Muscle-invasive Bladder Cancer Research Articles

P106 ENZYMES INVOLVED IN THE CATABOLISM OF TRYPTOPHAN IN THE PROGNOSIS OF BLADDER CANCER

Bladder cancer (BC) ranks third among the most common carcinomas in Brazil. Tumor immunology opens up perspectives for treatment, where the enzyme indoleamine 2,3-dioxygenase-1 (IDO1) stands out for degrading the amino acid tryptophan, initiating a cascade that culminates in the generation of catabolites (derived from kynurenine). These catabolites, in different associations, determine degrees of local immunosuppression. These catabolites are generated by other enzymes that have not yet been studied in BC. We analyzed the expression of enzymes involved in tryptophan catabolism in order to correlate them with the stage, recurrence, and progression of BC. Analysis of published microarray databases was performed using the NCBI (National Center of Biotechnology Information) and accessed through GEO Datasets (Gene Expression Omnibus). The descriptor “Bladder cancer” was used. Series that provided analysis of normal bladder tissue (Normal) versus BC, including cases of non-muscle invasive BC (CBNMI) and muscle invasive BC (CBMI), recurrence and progression. Statistical analysis was performed using the GEO2R and ROC curve was used. The transcripts were: Tryptophan 2,3-dioxygenase (TDO2), Indoleamine 2,3-dioxygenase (IDO1), Kynurenine Formamidase (AFMID), Kynureninase (KNYU), Kynurenine-oxoglutarate-transaminase 1 (KYAT1), and Kynurenine Monooxygenase (KMU). GSE13507 series was selected, with ten Normal samples and 165 BC samples, including 104 CBNMI and 61 CBMI cases. CBNMI was predicted by KYNU, AFMID, and KYAT1 (AUC of 0.625, 0.589, and 0.638, respectively; p<0.05), while for CBMI were, IDO1, TDO2, and KMO (AUC of 0.662, 0.633, and 0.601, respectively; p<0.05). No enzyme was found to be important in predicting progression; however, the IDO1 enzyme was predictive of recurrence (AUC of 0.366; p<0.05). A relationship between the two IDO1/KYNU was established, which improved the prediction of stage for CBNMI (AUC of 0.733, p<0.05), non-progression (AUC of 0.619, p<0.05), and non-recurrence (AUC of 0.626, p<0.05). The expression of enzymes involved in tryptophan catabolism may aid in the prognosis of BC. It is likely that these enzymes are involved in tumor immunomodulation, which will be explored in future studies.

Introduction of an Advanced Nurse Practitioner (ANP) Led Non-Muscle Invasive Bladder Cancer (NMIBC) Treatment and Surveillance Clinic in Tallaght University Hospital (TUH)

Introduction of an Advanced Nurse Practitioner (ANP) Led Non-Muscle Invasive Bladder Cancer (NMIBC) Treatment and Surveillance Clinic in Tallaght University Hospital (TUH)

2023TiP A phase I/II study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients (pts) with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

2023TiP A phase I/II study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients (pts) with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

1998P Preliminary results from a phase I study of T3011, an oncolytic HSV expressing IL-12 and anti-PD-1 antibody, for BCG-failure non-muscle-invasive bladder cancer (NMIBC)

1998P Preliminary results from a phase I study of T3011, an oncolytic HSV expressing IL-12 and anti-PD-1 antibody, for BCG-failure non-muscle-invasive bladder cancer (NMIBC)

2002P Efficacy and biomarker analysis of neoadjuvant disitamab vedotin combined immunotherapy in patients with muscle-invasive bladder cancer: A multi-center real-world study

2002P Efficacy and biomarker analysis of neoadjuvant disitamab vedotin combined immunotherapy in patients with muscle-invasive bladder cancer: A multi-center real-world study

2020TiP SOGUG-NEOWIN: A phase II, open-label, multi-centre trial evaluating the efficacy and safety of erdafitinib (ERDA) monotherapy and ERDA and cetrelimab (CET) as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) and FGFR gene alterations

2020TiP SOGUG-NEOWIN: A phase II, open-label, multi-centre trial evaluating the efficacy and safety of erdafitinib (ERDA) monotherapy and ERDA and cetrelimab (CET) as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) and FGFR gene alterations

2016P Evaluation of event-free survival (EFS) as a surrogate endpoint for overall survival (OS) in muscle-invasive bladder cancer (MIBC) following neoadjuvant (NAD) therapy

2016P Evaluation of event-free survival (EFS) as a surrogate endpoint for overall survival (OS) in muscle-invasive bladder cancer (MIBC) following neoadjuvant (NAD) therapy

LBA84 TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): Interim analysis of SunRISe-4 (SR-4)

LBA84 TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): Interim analysis of SunRISe-4 (SR-4)

Immunophenotypic and molecular changes during progression of papillary urothelial carcinoma.

Urothelial carcinoma has various molecular subtypes, each with different tumor characteristics. Although it is known that molecular changes occur during tumor progression, little is known about the specifics of these changes. In this study, we performed transcriptional analysis to understand the molecular changes during tumor progression. Formalin-fixed, paraffin-embedded tumor tissues were obtained from 12 patients with muscle-invasive bladder cancer (MIBC). The invasive and non-invasive papillary areas were identified in papillary urothelial carcinoma specimens. Immunohistochemistry (IHC) and mRNA sequencing were performed for each tumor area. Patients with CK5/6-negative and CK20-positive non-invasive papillary areas were selected and classified into the IHC switch subgroup (CK5/6-positive and CK20-negative in the invasive area) and the IHC unchanged subgroup (CK5/6-negative and CK20-positive in the invasive area) according to the IHC results of the invasive area. We identified differences in the mRNA expression between the non-invasive papillary and invasive areas of the papillary MIBC tissue samples. In both the non-invasive papillary and invasive areas, the IHC switch subgroup showed basal subtype gene expression, while the IHC unchanged subgroup demonstrated luminal subtype gene expression. The non-invasive papillary area showed a gene expression pattern similar to that of the invasive area. Therefore, even if the non-invasive papillary area exhibits a luminal phenotype on IHC, it can have a basal subtype gene expression depending on the invasive area.

LBA5 A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA)

LBA5 A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA)

The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis

Background and objectiveNeoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease. MethodsPatients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted. ResultsIncluded were 458 patients with a median age of 69 (IQR 63–76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18–5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55–3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11–2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32–11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12–7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43–12.3], P = 0.009) were predictive of disease relapse. ConclusionsPatients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.

Development and Optimization of a Bladder Cancer Algorithm Using SEER-Medicare Claims Data.

Categorizing patients with cancer by their disease stage can be an important tool when conducting administrative claims-based studies. As claims databases frequently do not capture this information, algorithms are increasingly used to define disease stage. To our knowledge, to date, no study has used an algorithm to categorize patients with bladder cancer (BC) by disease stage (non-muscle-invasive BC [NMIBC], muscle-invasive BC [MIBC], or locally advanced/metastatic urothelial carcinoma [la/mUC]) in a US-based health care claims database. A claims-based algorithm was developed to categorize patients by disease stage on the basis of the administrative claims portion of the SEER-Medicare linked data. The algorithm was validated against a reference SEER registry, and the algorithm's parameters were iteratively modified to improve its performance. Patients were included if they had an initial diagnosis of BC between January 2016 and December 2017 recorded in SEER registry data. Medicare claims data were available for these patients until December 31, 2019. The algorithm was evaluated by assessing percentage agreement, Cohen's kappa (κ), specificity, positive predictive value (PPV), and negative predictive value (NPV) against the SEER categorization. A total of 15,484 patients with SEER-confirmed BC were included: 10,991 (71.0%) with NMIBC, 3,645 (23.5%) with MIBC, and 848 (5.5%) with la/mUC. After multiple rounds of algorithm optimization, the final algorithm had an agreement of 82.5% with SEER, with a κ of 0.58, a PPV of 87.0% for NMIBC, and 76.8% for MIBC and a high NPV for la/mUC of 98.0%. This claims-based algorithm could be a useful approach for researchers conducting claims-based studies categorizing patients with BC at diagnosis.

1970MO Circulating tumor DNA (ctDNA) clearance with neoadjuvant durvalumab (D) + tremelimumab (T) + enfortumab vedotin (EV) for cisplatin-ineligible muscle-invasive bladder cancer (MIBC) from the safety run-in cohort of the phase III VOLGA trial

1970MO Circulating tumor DNA (ctDNA) clearance with neoadjuvant durvalumab (D) + tremelimumab (T) + enfortumab vedotin (EV) for cisplatin-ineligible muscle-invasive bladder cancer (MIBC) from the safety run-in cohort of the phase III VOLGA trial

Bladder Adjuvant RadioTherapy (BART): Acute and Late Toxicity from a Phase III Multicentre Randomized Controlled Trial: Acute and late toxicity in BART RCT.

To report toxicity from the multicentre phase III randomized trial of Bladder Adjuvant Radiotherapy (BART) after radical cystectomy (RC) and chemotherapy in high-risk muscle-invasive bladder cancer (MIBC). Patients with non-metastatic urothelial MIBC with ≥1 high-risk feature after RC: pT3-4, pN1-3, nodal yield <10, positive margin, or ≥cT3 downstaged with neoadjuvant chemotherapy; were randomized 1:1 to observation (Obs) or adjuvant radiotherapy (RT) at 4 centres, stratified by pN stage (N0, N+) and chemotherapy (neoadjuvant, adjuvant, none). Stoma-sparing IG-IMRT 50.4Gy/28# was prescribed to the cystectomy bed and pelvic nodes. Acute toxicity (≤3 months of RT/randomization) and late toxicity were assessed per protocol using CTCAE v5.0. Patients progressing within 3 or 6 months of randomization were excluded from acute or late toxicity analysis respectively. BART trial enrolled 153 patients (Obs=76, RT=77). About half (49%) had pN+. Nearly 90% received chemotherapy (70% neoadjuvant; most commonly gemcitabine plus cisplatin). In the RT arm, 63/77 completed radiotherapy per protocol with no toxicity-related RT termination. Of the 134 patients analyzable for acute toxicity, no difference was observed in grade 3 (Obs 4.2% vs RT 1.6%, p=0.34). Grade 2 effects were higher with RT (17.5% vs 1.1%, p<0.001), mainly diarrhea/enteritis or proctitis. Late toxicity was analyzable for 104 patients (Obs=57, RT=47) with median follow up of 27 months. Grade 3-4 toxicity were about 10% (Obs 10.5% vs RT 8.4%, p=0.62), and cumulative late grade 2+ toxicity was similar in both the groups (17.5% vs 23.3%, p=0.27). In the largest trial of adjuvant radiotherapy for high-risk urothelial MIBC, severe acute and late toxicity were low and similar with observation or radiotherapy. The oncological outcomes are awaited.

Intravesical Gemcitabine for Non-Muscle Invasive Bladder Cancer after Bacillus Calmette-Guerin Treatment Failure: A Prospective Study.

We prospectively enrolled 28 patients with recurrent NMIBC after previous intravesical treatment in the last year who declined or were unsuitable for cystectomy between 2021 and 2023. Gemcitabine at 2,000 mg/100 mL was instilled weekly for 6 weeks. Patients were assessed for response after 8 weeks, with subsequent evaluations scheduled every three months to one year. The findings demonstrated that out of the 28 patients, 20 (71.4%) exhibited a complete response to intravesical gemcitabine treatment, and 8 (28.6%) had no complete response. The average age of the participants was 60.25 years. The study identified significant differences in treatment response based on age but without significant differences based on gender. Furthermore, there was no noteworthy association between tumor stage and grade and treatment response. Moreover, among patients with low-grade tumors, 66.7% achieved a complete response, while 72.7% reached a complete response among those with high-grade tumors. Of the patients who reached a complete response, 28.6% experienced no recurrence during one year of follow-up, and 42.9% developed recurrent disease within one year of treatment initiation. Ten months following treatment, a patient developed muscle-invasive bladder cancer and went on to cystectomy. In conclusion, the results suggest that intravesical gemcitabine could represent a feasible choice for NMIBC patients unresponsive to BCG therapy and ineligible for or unwilling to undergo cystectomy.

162 a Retrospective Review of Radiation Therapy in Non-Metastatic Muscle-Invasive Bladder Cancer at a Tertiary Care University Hospital in Pakistan

162 a Retrospective Review of Radiation Therapy in Non-Metastatic Muscle-Invasive Bladder Cancer at a Tertiary Care University Hospital in Pakistan

1984P Efficacy and safety of disitamab vedotin combined with gemcitabine as neoadjuvant therapy for muscle-invasive bladder cancer: A multi-center, single-arm, phase II trial

1984P Efficacy and safety of disitamab vedotin combined with gemcitabine as neoadjuvant therapy for muscle-invasive bladder cancer: A multi-center, single-arm, phase II trial

1961O Nivolumab plus chemoradiotherapy in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), not undergoing cystectomy: A phase II, randomized study by the Hellenic GU Cancer Group

1961O Nivolumab plus chemoradiotherapy in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), not undergoing cystectomy: A phase II, randomized study by the Hellenic GU Cancer Group

2011P Neoadjuvant immunotherapy-driven bladder preservation for muscle-invasive bladder cancer: A multicenter, propensity score-matched cohort study

2011P Neoadjuvant immunotherapy-driven bladder preservation for muscle-invasive bladder cancer: A multicenter, propensity score-matched cohort study

A comparative study of survival outcomes between partial and radical cystectomy in octogenarians with muscle-invasive bladder cancer.

Neoadjuvant chemotherapy with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). Due to the concern about morbidity associated with RC, the elderly population considers bladder preservation alternatives. Guidelines suggest partial cystectomy (PC) can be considered a viable option in carefully selected individuals. We used the National Cancer Database (NCDB) to compare the overall survival (OS) among octogenarians treated with PC and RC. Using NCDB, we retrospectively evaluated individuals aged 80 years and above diagnosed with localized MIBC (cT2-4aN0M0) with tumor size less than 5 cm and urothelial histology between 2004 and 2018. Our primary cohort was divided into the RC cohort, which included patients who underwent RC with or without chemotherapy/radiotherapy, and the PC cohort, which included those who underwent PC. After propensity-matching, we compared the OS. Of 94,104 patients with MIBC, 2,528 octogenarians met our selection criteria. Among them, 313 were treated with PC, and 2,215 were treated with RC. A total of 151 (48.2%) PC patients had pelvic lymph node dissection, while 1,967 (88.8%) RC patients had lymph node dissection (P<0.001). The OS for matched PC and RC was 33.4 and 29.9 months, respectively (P=0.68). In T2 tumors, the OS for PC and RC was 37 and 33.5 months, respectively (P=0.52); for T3 tumors, the OS was 22.3 and 24.4 months, respectively (P=0.98). Our study compared PC and RC in octogenarians with localized MIBC and observed that PC is safe and not inferior to RC in carefully selected octogenarians. The role of PC needs further exploration by comparing or integrating with strategies like concurrent chemoradiation to improve the oncological and survival outcomes.