Treatment Of Invasive Bladder Cancer Research Articles

Initially metastatic bladder carcinoma in a 31-year-old patient.

Bladder cancer is the fifth most common malignancy, peaks in incidence after the sixth decade of life. reports of the clinical behavior of bladder cancer specifically in young patients are restricted to small series. While some hereditary syndromes such as Li-Fraumeni or retinoblastoma carry an increased risk of urothelial tumors at an early age. their low prevalence means that few clinicians see such cases. This pathology occurs mainly in the male patient and with a prevalence of 4 % in the male patient younger than 40 years old. The same identified factors found in the elderly patient were identified in the youthful patients. Clinically, like in the older patients, hematuria, irritative symptoms (urgency, frequency, dysuria) and clinical decline were described before the confirmed diagnosis. Bladder tumors are usually superficial before the age of 40 therefore have a low aggressivity rate. Treatment of invasive bladder cancer in young patients does not differ from the treatment at an old age. Also, the prognosis of patients under 40 years of age with bladder carcinoma is claimed to be better than of those presenting in later life.

Potential cellular intravesical therapy for non-muscle invasive bladder cancer: Nectin-4 targeted CAR-T cell therapy

Bladder cancer poses a significant global health challenge, particularly with its prevalence in males and the increasing incidence rates in Europe. While non-muscle invasive bladder cancer can be managed with localized treatments, its recurrence remains a concern. Intravesical Bacillus Calmette-Guérin therapy triggers an immune response against cancer cells, yet recurrences post- transurethral resection of bladder tumor persist. Thus, innovative strategies are needed. We propose the use of Nectin-4 targeted chimeric antigen receptor T cell therapy to prevent non-muscle invasive bladder cancer recurrence and progression. Nectin-4 is expressed in non-muscle invasive bladder cancer, making it an ideal target. CAR-T cells engineered with Nectin-4 receptors can specifically eliminate cancer cells. By directly applying these cells intravesically, the limitations of CAR-T cell access to solid tumors are circumvented. However, challenges persist, such as the immunosuppressive microenvironment of bladder cancer. This can be addressed by combining intravesical Bacillus Calmette-Guérin with CAR-T therapy or utilizing immune checkpoint inhibitors. CAR-T therapy-related toxicities, like cytokine release syndrome, can be managed with IL-6 and IL-1 receptor inhibitors. Our hypothesis suggests that Nectin-4 targeted CAR-T cells have the potential to revolutionize bladder cancer treatment. This therapy could not only eliminate cancer cells but also prevent recurrence and progression by inducing immune memory. Although further research is needed, this innovative approach shows promise in the treatment of non-muscle invasive bladder cancer.

Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette-Guérin Immunotherapy of Bladder Cancer.

The clinical management of bladder cancer continues to present significant challenges. Bacillus Calmette-Guérin (BCG) immunotherapy remains the gold standard of treatment for non-muscle invasive bladder cancer (NMIBC), but many patients develop recurrence and progression to muscle-invasive disease (MIBC), which is resistant to BCG. This review focuses on the immune mechanisms mobilized by BCG in bladder cancer tumor microenvironments (TME), mechanisms of BCG resistance, the dual role of the BCG-triggered NFkB/TNFα/PGE2 axis in the regulation of anti-tumor and tumor-promoting aspects of inflammation, and emerging strategies to modulate their balance. A better understanding of BCG resistance will help develop new treatments and predictive biomarkers, paving the way for improved clinical outcomes in bladder cancer patients.

Abstract P29: GSTT2 AND THE RESPONSE TO BCG IMMUNOTHERAPY

Abstract Whilst M. bovis Bacillus Calmette-Guérin (BCG) therapy remains the gold-standard for treatment of high-risk non-muscle invasive bladder cancer (BC), 30-40% of patients fail therapy, resulting in disease recurrence and progression. A better understanding of the underlying mechanisms of BCG therapy can aid in revealing key response pathways, which may lead to the discovery of new targets, and in turn new approaches to treat BC. The glutathione-S-transferase theta 2 (GSTT2) gene is a member of the GST family. Loss of GSTT2 expression has been associated with modulation of intracellular ROS and BCG survival in BC cell lines. Retrospective analysis of BC patients revealed that patients with the GSTT2B deletion responded better to fewer instillations of BCG. To understand these responses, wild-type (WT) and GSTT2-knockout (KO) mice were implanted with MB49-PSA BC cells, in subcutaneous and orthotopic settings. Once tumors were established, the mice were treated with four weekly BCG instillations, after which the subcutaneous tumors and bladders were harvested for downstream analysis. Single-cell RNA sequencing of whole-bladders was used to identify specific cell clusters within the bladder, and to analyze differential gene expression. Hmga2, Ahnak and Peak1 were found to be differentially expressed in bladders from WT and GSTT2-KO mice. These genes are known to be involved in pro- and anti-tumorigenic pathways such as epithelial-mesenchymal transition and inflammation. Additionally, quantitative real-time PCR analysis in the subcutaneous and orthotopic tumors revealed differences in the expression of immune-related genes, especially markers of immune exhaustion such as PD-L1 and CTLA-4. Flow cytometry analysis of subcutaneous tumors also revealed differences in T-cell infiltration. Thus, loss of GSTT2 may influence the response to BCG therapy, through modulating downstream signaling pathways and immune responses. Elucidating such pathways can lead to a better understanding of the mechanism of BCG and its role as a therapy for BC. Citation Format: Mugdha Patwardhan, Kane Toh, Edmund Chiong, Ratha Mahendran. GSTT2 AND THE RESPONSE TO BCG IMMUNOTHERAPY [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P29.

Comparison of red and green light for treating non-muscle invasive bladder cancer in rats using singlet oxygen-cleavable prodrugs with PPIX-PDT.

It has been 30 years since Photofrin-PDT was approved for the treatment of bladder cancer in Canada. However, Photofrin-PDT failed to gain popularity due to bladder complications. The PDT with red light and IV-administered Photofrin could permanently damage the bladder muscle. We have been developing a new combination strategy of PpIX-PDT with singlet oxygen-cleavable prodrugs for NMIBC with minimal side effects, avoiding damage to the bladder muscle layer. PpIX can be excited by either green (532 nm) or red (635 nm) light. Red light could be more efficacious invivo due to its deeper tissue penetration than green light. Since HAL preferentially produces PpIX in tumors, we hypothesized that illuminating PpIX with red light might spare the muscle layer. PpIX-PDT was used to compare green and red laser efficacy invitro and invivo. The IC50 of invitro PpIX-PDT was 18 mW/cm2 with the red laser and 22 mW/cm2 with the green laser. The invivo efficacy of the red laser with 50, 75, and 100 mW total dose was similar to the same dose of green laser in reducing tumor volume. Combining PpIX-PDT with prodrugs methyl-linked mitomycin C (Mt-L-MMC) and rhodamine-linked SN-38 (Rh-L-SN-38) significantly improved efficacy (tumor volume comparison). PpIX-PDT or PpIX-PDT + prodrug combination did not cause muscle damage in histological analysis. Overall, a combination of PpIX-PDT and prodrug with 635 nm laser is promising for non-muscle invasive bladder cancer treatment.

Abstract 1827: Exploring the feasibility and pharmacological mechanism of bufadienolides for the treatment of non-muscle invasive bladder cancer

Abstract The majority of diagnosed bladder cancer (BC) patients is presenting with non-muscle-invasive bladder cancer (NMIBC). Although NMIBC generally exhibits a favorable prognosis, a considerable number of patients suffer from short-term recurrence, and high risks of progression to the more aggressive muscle-invasive bladder cancer (MIBC). Therefore, there is an urgent need for innovative treatments to improve outcomes for patients with NMIBC. For centuries, traditional Chinese medicine (TCM) has played a significant role in Asian society, with ongoing research to investigate the intricate relationship between TCM and treatment of cancers. Bufadienolides, the principal active components in Chansu, are derived from the aqueous extract of the parotoid glands and the dried secretion of the Asiatic toad. Bufadienolides have been reported to demonstrate significant antitumor and anti-inflammatory activities. This study aims to evaluate the feasibility and elucidate the pharmacological mechanisms that underlie the anticancer effects of bufadienolides in NMIBC. Our experiments show that bufadienolides significantly decrease cell viability, induce cell-cycle arrest at the sub-G1 phase, and activate apoptosis in NMIBC cells (RT112 and RT4). Protein analysis reveals the activation of apoptosis-related proteins (PARP, caspase-3, -8, -9) by bufadienolides in NMIBC cells. In conclusion, our findings suggest that bufadienolides present promising potential as therapeutic agents for NMIBC treatment. Citation Format: Chih-Chieh Tu, Mei-Chuan Chen, Chun-Han Chen. Exploring the feasibility and pharmacological mechanism of bufadienolides for the treatment of non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1827.

Patterns of treatment of high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients among Arab urologists.

To understand the treatment plans suggested for BCG-unresponsive non-muscle invasive disease (NMIBC) patients in the Arab countries and therapeutic decisions applied for BCG-naive patients during BCG shortage time. A 10-minute online survey was distributed through the Arab Association of Urology (AAU) office to urologists in the Arab countries who treat patients with NMIBC. One hundred six urologists responded to the survey. The majority of urologists had treated, in the past 6 months, > 10 patients with NMIBC who were considered BCG-unresponsive (55% of respondents). Radical cystectomy (RC) was the most popular treatment option (recommended by 50%) for these patients. This was followed by intravesical chemotherapy (30%), repeat BCG therapy (12%), resection with ongoing surveillance (8%). Clinical trials and intravenous checkpoint inhibitors were never selected. The most preferred intravesical chemotherapy was by ranking: 60% gemcitabine, 19% mitomycin C, 8% docetaxel, 8% gemcitabine/docetaxel, 4% sequential gemcitabine/mitomycin C, and 1% valrubicin. The use of intravesical chemotherapy appears limited by Arab urologists due to concerns regarding clinical efficacy (fear of progression) and the lack of clear recommendations by urology societies. Given the BCG shortage, which may vary per Arab country, Arab urologists have adjusted by prioritizing BCG for T1 and carcinoma in situ (CIS) patients over Ta, adapting intravesical chemotherapy, and reducing the dose/strength of BCG administered. Most physicians report an eagerness to utilize novel therapies to address the BCG deficit, especially to try intravesical chemotherapy. Even though Arab urologists are in the majority of cases selecting RC for BCG-unresponsive cases, one-third of them are most recently initiating intravesical chemotherapy as an alternative option. To further assist Arab urologists in the appropriate selection of BCG unresponsive high risk NMIBC patient treatments, enhanced education and pathway protocols are needed.

Systemic versus localized Bacillus Calmette Guérin immunotherapy of bladder cancer promotes an anti-tumoral microenvironment: Novel role of trained immunity.

Treatment for higher-risk non-muscle invasive bladder cancer (NMIBC) involves intravesical immunotherapy with Bacillus Calmette Guérin (BCG); however, disease recurrence and progression occur frequently. Systemic immunity is critical for successful cancer immunotherapy; thus, recurrence of NMIBC may be due to suboptimal systemic activation of anti-tumor immunity after local immunotherapy. We previously reported that systemically acquired trained immunity (a form of innate immune memory) in circulating monocytes is associated with increased time-to-recurrence in patients with NMIBC treated with BCG. Herein, we used a mouse model of NMIBC to compare the effects of intravesical versus intravenous (systemic) BCG immunotherapy on the local and peripheral immune microenvironments. We also assessed whether BCG-induced trained immunity modulates anti-tumor immune responses. Compared with intravesical BCG, which led to a tumor-promoting immune microenvironment, intravenous BCG resulted in an anti-tumoral bladder microenvironment characterized by increased proportions of cytotoxic T lymphocytes (CTLs), and decreased proportions of myeloid-derived suppressor cells. Polarization toward anti-tumoral immunity occurred in draining lymph nodes, spleen, and bone marrow following intravenous versus intravesical BCG treatment. Pre-treatment with intravesical BCG was associated with increased rate of tumor growth compared with intravenous BCG pre-treatment. Trained immunity contributed to remodeling of the tumor immune microenvironment, as co-instillation of BCG-trained macrophages with ovalbumin-expressing bladder tumor cells increased the proportion of tumor-specific CTLs. Furthermore, BCG-trained dendritic cells exhibited enhanced antigen uptake and presentation and promoted CTL proliferation. Our data support the concept that systemic immune activation promotes anti-tumor responses, and that BCG-induced trained immunity is important in driving anti-tumor adaptive immunity.

Caregiver experiences of caring for family members with urostomy: a qualitative study.

In China, bladder tumors rank first for morbidity and mortality among urological and reproductive system tumors. Total radical cystectomy plus urinary flow conversion is the gold standard for the treatment of muscle-layer invasive bladder cancer. With an increasing number of radical cystectomies each year, the number of patients living with urostomy is growing. After discharge, primary care of urostomy patients is given at home, and high demands are placed on home caregivers due to issues of privacy and the complexity of replacing the urostomy device. This research explored the challenges faced by the family caregivers of urostomy patients. We used descriptive qualitative research methods to conduct interviews with twenty-five family caregivers of patients with urostomy. Survey subjects were from five general hospitals. All interviews were recorded, transcribed, and analyzed using thematic analysis. Three critical challenges were identified-confusion, family crisis, and struggle psychology. Within these three themes, six sub-themes wereconstructed by coders. They were knowledge and skill deficiency, strong insecurities and uncertainties, role conflict, economic burden, emotional overwhelmed and calm acceptance. Family caregivers play a critical role in patient care, and especially in urostomy care. Caregiving is associated with significant challenges that hinder the family caregiver's ability to effectively care for the patient, further diminishing the caregiver's quality of life. Therefore, healthcare professionals should consider the challenges faced by family caregivers and take measures to obviate them through education, preparation, and support.

Does radical cystectomy have a better prognosis than bladder conservative treatment in the real world?

To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world. Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression-free survival, and rehospitalization. Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression-free survival (HR: 1.83, 95% CI: 1.12-3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99-3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03). Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life.

PIVOT-006: A phase 3, randomized study of cretostimogene grenadenorepvec versus observation for the treatment of intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) following transurethral resection of bladder tumor (TURBT).

TPS715 Background: Guidelines for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) recommend adjuvant intravesical (IVE) therapy or surveillance. Despite this, 30–60% of patients still recur, and these Guideline recommendations are lacking level-1 evidence. Thus, there is a considerable gap in knowledge and an unmet medical need for improved therapies in the adjuvant setting. Cretostimogene Grenadenorepvec is an oncolytic adenovirus designed to preferentially replicate in and kill cancer cells. The vector is transcriptionally regulated by the E2F promoter that is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, common in most IR-NMIBC bladder tumors. Additionally, the virus is engineered to selectively express GM-CSF, in order to induce a robust systemic anti-tumor immune response. PIVOT-006 is an open-label, multi-center, randomized Phase 3 study designed to assess the efficacy and safety of intravesical Cretostimogene after TURBT versus TURBT alone. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed IR-NMIBC with absence of nodal or metastatic disease at screening. IR-NMIBC, as defined by American Urologic Association-Society of Urologic Oncology Guidelines on NMIBC, is either a Low Grade (LG) stage Ta tumor that recurs within 12 months of prior LG or High Grade (HG) bladder cancer, a solitary LGTa tumor &gt;3cm in size, multifocal LGTa tumors, primary HGTa lesion &lt; 3cm in size, or a LGT1 tumor. Participants will be stratified by receipt of perioperative chemotherapy and tumor grade. Pts (N~450) will be randomized 1:1 to receive intravesical Cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2). Single dose perioperative intravesical chemotherapy at the time of TURBT is permitted. If intravesical NMIBC recurrence is noted in Cohort 2, participants will be eligible to receive intravesical Cretostimogene. In Cohort 1, intravesical Cretostimogene will be instilled in combination with n-dodecyl-B-D-maltoside (DDM, an inactive detergent) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples. The primary outcome measure is recurrence free survival. Secondary outcome measures include safety, tolerability, progression free survival, and time to next intervention. Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.

Recurrent Bacteriuria as a Prognosis Marker in the Adjuvant Treatment of Non-Muscle Invasive Bladder Cancer

PurposeBacteriuria may affect the response to adjuvant therapy in non-muscle invasive bladder cancer (NMIBC). The main aim of this study was to examine the effect of recurrent bacteriuria (RB) on the prognosis of NMIBC in women receiving intravesical therapy. Materials and MethodsWe designed a prospective observational study from 2012 to 2019. We included women with bladder cancer treated with transurethral resection of the bladder (TURB) and adjuvant intravesical treatment. Significant bacteriuria was defined as a presence in urine cultures at or above 100,000 colony-forming units per millilitre. The recurrent bacteriuria group included patients with significant bacteriuria in at least two determinations in 6 months or in 3 or more determinations in a year. The institutional board approved the study. ResultsOne hundred thirty-six patients diagnosed with NMIBC participate in the study, of whom 100 met the inclusion criteria. During follow-up, 48 were categorized in the RB group and 52 formed the non-bacteriuria group (NB). RB Group Had a Better OutcomeEight patients (16.67%) experiencing a recurrence of the same grade, with no progression to a higher-grade tumor or muscle-invasive tumor. In the NB group, 18 (34.6%) patients presented a recurrence (P = .001) and 22 (42.3%) progressed to a higher-grade tumor or muscular invasion (P = .001). The presence of RB was identified as a predictor of good response in multivariate regression with a relative risk of 0.13 (P = .018) ConclusionsFemale patients with RB had a better response to adjuvant treatment for NMIBC. The RB group showed lower rates of tumor recurrences and progression.

Robot-assisted radical cystectomy with neobladder diversion in females: safety profile and functional outcomes

ObjectiveRadical cystectomy (RC) is a standard treatment for localized muscle invasive bladder cancer and high-risk or very high-risk non-muscle invasive bladder cancer. In women, traditionally RC is performed with hystero-adnexectomy and resection of the anterior vaginal wall, often resulting in sexual disorders. Vaginal-sparing techniques have been developed to improve functional outcomes. The present study explores the safety and the functional outcome of this approach. MethodsWe retrospectively analyzed all consecutive female patients undergoing robot-assisted RC (RARC) with neobladder diversion between October 2017 and February 2022. The indications for vaginal-sparing RC were absence of tumor on bladder neck or urethra and no sign of infiltration of posterior bladder wall at preoperative staging on MRI. Functional results were evaluated with the aid of five questions out of the Bladder Cancer Index (BCI) questionnaire. Complications were reported according to Clavien-Dindo classification and cancer control was evaluated for recurrence free and cancer specific survival. ResultsA total of 22 female patients underwent RARC with neobladder. Neoadjuvant chemotherapy was given in 17 (77%) cases. Clavien-Dindo III-IV complications occurred in four (18%) cases. After a mean follow-up of 29 (interquartile range 16–44) months, six patients (27%) developed distant metastases, and one woman (5%) loco-regional relapse. Sexual-sparing surgery was performed in 19 (86%) patients, in the others the anterior vaginal wall was resected, but neobladder was still performed. During daytime, no patients reported total incontinence and 73% reported total continence or only occasional leaks. Sexual results showed that 47% of women regained sexual activity after surgery, with a quality reported as “good” or “very good” in 40% of all 19 cases. ConclusionRARC in female with anterior vaginal wall preservation is feasible. The approach showed a good safety profile, with satisfying results on continence and sexual activity. Sexual-sparing approaches should be carried out after correct patient selection.

Theranostic imaging and treatment of chemotherapy resistant muscle invasive bladder cancer by targeting FAP and CXCR4: The Bladder BRIDGister experience.

550 Background: Patients with muscle invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NACT) have improved prognosis. Previously we did show that luminal tumors respond better to NACT (Ecke et al 2022), while the radioligand targets CXCR4 and FAP are found in chemoresistant, stroma-associated tumors. The objective of this study was to exploit the expression of CXCR4 &amp; FAP for theranostic imaging &amp; treatment in selected patients by radioligand instillation into the bladder to justify subsequent adopted clinical trials within the Bladder BRIDGister framework. Methods: FFPE tumor tissues from 511 TURB samples were prospectively collected as part of the Bladder BRIDGister. RNA was extracted by commercial kits, relative gene expression of subtyping markers and radioligand target genes were analyzed by RT-qPCR. Hierarchical clustering, Kruskal-Wallis and contingency tests were done by JMP 9.0.0 (SAS software). PET/CT Imaging by CXCR4 and/or FAP instillation was performed in selected patients followed by systemic radioligand application after completion of cisplatinum based NACT to enable improved staging. Results: The prospective molecular registry cohort consisted of 511 bladder cancer patients included into the Bladder BRIDGister (median age: 75, male 74% vs. female 26%) with 5% Tis, 54% Ta, 16% T1 and 15% T2 stage and concomitant CIS being in 7%. CXCR4 expression was negatively associated with ERBB2 &amp; FGFR3 mRNA (r=-0,3021 and r=-0,3326, p&lt;0,0001). Inverse relation of FAP expression with ERBB2 &amp; FGFR3 was even more pronounced (r=-0,4883 and r=-0,5177, p&lt;0,0001). Clustering validated that CXCR4 and FAP are elevated in non-luminal tumors not responding to NACT. Exemplarily one stromal rich pT2 G3 MIBC patient with elevated FAP expression, who was predicted to be unresponsive to NACT, was selected for FDG and FAP PET/CT imaging after two cycles of NACT. Indeed metastatic lesion were detected in the liver and pancreatic tissue. FAP imaging revealed to be more sensitive than conventional FDG imaging. In a next step 68Ga-CXCR4 was instilled into the bladder of a patient with NACT-resistant MIBC rejecting cystectomy to establish a non-systemic approach for radioligand therapy. Theranostic instillation imaging revealed strong uptake into the invading MIBC and subsequent instillation therapy with 177Lu-FAP led to partial remission and increased immune cell infiltration indicating initial effectivity. Conclusions: Expression of the radioligand targets CXCR4 and FAP are associated with aggressive stromal and basal like tumors being resistant to NACT. This could be validated by selecting patients for FAP &amp; CXCR4 PET/CT imaging. Instillation of radioligands into the bladder revealed to be safe with first signs of effectivity justifying clinical approaches as part of phase 1 / 2 clinical trials.

Retracted: The Use of BT-ESD Technology under General Intravenous Anesthesia in the Treatment of Nonmuscle Invasive Bladder Cancer and the Effect of PI3K/Akt Signaling Pathway on Tumor Recurrence.

[This retracts the article DOI: 10.1155/2021/8860745.].

Hydrogel: a new material for intravesical drug delivery after bladder cancer surgery.

The standard treatment for non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT). However, this procedure may miss small lesions or incompletely remove them, resulting in cancer recurrence or progression. As a result, intravesical instillation of chemotherapy or immunotherapy drugs is often used as an adjunctive treatment after TURBT to prevent cancer recurrence. In the traditional method, drugs are instilled into the patient's bladder through a urinary catheter under sterile conditions. However, this treatment exposes the bladder mucosa to the drug directly, leading to potential side effects like chemical cystitis. Furthermore, this treatment has several limitations, including a short drug retention period, susceptibility to urine dilution, low drug permeability, lack of targeted effect, and limited long-term clinical efficacy. Hydrogel, a polymer material with a high-water content, possesses solid elasticity and liquid fluidity, making it compatible with tissues and environmentally friendly. It exhibits great potential in various applications. One emerging use of hydrogels is in intravesical instillation. By employing hydrogels, drug dilution is minimized, and drug absorption, retention, and persistence in the bladder are enhanced due to the mucus-adhesive and flotation properties of hydrogel materials. Furthermore, hydrogels can improve drug permeability and offer targeting capabilities. This article critically examines the current applications and future prospects of hydrogels in the treatment of bladder cancer.

BCG immunotherapy promotes tumor-derived T-cell activation through the FLT3/FLT3LG pathway in bladder cancer.

Bladder instillation therapy is a common treatment for superficial or nonmuscle invasive bladder cancer. After surgery or reresection, chemotherapy drugs (epirubicin) or medications such as Bacillus Calmette-Guérin (BCG) are used for bladder instillation therapy, which can reduce the risk of bladder cancer recurrence and progression. However, the specific mechanism by which BCG stimulates the antitumor response has not been thoroughly elucidated. Additionally, although BCG immunotherapy is effective, it is difficult to predict which patients will have a positive response. In this study, we explored the BCG-induced immune response and found that high levels of Fms-related receptor tyrosine kinase 3 ligand (FLT3LG) were expressed after BCG treatment. This FLT3LG can directly act on CD8+ T cells and promote their proliferation and activation. The use of FLT3 inhibitors can neutralize the antitumor effects of BCG. In vitro experiments showed that FLT3LG can synergize with T-cell receptor activators to promote the activation of tumor-derived T cells. This study partially elucidates the mechanism of CD8+ T-cell activation in BCG immunotherapy and provides a theoretical basis for optimizing BCG instillation therapy in bladder cancer.

膀胱部分切除术在肌层浸润性膀胱癌治疗中的作用分析

膀胱部分切除术在肌层浸润性膀胱癌治疗中的作用分析

Comparative Analysis of Very Reduced vs Full Dose BCG Treatment for High-Risk Non-Muscle Invasive Bladder Cancer: A Contemporary Experience from Chile

BACKGROUND: Adjuvant bacillus Calmette-Guérin (BCG) is recommended for high-risk (HR) non-muscle invasive bladder cancer (NMIBC), but BCG shortages have led to exploration of reduced-dose regimens and shortened maintenance durations out of necessity, with limited data on treatment efficacy in Latin America. OBJECTIVE: Oncological outcomes of HR-NMIBC patients treated with reduced (RD,1/4th dose) vs full dose (FD) BCG instillations of Danish Strain 1331 BCG. METHODS: We performed a retrospective study of HR-NMIBC patients treated with BCG between 2003 and 2022 at our center in Santiago Chile. We stratified patients according to either RD (1/4th dose) or FD BCG. Univariate and multivariable Cox regression models were used to predict recurrence. Kaplan-Meier method was used to calculate survival estimates. RESULTS: Of a total of 200 patients, 116 (58%) had RD and 84 (42%) FD BCG. Median follow-up was 57 months (IQR: 29–100). Patients who received FD BCG had a lower risk of recurrence (HR: 0.41, 95% CI 0.22–0.74) and high-grade (HG)-recurrence (HR: 0.30, 95% CI 0.15–0.61; p = 0.001). More patients in the RD vs FD group progressed to MIBC (10/84 vs 2/116; p = 0.18). Additionally, patients were less likely to stop BCG treatment in the RD group compared to the FD group due to toxicity (5% vs 11%, p = 0.14). CONCLUSIONS: A 1/4th dose of Danish Strain 1331 BCG treatment was associated with worse recurrence free rate and HG-recurrence rate in our cohort. Patients with RD had lower discontinuation treatment rates due to a reduced toxicity profile. These findings would suggest that RD BCG would compromise oncological outcomes in HR-NMIBC patients.

Intravesical Ty21a treatment of non-muscle invasive bladder cancer induces immune responses that correlate with safety and may be associated to therapy potential

BackgroundStandard of care treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette Guérin (BCG) is associated with side effects, disease recurrence/progression and supply shortages. We recently showed in...