EAU 2018: How Should I Manage a Patient with Tumour Recurrence Despite Adequate BCG?

Copenhagen, Denmark (UroToday.com)  This is one of a series of case-based debates. Each is set up as follows: 2 min case-presentation, 5-min discussant presentation (two sides of the debate, discussion), summary 2 minutes. This series was arranged by Dr. Kamat, Dr. Grossman, and Dr. Stenzl.

Summary | Case Presentation: 64 year old man, a healthy triathlete , who presents with gross hematuria. CTU demonstrates normal upper tracts. Cystoscopy – 3 cm right lateral wall tumor. TURBT – T1 HG pure urothelial carcinoma, muscle present but not involved.

  • Re-TURBT: small focus CIS, no other lesions. Base of tumor negative.
  • 6 weeks induction BCG
  • 3+6 month cysto negative
  • 9 month cysto – 0.5 cm tumor at the dome
  • TURBT: Ta HG TCC + CIS (muscle present and not involved)
  • Rest of the bladder negative on WLC and BLC
By definition, this patient is BCG unresponsive. There are 3 qualifications for this definition:

1. Recurrence of HG disease while on BCG maintenance – as in this patient
2. Persistent HG disease at 6 months cysto after induction BCG and maintenance BCG
3. Progression from Ta/Tis  T1 at 3 month cysto after induction BCG

Discussant  1: P. Gontero – the case for conservative management

He started by stating that he, clinically, would not conservatively treat the patient – as he is BCG unresponsive (FDA designation) or BCG refractory (EAU guidelines), and he is young, otherwise healthy. 

Per the EAU guidelines – recommendation is for Radical Cystectomy. Bladder sparing is only for patients unfit for surgery.

What are this patient’s risks?

1. Risk of progression to MIBC. Can it be predicted?
- Unfortunately, there are no risk tables for this disease space
- Additionally, the impact of CIS is unknown
- While we know that patients that are downstaged probably do better than those who are not, we have no hard numbers

2. Risk of understaged MIBC.
- At re-TURBT he has a 41% risk of persistent NMIBC, but 0% risk of MIBC
- Plus, as he had a good quality BLC, this is likely superior to a WLC alone

3. Risk of dying of Bladder cancer
- According to SWOG study, patients who do not have a CR with BCG therapy had a higher risk of 5-year cancer death than those that did (62% vs. 77% CSS 5-years)
- But, specific salvage therapy is not recommended

Then, he addressed the role of early cystectomy. As in one of his previous talks, he again addressed the fact that early cystectomy is not a guaranteed cure. While early cystectomy is better than delayed cystectomy, in this patient (considered a delayed cystectomy), he would have a 75% 5-year CSS. 

Current second-line intravesical agents are inferior to cystectomy, for sure – gemcitabine, doxetaxel, Thermochemo. However, he notes that while recurrence rates are high, 2-year progression rates are low - ~5%. So, a 2-year interval for attempting conservative therapy may be reasonable and safe.

Novel immunotherapies (immune checkpoint inhibitors) may help bridge this gap, though trials are ongoing. Hence, the best option is novel conservative therapies on clinical trial.

Discussant 2: J. Palou Barcelona, from Spain made the following key points.

1. Patients with CIS are at inherently higher risk.
2. Discussion with patients is the key – while cystectomy and conservative options are available, patients must understand that there is a window of opportunity between the two. Balance between bladder sparing and disease progression.
3. Prostatic urethra must be sampled – it may be a source of recurrence that has not yet been evaluated.
4. Patients with BCG failure likely do worse than patients with T2 disease who get cystectomy up front!

He would argue for cystectomy in this patient due to age, +CIS, and persistent HG disease.

Presented by: Ashish Kamat, MD Houston, TX US

Discussants: P. Gontero, Turin, Italy and J. Palou, Barcelona, Spain

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

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