Symptom-guided reduction of BCG dwell time: findings from the north-REG randomized trial

Abstract

Objectives

To evaluate the impact of personalized dwell-time (DT) reductions on symptom prevalence and systemic toxicities in patients undergoing Bacillus Calmette–Guérin (BCG) instillation for non-muscle invasive bladder cancer (NMIBC).

Methods

Within a multinational randomized controlled trial (North-REG Dwell Time Study [NCT04701151]), 225 patients provided daily electronic patient-reported outcomes data during BCG induction and maintenance cycles. Participants were randomized 1:1, stratified by clinical site, sex, and concomitant carcinoma in situ, to either a standard care arm (control) or an intervention arm. Toxicity was analysed using a ‘worst-day’ principle to capture peak symptom burden. All patients initially received a standard 120-min DT. In the intervention group, algorithm-guided DT reductions (to 60 or 30 min) were triggered by real-time symptom severity, whereas the control group maintained a 120-min DT.

Results

At baseline, 69% vs. 71% (control vs. intervention) of participants reported pre-existing symptoms, primarily lower urinary tract symptoms such as pollakiuria and urgency. During induction, the intervention group experienced significantly lower rates of urgency at week 3 (34% vs. 47%, P = 0.04) and week 6 (32% vs. 49%, P = 0.01). Significant reductions were also observed during maintenance at week 9 for systemic symptoms (30% vs. 61%, P < 0.001) and fatigue (22% vs. 47%, P = 0.001). Total adherence to the 15-instillation protocol was 38% in the intervention group and 40% in the control group.

Conclusion

Daily electronic patient-reported outcomes monitoring revealed that patients with NMIBC have a high baseline symptom burden prior to BCG therapy. Symptom-guided DT reductions may reduce local urgency and systemic toxicity and improve treatment tolerability. However, treatment completion does not seem to be affected.