EAU 2023: Immunological Changes Following Blue Light Cystoscopy with Hexaminolevulinate in Bladder Cancer

(UroToday.com) The 2023 European Association of Urology (EAU) annual congress held in Milan, Italy between March 10^th and 13^th, 2023 was host to an abstract session addressing cell biology, novel biomarkers, and trials in non-muscle invasive bladder cancer. Professor Lars Dyrskjøt presented the results of a study evaluating immunological changes following blue light cystoscopy with hexaminolevulinate in bladder cancer.

Studies have demonstrated that photodynamic diagnosis, via an improved sensitivity, may enhance tumor detection, and thus improve complete tumor resection during transurethral resection of bladder tumors (TURBTs). Hexaminolevulinate is a commonly used photosensitizing agent in this setting. Hexaminolevulinate is administered intravesically with photoactive porphyrins preferentially accumulating in bladder lesions, which upon illumination with a blue light cystoscope system releases energy as red fluorescent light, enhancing tumor visualization.

TURBT performed with hexaminolevulinate-enhanced blue light imaging has been shown to reduce bladder cancer recurrence rates, compared to white light cystoscopy.¹ A recent study using an orthotopic model of bladder cancer in rats demonstrated that utilization of hexaminolevulinate blue light is associated with enhanced immune activation, as evident by tumor infiltration with CD3+ and CD8+ T cells.² This suggests a potential clinical treatment effect beyond pure visualization and detection. As such, the investigators evaluated for changes in the tumor microenvironment in bladder cancer patients treated with blue light cystoscopy-guided TURBT compared with white light cystoscopy-guided TURBT.

This study included a total of 39 patients with bladder cancer who subsequently underwent a radical cystectomy. Of these 39 patients:

• 19 underwent blue light cystoscopy-enhanced TURBT
• 20 underwent white light cystoscopy

Formalin-fixed, paraffin-embedded (FFPE) tissue blocks (n=78) were collected from paired TURBT and cystectomy specimens for all 39 patients. The yumor tissue was stained using multiplex immunofluorescence (CD3, CD8, FOXP3, CD20, CD68, and CD163) and immunohistochemistry (pan-cytokeratin, programmed death 1 [PD-1], and programmed death ligand 1 [PD-L1]). A digital image analysis quantified staining results within the carcinoma cell and stromal parts of the tumor.

There were significant differences in the expression profiles of several immune cell markers when comparing the radical cystectomy tumor specimens between the two cohorts. The investigators noted a decrease in stromal infiltration of both cytotoxic T lymphocytes (CTLs; p=0.024) and B cells (p=0.041) in the blue light-TURBT group

Among TURBT specimens, the investigators found:

• A lower fraction of stroma cells expressing PD-1 in the blue light TURBT group (p = 0.011).
• A significantly higher ratio of macrophages to T cells in the stroma region in blue light cystoscopy guided TURBT group (p = 0.008).

The investigators concluded that in this small pilot study of bladder cancer patients undergoing a radical cystectomy, exposure to hexaminolevulinate within the context of blue-light enhanced-TURBT may affect the immune cell composition and tumor microenvironment. Further studies are needed to verify this and document a clinical impact.

Presented by: Professor Lars Dyrskjøt, Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

1. Maisch P, et al. Blue versus white light for transurethral resection of non-muscle invasive bladder cancer. Cochrane Database Syst Rev, 2021.
2. Lamy L, et al. Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate and Blue Light in Combination with Checkpoint Inhibitor in an Orthotopic Model of Rat Bladder Cancer. Biomedicines, 2022.