Immune Therapies in Non-Muscle Invasive Bladder Cancer

Abstract

Non-muscle invasive bladder cancer (NMIBC) continues to be a challenging disease to manage. Treatment involves transurethral resection and, often, intravesical therapy. Appropriate patient selection, accurate staging, and morphological characterization are vital in risk-stratifying patients to those who would most benefit from receiving intravesical therapy. Bacillus of Calmette and Guérin (BCG) continues to be the first-line agent of choice for patients with intermediate- and high-risk NMIBC. Treatment should begin with the standard induction course of 6 weekly treatments. The inclusion of subsequent maintenance courses of BCG is imperative to optimal therapeutic response. While patients with intermediate-risk disease should receive 1 year of maintenance therapy, high-risk patients benefit from up to 3 years of maintenance therapy. BCG use should not be used in low-risk patients with de novo Ta, low-grade, solitary, <3-cm tumors. Conversely, patients with muscle-invasive disease should forgo intravesical immunotherapy and proceed directly to radical cystectomy. Cystectomy also should be considered in patients with multiple T1 tumors, T1 tumors located in difficult to resect locations, residual T1 on re-resection, and T1 with concomitant CIS. Although promising new immunotherapeutic agents, such as Urocidin, protein-based vaccines, and immune check point inhibitors are undergoing preclinical and clinical investigation, immunotherapy in bladder cancer remains largely reliant on intravesical BCG with surgical consolidation as the standard salvage treatment for patients with BCG failure.

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma

“…This panel met initially in December 2014 with the goal of generating consensus recommendations for the clinical use of immunotherapy for bladder cancer. Discussion at this meeting centered on the various consensus papers recently published, and how these might be refined, or variations better explained [ 3 ].…”

Moving Immunoprevention Beyond Virally Mediated Malignancies: Do We Need to Link It to Early Detection?

“…However, even in these settings, it has been shown that there are changes in adjacent “normal” mucosa that predict the risk of recurrence (13), thereby making a case for targeting these abnormal cells to reduce recurrence. The presence of immune infiltration has now been demonstrated in diverse preneoplastic states including intraductal papillary mucinous neoplasms (IPMNs) that precede pancreatic cancer (14, 15), oral leukoplakia as a precursor to oropharyngeal cancer (16), non-invasive bladder cancer (17), bronchial lesions preceding lung cancer (18–20), and ductal carcinoma in situ (DCIS) of the breast (21–24). One of the earliest examples of specific immune responses to human preneoplasia in the tumor microenvironment was in the setting of monoclonal gammopathy of undetermined significance (MGUS), which serves as a precursor to myeloma (MM) (25).…”

“…Nonetheless, MUC-1 vaccination is currently being tested in the context of a phase III trial. Instillation of Bacillus Calmette Guerin (BCG) has been shown to mediate the regression of in situ bladder cancer lesions but is ineffective in the setting of more advanced muscle-invasive lesions (17). Vaccination in the neoadjuvant setting has been trialed to evaluate the induction and anti-tumor effects of vaccination for preneoplasia.…”

Immunosuppressive effect of bladder cancer on function of dendritic cells involving of Jak2/STAT3 pathway

“…Therefore, cancer immunotherapy involving of DCs acts as a promising method. The DC-based strategies not only prevent cancer recurrence, but also reduce its progression and metastasis [ 7 – 10 ]. Meanwhile, cytokines secreted from DCs play a vital role in antitumor response [ 11 ].…”