Summary | Case Presentation: This case focused on recurrent low-grade NMIBC. 60 year old woman with multiple small papillary tumors on surveillance cystoscopy. Prior cystoscopies were all low-grade Ta disease. TURBT demonstrates multifocal LG Ta TCC. By definition, this patient is “intermediate” risk. Therefore, both intravesical BCG and chemotherapy are options.
- Patient went on to receive 6 cycles of mitomycin-C – recurred 6 months later
- Went on to receive induction BCG, recurred 4 months later
- Still LG Ta disease
Discussant 1: P.U. Malstrom (Uppsala, Sweden)
Dr. Malstrom started by highlighting that this patient is at a much higher risk of recurrence than progression – hence, progression is not that much of a concern.
- 62-78% risk of recurrence
- 6% risk of progression at 5-years
However, if active treatment is preferred, there are a few alternatives, albeit many with inferior results.
1) Chemotherapy alternatives
- Doxurubicin, epirubicin, IFN-alpha and IFN-gamma were associated with decreased risk of recurrence than TURBT alone (RR 0.63 to 0.80) – while not as good as MMC and BCG, still somewhat effective
- Intravesical gemcitabine (Shelley BJUI 2012) – systematic review of 6 trials, 704 patients
- Similar in intermediate risk, but works well in BCG refractory disease
- However, evidence limited due to differences in clinical setting
- Epirubicin+interferon – Marttila Eur Urol 2016 – when compared to BCG, for frequently recurrent LG TaT1 disease, effective but not as much as BCG
2) Device-assisted intravesical therapy
- Electromotive drug administration (EMDA) – in conjunction with chemotherapy
- Systematic review 2017 – reviewed 3 trials (all with the same PI)
- Quality of evidence for efficacy was unable to be addressed
- May provide some benefit
- Chemohypothermia
- Systematic review 2016 – promising results but lacked high quality clinical trials
- Larger trial data is needed!
Discussant 2: P. Black
Dr. Black, for the most part, agreed with the points made by Dr. Malstrom. He added that, as the risk of progression is so low, radical cystectomy is not part of the discussion! He feels that additional intravesical therapy is unlikely to succeed – as demonstrated by lack of efficacy above. Novel therapies represent this patient’s only real chance of NMIBC control.
Novel therapies fall into three categories:
1) Immunotherapy
- Immune checkpoint blockade – trials ongoing
- Enhanced BCG
- Check the strain! Growing evidence that not all strains are equivalent. However, now that this patient has received BCG already, switching strains unlikely to be beneficial.
- Many trials testing BCG adjuncts that may enhance BCG efficacy – many with promising early results, but all pending clinical trial. Includes IL15-superagonist complex (ALT-803), caspase-3 expression, and secretion of listeriolysin.
2) Targeted therapy
- Non-specific to bladder cancer
- Includes rAD-IFN alpha-2B (Nadofaragene firadenovec (Adstiladrin®)), BC819, and Oportuzamab
3) Precision therapy
- Targets pathways specific to bladder cancer
- One ripe potential target is FGF3 targeting agents – with 70-80% expression in low-grade disease, this could be an important player in this disease space.
He recommends clinical trial enrollment!
Presented by: M. Roupret Paris, France
Discussants: P. Black, Vancouver, Canada and P.U. Malstrom, Uppsala, Sweden
Written by: Thenappan Chandrasekar, MD Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark