While survival rates for the majority of patients with non-muscle invasive bladder cancer (NMIBC) are favorable, bladder cancer has a relatively high risk of disease recurrence and progression that can significantly impact a patient’s quality of life and eventual cancer outcome. Depending on the grade and stage at initial diagnosis, up to 61% of patients with NMIBC will experience recurrence within the first year after initial resection, and up to 78% will experience recurrence within five years. In addition, there is a high risk for progression to muscle-invasive bladder cancer, with approximately 17% of patients progressing at one year and 45% progressing at five years. Thus, the journey of patients with NMIBC is frequently characterized by multiple tumor recurrences and repeated therapeutic interventions over the course of their care, typically requiring lifelong monitoring. These statistics help to explain why bladder cancer is one of the most expensive cancers to manage, accounting for almost $3.7 billion in direct costs in the US each year.
Recently updated clinical practice guidelines (April 2016) that include a joint effort between the American Urological Association (AUA) and the Society of Urologic Oncology (SUO) provide guidance for improving bladder cancer care by emphasizing that early and accurate diagnosis, proper risk stratification, and precise and thorough resection of the tumor before other treatments are started are paramount in the care of patients with NMIBC. The updated guidelines are particularly notable for providing a risk-stratified approach for post-surgical management of NMIBC, emphasizing that continued risk evaluation and classification is necessary for optimizing and individualizing the care of patients prior to each treatment decision.
The guidelines specify that at the time of each cancer recurrence a clinician should assign a risk group and classify a patient as low, intermediate or high risk, by considering factors that have been shown to have a significant impact of recurrence and progression (e.g., tumor size, tumor focality, grade, and stage). Importantly, the clinical guidelines also provide evidence for other factors that predict for a high-risk of progression, including lymphovascular invasion, prostatic urethral involvement, variant histology, any carcinoma in situ (CIS) and poor response to bacillus Calmette-Guérin (BCG) intravesical therapy. The inclusion of response to prior BCG therapy as a factor in prognosis is a unique element in the new risk stratification system that considers data demonstrating that patients who have persistent or recurrent disease at 6 months following BCG therapy have an increased risk of disease progression. Furthermore, the guidelines recommend that intermediate-risk patients who do not respond to BCG therapy should be re-stratified to the high-risk group, as the disease may be more aggressive than clinical or pathologic features suggest.
The updated guidelines also underscore the critical importance of a precise and complete transurethral resection of the bladder tumor (TURBT) to enhance accurate risk stratification, improve effectiveness of adjuvant therapies, and ultimately decrease recurrence. To achieve this, the guidelines include a new recommendation for the use of enhanced cystoscopy techniques at the time of TURBT to overcome the possibility of unrecognized residual disease at the operation’s completion.
Specifically, the guidelines state that clinicians should offer blue light cystoscopy (BLC), if available, as an adjunct to traditional white light cystoscopy (WLC) to increase tumor detection and decrease recurrence and improve staging and risk stratification (Moderate Recommendation; Evidence Strength: Grade B). An estimated 10% to 20% of bladder tumors are missed using traditional WLC alone, and 34%-76% of patients have evidence of residual tumor on repeat TURBT 2-6 weeks later. The updated AUA/SUO guidelines also state that clinicians may consider use of narrow band imaging (NBI) at the time of TURBT (Conditional Recommendation; Evidence Grade: C). BLC selectively identifies cells with higher rates of proliferation after administering intravesical hexaminolevulinic acid, thus allowing for the tumor and tumor margins to be directly identified by red fluorescence when exposed to blue light. NBI is an optical imaging technology that improves visibility of blood vessels and other mucosal structures, including some tumors.
Improved cancer detection using BLC, particularly of CIS, may lead to modifications in the treatment strategy and potentially have an impact on disease progression. Hexaminolevulinate (HAL, Cysview®) is currently the only optical imaging agent approved in the US and Europe for use with BLC. A meta-analysis of detection data using raw pooled data from nine prospective trials demonstrated that HAL-BLC significantly improved the detection of bladder cancers.
Similar recommendations for the use of enhanced cystoscopy using BLC technology in NMIBC management have been added to other major guidelines including those by the National Comprehensive Cancer Care Network (NCCN), the EAU and the National Institute for Health and Care Excellence (NICE) in the UK. All emphasize that early and accurate diagnosis and precise and thorough resection of the tumor before other treatments are started remain the most critical factors affecting outcomes in the patient’s journey with bladder cancer.
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Kamal S. Pohar, MD is Associate Professor of Urology at Ohio State University Wexler Medical Center. Dr. Pohar serves as a consultant and clinical trial investigator for Photocure.Ashish M. Kamat, MD is a Professor of Urology and Director of Urologic Oncology Fellowship at M.D. Anderson Cancer Center. Dr. Kamat serves as a consultant and clinical trial investigator for Photocure.