Treatment Outcomes of High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) in Real-World Evidence (RWE) Studies: Systematic Literature Review (SLR)

Abstract

Background: To date, there has been limited synthesis of RWE studies in high-risk nonmuscle invasive bladder cancer (HR-NMIBC). The objective of this research was to conduct a systematic review of published real-world evidence to better understand the real-world burden and treatment patterns in HR-NMIBC. Methods: An SLR was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the scope defined by the Population, Intervention Comparators, Outcomes, and Study design (PICOS) criteria. EMBASE, MEDLINE, and Cochrane databases (Jan 2015-Jul 2020) were searched, and relevant congress abstracts (Jan 2018-Jul 2020) identified. The final analysis only included studies that enrolled ≥100 patients with HR-NMIBC from the US, Europe, Canada, and Australia. Results: The SLR identified 634 RWE publications in NMIBC, of which 160 studies reported data in HR-NMIBC. The average age of patients in the studies was 71 years, and 79% were males. The rates of BCG intravesical instillations ranged from 3% to 86% (29-95% for induction and 8-83% for maintenance treatment). Five-year outcomes were 17-89% recurrence-free survival (longest survival in patients completing BCG maintenance), 58-89% progression-free survival, 71-96% cancer-specific survival (lowest survival in BCG-unresponsive patients), and 28-90% overall survival (lowest survival in patients who did not receive BCG or instillation therapy). Conclusion: BCG treatment rates and survival outcomes in patients with HR-NMIBC vary in the real world, with better survival seen in patients completing maintenance BCG, responding to treatment, and not progressing to muscle-invasive disease. There is a need to better understand the factors associated with BCG use and discontinuation and for an effective treatment that improves outcomes in HR-NMIBC. Generalization of these results is limited by variations in data collection, reporting, and methodologies used across RWE studies.

Treatment patterns and outcomes of BCG-treated non-muscle invasive bladder cancer patients in Germany

“…Of the 1,049 BC patients who received BCG from our cohort, 11% showed recurrence during the study period, as de ned according to intravesical dispensation of mitomycin, epirubicin, gemcitabine or doxorubicin. A recent SLR described ve-year recurrence-free survival in high-risk NMIBC patients to range from 17-89%, highlighting important variations across RWE studies (19). Another recent study has estimated a 5-year recurrence rate ranging between 56 and 77%, depending on disease grade (20).…”

Recent advancements in the diagnosis and treatment of non‐muscle invasive bladder cancer: Evidence update of surgical concept, risk stratification, and BCG‐treated disease

“…CSS and OS were significantly shorter in BCG‐unresponsive patients compared to non‐BCG‐unresponsive patients with 5‐year CSS (90.6% vs. 97.3%, p < 0.0001) and 5‐year OS (82.9% vs. 92.4%, p < 0.0001). In addition, a larger systematic literature review of 160 studies reporting high‐risk NMIBC from the USA, Europe, Canada, and Australia demonstrated that the 5‐year CSS rate of BCG‐unresponsive disease treated with intravesical therapy was only 71% 79 …”

“…The EORTC risk table 51 The CUETO risk table 52 The J-NICE risk table 61 The TMDU risk table 63 BCG-unresponsive disease treated with intravesical therapy was only 71%. 79 Although a few reports have been published, real-world evidence from Japan is limited. Our previous single-center retrospective study showed that 49 (30%) out of 165 patients treated with BCG developed BCG-failure disease, and BCG-unresponsive disease (n = 18) was associated significantly with a high risk of progression compared with non-BCG-unresponsive disease (n = 31, p = 0.03).…”

The evolving role of checkpoint inhibitors in the treatment of urothelial carcinoma

“…The main treatment for high-risk nonmuscle invasive bladder cancer (HR-NMIBC; T1, high-grade Ta and/or carcinoma in situ) is transurethral resection of bladder tumour followed by bacillus Calmette-Guérin (BCG) bladder-perfusion therapy. 53 However, only 50% of patients benefit from BCG. 54 In response to the dilemma of some patients not of UC specimens.…”