Bacillus Calmette-Guerin (BCG) is a standard immunotherapy for non-muscle-invasive bladder cancer (NMIBC) that significantly reduces recurrence and progression risks. However, the optimal BCG dose remains unclear, with dose reduction explored to minimize side effects. During the global BCG shortage, the NCCN guidelines recommend using one-third of the standard dose for induction therapy, along with maintenance therapy, based on clinical trials showing similar efficacy between the reduced and standard doses. This study compares the safety and side effects of full-dose (120 mg) versus one-third dose (40 mg) of Sii Onco BCG in NMIBC patients.

From August 2023, we prospectively enrolled patients with histologically confirmed, completely resected T1, high-grade Ta, low-grade Ta with multifocality, tumor size ≥3 cm, recurrence within one year, and carcinoma in situ (CIS). Patients underwent transurethral resection followed by repeated intravesical BCG instillations (40 mg or 120 mg) per the induction and maintenance schedule at 3, 6, 12, 15, 18, and 24 months. Tumor recurrence and progression were monitored with cystoscopy, and adverse effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Overactive Bladder Symptom Score (OABSS). The association between a single risk factor (i.e., clinically relevant variables) and the occurrence of adverse events across different dosage levels was assessed using generalized estimating equations (GEE). The GEE model specified a logit link function and assumed an autoregressive correlation structure of order 1 (AR(1)) to account for within-subject correlations arising from repeated measurements.

A total of 32 patients were enrolled, with 15 in low-dose group and 17 in full-dose group. The average number of BCG instillations was 10.3 for the low-dose group and 8.4 for the full-dose group (p = 0.003). No significant differences were observed between groups regarding gender, age, tumor number, size, or risk classification. The severity and incidence of side effects were similar, with frequency and dysuria being the most common. The full-dose group had a higher OABSS (OR 1.83), and three patients discontinued BCG instillation due to discomfort, resulting in a 18% discontinuation rate, while none discontinued in the low-dose group.

Low-dose BCG (40 mg) was associated with fewer treatment discontinuations compared to full-dose (120 mg), suggesting improved adherence without compromising safety. Although side effect rates were similar, full-dose BCG led to higher overactive bladder symptom scores, indicating increased urinary irritation. These findings suggest that dose reduction may enhance tolerability while maintaining safety in NMIBC patients. However, as an observational study, potential bias may exist, and further large-scale, long-term research is needed to confirm these results and assess the impact on cancer recurrence and progression.

Frequency and dysuria were the most common side effects, with similar severity and incidence between groups. The low-dose group had a higher number of instillations and no discontinuations due to side effects. In contrast, the full-dose group had a 18% discontinuation rate, suggesting that incomplete adherence to the full treatment may negatively impact long-term prognosis.