What’s new in high-risk non-muscle invasive bladder cancer?

At EAUN17 in London I attended the Thematic Session ‘High-risk non-muscle invasive bladder cancer: What’s new?‘ since patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) are among the patients treated in our Cancer Institute. During the past years, as a nurse specialist working in the uro/oncology field, I´m faced with several issues, such as the following:

1. The shortage of BCG in 2014 which challenges us to present an adequate alternative to patients who can be treated with bladder sparing. The question is, are there alternatives when this happens again in the future?; and the
2. Requests for a second opinion from patients with high-risk non muscle-invasive bladder cancer. Patients have asked if there are new local treatments available in our hospital since previous standard local treatments have failed and they want to be treated with bladder-sparing procedures.

Thus, the question is: Are there any new developments in local treatment and how effective are these new treatments? The session ‘High risk non-muscle invasive bladder cancer: What’s new?” caught my attention since all the issues I mentioned earlier were covered. In this article, I present some of the highlights.

Disease characteristics
HR-NMIBC is a type of tumor with a high-risk of recurrence and a significant risk for progression to muscle-invasive bladder cancer (MIBC).

This table summarizes the characteristics of high risk non-muscle invasive bladder cancer:

Criteria for High risk non-muscle invasive bladder cancer1
Any of the following:

  • T1
  • G3 (HG)
  • CIS
  • multiple and recurrent and  >3 cm Ta G1-2

This is 10% of the non-muscle invasive bladder cancers

Non muscle-invasive bladder cancer accounts 70% of the bladder cancer population. 10% of this is high-risk non-muscle invasive.

This table summarizes the recurrence rate of high-risk non-muscle invasive bladder cancer in relation to the criteria of high-risk non-muscle invasive bladder cancer:

This table summarizes the progression rate of high-risk non-muscle invasive bladder cancer in relation to the criteria of high-risk non-muscle invasive bladder cancer:

Treatment of these patients is a major challenge to the urologist. The most important question in the treatment strategy is: What is the right time to move from a non-invasive treatment using bladder instillations to the invasive treatment of cystectomy?

This slide shows the difference in survival after cystectomies among patients with primary muscle invasive bladder cancer and patients who progressed from non-muscle invasive bladder cancer to muscle-invasive bladder cancer.


In addition to the well-known and standard treatment with BCG, there are new types of bladder instillations.

  1. Synergo®: This treatment involves circulation of cold mitomycin (MMC) through a special trans-urethral catheter combined with radiofrequency radiation of bladder wall.

There are several studies performed with good results.

  • 105 patients2
  • Recurrent papillary NMIBC, no CIS
  • 1-yr RFS 85%, 2-yr RFS 56%
  • 38% BCG-refractory patients, 2-yr RFS 44%
  • 49 patients 3
  • CIS in combination with papillary tumours
  • Complete response at 3 months 92% (45/49 patients)
  • 35% BCG-refractory patients
  • 49% recurrence in 27 months FU

2. HIVEC: This treatment involves heating of the MMC outside the bladder and the circulation of the heated MMC through a special trans-urethral catheter into the bladder.

At the moment there are studies underway to determine the effect of this treatment. The data are not yet available.

The effect of the therapy is obtained through the contact of the warm mitomycin with the bladder wall. The heat increases the extracellular space resulting in enhanced penetration of the drug and accelerated drug action. Both of these methods have a treatment time of one hour.

3. Electro Motive Drug Administration (EMDA) is a treatment in which iontophoresis technique is applied. A combined therapy of medication in the bladder and electric tension ensures that the medication penetrates deeper into the bladder wall. The treatment time is 25 minutes.

Several studies have been performed for this treatment.

These treatments are not available in all hospitals. If the patient wants to be treated with one of these methods, he should be referred to one of the centres.

Overview of available therapies
This session gave me a good overview of the available local treatments and their effectiveness. By learning some insights from this session enables me to adequately inform patients about the possible alternatives in cases when bladder-saving procedures are the potential best options.
The presentation has also made me more aware of the importance that the patient must be well-informed about the risk of recurrence and progression of the disease and the risks he takes when he postpones invasive therapy. The take home message was: ‘Bladder preserving strategies in high-risk NMIBC are risky, but can be performed in selected, well-informed patients’


  1. M. Babjuk et al. EAU Guidelines on Non-muscle-invasive (Ta, T1 and CIS) Bladder Cancer. European Association of Urology 2017.
  2. Nativ et al. Combined thermo-chemotherapy for recurrent bladder cancer after BCG. J Urol 2009;182:1313-7.
  3. Witjes et al. Intravesical hyperthermia and mitomycin-C for CIS of the urinary bladder. World J Urol 2009;27:319-24.

Jolanda Bloos-Van Der Hulst, MANP, Nurse Specialist Uro-oncology, Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (NL),