A recent systematic review and meta-analysis conducted by Rose et al., under the Société Internationale d’Urologie in 2022, investigated the efficacy of different interventions in recent trials that specifically included patients meeting the FDA’s BCG-unresponsive definition. The primary endpoints examined were:
- Complete response rate for CIS±Ta/T1 tumours.
- Recurrence-free rate for patients with papillary-only disease.
- Disease-free rate in studies enrolling both papillary and CIS tumours (Ta/T1/CIS).
The review identified eleven studies using nine different therapeutic agents, encompassing a total of 909 patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). The outcomes at 3, 6, and 12 months were reported as follows:
- Complete response rate in CIS±Ta/T1 tumors was 44% at 3 months, 38% at 6 months, and 25% at 12 months.
- Recurrence-free rate in papillary-only disease was 73% at 3 months, 58% at 6 months, and 48% at 12 months.
- Disease-free rate in combined Ta/T1/CIS tumors was 48% at 3 months, 22% at 6 months, and 43% at 12 months.
The studies showed relatively low levels of heterogeneity among those restricted to papillary-only or CIS±Ta/T1 tumours. The authors noted that future randomised controlled trials would be necessary, likely requiring stratification between papillary-only and CIS±Ta/T1 tumours to improve the understanding and treatment of BCG-unresponsive NMIBC.
The authors emphasised the importance of future research in this area, specifically pointing out the need for randomised controlled trials (RCTs) that could provide more robust and definitive evidence. They suggested that these future studies should focus on stratifying patients between those with papillary-only disease and those with CIS±Ta/T1 tumours. This stratification would help in understanding the differential response to treatments and could potentially lead to more tailored and effective therapeutic approaches for each subgroup.
Additionally, the review highlighted the need for consistent and standardised definitions and outcome measures in trials to ensure comparability and reliability of results. The variability in the therapeutic agents used across the identified studies underscores the ongoing exploration and need for innovation in treatment options for BCG-unresponsive NMIBC.
The findings of this systematic review and meta-analysis also highlight the relatively high initial response rates that decrease over time, particularly beyond the 6-month mark. This trend suggests a need for ongoing monitoring and potentially additional or combination treatments to sustain response rates and prevent recurrence.
Overall, Rose et al. concluded that while some progress has been made in the treatment of BCG-unresponsive NMIBC, there remains a significant need for further high-quality research. Future studies should aim to refine and optimise treatment protocols, improve long-term outcomes, and ultimately enhance the quality of life for patients suffering from this challenging condition.
The review also called attention to the clinical implications of their findings. For clinicians, understanding the varying response rates at different time points can aid in more accurate prognostication and in developing follow-up schedules tailored to patient needs. The decrease in response rates over time indicates that patients who initially respond to treatment require vigilant long-term monitoring to detect and manage recurrences early.
Moreover, the relatively low levels of heterogeneity observed in studies focusing on either papillary-only or CIS±Ta/T1 tumours suggest that patient characteristics and tumour biology within these subgroups may be more homogeneous than previously thought. This insight could facilitate more precise patient selection for future trials and potentially improve the generalisability of study results.
For policymakers and healthcare providers, the findings highlight the urgent need for investment in research focused on BCG-unresponsive NMIBC. The development of new therapeutic agents and strategies is vital, particularly in light of the limited efficacy of current treatments over the long term. The support for such research could lead to significant advancements in patient outcomes and potentially reduce the overall burden of this disease on healthcare systems.
In conclusion, Rose et al. provided a comprehensive analysis of the current state of therapeutic interventions for BCG-unresponsive NMIBC. Their findings highlight both the progress made and the considerable challenges that remain. The call for future randomised controlled trials with specific stratifications and standardised outcomes is a crucial step forward. As research continues to evolve, there is hope for more effective and sustained treatment options that will improve survival and quality of life for patients with this challenging form of bladder cancer.
Link to the original study:
