Editorial
New Challenges of Urothelial Carcinoma
Patrizia Straccia*
Division of Anatomic Pathology and Histology, Catholic University of Sacred Heart, Italy
*Corresponding author: Patrizia Straccia, Division of Anatomic Pathology and Histology, Catholic University of Sacred Heart, Italy
Published: 02 Jan, 2018
Cite this article as: Straccia P. New Challenges of
Urothelial Carcinoma. Clin Oncol. 2018;
3: 1394.
Editorial
Urothelial Carcinoma (UC) of the bladder is a major cause of morbidity and mortality
worldwide, causing an estimated 150,000 deaths per year [1].
Although the treatment for UC has improved over the last several decades, diagnostic techniques
have progressed more slowly. Cystoscopy is still considered the best method for diagnosing UC, but
it is invasive, uncomfortable, and can only detect approximately 90% of lesions. On the other side,
urine cytology has the advantages of being a simple, cost-effective, and non invasive test, while has
shown a wide range of sensitivity (11%-76%) depending on the specimen type, clinical setting and
grade of urothelial tumors. Because cystoscopies are invasive and cytology has poor sensitivity, a
non invasive, highly sensitive and specific marker have been sought as alternatives to cystoscopy and
cytology for the detection and surveillance of bladder cancer. Urine markers have been evaluated in
all clinical scenarios, but often they are not routinely utilized. The limitations of established bladder
cancer biomarkers requires us to identify better molecular parameters that could be clinically useful
for diagnosis and prognosis, in particular, for the high-risk patient groups that are usually at high
risk of progression, recurrence and metastasis. The efficacy of immunotherapy in non-muscle
invasive urothelial carcinoma of the bladder was first established in 1976 with Bacillus Calmette-
Guerin, but no immunotherapy has been approved for the treatment of advanced disease.
Over time, an improved understanding of immuno biology uncovered the importance of
immune checkpoints in facilitating tumor escape, leading to the development of multiple novel
therapeutics targeting the CTLA-4 (cytotoxic T-lymphocyte-associated protein 4, CD152) and
PD-1/PD-L1 (programmed cell death protein 1, CD279; programmed death-ligand 1, CD274)
immune checkpoints. Once the immune check points have been blocked, the equilibrium between
the auto immunity and immune tolerance will be affected [2]. In particular, melanoma, Renal
Cell Carcinoma (RCC), and Non-Small Cell Lung Cancer (NSCLC) have demonstrated durable
responses to immune check point inhibition. In the tumor micro environment, PD-1 and its ligand
PD-L1 perform a vital role in tumor progression and survival by escaping tumor neutralizing
immune surveillance. It has been found that PD-1 is expressed on a variety of immune cells, such
as monocytes, T cells, B cells, dendritic cells, and tumor-in filtrating lymphocytes (TILs). However,
PDL-1 is expressed in tumor cells and Antigen Presenting Cells (APCs), and the engagement of
PDL1 with PD-1 of T cell creates T cell dysfunction, exhaustion, neutralization, and interleukin-10
(IL-10) production in a tumor mass [3].
In 2016, the FDA approved using Atezolizumab for treating patients who have advanced or
metastatic urothelial carcinoma in which their diseases worsen during or after using platinumcontaining
chemotherapy. Atezolizumab was approved based on a multi-center single-arm trial
that had 310 patients. It was found that Atezolizumab showed good activity as immune check point
inhibitors. It was noted that as the expression of PD-L1 increases, the response increases [4].
Currently, the prognostic value of PD-L1 IC expression is unknown, with conflicting reports in
the literature, although it does not appear to be associated with validated adverse risk factors.
Ultimately, immunotherapy, and immune check point inhibition in particular, has led to
a paradigm shift in oncology, requiring development of new radiographic response criteria and
altering expectations for durable responses with therapy. The promising efficacy of these agents
combined with an increasing understanding of the complicated interactions between the immune
system and tumor foster optimism for progress in biomarker development in this field.
References
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- Alsaab H, Sau1 S, Alzhrani R, Katyayani Tatiparti, Ketki Bhise, Sushil K Kashaw, et al. PD-1 and PD-L1 Check point Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front Pharmacol. 2017;8:561.
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- Rosenberg JE, Hoffman-CensitsJ, Powles T et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multi centre, phase 2 trial. Lancet. 2016; 387(10031):1909-20.