Treatment for Bladder Cancer

Dear Colleagues, 

After years of stable therapy approaches in non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), uro-oncology dealing with this frequent tumour entity is finally facing several paradigmatic changes.

Nowadays, local and systemic immunotherapies are used for the management of bladder cancer (BC) in daily practice. BCG has been administered since 1976 in patients with NMIBC. Despite its efficacy, disease progression is observed in nearly 30% of patients. Given the antitumor activity of immune checkpoint inhibitors in metastatic setting, these therapies are currently investigated in NMIBC. Pembrolizumab is now approved by the Food and Drug Administration (FDA) for the treatment of patients with BCG-unresponsive, high-risk, NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have not elected to undergo cystectomy. Several phase 2 and 3 trials are ongoing to investigate the efficacy of programmed cell death PD(L)1 inhibitors combined with BCG all over the world.

Although anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) therapy has been established as one of the standard therapies for BC many unknown factors remain to be resolved concerning the mechanism of anti–PD-1 mAb therapy. PD-1 is expressed on the cell surface of activated cytotoxic T lymphocytes (CTLs) that can recognize certain tumor antigens and acquire tumoricidal activity. Also, when PD-1 binds to programmed cell death ligand 1 (PD-L1) on tumor cells, a suppressive signal will be sent to CTLs, resulting in inactivation of CTLs and immune escape of the tumor cells. Treatment with anti–PD-1 or anti–PD-L1 mAbs inhibits the interaction of PD-1 and PD-L1 and revitalizes the tumoricidal CTLs, providing significant antitumor activity, even to highly advanced malignant tumors. Thus, PD-L1 expression in tumor tissue seemed to represent a promising prognostic factor for anti–PD-1 mAb therapy against BC.

However, as it became clear that anti–PD-1 mAb therapy might be effective in BC without PD-L1 expression, PD-L1 expression in tumor tissue as a biomarker for anti–PD-1 mAb therapy should be reconsidered. Thus, the mechanism of how anti–PD-1 mAb therapy is effective against PD-L1 BC warrants further investigation. Recently, it was suggested that blockade between PD-1 on T cells and PD-L1 on antigen-presenting cells (APCs) could induce antitumor immunity, even if tumor cells have no PD-L1 expression.

Although it is known that the blood levels of soluble programmed cell death ligand 1 (sPD-L1) are elevated in various malignancies, the nature of sPD-L1 has not been thoroughly elucidated especially for BC. In this special issue of CANCERS, we are focusing this potential novel biomarker.

Additionally in December 2019, the FDA granted accelerated approval to the novel nectin-4-targeting antibody-drug conjugate, enfortumab vedotin, for the treatment of platinum-refractory and immune checkpoint blockade-refractory locally advanced or metastatic urothelial carcinoma. Antibody-drug conjugates represent a new therapeutic modality in urothelial cancer this other appealing new therapies are merging.

Prof. Dr. Lukas Lusuardi
Guest Editor

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• non-muscle invasive bladder cancer
• muscle invasive bladder cancer
• robotic surgery