Best of EAU: Highlights on bladder cancer

In the Best of EAU21 session on bladder cancer, Prof. Morgan Rouprêt (Pitié-Salpêtrière Hospital, Paris, France) highlighted 4 noteworthy abstracts [1]. Omitting antimicrobial prophylaxis appears safe in patients undergoing transurethral resection of bladder tumour (TURB); a biomarker test may help to reduce unnecessary cystoscopies in patients with non-muscle invasive bladder cancer (NMIBC); molecular subtyping can improve clinical risk stratification by identification patients at risk of Bacillus Calmette-Guérin (BCG) failure; and nadofaragene firadenovec represents a potential novel treatment option for patients with high-grade BCG-unresponsive NMIBC.

Antimicrobial prophylaxis in TURB

A multicentre, randomised controlled trial assessed whether omitting antimicrobial prophylaxis is safe in patients undergoing TURB. The primary endpoint was post-operative fever.

Of 459 included patients, 202 (44.1%) received antimicrobial prophylaxis and 257 (55.9%) did not. Results indicated that fever occurred in 6 (2.9%) patients with antimicrobial prophylaxis versus 8 (3.1%) without antimicrobial prophylaxis (P=0.44). Furthermore, no differences were found for (clot) retention (P=0.20), tumour size (P=0.20). A multivariable, logistic regression demonstrated no significant harm in omitting antimicrobial prophylaxis when controlled for (clot) retention and tumour size (P=0.85). This data demonstrated that omitting antimicrobial prophylaxis was safe in patients undergoing TURB without an indwelling, pre-operative catheter/nephrostomy/DJ and a negative pre-operative urinary culture [2].

Reducing the frequency of follow-up cystoscopies

To detect recurrence and progression, patients with NMIBC require frequent follow-up cystoscopies. The current multicentre study assessed whether the urinary biomarker test ADXBLADDER could aid in reducing unnecessary follow-up cystoscopies, improving quality of life, and decreasing costs [3].

Of all included patients (n=1,416), 126 (8.9%) experienced a recurrence, 41 (2.9%) of whom recurring with a high-grade tumour and/or carcinoma in situ (CIS). In a subgroup of 721 patients with non-invasive, low-grade tumour (no CIS) at the previous visit, 85 (11.8%) recurred, 13 (1.8%) had a high-grade tumour and/or CIS. ADXBLADDER was the only significant variable for high-grade tumour and/or CIS in patients that previously had a low-grade tumour without CIS. ADXBLADDER had a sensitivity of 69.2% and a specificity of 75%. A less intensive follow-up surveillance schedule utilising this ADXBLADDER test could lead to a reduction of up to 60% in unnecessary cystoscopies during follow-up.

Transcriptome sequencing of BCG-treated bladder cancer

Patients with T1 high-grade bladder cancer undergo TURB followed by adjuvant intravesical instillations with BCG. Current clinical risk stratification is insufficient to identify patients at risk of BCG failure. To this end, the current study aimed to identify molecular predictors of BCG failure.

Gene expression profiling of primary BCG-naïve patients with T1 high-grade bladder cancer identified 3 molecular subtypes that corresponded to clinical outcome after BCG therapy. So, molecular subtyping can improve clinical risk stratification by identification of patients with BCG subtype 3 tumours that are more suitable candidates for early radical cystectomy or novel bladder-sparing treatments given the poor outcome if treated by BCG [4].

Gene therapy for NMIBC

Despite optimal treatment, >50% of patients with NMIBC who have an initial response to BCG will experience recurrence and progression. Because treatment options are limited, there is an unmet need for local, effective, bladder-preserving treatment options.

Nadofaragene firadenovec is a non-replicating recombinant type 5 adenovirus vector-based gene therapy that delivers a copy of the human IFNA2b gene. Its safety and efficacy were assessed in a phase 3 trial (NCT02773849) that included 157 patients with high-grade, BCG-unresponsive NMIBC [5].

The results demonstrated no significant differences in response rates at 3 and 15 months between diverse subgroups, including men versus women, age groups, BCG-refractory versus BCG-relapsed, ≤3 versus >3 prior lines of treatment, 0 or ≥1 prior non-BCG regimens, and ≤3 or >3 prior courses of BCG.

These results demonstrated that nadofaragene firadenovec is effective regardless of patient characteristics or prior treatment history. Nadofaragene firadenovec represents a potential novel treatment option for patients with high-grade BCG-unresponsive NMIBC that advance in the current treatment paradigm.

1. Rouprêt M. Best of EAU21: Bladder Cancer. EAU21 Virtual, 8–12 July 2021.
2. Baten E, et al. P0733, EAU21 Virtual, 8–12 July 2021.
3. Sylvester RJ, et al. P0725, EAU21 Virtual, 8–12 July 2021.
4. De Jong FC, et al. P0442, EAU21 Virtual, 8–12 July 2021.
5. Narayan V, et al. P0745, EAU21 Virtual, 8–12 July 2021.

 

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Posted on 31 August, 2021