BCG Not Supported For Patients With High-Risk NMIBC

Author: By Shreeya Nanda, Senior medwireNews Reporter

medwireNews: Treatment with Bacillus Calmette-Guérin (BCG) does not delay disease progression in patients with non-muscle-invasive bladder cancer (NMIBC) categorised as high risk according to the new European Association of Urology (EAU) criteria, findings indicate.

However, individuals with very high-risk disease do benefit from BCG relative to transurethral resection of bladder tumour (TURBT) with or without chemotherapy, noted presenting author Paolo Gontero, from the University of Turin School of Medicine in Italy, at the 37th Annual European Association of Urology Congress in Amsterdam, the Netherlands.

Outlining the rationale for the study, he explained that “[t]he role of BCG on disease progression of NMIBC remains controversial with a 2002 literature-based meta-analysis showing a positive impact and a subsequent 2009 individual patient data meta-analysis reporting a non-significant trend compared to Mitomycin C.”

The team therefore investigated the impact of BCG on progression in the new EAU high- and very high-risk prognostic groups in a cohort comprising 5295 patients diagnosed with primary NMIBC at one of 17 institutions and treated at their physician’s discretion with BCG, TURBT followed by intravesical chemotherapy or TURBT alone.

Paolo Gontero pointed out to the audience that the TURBT groups of this study population were previously used to develop the new EAU risk groups, which take into account the WHO 1973 and 2004/2016 grading classifications.

Among the 1657 patients considered high risk based on WHO 2004/2016 grading, disease progression – defined as the development of muscle-invasive and/or nodal and/or metastatic disease – occurred in a comparable 12.4% of those who received BCG and 9.2% of those given TURBT with or without chemotherapy.

And there was no significant difference in time to progression between the treatment groups, even after adjusting for other pathological prognostic factors and repeat TURBT.

By contrast, in the 368 very high-risk patients as per WHO 2004/2016 grading, 21.6% of BCG-treated patients experienced progression compared with 31.3% of those who received TURBT with or without chemotherapy (hazard ratio=1.93).

After adjustment for confounding factors, use of BCG was associated with a significant 48% reduction in the risk of progression in these patients relative to TURBT with or without chemotherapy.

“Analyses of risk categories based on the 1973 WHO grading system yielded similar results,” reported the presenter.

Speaking to medwireNews, Paolo Gontero said that “while the lack of impact on the high-risk category may not be unexpected (given the [previous] controversial findings on disease progression), the efficacy on the very high-risk category was rather a surprise.”

Nevertheless, he believes the data are “too premature” to prompt a change in the current treatment guidelines.

“In spite of the lack of impact on progression in the high-risk category, BCG remains the most powerful intravesical treatment for recurrence and should therefore represent the initial treatment of choice for this disease category”, Paolo Gontero stressed.

“Conversely, in spite of the efficacy of BCG, a bladder cancer at very high risk of progression still carries a significant risk to undergo disease progression at 5 years and hence radical surgery remains the mainstay treatment option.”

Looking to the future, he said: “While I find it difficult to propose an RCT [randomised controlled trial] comparing BCG versus cystectomy in very high-risk patients, I think the lack of efficacy on progression makes an RCT to compare BCG versus chemotherapy feasible in high-risk disease.

“This could help to position a better tolerated treatment option in the context of a disease where BCG has always been considered the only acceptable option.”

Reference

• Gontero P, Dominguez-Escrig JL, Van Rhijn BWG, et al. Assessing the impact of BCG on progression of NMIBC in the new EAU high risk and very high-risk groups. 37th Annual EAU Congress; Amsterdam, the Netherlands: 1–4 July 2022.