Sequential administration of Bacillus Calmette-Guerin (BCG) and Electromotive Drug Administration (EMDA) of mitomycin C (MMC) for the treatment of high-grade nonmuscle invasive bladder cancer after BCG failure.

BACKGROUND: There is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed. OBJECTIVE: We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients. RESULTS AND LIMITATIONS: Twenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1-82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9-67.8) at 1 year and 27.2% (95% CI 13.6-54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study. CONCLUSIONS: EMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance.

Canadian experience of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy for muscle-invasive bladder cancer.

INTRODUCTION: Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Neoadjuvant chemotherapy (NAC) was proven to cause pathological downstaging. For this reason, we evaluated whether receipt of NAC decreases local bladder recurrences in TMT patients. METHODS: We retrospectively analyzed our TMT database for all patients treated between 2003 and 2017. Patients were treated with maximal transurethral resection of bladder tumor (TURBT) followed by chemotherapy/radiotherapy with or without NAC. Baseline demographic and tumor characteristics were recorded. Rates of local and systemic recurrence were analyzed per receipt of NAC. Overall recurrence-free survival (RFS) and bladder (b)RFS were analyzed using the Kaplan-Meier method and Cox proportional hazards modelling. RESULTS: Median age and followup periods were 72 years and 3.6 years, respectively. Fifty-four patients had NAC and concurrent chemoradiation (NAC-TMT) vs. 70 patients who had concurrent chemoradiation only (TMT). Carcinoma in situ (CIS) was present in 31% of the patients in NAC-TMT group compared to 24% in TMT group (p=0.40). After treatment, 24 (44%) and 31 (44%) patients in NAC-TMT and TMT groups, respectively, had bladder tumor recurrence. Overall RFS at three years was 46% and 50% in NAC-TMT and TMT groups, respectively (p=0.70). BRFS at three years was 55% and 69% in NAC-TMT and TMT groups, respectively (p=0.27). Multivariable analyses found that the presence of concomitant CIS (hazard ratio [HR] 2.13; 95% confidence interval CI 1.06-4.27; p=0.0036) was the primary factor associated with local bladder recurrence. CONCLUSIONS: Receipt of NAC does not obviate the risk of bladder recurrence post-TMT. Patients with CIS should be monitored especially closely for local recurrence.

Molecular Characterization of Bladder Cancer.

PURPOSE OF REVIEW: Bladder cancer (BCa) management had remained unchanged for 20+ years with clinicians, in contrast to many other cancer types, rarely relying on molecular characteristics to guide management. The past 5 years have yielded significant advances in our knowledge of the molecular basis of BCa and concurrent advances in systemic therapy. We aim to highlight the key developments and potential future direction of BCa management. RECENT FINDINGS: Next-generation sequencing (NGS) has drastically altered the understanding of muscle-invasive BCa (MIBC) and non-muscle invasive BCa (NMIBC). MIBC molecular subtyping efforts from several groups worldwide grouped into an international consortium into five classes, broadly grouped into basal and luminal subtypes, have attempted to improve prediction of clinical outcomes and treatment response, either chemotherapy or immunotherapy. NMIBC molecular subtyping is yielding similar disease stratification, superior to histopathology alone. Additionally, with new actionable targets being identified for patients non-responsive to traditional therapy, ongoing and upcoming clinical trials are increasingly emphasizing the importance of the molecular testing. The molecular characterization of bladder cancer is rapidly progressing and will likely alter treatment paradigms in the near future.

Treatment of bladder cancer in the elderly.

As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes.

Food for Thought: Are Radiation Therapists Able to Recognize Patients Who Would Benefit from Dietary Counseling?

Malnutrition is commonly seen in cancer patients before starting treatment and can worsen as they undergo radiation therapy. At the Odette Cancer Centre, there is currently no protocol or guideline for radiation therapists (RTs) to refer patients to registered dietitians before or during treatment. The aim of our study was to determine if RTs across Canada were able to identify and/or recognize nutrition-related side effects in patients during their course of radiation treatment who would require/benefit from a referral to a registered dietitian for additional support. An e-mail invitation with a link to an electronic questionnaire was distributed to RTs across Canada. Overall, 137 RTs responded (11% response rate) from across the country. Most respondents practice as treatment delivery therapists (75%). Seventy-five percent indicated that they were asked for advice on nutrition-related issues by patients. Self-assessment revealed RTs are more knowledgeable than confident in both recognizing patients requiring nutrition intervention and providing proper care. Analysis of open-ended questions indicates that RTs are knowledgeable in recognizing and providing appropriate interventions to patients. As RTs are positioned to be the first line to screen patients, they can provide quick and easy access to information and interventions in addition to making patient referrals to dietitians for additional support. To improve their confidence, educational sessions can be held with proper referral algorithms made available to RTs. This will provide better quality of care and improve the continuity of care, leading to improved patient care with better patient outcomes.