Muscle-invasive Bladder Cancer Research Articles

An ensemble learning model for predicting cancer-specific survival of muscle-invasive bladder cancer patients undergoing bladder preservation therapy.

More muscle-invasive bladder cancer (MIBC) patients are now eligible for bladder-preserving therapy (BPT), underscoring the need for precision medicine. This study aimed to identify prognostic predictors and construct a predictive model among MIBC patients who undergo BPT. Data relating to MIBC patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2016. Eleven features were included to establish multiple models. The predictive effectiveness was assessed using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curve (CIC). SHapley Additive exPlanations (SHAP) were used to explain the impact of features on the predicted targets. The ROC showed that Catboost and Random Forest (RF) obtained better predictive discrimination in both 3- and 5-year models [test set area under curves (AUC) =0.80 and 0.83, respectively]. Furthermore, Catboost showed better performance in calibration plots, DCA and CIC. SHAP analysis indicated that age, M stage, tumor size, chemotherapy, T stage and gender were the most important features in the model for predicting the 3-year cancer-specific survival (CSS). In contrast, M stage, age, tumor size and gender as well as the N and T stages were the most important features for predicting the 5-year CSS. The Catboost model exhibits the highest predictive performance and clinical utility, potentially aiding clinicians in making optimal individualized decisions for MIBC patients with BPT.

Recent Advances in Drug Delivery Strategies for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: A Brief Review from 2018 to 2024.

High-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) is a condition that is typically treated with Bacillus Calmette-Guérin (BCG) therapy. Unfortunately, NMIBC is characterized by high recurrence, with a significant percentage of BCG patients ultimately requiring radical cystectomy. As a consequence, the development of effective new therapies to avoid RC has become a rapidly evolving field to address this unmet clinical need. To date, three biologics-Keytruda, Adstiladrin, and Anktiva-have been approved by the FDA, and multiple drug modalities, particularly gene therapies, have shown promising results in clinical trials. Advances in drug delivery strategies, such as targeted delivery, sustained release, and permeabilization of protective layers, are critical in overcoming the challenges posed by therapeutic intervention in bladder cancer. This review focuses on high-risk BCG-unresponsive NMIBC therapies that have been or are currently being investigated in clinical trials, offering a broad overview of the delivery system designs and up-to-date clinical outcomes that have been reported as of July 2024. It aims to inform the development of future drug delivery systems for second-line therapies in high-risk BCG-unresponsive NMIBC.

1029: Concomitant Chemotherapy in Trimodal Treatment of Patients with Muscle Invasive Bladder Cancer.

1029: Concomitant Chemotherapy in Trimodal Treatment of Patients with Muscle Invasive Bladder Cancer.

2428: Radiotherapy or cystectomy in muscle-invasive bladder cancer: Outcomes with two clinical pathways

2428: Radiotherapy or cystectomy in muscle-invasive bladder cancer: Outcomes with two clinical pathways

Varying the intensity of cystoscopic surveillance for high-risk non-muscle-invasive bladder cancer.

To compare the clinical, economic, and health utility outcomes associated with alternative cystoscopic surveillance regimens for high-risk non-muscle-invasive bladder cancer (HRNMIBC). We performed real-world clinical data-driven microsimulations of a hypothetical cohort of 100 000 patients diagnosed with HRNMIBC at age 70 years. The cohort was simulated to undergo alternative surveillance regimens recommended by five guidelines, and two hypothetical regimens-surveillance intensity escalation and de-escalation-which had a surveillance intensity moderately higher and lower, respectively, than the guideline-recommended regimens. We evaluated the 10-year cumulative incidence of muscle-invasive bladder cancer (MIBC), cancer-specific survival (CSS), overall survival (OS), and cost-effectiveness from a United States healthcare payer perspective. The guideline-recommended surveillance regimens led to an estimated 10-year cumulative incidence of MIBC ranging from 11.0% to 11.6%, CSS 95.0% to 95.2%, and OS 69.7% to 69.8%. Surveillance intensity escalation resulted in a 10-year cumulative incidence of MIBC of 10.5% (95% confidence interval [CI] 10.3-10.7%), CSS of 95.4% (95% CI 95.2-95.5%), and OS of 69.9% (95% CI 69.6-70.1%), vs 11.9% (95% CI 11.7-12.1%), 94.9% (95% CI 94.8-95.1%), and 69.6% (95% CI 69.3-69.9%), respectively, from surveillance intensity de-escalation. By increasing surveillance intensity, the number-needed-to-treat to prevent one additional MIBC progression over 10 years was ≥80, and ≥257 to avoid one additional cancer-related mortality. Compared to surveillance intensity de-escalation, higher-intensity regimens incurred an incremental cost of ≥$336 000 per incremental quality-adjusted life year gained, which well exceeded conventional willingness-to-pay thresholds, ≥$686 000 per additional MIBC progression prevented, and ≥$2.2 million per additional cancer-related mortality avoided. In microsimulations testing a wide range of cystoscopic surveillance intensity for patients newly diagnosed with HRNMIBC, moderate surveillance de-escalation appears associated with an insignificant change in 10-year OS and furthermore is cost-effective vs higher-intensity surveillance regimens. These results suggest that moderate surveillance de-escalation can reduce costs of care without compromising life expectancy for many patients.

Sex differences in muscle-invasive bladder cancers: A study of a French regional population

ObjectivesAlthough men have a higher risk of developing a bladder cancer, women appear to have a poorer prognosis and a more advanced stage at diagnosis. We performed a retrospective population-based study on muscle invasive bladder cancer (MIBC) using data from a cancer registry in a French department to compare overall and specific survival data according to sex. Material and methodsWe included all patients living in the department of Hérault and diagnosed with MIBC between January 1, 2017 and December 12, 2019. Univariable and multivariable analyses were performed on all variables of interest. ResultsWe included 124 women and 432 men. There was no significant difference in age or stage at diagnosis according to sex. Squamous cell carcinomas were more common in women (P<0.001). Cystectomy was more frequent in men than in women (50.7% vs 35.4%) (P=0.0039). By multivariable analysis, the independent factors for being treated by cystectomy were sex (P=0.004), age (P<0.001) and stage (P<0.001). Forty-seven percent of women received no treatment or palliative treatment. Overall mortality was 79% in women and 63.2% in men (P<0.001). The median specific survival was 10.8months in women and 32.7months in men (P<0.0001). By multivariable analysis, the independent risk factors for mortality were female sex (P=0.047), cT4 stage (P=0.005) and absence of cystectomy (P<0.001). ConclusionsOur study shows that women are less often treated with cystectomy and have worse prognosis than men. The reasons for this gender difference are multifactorial.

The Role of Spinal Anaesthesia with and without Intrathecal Opioid Coadministration in Improving Oncologic Outcomes after Endoscopic Transurethral Cancer Surgery

Spinal anaesthesia (SA) (compared to general) improves postoperative oncologic outcomes in transurethral resection of the bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). Intrathecal coadministration of opioids does not affect NK cells function, and improves postoperative opioid sparing as well. There are no comparative data on oncologic outcomes of SA with/without intrathecal opioid in TURBT, which is the aim of our study. Seventy ASA I-III patients with NMIBC, aged ≥ 43 (range 43-90), who underwent one or more TURBT under SA were examined retrospectively. Of them, 36 received levobupivacaine 15 mg (L group) and 34 levobupivacaine 12.5 mg + fentanyl 12.5 mcg (LF group) intrathecally. All patients received scheduled Paracetamol 1.0 g/6 h, optional NSAIDs and as needed Tramadol as well. Data regarding demographics, ASA and CCI scores, analgesics consumption, urethrotomies, tumour-related factors (size, number, grade, stage, prior disease-recurrence, adjuvant therapy), tumour risk (low, intermediate, high), oncologic outcomes (recurrence rate/free time after TURB during the regular cystoscopy every 3 months/first year, every six months thereafter) were explored as well. LF patients were older, with less analgesics consumption and with a tendency towards longer recurrence-free time compared to L patients (p=0.074). The recurrence at three months along with prior and new disease-recurrences comprise our minority (n=27) with aggressive course of the disease. Among the rest the majority, LF subgroup (n=19) had lower recurrence rate than L subgroup (n=24) (p=0.03). As part of multimodal analgesic strategy, SA with intrathecal opioid coadministration may play a significant complementary role regarding oncologic outcomes after TURBT for NMIBC.

The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non–muscle-invasive Bladder Cancer

Grade is an important determinant of progression in non–muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell’s C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.

Topography and Lateralization of Nodal Metastases in Muscle-Invasive Bladder Cancer Using Super-Extended Pelvic Lymph Node Dissection with the Sentinel Lymph Node Technique.

Background: This study assessed the topography and lateralization of lymph node (LN) metastases in muscle-invasive bladder cancer (MIBC) patients using super-extended pelvic lymph node dissection (sePLND) with sentinel lymph node dissection (SLND). Methods: We analyzed 54 MIBC patients who underwent cystectomy with sePLND and SLND. Tumor location was classified using cystoscopy. Nanocolloid-Tc-99m was injected peritumorally. Preoperative SPECT/CT lymphoscintigraphy and an intraoperative gamma probe were used for SLN detection. Results: A total of 1414 LNs, including 192 SLNs, were resected from 54 patients. Metastases were found in 72 LNs from 22 patients (41%). The obturator fossa was the primary site for LN metastases (37.5%). SLNs were most common in the external iliac region (34.4%). In 36% of the patients with positive LNs, metastases were identified only through sePLND. In 9% of the patients, metastases were found solely in the pararectal region, identified through SLND. Tumor lateralization correlated with ipsilateral positive LNs, but 20% of the patients had contralateral metastases. Conclusions: The pararectal region may be the exclusive site for positive LNs in MIBC. The obturator fossa is the most prevalent region for LN metastases. Unilateral PLND should be avoided due to the risk of contralateral metastases. Combining sePLND with SLND improves staging.

Novel systemic treatment options for advanced bladder cancer

Systemic treatment of urothelial carcinoma of the bladder requires complex approaches and is constantly evolving. Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy remains the current standard of care for muscle-invasive advanced bladder cancer. For patients ineligible for cisplatin, adjuvant treatment with nivolumab is recommended. Innovative perioperative combinations could transform the treatment landscape in the future. First-line treatment for metastatic urothelial carcinoma has long been dominated by platinum-based combinations, recently followed by the immune checkpoint inhibitor avelumab as maintenance therapy; however, recent results on the use of enfortumab vedotin and pembrolizumab in the first-line setting are expected to fundamentally change the treatment options. In subsequent lines of treatment, the not yet approved erdafitinib, as the first targeted therapy for advanced urothelial carcinoma, offers an important alternative and underscores the need for molecular testing.

Treatment Strategies for BCG Unresponsive Non-muscle Invasive Bladder Cancer

Treatment Strategies for BCG Unresponsive Non-muscle Invasive Bladder Cancer

Perioperative complications of orthotopic neobladder after radical cystectomy for carcinoma of urinary bladder: A Retrospective Study

Background: The gold standard treatment for muscle-invasive bladder cancer is radical cystectomy (RC) with urinary diversion. Urinary diversion is performed in either as continent or incontinent forms. Orthotopic neobladder has the benefits of continent reservoir with voiding from the urethra. The mortality and morbidity rates ranged from 0 to 9.0% and 30 to 70%, respectively in various reports. For surgical outcome assessment, Clavien-Dindo classification is widely accepted for classification of complications of most of the surgical procedures. This study will be helpful to identify the potential complications and possibly minimize the morbidity and mortality of this surgery in the future. Materials and Methods: Data of 20 consecutively enrolled patients who underwent radical cystectomy and orthotopic neobladder form January 2023 to July 2024 at Urology unit of B.P. Koirala Memorial Cancer Hospital were taken for study from hospital medical records. The various demographic data and perioperative parameters were recorded. The early complications were defined as the complications during the period of hospitalization and up to 30 days of surgery, they were enlisted and then classified according to Clavein-Dindo Classification and the continence was reviewed at 1 month of surgery after catheter removal and after 3 months of surgery. Data was entered in SPSS 27 software and analyzed. Results: Complications were seen in 18 (90%) patients out of which 1 (5%) patients had Grade I complication, 12 (60%) patients had Grade II, 3 (15%) patients had grade IVA and 2(10%) had died. 5 (25%) patients developed high grade(≥ Grade III) complications. Mortality rate was 5%. Conclusion: Radical cystectomy with any forms of diversion is associated with high rate of morbidity and mortality. In order to identify and minimize the complications of this surgery in future, Clavein-Dindo classification is the standardized way of reporting the complications.

German expert consensus on programmed cell death ligand1 (PD-L1) testing in perioperative systemic therapy of muscle invasive bladder cancer

The risk of recurrence in patients with muscle invasive bladder cancer (MIBC) after radical cystectomy depends on the pathological tumor stage. In particular, patients with lymph node metastasis (pN+), locally advanced (≥pT3), or residual muscle invasive tumor despite neoadjuvant chemotherapy are at high risk. Currently, the importance of adjuvant therapy with immune checkpoint inhibitors is increasing in the context of perioperative systemic therapeutic concepts. The indication for the PD‑1 inhibitor nivolumab currently approved in the European Union requires testing of PD-L1 (programmed cell death ligand1) protein expression by immunochemistry in tumor tissue. Focusing on MIBC patients at high risk of recurrence, new questions arise regarding the implementation and interpretation of PD-L1 testing. An interdisciplinary group of experts from Germany has discussed relevant issues from aclinicopathological point of view and developed practical recommendations to facilitate the implementation of validated and quality-assured PD-L1 testing for the approved indications in daily clinical practice.

Establish TIIC signature score based the machine learning fusion in bladder cancer

BackgroundBladder cancer is a prevalent malignant tumor with high heterogeneity. Current treatments, such as transurethral resection of bladder tumor (TURBT) and intravesical Bacillus Calmette-Guérin (BCG) therapy, still have limitations, with approximately 30% of non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC), and a substantial number of MIBC patients experiencing recurrence after surgery. Immunotherapy has shown potential benefits, but accurate prediction of its prognostic effects remains challenging.MethodsWe analyzed bladder cancer RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and used various machine learning algorithms to screen for feature RNAs related to tumor-infiltrating immune cells (TIICs) from single-cell data. Based on these RNAs, we established a TIIC signature score and evaluated its relationship with overall survival (OS) and immunotherapy response in bladder cancer patients.ResultsThe study identified 171 TIIC-RNAs and selected 11 TIIC-RNAs with prognostic value through survival analysis. The TIIC signature score established using a machine learning fusion method was significantly associated with OS and showed good predictive performance in different datasets. Additionally, the signature score was negatively correlated with immunotherapy response, with patients with low TIIC feature scores showing better survival outcomes after immunotherapy. Further biological functional analysis revealed a close association between the TIIC signature score and immune regulation processes, cellular metabolism, and genetic variations.ConclusionThis study successfully constructed and validated an RNA signature scoring system based on tumor-infiltrating immune cell (TIIC) features, which can effectively predict OS and the effectiveness of immunotherapy in bladder cancer patients.

Long-term outcomes of bladder-sparing therapy vs radical cystectomy in BCG-unresponsive non-muscle-invasive bladder cancer.

To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

Effect of complete transurethral resection on oncologic outcomes after radiation therapy for muscle-invasive bladder cancer.: Transurethral resection in radiation therapy.

To compare the oncologic outcomes of patients with non-metastatic muscle-invasive bladder cancer (MIBC) undergoing complete versus incomplete transurethral tumor resection (TURBT) prior to radiation therapy. Patients with non-metastatic MIBC who underwent curative-intent radiation therapy between 2002 and 2018 at ten Canadian institutions were retrospectively evaluated. Inverse probability of treatment weighting was performed using baseline characteristics. Differences in survival outcomes by complete and incomplete TURBT were analyzed. Of the 757 patients included, 66% (498) had documentation of a complete and 34% (259) an incomplete TURBT. Before adjustment, 121 (47%) and 45 (9%) patients who underwent incomplete and complete TURBT, respectively, were diagnosed with cT3-4 tumor (p < 0.001). After weight-adjustment, all baseline cohort characteristics were balanced (absolute standardized differences < 0.1). The adjusted median follow-up was 27 months. Adjusted survival analyses showed no significant difference in 5-year overall survival (48% vs 52%, 1.03 [0.82-1.29]; p = 0.8), cancer-specific survival (64% vs 61%, 0.93 [0.70-1.25]; p = 0.7), metastasis-free survival (43% vs 46%, 0.97 [0.79-1.19]; p = 0.8), and disease-free survival (32% vs 35%, 0.95 [0.79-1.15]; p = 0.7) between the two groups. Complete TURBT may be associated with clinical organ-confined disease. Extent of TURBT was not independently associated with oncologic outcomes in patients with MIBC treated with radiation therapy.

Pelvic organ-preserving radical cystectomy versus standard radical cystectomy in female patients diagnosed with bladder cancer

BackgroundPelvic organ-preserving radical cystectomy (POPRC) has been reported to result in a better postoperative quality of life in female with bladder cancer compared to standard radical cystectomy (SRC). However, its oncological outcomes remain a concern.Patients and methodsFemale patients with bladder cancer who underwent POPRC or SRC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to identify predictors of POPRC usage. To avoid the potential impact of baseline differences between groups on survival, a 1:2 propensity score matching (PSM) was implemented. After that, Kaplan-Meier curves and Log-rank tests were used to determine the significance of overall survival (OS) differences between patients in the SRC group and POPRC group. Finally, subgroup analysis based on predetermined indicators was performed.ResultsA total of 2193 patients were included with a median follow-up of 53 months, of whom 233 (10.6%) received POPRC and 1960 (89.4%) received SRC. No definitive predictors of POPRC were identified. Before PSM, POPRC resulted in comparable OS to SRC (HR = 1.09, p = 0.309), while after PSM, POPRC was associated with significantly worse OS (HR = 1.23, p = 0.038). In subgroup analyses, POPRC led to non-inferior OS (HR = 1.18, 95%CI 0.71–1.95, p = 0.531) in patients with non-muscle invasive bladder cancer (NMIBC) and T2 patients (HR = 1.07, p = 0.669), but significantly worse OS in T3 patients (HR = 1.41, p = 0.02).ConclusionCurrently, patients undergoing POPRC have not undergone strict screening, and candidates for POPRC should have more stringent criteria in the future to achieve satisfactory oncological outcomes. However, flaws in the study make more evidence needed to support our findings.

Adverse drug reactions of intravesical instillation therapy for bladder cancer: based on FDA adverse event reporting system

ABSTRACT Background Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment. Study design and methods Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events. Results The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity. Conclusion This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.

Markers in Identifying Pathological Complete Response Status in Muscle Invasive Bladder Cancer Patients Who Achieved Clinical Complete Response After Neoadjuvant Chemotherapy

BackgroundPrior research has demonstrated a discrepancy between pathologic and clinical staging in individuals with muscle-invasive bladder cancer (MIBC) following neoadjuvant chemotherapy (NAC). These findings were the major reasons for the under-usage of the bladder preservation strategy. Hence, we aim to explore the reliable markers in identifying pathological complete response (ypCR) status in MIBC patients who achieved clinical complete response (cCR) after NAC. MethodsBetween January 2016 and April 2023, 161 consecutive MIBC patients treated with NAC and achieved cCR were enrolled in the study. Patient clinicopathologic information was documented. Multivariate binary logistic regression was used for determining adjusted odds ratios (OR) and 95% confidence intervals (CI). It considered statistically significant when a P < .05. ResultsOf the 161 MIBC patients with cCR after NAC, 64.0% (103/161) achieved ypCR after RC. The independent factors for ypCR status were the origin of MIBC (secondary vs. Primary) with odds ratios (OR) of 0.433 (P = .027), the pathological type (pure vs. mixed) with OR of 3.556 (P = .003), concurrent carcinoma in situ (yes vs. no) with OR of 0.360 (P = .016), and lymphovascular invasion (yes vs. no) with OR of 0.271 (P = .007). ConclusionThis study demonstrated that primary MIBC, pure UC pathological type, absence of concurrent CIS, and LVI were significant predictors of ypCR in MIBC patients who achieved cCR after NAC and before surgery. These findings may contribute to the decision-making process of bladder preservation strategy in selected patients.

New therapeutic approaches for non-muscle invasive bladder cancer-is organ preservation also possible after BCG (Bacillus Calmette Guérin)?

Bacillus Calmette-Guérin (BCG) therapy is the standard of care in the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). In the absence of aresponse to BCG and persistent high-grade disease, cystectomy is recommended depending on the clinical risk. Avariety of targeted therapy approaches, which aim at immune- and gene-based molecular targets, such as PD-(L)1 and FGFR, are currently being investigated in randomized studies for BCG-unresponsive NMIBC. Furthermore, novel forms of application for instillation therapy, such as the TAR device, in combination with gemcitabine or erdafitinib are being investigated in clinical trials in order to extend the duration of action of the active substance on the urothelium. Thus, there are now many developments that could make bladder-preserving therapy with comparable survival data possible as an alternative to BCG or in the event of BCG failure. In the future, it will be necessary to clarify how BCG response can be predicted by using molecular markers and how to define risk groups that should primarily be given an alternative therapy to BCG.