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Transformative Evidence

Bladder Cancer Detection

Curated by Clinicians: Educational Forum with Videos, Abstracts and Conference Information
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Background: Cxbladder diagnostic tests combine genomic information from urinary mRNA with phenotypic information to either rule out low-risk individuals or identify patients at a high risk of urothelial carcinoma (UC).

Objective: To evaluate the performance of Cxbladder and urine cytology, and Cxbladder's adjudication of atypical cytology and equivocal cystoscopy.

PURPOSE: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance.

MATERIALS AND METHODS: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy.

Blue light cystoscopy (BLC) with hexaminolevulinate (HAL) during transurethral resection of bladder cancer improves detection of non-muscle-invasive bladder cancer (NMIBC) and reduces recurrence rates.

Purpose: To evaluate the utility of blue light flexible cystoscopy (BLFC) for surveillance of non-muscle invasive bladder cancer (NMIBC). This was a prospective cohort of consecutive patients who underwent office BLFC for NMIBC. Clinical information was collected including cystoscopic findings and pathologic data.

Photodynamic diagnosis using the optical imaging agent hexaminolevulinate (HAL, Hexvix®, Ipsen Pharma GmbH, Ettlingen, Germany) as an adjunct to white light cystoscopy (WLC) during the initial transurethral resection of bladder tumours (TURB) improves the detection rate of bladder cancer and leads to fewer recurrences.

Presented by Anne K. Schuckman, MD
The optimizing personalized management of non-muscle-invasive bladder cancer session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) included a presentation from Dr. Anne Schuckman discussing which patients with high-risk non-muscle-invasive bladder cancer may benefit from radical cystectomy.
Blue light cystoscopy (BLC) with hexaminolevulinate (HAL) during transurethral resection of bladder cancer improves detection of non- muscle-invasive bladder cancer (NMIBC) and reduces recurrence rates. Flexible BLC was approved by the FDA in 2018 for use in the surveillance setting and was demonstrated to improve detection.

Diagnosis:

Clinical Presentation

There are no reliable screening tests available for detecting bladder cancer; hence the diagnosis is usually made based on clinical signs and symptoms. Painless hematuria – microscopic or gross – is the most common presentation and a hematuria investigation in an otherwise asymptomatic patient detects bladder neoplasm in roughly 20% of gross and 5% of microscopic cases.1,2
The American Urological Association (AUA) recommends that non-muscle invasive bladder cancer (NMIBC) patients with persistent or recurrent Ta or CIS should receive a second induction course of Bacillus Calmette-Guerin (BCG) after the first course. However, a significant number of patients decline. Real-world data evaluating the efficacy of a second BCG induction course is needed.

Nearly 80% of patients presenting with bladder cancer (BC) present with nonmuscle-invasive bladder cancer (NMIBC). Despite radical treatment, many of these patients experience disease progression. A surveillance program combining regular cystoscopy, upper urinary tract imaging, and urine cytology is typically instated to detect recurrence after radical treatment of NMIBC. This surveillance program has several shortcomings; amongst them the invasive nature of cystoscopy alongside the limited sensitivity (approximately 48%) of urine cytology.

Surveilling recurrent urothelial carcinoma (UC) requires frequent cystoscopy, which is invasive, expensive and time-consuming. An accurate urinary biomarker has the potential to reduce the number of cystoscopies required during post-treatment surveillance.

Published Date: October 2020

In 2020, approximately 81,000 cases of urothelial carcinoma of the bladder will be diagnosed in the United States, with nearly 18,000 associated deaths.1 Bladder cancer disproportionally affects men and is associated with well-defined environmental risk factors—tobacco use underlies approximately 50% of cases.2 Nonmuscle-invasive bladder cancer (NMIBC) is primarily managed by transurethral resection, risk-stratified use of intravesical chemotherapeutic or immunotherapeutic agents, and close surveillance.

Published Date: September 2018

More than 81,000 individuals are diagnosed with bladder cancer in the United States every year, of whom 75% have non-muscle invasive disease.1,2 Unfortunately, half these cases recur despite transurethral resection of bladder tumor (TURBT), and from 5% to 25% of repeated recurrences progress to muscle-invasive disease.3,4,5

Blue light cystoscopy (BLC) using hexaminolevulinate (HAL/Cysview/Hexvix) has been previously shown to improve detection of non-muscle-invasive bladder cancer (NMIBC). Herein, we evaluated the detection of malignant lesions in a heterogenous group of patients in the real world setting and documented the change in risk category due to upstaging or upgrading.

Blue-light cystoscopy (BLC) is a photodynamic diagnostic technique that augments the detection of occult disease missed under traditional white light. Instillation of hexaminolevulinate, a heme precursor, causes preferential accumulation of protoporphyrin IX and other photoactive porphyrins in neoplastic cells, which are then excited under the wavelength of blue light (~450 nm) to fluoresce red. The sensitivity of BLC in detecting cancerous lesions is much higher than that of white-light alone (91% vs. 76%) and used together, BLC plus WLC has a sensitivity of 98.5%.1 

A 90-year old man with no significant past medical history presented to urology clinic complaining of gross hematuria, urinary frequency, and dysuria. Previous urine cytology was atypical but two white-light cystoscopies failed to show any lesions.

Conference Coverage
Conference Highlights from Recent Conference Coverage
Presented by Max Kates, MD

There have been several recent single-arm trials in the Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) setting. The first question that arises is whether these single-arm trials are enough or do we need to randomize patients for our future trials.

Presented by Marc-Oliver Grimm, MD
In an oral presentation in the New Trials Update session at the 12th European Multidisciplinary Congress on Urological Cancers (EMUC), Dr. Marc-Oliver Grimm discussed the results of the NIMBUS trial, Treatment of High-Grade Non-Muscle Invasive Urothelial Carcinoma of the Bladder
Presented by Nathan Brooks, MD
Dr. Nathan Brooks, Society of Urologic Oncology (SUO) Fellow at the MD Anderson Cancer Center, Houston, Texas, USA presented “Correlation Between Body Mass Index (BMI), diabetes mellitus (DM), and Outcomes in Patients Treated with Bacillus Calmette Guerin (BCG)
Presented by J. Alfred Witjes, MD, PhD
J. Alfred Witjes, MD, PhD, began his talk explaining that he believes cystoscopy is still needed in the primary diagnosis of bladder tumors. Cystoscopy gives important information regarding multiplicity, size, stage, the grade of bladder tumors, and OR planning.
Presented by Ashley Alford, MD
Prior randomized controlled trials have demonstrated that the use of blue light cystoscopy (BLC) is associated with improved detection of both carcinoma-in-situ and papillary bladder tumors. As a result, BLC is recommended for use in patients with a history of non-muscle-invasive bladder cancer
Presented by Hamed Ahmadi, MD
Blue light cystoscopy has been shown to not only increase the detection rate of non-muscle invasive bladder cancer (20% for any tumor) including carcinoma in situ (CIS; 25-43%), it also decreases recurrence (27% at 12 months) and progression rates (24% at 24 months).
Presented by Marie Andersson, MD
The diagnostic process may be extensive in patients with non-muscle invasive bladder cancer (NMIBC) who have positive or suspicious urinary cytology when white-light flexible cystoscopy is negative. The next step in management is typically to proceed with resection biopsies
Presented by Anne Schuckman, MD
At the American Urological Association (AUA) 2020 Virtual annual meeting, Dr. Anne Schuckman discussed blue light cystoscopy for bladder cancer and several of her tips and tricks. Dr. Schuckman notes that there are over 75,000 new bladder cancer diagnoses per year, leading to more than 15,000 deaths. The prevalence of bladder cancer is >550,000 cases, making it the highest per capita treatment cost due to recurrent disease and multiple recurrences.
Presented by Wassim Kassouf, MD, FRCS
San Francisco, California (UroToday.com) Treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) remains a significant
Presented by Eugene Shkolyar, MD
The gold standard for evaluation and diagnosis of new bladder cancer and for surveillance of patients with non-muscle invasive bladder cancer (NMIBC) remains cystoscopy. However, as has been clearly demonstrated before, cystoscopy is not a perfect test – besides being user dependent, white light cystoscopy
Presented by Gorm von Gohren Edwin
More than 81,000 individuals are diagnosed with bladder cancer in the United States every year, of whom 75% have non-muscle invasive disease. Unfortunately, half these cases recur despite transurethral resection of bladder tumor (TURBT), and from 5% to 25% of repeated recurrences progress
Presented by Yair Lotan, MD
Yair Lotan, MD discussed the use of blue light cystoscopy with CYSVIEW® in patients with non-muscle invasive bladder cancer (NMIBC). Dr. Lotan notes that there are several unmet medical needs with regards to NMIBC. First, it is associated with a high risk of recurrence, with up to 61% of patients recurring in the first year, and up to 78% within 5 years. Second, NMIBC may progress to muscle invasion
Presented by Ricardo Leão, MD
Barcelona, Spain (UroToday.com) Up to 3/4 of non-muscle invasive bladder cancer (NMIBC) patients will endure recurrence during their lifetime. Disease follow up is invasive, costly and long and consists of cystoscopy, cytology, and imaging. The most prevalent non-invasive approach for the diagnosis of recurrence remains urinary cytology,
Presented by Yair Lotan, MD
Barcelona, Spain (UroToday.com) At the urogenital cancer treatment session, Dr. Yair Lotan discussed the impact of blue light flexible cystoscopy and utilization in the clinic setting. Dr. Lotan notes that there are several unmet medical needs with regards to non-muscle invasive bladder cancer (NMIBC). First, it is associated with a high risk of recurrence, with up to 61% of patients recurring in the first year, and up to 78% within 5 years.