Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer.

PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

Contemporary Patterns of Multidisciplinary Care in Patients With Muscle-invasive Bladder Cancer.

BACKGROUND: Multidisciplinary clinics integrate the expertise of several specialties to provide effective treatment to patients. This exposure is especially relevant in the management of muscle-invasive bladder cancer (MIBC), which requires critical input from urology, radiation oncology, and medical oncology, among other supportive specialties. MATERIALS AND METHODS: In the present study, we sought to catalog the different styles of multidisciplinary care models used in the management of MIBC and to identify barriers to their implementation. We surveyed providers from academic and community practices regarding their currently implemented multidisciplinary care models, available resources, and perceived barriers using the Bladder Cancer Advocacy Network and the Genitourinary Medical Oncologists of Canada e-mail databases. RESULTS: Of the 101 responding providers, most practiced at academic institutions in the United States (61%) or Canada (29%), and only 7% were from community practices. The most frequently used model was sequential visits on different days (57%), followed by sequential same-day (39%) and concurrent (1 visit with all providers; 22%) models. However, most practitioners preferred a multidisciplinary clinic involving sequential same-day (41%) or concurrent (26%) visits. The lack of clinic space (58%), funding (41%), staff (40%), and time (32%) were the most common barriers to implementing a multidisciplinary clinic. CONCLUSION: Most surveyed practitioners at academic centers use some form of a multidisciplinary care model for patients with MIBC. The major barriers to more integrated multidisciplinary clinics were limited time and resources rather than a lack of provider enthusiasm. Future studies should incorporate patient preferences, further evaluate practice patterns in community settings, and assess their effects on patient outcomes.

Adherence to surveillance guidelines after radical cystectomy: a population-based analysis.

OBJECTIVES: Surveillance after radical cystectomy is recommended to detect tumor recurrence and treatment complications. We evaluated adherence to National Comprehensive Cancer Network (NCCN) guidelines using a large population-based database. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients aged ≥66 years diagnosed with nonmetastatic bladder cancer who had undergone radical cystectomy between 2000 and 2007. Medicare claims information identified recommended surveillance tests for 2 years after cystectomy as outlined in the NCCN guidelines. Adherence was defined as receipt of urine cytology and imaging of the chest, abdomen, and pelvis in each year. We evaluated the effect of patient and provider characteristics on adherence, controlling for demographic and disease characteristics. RESULTS: Of 3,757 patients who had undergone radical cystectomy, 2,990 (80%) were alive after 2 years. Adherence to all recommended investigations was 17% for the first and the second years following surgery. Among patients surviving 2 years, only 9% had complete surveillance in both years. In either year, adherence was less likely in patients with advanced pathologic stage (III/IV) (adjusted odds ratio [AOR] = 0.74, 95% CI: 0.60-0.91) and unmarried patients (AOR = 0.82, 95% CI: 0.68-0.99). Adherence was more likely in patients treated by high-volume surgeons (AOR = 2.00, 95% CI: 1.70-2.36) and those who saw a medical oncologist (AOR = 1.52, 95% CI: 1.27-1.82). We also observed significant geographic variability in adherence. CONCLUSION: Patterns of surveillance after radical cystectomy deviate considerably from NCCN recommendations. Despite increased utilization of radiographic imaging investigations, the omission of urine cytology significantly contributed to the low rate of overall adherence to surveillance guidelines. Uniform adherence to surveillance guidelines was observed in patients treated by high-volume surgeons. This suggests an important opportunity for quality improvement in bladder cancer care.

The mechanism of action of BCG therapy for bladder cancer--a current perspective.

Bacillus Calmette-Guérin (BCG) has been used to treat non-muscle-invasive bladder cancer for more than 30 years. It is one of the most successful biotherapies for cancer in use. Despite long clinical experience with BCG, the mechanism of its therapeutic effect is still under investigation. Available evidence suggests that urothelial cells (including bladder cancer cells themselves) and cells of the immune system both have crucial roles in the therapeutic antitumour effect of BCG. The possible involvement of bladder cancer cells includes attachment and internalization of BCG, secretion of cytokines and chemokines, and presentation of BCG and/or cancer cell antigens to cells of the immune system. Immune system cell subsets that have potential roles in BCG therapy include CD4(+) and CD8(+) lymphocytes, natural killer cells, granulocytes, macrophages, and dendritic cells. Bladder cancer cells are killed through direct cytotoxicity by these cells, by secretion of soluble factors such as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), and, to some degree, by the direct action of BCG. Several gaps still exist in our knowledge that should be addressed in future efforts to understand this biotherapy of cancer.

ICUD-EAU International Consultation on Bladder Cancer 2012: Urothelial carcinoma of the prostate.

CONTEXT: The Second International Consultation on Bladder Cancer recommendations on urothelial carcinoma (UC) of the prostate were presented at the 2011 European Association of Urology Congress in Vienna, Austria, on March 18, 2011. OBJECTIVE: Our aim is to summarize the Second International Consultation on Bladder Cancer recommendations on UC of the prostate to help clinicians assess the current evidence-based management. EVIDENCE ACQUISITION: The committee performed a thorough review of new data and updated previous recommendations. Levels of evidence and grades of recommendation were assigned based on a systematic review of the literature that included a search of online databases and review articles. EVIDENCE SYNTHESIS: Once a non-muscle-invasive high-grade tumor or carcinoma in situ (CIS) of the bladder has been diagnosed, careful follow-up of the prostatic urethra is necessary. Noninvasive UC including CIS of the prostate should be treated with intravesical bacillus Calmette-Guérin (BCG) following endoscopic resection. A transurethral resection of the prostate may improve contact of BCG with the prostatic urethra, and it appears that response rates to BCG are increased (level of evidence: 3). Transurethral biopsy of the prostatic urethra is effective in identifying prostatic involvement but may not accurately reveal the extent of involvement, particularly with stromal invasion. Stromal invasion by UC of the prostate carries a poor prognosis. Radical cystoprostatectomy is the treatment of choice for locoregional control in patients with prostatic stromal invasion. CONCLUSIONS: These recommendations contain updated information on the diagnosis and treatment of UC of the prostate. However, prospective trials are needed to further elucidate the best management of these patients.