Abstract
Non-muscle-invasive bladder cancer (NMIBC) is characterized by a high rate of cure, but also by a non-negligible probability of recurrence and risk progression to muscle-invasive disease. NMIBC management requires a proper local resection and staging, followed by a risk-based treatment with intravesical agents. For many years, the current gold standard treatment for patients with intermediate or high-risk disease is transurethral resection of the bladder (TURB) followed by intravesical bacillus Calmette–Guérin (BCG) instillations. Unfortunately, in about half of high-risk patients, intravesical BCG treatment fails and NMIBC persists or recurs early. While radical cystectomy remains the gold standard for these patients, new therapeutic targets are being individuated and studied. Radical cystectomy in fact can provide an excellent long-term disease control, but can deeply interfere with quality of life. In particular, the enhanced immune checkpoints expression shown in BCG-unresponsive patients and the activity of immune checkpoints inhibitors (ICIs) in advanced bladder cancer provided the rationale for testing ICIs in NMIBC. Recently, pembrolizumab has shown promising activity in BCG-unresponsive NMIBC patients, obtaining FDA approval. Meanwhile multiple novel drugs with alternative mechanisms of action have proven to be safe and effective in NMIBC treatment and others are under investigation. The aim of this review is to analyse and describe the clinical activity of new emerging drugs in BCG-unresponsive NMIBC focusing on immunotherapy results.
Highlights
Bladder cancer (BC) represents the tenth most common cancer worldwide and the fifth diagnosed in high-income countries [1]
Cancer-specific 5-year survival is estimated to be more than 90% in Non-Muscle-Invasive Bladder Cancer (NMIBC), this percentage drops to 50% to 82% in muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC), while only a small percentage of metastatic BC patients is alive at 5 years from diagnosis [4]
Radical cystectomy with pelvic lymph nodes dissection and urinary diversion still represents the backbone of bacillus Calmette–Guérin (BCG)-unresponsive NMIBC treatment, but this surgical procedure can negatively affect patients’ quality of life
Summary
Bladder cancer (BC) represents the tenth most common cancer worldwide and the fifth diagnosed in high-income countries [1]. Patients with high grade Ta or T1 are included in intermediate or high-risk group and the current gold standard treatment is TURB followed by six-weekly induction of intravesical bacillus Calmette–Guérin (BCG) instillation followed by maintenance [7]. BCG-unresponsive tumours do not benefit from further BCG instillations and current guidelines recommend early RC with urinary diversion as a preferred option [5,6,7]. This major surgical procedure can provide an excellent long-term disease control, but can negatively impact on quality of life and not all patients are eligible for or accept this procedure [11,12].
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