Immunotherapy in non-muscle-invasive bladder cancer: current status and future directions
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TOPIC PAPER
Immunotherapy in non‑muscle‑invasive bladder cancer: current status and future directions John L. Pfail1 · Andrew B. Katims1 · Parissa Alerasool2 · John P. Sfakianos1 Received: 17 July 2020 / Accepted: 1 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Patients harboring high-grade non-muscle-invasive bladder cancer (NMIBC) experience high rates of both recurrence and progression. Currently, few treatment options besides cystectomy exist for this at-risk population, especially those with BCG-unresponsive disease. The purpose of this review is to present the current status and describe future directions of immunotherapy in NMIBC. Methods The PubMed and Google Scholar databases were searched for articles pertaining to immunotherapy in NMIBC. Relevant planned and ongoing clinical trials were identified using www.ClinicalTrials.gov. Published randomized control trials, reviews, other retrospective and prospective studies deemed relevant were used in this review paper. Results Novel immunotherapies used in the treatment of high-grade NMIBC and BCG-unresponsive disease allow patients more options and have the potential to reduce the need for radical cystectomy. Currently, several options target the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis as this mechanism of immunotherapy has been shown to be effective in several cancers, including bladder, melanoma, and lung cancers. In addition, other immunotherapy options for the treatment of NMIBC include viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines. Conclusions The current landscape of immunotherapy in bladder cancer is rapidly evolving, with much literature pertaining to muscle-invasive and metastatic disease. However, the implementation of these treatment options in high-grade NMIBC may allow patients to avoid life-altering surgery. Reliable biomarkers for response are needed to further select patients who may benefit from such therapies. Keywords Urinary bladder neoplasms · Recurrence · Immunotherapy · Pembrolizumab · Checkpoint inhibitors
Introduction Bladder cancer (BC) is the fifth most commonly diagnosed cancers in the United States with an expected 81,400 new cases and 17,980 deaths in 2020 [1]. Of diagnosed patients, roughly 80% present with non-muscle-invasive bladder cancer (NMIBC), including tumor stages Ta and T1 and carcinoma in situ (CIS) [2]. The risk of recurrence and progression in patients harboring NMIBC remains substantial, * John P. Sfakianos [email protected] 1
Department of Urology, Icahn School of Medicine at Mount Sinai Hospital, 1425 Madison Avenue, 6th Floor, New York City, NY 10029, USA
School of Medicine, New York Medical College, Valhalla, NY, USA
2
with 5 year probabilities ranging from 31–78% to 1–45%, respectively [3]. Intravesical instillation of the bacterium Bacillus Calmette–Guerin (BCG) remains the gold standard treatment for both intermediate and high-ri
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