Expert review: an update in current and developing intravesical therapies for non-muscle-invasive bladder cancer

Abstract

Non-muscle-invasive bladder cancer is a highly prevalent disease and recurrences, after initial therapy, are common. Consequently, the healthcare costs for non-muscle-invasive bladder cancer are high. Despite a primary adequate response to adjuvant intravesical treatment, many patients suffer from recurrences, and some even from progression. To date, cystectomy remains the only option for those non-responding patients with high risk of recurrence and progression. Mainly because outcome after progression, in this group, is poor. Therefore, new intravesical therapies are needed. Moreover, new accurate and individual parameters, to distinguish responder from non-responders, will provide additional benefit in clinical decision-making. In this review, current diagnostics and therapies will be discussed. In addition, we will elucidate developing therapies in non-muscle-invasive bladder cancer.

Keywords::

• Bacillus Calmette–Guerin
• BCG failure
• chemotherapy
• early cystectomy
• immunotherapy
• intravesical therapy
• non-muscle-invasive bladder carcinoma
• transurethral resection of bladder tumor
• urothelial carcinoma

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Non-muscle-invasive bladder cancer (BC) is a common malignancy with wide range of oncologic outcomes and high rates of recurrence and progression.

• • A good initial transurethral resection is essential for good staging and prognosis.

• • Fluorescence techniques can be used to optimize visualization of the tumor, especially carcinoma in situ.

• • In low-risk non-muscle-invasive BC, a single postoperative instillation of chemotherapy is recommended and sufficient.

• • In intermediate-risk non-muscle-invasive BC, 1 year of intravesical treatment with either chemotherapy or Bacillus Calmette–Guerin (BCG) is recommended.

• • In high-risk disease, BCG induction, followed by at least 1 year of full dose of maintenance therapy is recommended; 3 years as well as adjustment of the dose might be considered.

• • Most patients with recurrence or relapse after BCG can be offered a second course or a combination of intravesical hyperthermia and chemotherapy.

• • In patients with primary BCG failure, a cystectomy should be strongly advised, since the outcome in progressive disease is far worse.

• • Gender, concomitant carcinoma in situ, methylation status of tumor tissue, depth of invasion (pT1 sub-staging) and a combination of urinary markers (with emphasis on urinary IL-2) might be helpful tools in predicting the risk of tumor progression/treatment failure.

• • New promising intravesical treatment options are gemcitabine, taxanes, IFN-α in addition to BCG, apaziquone, chemo-hyperthermia and electromotive drug administration.

• • Electromotive drug administration seems promising as a neoadjuvant treatment to improve transurethral resection of a bladder tumor outcome.

Notes