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

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.