Urothelial Cancer Articles

There is no current standard of care for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after neoadjuvant chemotherapy and surgical resection or for those who cannot receive or decline cisplatin-based perioperative chemotherapy.

Cancer can be traced back to the Iron Age. Both the ancient Egyptians and Hippocrates dealt with the disease. Urological tumor treatment is an integral part of urology and has undergone interesting developments.

Perioperative chemotherapy has become a standard treatment for muscle invasive bladder cancer and is recommended by national and international guidelines. The treatment of metastatic urothelial cancer evolved by the use of immune-modulating therapies like checkpoint inhibitors.

CHICAGO, IL USA (UroToday.com) - Cisplatin-based chemotherapy regimens are the backbone of treatment of metastatic and muscle-invasive urothelial cancer.

Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies.

Urothelial carcinoma (UC) of the luminal molecular subtype is associated with lower rates of pathological upstaging from clinical stage T1-T2 to non-organ confined (NOC; ≥pT3 and/or pN+) disease at radical cystectomy (RC).

Lymph node involvement in bladder cancer is common and has prognostic implications. Early and accurate identification of metastatic lymph nodes is, therefore, important in ensuring appropriate patient triage and management.

This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder.

Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second line. Vinflunine is the only treatment approved in this setting by the European Medicines Agency (EMA) and taxanes are also widely used in second line.

The COVID-19 pandemic has resulted in delays in the treatment of patients with urological malignancies. The management of bladder cancer (BC) in particular poses a significant challenge given the recurrent nature of the disease and the intense follow-up regime required for many cases.

Urothelial carcinoma remains a devastating disease with a poor prognosis. Though immune therapy with Bacillus Calmette-Guérin (BCG) has been used for localized bladder cancer for years, only immune-checkpoint blockade with antiprogrammed cell-death 1 (anti-PD-1) and antiprogrammed cell-death ligand 1 (anti-PD-L1) inhibitors have demonstrated improvement in survival of patients with metastatic disease.

Urothelial cancer is the second most common cancer, and cause of cancer death, related to the genitourinary tract. The goals of surveillance imaging after the treatment of urothelial cancer of the urinary bladder are to detect new or previously undetected urothelial tumors, to identify metastatic disease, and to evaluate for complications of therapy.

Immune checkpoint inhibitors (ICIs) have made important breakthrough in anti-tumor therapy, however, no single biomarker can accurately predict their efficacy. Studies have found that tumor microenvironment is a key factor for determining the response to ICI therapy.

Urothelial carcinoma (UC) of the bladder and upper urinary tract still results an open challenge for clinical oncologists. Excluding selected patients who will particularly benefit from chemo-radiotherapy combined to endoscopic tumour removal, surgery represents the only curative approach for localized stages.

The results of 2 studies exploring adjuvant immune checkpoint inhibition (aCPI) in high-risk muscle-invasive urothelial cancer have yielded conflicting results. A trial employing placebo as the control arm demonstrated a significant prolongation in disease-free survival (DFS) whereas a trial employing observation as the control arm (IMvigor010) demonstrated no prolongation in DFS with CPI.

This article summarizes the role of adjuvant chemotherapy in muscle-invasive and transitional cell carcinoma of the bladder and upper urinary tract.

The Urologic clinics of North America. 2018 Feb 21 [Epub]

Tala Achkar, Rahul A Parikh

Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Medical Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA.

The present systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used chemotherapy regimens for first-line therapy of advanced or metastatic urothelial carcinoma of the bladder (UCB).

Introduction: The immune checkpoint inhibitors (ICI) programmed cell death protein and ligands 1 (PD1- and PD-L1) as well as cytotoxic T-lymphocyte-associated protein 4 have demonstrated clinical efficacy in genitourinary cancer.

Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer.

The use of antiangiogenic agents in cancer therapy has become an attractive target in oncological research. However, concerning the uro-oncological field, current guidelines only recommend the use of antiangiogenic agents in metastatic renal cell cancer.

Introduction The therapeutic landscape for urothelial carcinoma has changed significantly over the past few years with the addition of immunotherapy to platinum-based chemotherapy. Targeted therapy against FGFR (fibroblast growth factor receptor) is now also approved for the minority of patients with FGFR aberrations.

Tumor mutational burden (TMB) and APOBEC mutational signatures are potential prognostic markers in patients with advanced urothelial carcinoma (aUC). Their utility in predicting outcomes to specific therapies in aUC warrants additional study.

Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses.

We investigated the functional role of ATF2, a transcription factor normally activated via its phosphorylation in response to phospho-ERK/MAPK signals, in the outgrowth of urothelial cancer. In both neoplastic and non-neoplastic urothelial cells, the expression levels of androgen receptor (AR) correlated with those of phospho-ATF2.

After years of trials, Programmed Death Ligand and Receptor targeting finally debuts as a firstline therapy in combination and as a single agent regimen at the 2016 European Society of Medical Oncology (ESMO) Congress.

Over the last decade, the improvement in molecular techniques and the acquisition of genomic information has transformed and increased the quality of patient care and our knowledge of diseases. Areas covered: Protein expression levels in immunohistochemistry and molecular biomarkers are reported for their ability to predict recurrence, progression, development of metastases, or patient survival.

Bladder recurrences have been reported in 22-47% of patients after surgery for upper urinary tract urothelial carcinoma (UTUC). This collaborative review focuses on risk factors for and treatment strategies to reduce bladder recurrences after upper tract surgery for UTUC.

To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa.

A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals.

Although immune checkpoint inhibitors (ICIs) are increasingly used as second-line treatments for urothelial cancer (UC), only a small proportion of patients respond. Therefore, understanding the mechanisms of response to ICIs is critical to improve clinical outcomes for UC patients.

Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents.

Objective: Sarcopenia, or the age-related loss of skeletal muscle mass and function, has been investigated as a potential marker of adverse outcomes among surgical patients. Our aim was to assess for changes in psoas muscle volume (PMV) following administration of neoadjuvant chemotherapy (NAC) in patients with bladder cancer and to examine whether changes in PMV following NAC are predictive of perioperative complications, pathologic response or survival.

We explored changes in perceptions of cure among patients with genitourinary (GU) cancers starting Immune checkpoint inhibitors (ICIs) therapy.

This longitudinal study assessed patients before starting therapy and 3-months later with a questionnaire that included patient perceptions of ICIs and the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale.

Checkpoint inhibitors are monoclonal antibodies attach to several different receptors on T-cells or tumour cells expressing receptors for cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1) and their ligand (PD-L1).

Cell-free circulating DNA (cfDNA) can be used for noninvasive profiling of tumor genomic aberrations. We hypothesized that molecular alterations may inform prognostication in advanced urothelial carcinoma (aUC).

The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness.

Metastatic bladder cancer is an aggressive disease that can often be difficult to diagnose and stage with conventional cross-sectional imaging. The primary objective of this study was to determine the clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/MRI for surveillance and restaging of patients with muscle-invasive, locally advanced, and metastatic bladder cancer compared to conventional imaging methods.

Neoadjuvant chemotherapy (neoCTX) has been recommended as the optimal strategy in surgically resectable neuroendocrine carcinoma (NEC) of the urinary tract (NEC-URO).

To determine the systemic therapy regimen and timing, which are most active against NEC-URO.

The purpose of the present guideline is to recommend surgical or systemic treatment for metastatic testicular cancer; T3b or T4, or node-positive, and metastatic renal cell cancer (rcc); and T3, T4, or node-positive upper tract urothelial (utuc) cancer.

Characterization of the different genomic alterations (GAs) in urothelial carcinoma (UC), by site of origin, may identify contrasting therapeutic opportunities and inform distinct putative pathogenetic mechanisms.

Programmed Death-Ligand (PD-L1) expression has predictive value for response to immune-checkpoint inhibitor treatment in urothelial cancer patients. The consistency of PD-L1 expression amongst different specimen types is however unknown.

To provide an overview of treatment modalities for management of upper tract urothelial carcinoma (UTUC).

In accordance with the standards for a scoping review, data presentation and discussion at the Consultation on UTUC in Stockholm, 6-7 September 2018, consensus was reached on the latest and most important treatment recommendations for UTUC.

Radical nephroureterectomy with en bloc bladder cuff excision and regional lymphadenectomy is the gold standard for the management of high-grade and high-risk upper tract urothelial carcinomas (UTUC).

The regulation of immune responses occurring during Bacillus Calmette-Guerin (BCG) therapy need to be better scrutinized in order to identify new targetable pathways for non-muscle invasive bladder cancer treatment.

Neoadjuvant chemotherapy (NACT) is recommended for muscle-invasive bladder cancer, and robust treatment response may result in lack of grossly identifiable tumor in the cystectomy specimen. Current gross examination and reporting protocols, however, do not include specific guidance on the approach to these specimens.

Recent research in next-generation sequencing characterized the genomic landscape of urothelial cancer. However, the majority of the studies focused on bladder cancer (BC). Upper urinary tract urothelial carcinomas (UTUC) and BC share some histological characteristics, but, considering the differences in terms of embryologic precursors, epidemiology, genetics, medical and surgical management and response to therapy, UTUC and BC should be considered as two distinct diseases.

Although radical cystectomy is considered the gold standard approach for patients with muscle-invasive bladder cancer, tri-modal therapy (TMT) is a well-tolerated and efficacious alternative to radical cystectomy that is underutilized in inoperable patients and rarely offered to cystectomy candidates in the USA.

Harnessing the host immune system to combat genitourinary cancers has key theoretical advantages over other anticancer strategies including specificity and memory which should translate to favorable tolerability and response durability in the clinic.

En bloc resection of bladder tumor (ERBT) has attracted interest as a potentially superior technique to transurethral resection of bladder tumor (TURBT) to obtain detrusor muscle in the specimen. Different ERBT techniques have been described, with bipolar electrocautery and laser being the more favored energy modalities.