The European Association of Urology (EAU) Congress is the largest and most influential urology conference in Europe and will showcase the latest and most relevant scientific advances in the field of urology. The conference selected 17 abstracts for discussion as the Best Abstract

2024/05/0916:18:33 regimen 1234

The European Association of Urology (EAU) Congress is the largest and most influential urology conference in Europe and will showcase the latest and most relevant scientific advances in the field of urology. The conference selected 17 abstracts for discussion as the Best Abstract - DayDayNews

The European Association of Urology (EAU) Congress is the largest and most influential urology conference in Europe and will showcase the latest and most relevant scientific advances in the field of urology. The conference selected 17 abstracts for discussion as the Best Abstract section. One of them, a study on a new risk stratification method for high-risk non-muscle invasive bladder cancer, deserves attention. Yimaitong summarizes it as follows.

Research Background

Bacillus Calmette-Guerin (BCG) infusion is the standard treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC), but only 50% of patients can benefit from it. The study conducted risk stratification based on clinicopathological characteristics. The molecular characteristics of BCG treatment failure have not been fully studied. This study aimed to improve risk stratification of high-risk NMIBC and identify molecular correlates of treatment failure through whole-transcriptome analysis.

Research Methods

Researchers conducted a retrospective analysis of patients with primary high-risk NMIBC who received BCG therapy. Cohort A included 132 BCG-naïve patients (69 BCG non-responders vs 63 BCG responders) and 44 patients who relapsed after BCG treatment. RNA sequencing was performed on the above patients. The primary endpoint was progression-free survival (PFS), defined as the time from diagnosis to progression to muscle-invasive or (lymph node) metastatic bladder cancer. The study used consensus clustering method to analyze molecular subtypes, followed by differential expression analysis, pathway analysis, immune deconvolution and regulatory analysis to study the subtypes related to PFS. The results were validated in cohort B (151 BCG treatment-naïve patients).

Research Results

RNA sequencing analysis showed that there are 3 BCG response subtypes (BRS). Multivariate analysis results showed that compared with BRS1/2 patients, BRS3 patients had shorter PFS (cohort A, p<0.01).> macrophages ) confirmed that BRS3 tumors highly express EMT-basal markers and have immunosuppressive characteristics. The association between BRS and PFS was verified in Cohort B. The

BRS stratification method can improve the currently recommended risk stratification method based on clinical case variables. Relapse after BCG treatment is mostly BRS3 subtype. The study also discovered several druggable regulators of BRS3 (TGFβ, DDR2, etc.) related to resistance to checkpoint inhibitors, which can be used as potential molecular targets and new treatment options for patients who do not respond to BCG.

Conclusion

Molecular typing revealed that tumors in high-risk NMIBC patients are aggressive and poorly responsive to BCG. This study provides a novel clinical tool to improve the identification of patients with NMIBC who are at higher risk of progression and help patients choose early radical cystectomy or receive subtype-directed therapy.

References:

De Jong F.C., Laajala T.D., Hoedemaeker R.F. et al. Non-muscle invasive bladder cancer subtypes with differential response to intravesical bacillus Calmette-Guerin treatment. 37th Annual EAU Congress. Abstract 0068.

Editor: LR

Reviewer: LR

Execution: LR

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