and radiotherapy treatments can pleasingly improve outcomes for patients with MIBC.

Treatment trends of muscle invasive bladder cancer: Evidence from the Surveillance, Epidemiology, and End Results database, 1988 to 2013

ObjectiveGuidelines for muscle-invasive bladder cancer (MIBC) recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) program have been poorly described. MethodsUsing the SEER database, we collected data of MIBC according to the American Joint Commission on Cancer. We considered differences in patient demographics and tumor characteristics based on three treatment groups: chemotherapy (both adjuvant and neoadjuvant) with radical cystectomy, radical cystectomy, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends were included for each treatment group. Kaplan-Meier curves were performed to compare cause-specific survival. A Cox proportional-hazards model was utilized to describe predictors of survival. ResultsOf 16 728 patients, 10 468 patients received radical cystectomy alone, 3236 received chemotherapy with radical cystectomy, and 3024 received chemoradiotherapy. Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American; stage III patients tended to be divorced. Patients who received chemotherapy with radical cystectomy tended to be males; stage II patients were less likely to be Asian than Caucasian. Stage III patients were less likely to receive chemoradiotherapy as a treatment option than stage II. Chemotherapy with radical cystectomy and chemoradiotherapy are both underutilized treatment options, though increasingly utilized. Kaplan-Meier survival curves showed significant differences between stage II and III tumors at each interval. A Cox proportional-hazards model showed differences in gender, tumor stage, treatment modality, age, and marital status. ConclusionRadical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends. Significant disparities exist in those who receive radical cystectomy over chemoradiotherapy for treatment.

The Influence of Lymph Node Count on Oncological Outcome of Radical Cystectomy in Chemotherapy Pre-Treated and Chemotherapy-Naïve Patients with Muscle Invasive Bladder Cancer.

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) remains the mainstay of treatment for muscle-invasive bladder cancer (MIBC). The extent of PLND and number of removed lymph nodes (LNs) have been associated with improved staging and survival outcomes in several series of RC patients. Neoadjuvant chemotherapy (NAC) has become standard of care for cisplatin-eligible patients qualified to RC, yet few studies on PLND stratified cases according to the receipt of NAC. We aimed to address this issue and reevaluate the prognostic value of PLND nodal yields in series of patients who underwent RC on the verge of the NAC era. This single-center, retrospective, clinical follow-up study enrolled 439 consecutive patients, out of whom 83 received NAC. We analyzed survival outcome of RC according to the number of removed nodes between NAC and non-NAC subgroups. We found PLND thresholds of 10 and 15 LNs prognostically meaningful in our study cohort, and this association was particularly pronounced in the non-NAC subgroup. Higher numbers of LNs provided a 25% reduction in risk of all-cause mortality and correspondingly correlated with up to a 14% increase in 3-year overall survival. The receipt of NAC diminished the benefit of adequate PLND, as the number of retrieved LNs was not associated with survival in the NAC-RC cohort. Given the limitations of our study, additional research is needed to verify these findings.

Setting standards for cystectomy using the British Association of Urological Surgeons Complex Operations Reports, 2016–2018

Objective: To produce comprehensive standards for cystectomy using contemporary data collected across a nation. Patients and methods: Surgical departments upload cystectomy data to the British Association of Urological Surgeons (BAUS) Complex Operations Database. Analysis of 2016–2018 data was performed for all recorded 5288 patients undergoing cystectomy in England. Logistic regression with general linear models was used to assess differences in patient selection between operative modalities. Analysis involved assessment of case selection, operative decisions and outcomes, case volume and pathological outcomes. Results: Using national Hospital Episode Statistics, the BAUS cystectomy dataset was estimated 93% complete. Median age was 70 years (interquartile range 63–75) and 75% were male. Charlson comorbidity index ⩽2 was reported in 87%. Primary treatment of muscle-invasive bladder cancer accounted for 46% of cases. Commonest preoperative disease stages were T2N0 and T1N0 (35% and 25% respectively). Robotic-assisted (RAC), laparoscopic (LC) and open cystectomy (OC) were performed in 41%, 5.5% and 54% of cases respectively. T-stage distribution differed by operative modality. Transfusion rates were 3.7% for RAC, 6.0% for LC and 18% for OC. Increasing positive surgical margin rates were observed with increasing T-stage, up to T3. The conversion-to-open rate for minimally-invasive surgery was 1.7%. Median annual centre and surgeon case volumes were highest for RAC. Median length of stay was 7, 10 and 10 days for RAC, LC and OC respectively. Postoperative histological upstaging was common (33% of cT1, 50% of cT2 cases). Lymph node positive rates were 28% for muscle-invasive bladder cancer. Conclusion: Analysis of this data provides understanding of ‘real-world’ cystectomy practice. Presentation of data specific to operative modality allows surgeons and centres to benchmark their respective practices. These findings offer to enhance patient and public understanding beyond that currently facilitated by publicly-facing information sources. They carry relevance by describing a near-complete and large volume of modern practice in a publicly funded healthcare system. Level of evidence: 2b

Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle-Invasive Bladder Cancer.

The development of photothermal agents with high photothermal conversion efficiency (PCE) can help to reduce drug and laser dosage, but still remains a big challenge. Herein, a novel approach is reported to design photothermal agents with high PCE values by promoting nonradiative heat generation processes through the cooperation of twisted intramolecular charge transfer (TICT) and molecular motions. Within the designed molecule 2DMTT-BBTD, the tetraphenylethenes act as molecular rotors, the long alkyl chain grafted thiophene helps to twist the molecular geometry to facilitate TICT state formation and preserve molecular motions in aggregate, while the strong electron-withdrawing BBTD unit enhances TICT effect. 2DMTT-BBTD exhibits NIR-absorption and a high PCE value of 74.8% under 808nm laser irradiation. Gambogic acid (GA) which surmounts tumor cell thermotolerance by inhibiting heat shock protein 90 (HSP90) expression is coloaded into the nanoparticles, RGD peptide is further introduced to the nanoparticle surface to improve tumor accumulation. The resultant nanoparticles facilitate the effective low-temperature hyperthermia therapy of muscle-invasive bladder cancer (MIBC) with minimal damage to surrounding heathy tissues. This work delivers a new design concept for development of highly efficient photothermal agents, which also provides a safer approach for noninvasive treatment of MIBC and other malignant tumors.

PD55-02 MOLECULAR SUBTYPING TO STRATIFY THE TREATMENT OF MUSCLE-INVASIVE BLADDER CANCER: A COST EFFECTIVENESS ANALYSIS

You have accessJournal of UrologyBladder Cancer: Invasive IV (PD55)1 Sep 2021PD55-02 MOLECULAR SUBTYPING TO STRATIFY THE TREATMENT OF MUSCLE-INVASIVE BLADDER CANCER: A COST EFFECTIVENESS ANALYSIS Diana Magee, Douglas Cheung, Beate Sander, and Girish Kulkarni Diana MageeDiana Magee More articles by this author , Douglas CheungDouglas Cheung More articles by this author , Beate SanderBeate Sander More articles by this author , and Girish KulkarniGirish Kulkarni More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002089.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The gold standard treatment for muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy. However, response to NAC is unpredictable. Molecular subtypes allow for an improved ability to select a tailored treatment course. Our study aimed to assess the cost-effectiveness of molecular subtyping in the management of MIBC. METHODS: A two-dimensional Markov microsimulation model was developed using TreeAge Pro comparing three strategies: NAC at current usage rates (36%), universal NAC usage, and molecular subtype-directed care. Model probabilities and utilities were derived from the published literature. Four distinct subtypes of MIBC were modelled based on the Seiler classification. Cost of each phase of care was obtained from primary data and the Canadian Institute for Health Information patient cost estimator. The primary outcomes were quality-adjusted life years (QALYs), cost (CAD), overall survival (OS) and the incremental cost-effectiveness ratio (ICER). RESULTS: The predicted QALYs were 8.34, 8.73, and 9.14 with costs of $62,478, $76,962, and $62,579 for NAC at current usage rates, universal NAC usage, and subtype-directed care, respectively. Probabilistic sensitivity analysis shown in Figure 1. OS at 10 years was 39.2%, 40.8% and 42.8% for NAC at current usage rates, universal NAC usage, and subtype-directed care, respectively. When comparing subtype-directed care to current rates of NAC usage the ICER was $127/QALY. Subtype-directed care dominated universal NAC usage. CONCLUSIONS: We demonstrated that in patients with MIBC a molecular subtype directed approach to the administration of NAC results in improved OS and greater QALYs; moreover, it is cost-effective within a single payer healthcare system. A push for the universal use of NAC will result in improved survival compared with what our current rates of use achieve but it is likely not the best approach considering the drawbacks of chemotherapy including toxicity and unequal response. This model is built upon the available literature and as such requires validation prior to clinical implementation. Source of Funding: This project was funded by a grant from the Canadian Urologic Oncology Group © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e997-e997 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diana Magee More articles by this author Douglas Cheung More articles by this author Beate Sander More articles by this author Girish Kulkarni More articles by this author Expand All Advertisement Loading ...

PD37-08 PHOSPHATIDYLDIGLYCEROL-BASED THERMOSENSITIVE LIPOSOMES SHOW SUPERIOR THERAPEUTIC EFFICACY AGAINST MUSCLE-INVASIVE BLADDER CANCER IN VIVO

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (PD37)1 Sep 2021PD37-08 PHOSPHATIDYLDIGLYCEROL-BASED THERMOSENSITIVE LIPOSOMES SHOW SUPERIOR THERAPEUTIC EFFICACY AGAINST MUSCLE-INVASIVE BLADDER CANCER IN VIVO Iris Brummelhuis, Michiel Simons, Lars Lindner, Simone Kort, Sytse de Jong, Martin Hossann, Alfred Witjes, and Egbert Oosterwijk Iris BrummelhuisIris Brummelhuis More articles by this author , Michiel SimonsMichiel Simons More articles by this author , Lars LindnerLars Lindner More articles by this author , Simone KortSimone Kort More articles by this author , Sytse de JongSytse de Jong More articles by this author , Martin HossannMartin Hossann More articles by this author , Alfred WitjesAlfred Witjes More articles by this author , and Egbert OosterwijkEgbert Oosterwijk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002047.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recommended treatments for muscle-invasive bladder cancer (MIBC) are associated with substantial morbidity. Hyperthermia (HT) triggered drug release from phosphatidyldiglycerol-based thermosensitive liposomes (DPPG2-TSL) might prevent surgical bladder removal and toxicity from systemic chemotherapy. We aimed to assess the efficacy of DPPG2-TSL encapsulated doxorubicin (DOX; DPPG2-TSL-DOX) combined with bladder HT, compared to free systemic and intravesical DOX, in a syngeneic orthotopic rat urothelial carcinoma model. METHODS: A total of 191 female Fischer F344 rats were used. Bladder tumors were initiated by inoculation of AY-27 cells and tumor bearing rats were selected with cystoscopy and semi-randomized over treatment groups. At day 5 and 8, animals were treated with 2 mg/kg DOX in different treatment modalities: intravenous (iv) DPPG2-TSL-DOX with HT, iv free DOX without HT, intravesical DOX without HT, intravesical DOX with HT or no treatment (control group), respectively. Animals were euthanized at day 14 and complete tumor response was assessed by histopathological evaluation. RESULTS: Treatment with iv DPPG2-TSL-DOX with HT resulted in the highest rate of animals with complete tumor response of 70%, which was significantly better than iv free DOX (18%, p=0.02) and no treatment (0%, p=0.001), and non-significantly better than intravesical DOX with (43%, p=0.35) or without HT (50%, p=0.41; Figure 1). All rats receiving intravesical DOX with HT (7/7) and 24% (5/21) of rats treated with DPPG2-TSL-DOX containing the same DOX dose with HT had to be euthanized before day 14 because of >15% body weight loss, while some rats showed dilated ureters (3/7 and 4/21) and urine retention (2/7 and 1/21, respectively).Figure 1. Tumor stage as determined by histopathological evaluation per group. Green colored parts of bars represent T1 tumors, and purple T2. CONCLUSIONS: Treatment with DPPG2-TSL-DOX combined with intravesical HT outperformed systemic and intravesical DOX in a syngeneic orthotopic rat UC model. There might be a role for DPPG2-TSL encapsulating chemotherapeutics in treatment of MIBC in the future. Source of Funding: This study was partially sponsored by Thermosome © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e658-e658 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Iris Brummelhuis More articles by this author Michiel Simons More articles by this author Lars Lindner More articles by this author Simone Kort More articles by this author Sytse de Jong More articles by this author Martin Hossann More articles by this author Alfred Witjes More articles by this author Egbert Oosterwijk More articles by this author Expand All Advertisement Loading ...

Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

BackgroundThe standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis.Methods and findingsWe applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized bladder cancer. The average age of patients was 69 years (range: 50 to 86), of whom 76% (32/42) were male, 64% (27/42) were smokers, and 76% (32/42) had a confirmed diagnosis of MIBC. Among MIBC patients, 59% (19/32) received neoadjuvant chemotherapy. utDNA variant calling was performed noninvasively without prior sequencing of tumor tissue. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. utDNA analysis revealed a median utDNA level of 0% in healthy adults and 2.4% in bladder cancer patients. When patients were classified as those who had residual disease detected in their surgical sample (n = 16) compared to those who achieved a pathologic complete response (pCR; n = 26), median utDNA levels were 4.3% vs. 0%, respectively (p = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD detection was highly correlated with the absence of pCR (p < 0.001) with a sensitivity of 81% and specificity of 81%. Leave-one-out cross-validation applied to the prediction of pathologic response based on utDNA MRD detection in our cohort yielded a highly significant accuracy of 81% (p = 0.007). Moreover, utDNA MRD–positive patients exhibited significantly worse progression-free survival (PFS; HR = 7.4; 95% CI: 1.4–38.9; p = 0.02) compared to utDNA MRD–negative patients. Concordance between urine- and tumor-derived mutations, determined in 5 MIBC patients, was 85%. Tumor mutational burden (TMB) in utDNA MRD–positive patients was inferred from the number of non-silent mutations detected in urine cfDNA by applying a linear relationship derived from The Cancer Genome Atlas (TCGA) whole exome sequencing of 409 MIBC tumors. We suggest that about 58% of these patients with high inferred TMB might have been candidates for treatment with early immune checkpoint blockade. Study limitations included an analysis restricted only to single-nucleotide variants (SNVs), survival differences diminished by surgery, and a low number of DNA damage response (DRR) mutations detected after neoadjuvant chemotherapy at the MRD time point.ConclusionsutDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment. utDNA MRD detection also correlated significantly with PFS. Furthermore, utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer in the future.

PO-1399 Vinorelbine in Bladder-Preserving Multimodality Treatment for Muscle-Invasive Bladder Cancer

PO-1399 Vinorelbine in Bladder-Preserving Multimodality Treatment for Muscle-Invasive Bladder Cancer

Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives.

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

Radical Cystectomies at the University Teaching Hospital, Lusaka: Baseline Characteristics, Short-term Complications, and Role of Nursing Care

Bladder cancer is the ninth most common cancer in the world and the 11th most common cancer in Zambia. Bladder cancer is of three histological types, Squamous cell cancer, Transitional cell cancer, and Adenocarcinoma. The most common histological type in Zambia is Squamous cell cancer accounting for 60 percent of cases of muscle-invasive bladder cancer. The treatment of muscle-invasive bladder cancer is radical cystectomy, Lymph node dissection, and urinary diversion. Globally, radical cystectomy is associated with high morbidity and mortality. The most common diversion used was uretero-sigmoidostomy, accounting for 60 percent of cases. In our case series, the most common complications were wound dehiscence, hypo-proteinemia, bowel ileus, deep vein thrombosis, and electrolyte imbalance. Identification and prevention of complications associated with this procedure play a crucial role in improving survival for these patients. The role of nursing staff in the early recognition of these complications cannot be overemphasized.

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study

BackgroundOpen radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. ObjectiveTo assess the cost-effectiveness of RARC compared to ORC in bladder cancer. Design, setting, and participantsThis economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. Outcome measurements and statistical analysisOver 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. Results and limitationsThe mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791–€18 720) for ORC and €21 266 (95% CI €19 163–€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431–€22 642) for ORC and €24 896 (95% CI €21 925–€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74–0.85) compared to 0.81 QALYs (95% CI 0.77–0.85) for ORC patients, resulting in a mean QALY difference of −0.02 (95% CI −0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. ConclusionsRARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. Patient summaryThis study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive.This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214).