Urothelial cancer (UC) is the second most common cancer of the urinary tract with approximately 81,400 new diagnosed cases and 17,980 deaths each year (1). UC involves various sections of the urinary tract, has different tumor stages and grades, and mostly occurs in the bladder or involves the upper urinary tract (2). Various complex treatment methods for UC include endoscopic surgery, open and minimally invasive surgery, intravesical therapy, chemotherapy, radiation therapy, and immunotherapy (2). It is very important to understand the nature of these UC and to classify the risks that determine the appropriate stage and type of treatment required. In this context, the diagnostics section includes topics on the histologic variant, one of the many issues of UC, the implications of treatment and prognosis for the recently highlighted molecular biomarker, and the recently developed and noninvasive urinary biomarkers. One of the many features of UC is its diverse morphological appearance due to molecular heterogeneity as can be seen in patients with UC with various histologic variants (3). The association between histologic variants and the clinical prognosis is being identified increasingly, with some types showing distinct molecular variations, helping in targeted therapy (3). In addition, recent reports have suggested methods classifying molecular subtypes based on RNA expression profiles to be related to prognosis (4). In UC diagnosis and monitoring, periodic invasive cystoscopy has been traditionally performed as well as urine tests, computed tomography, and magnetic resonance imaging (MRI). While these methods are reliable, they might be very uncomfortable and painful for the patient. Recently, there have been several studies on testing methods that are noninvasive. Although these methods lack formal indications, noninvasive urine biomarkers are available and potential factors are present (5). The treatment section covers novel systemic therapeutic agents used in metastatic UC in the era of immune checkpoint inhibitors. It also includes high-risk NMIBC and immunotherapy for MIBC in the setting of unresponsive Bacillus Calmette-Guérin (BCG), a recent subject of active clinical trials. Systemic cytotoxic chemotherapy has been the standard treatment for metastatic UC for decades (6). However, after the first platinum-based chemotherapy, the survival period of patients with relapse was mostly less than 2 years, and new treatments were needed. It has been used in patients with NMIBC who were at high risk for decades after BCG treatment in the 1970s (7). There have been no breakthrough immune drugs that considered the immune sensitivity of bladder cancer. Recently, immune-checkpoint inhibitors targeting programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways have demonstrated significant long-term antitumor activity (8), as well as safety. Following atezolizumab, which was approved in May 2016, nivolumab, avelumab, durvalumab, and pembrolizumab were approved and used for metastatic UC (8). Recently, pembrolizumab has also been approved by the Food and Drug Administration and used in the treatment of patients with BCG unresponsive NMIBC (9). It also introduces various topics such as the role of steroid hormone receptor signaling pathways in UC and neoadjuvant chemotherapy and nephron-sparing approaches in upper tract UC. The editors wanted to introduce an interesting and varied topic of UC and would like to thank prominent researchers of bladder cancer around the world who participated in this topic.
Provenance and Peer Review: This article was commissioned by the editorial office, Translational Cancer Research, for the series “Urothelial Carcinoma”. The article did not undergo external peer review.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-2020-uc-10). The series “Urothelial Carcinoma” was commissioned by the editorial office without any funding or sponsorship. HDY, HSK and JHK served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30. [Crossref] [PubMed]
- Chang SS, Bochner BH, Chou R, et al. Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. J Urol 2017;198:552-9. [Crossref] [PubMed]
- Ku JH, Yuk HD, Godoy G, et al. Prognostication in Patients Treated with Radical Cystectomy for Urothelial Bladder Carcinoma: A New Simplified Model Incorporating Histological Variants. Bladder Cancer 2018;4:195-203. [Crossref] [PubMed]
- Yuk HD, Jeong CW, Kwak C, et al. Clinical outcomes of muscle invasive bladder Cancer according to the BASQ classification. BMC Cancer 2019;19:897. [Crossref] [PubMed]
- Hermanns T, Savio AJ, Olkhov-Mitsel E, et al. A noninvasive urine-based methylation biomarker panel to detect bladder cancer and discriminate cancer grade. Urol Oncol 2020;38:603.e1-7. [Crossref] [PubMed]
- Yuk HD, Jeong CW, Kwak C, et al. Survival benefit of neoadjuvant chemotherapy in pathologic T2N0 or lower urothelial carcinoma patients: evidence to support the use of neoadjuvant chemotherapy. Transl Androl Urol 2020;9:1270-7. [Crossref] [PubMed]
- Yuk HD, Jeong CW, Kwak C, et al. Elevated Neutrophil to Lymphocyte Ratio Predicts Poor Prognosis in Non-muscle Invasive Bladder Cancer Patients: Initial Intravesical Bacillus Calmette-Guerin Treatment After Transurethral Resection of Bladder Tumor Setting. Front Oncol 2019;8:642. [Crossref] [PubMed]
- Tan WP, Tan WS, Inman BA. PD-L1/PD-1 Biomarker for Metastatic Urothelial Cancer that Progress Post-platinum Therapy: A Systematic Review and Meta-analysis. Bladder Cancer 2019;5:211-23. [Crossref] [PubMed]
- Meng MV, Gschwend JE, Shore N, et al. Emerging Immunotherapy Options for bacillus Calmette-Guérin Unresponsive Nonmuscle Invasive Bladder Cancer. J Urol 2019;202:1111-9. [Crossref] [PubMed]