Intravesical thermochemotherapy in the treatment of high-risk and very high-risk non-muscle-invasive urothelial bladder cancer: a single-arm study.

AIM: Intravesical thermochemotherapy, also known as HIVEC (Hyperthermic Intra-VEsical Chemotherapy), represents an alternative adjuvant topical treatment for non-muscle-invasive urothelial bladder cancer (NMIBC). High-risk (HR) and very HR tumors carry a substantial risk of recurrence and progression. In this study, we present our own results using HIVEC as an alternative to unavailable Bacillus Calmette-Guérin (BCG) vaccine in the treatment of such groups of patients. METHODS: During the period of November 2014-June 2022, a total of 47 patients with HR and very HR NMIBC underwent treatment with HIVEC after transurethral resection. They were given an induction of 6 instillations with/without a maintenance. The aim was to evaluate the time to recurrence, event-free survival (recurrence or progression), as measured by Kaplan-Meier analysis, the effect of maintenance treatment and other factors on survival (log-rank test and multivariable Cox regression analysis), and complications. RESULTS: The median follow-up for patients who did not experience an event was 32 months. The median time to HR (high grade and/or T1 tumor) recurrence in those who recurred was 15 months. The survival rate without HR recurrence at 12, 24, and 48 months was 84, 70, and 59%, respectively. Progression was detected in 10.6% of patients, which translated to 89% of patients living without progression after 24 months. Maintenance treatment (defined as more than six instillations) and presence of CIS significantly correlated with risk of HR recurrence (Hazard ratio 0.34 and 3.12, respectively). One female patient underwent salvage cystectomy due to contractory bladder, and 19.1% of patients experienced transient lower urinary tract symptoms. CONCLUSION: Based on our experience, HIVEC represents an adequate and safe alternative treatment for HR and very HR NMIBC in situations where BCG is not available or radical cystectomy is not an option for the patient. However, high-quality data from prospective randomized studies are still lacking, and thus, thermochemotherapy should still be regarded as an experimental treatment modality.

Transurethral resection of bladder cancer with or without fluorescence.

PURPOSE OF REVIEW: Transurethral resection of bladder cancer (TURBT) is in its standard form an inherently imperfect technique. Fluorescence-guided photodynamic diagnosis (PDD) represents one way to improve the outcome by enhancing tumour detection. Fluorescence has been used in connection with bladder cancer since the 1970s, with a number of studies being published since then. However, the method is still not recommended as a standard part of TURBT mainly because of the limited level of evidence of concerned studies, questionable cost-effectiveness and even contradictory results. The review lists the latest articles covering this topic. RECENT FINDINGS: Several recently published meta-analyses reviewed a series of randomized controlled trials (RCTs) concerning PDD assisted TURBT. Results were generally supporting the positive effect on reduction of recurrence rate. However, the mentioned meta-analyses are overlapping in terms of reviewed RCT that provide only a low level of evidence according to a recent Cochrane review. Supposed limitations of PDD (timing of the procedure, low specificity) and possible solutions are also covered. SUMMARY: Most of the published data confirmed reduced early recurrence rate after PDD assisted TURBT comparing to standard TURBT. Its impact on late recurrence rate, progression rate or cost-effectiveness has not been sufficiently demonstrated.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex.

Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.