Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy associated with a high risk of progression and metastasis. Neoadjuvant systemic therapy (NST) is increasingly used to improve surgical and oncologic outcomes in patients with MIBC. This study aimed to evaluate the preliminary oncologic outcomes of NST for MIBC using data derived from a single-institutional collaboration database.

This retrospective study included patients diagnosed with stage II to IIIA muscle-invasive bladder cancer (MIBC) who received neoadjuvant systemic therapy (NST) between January 2011 and December 2024. Three NST regimens were administered: immunotherapy alone, cisplatin-based chemotherapy alone and a combination of immunotherapy plus cisplatin-based chemotherapy. Following NST, patients underwent varying surgical management: some received partial or radical cystectomy, while others underwent surveillance. The primary endpoint was pathologic downstaging (pT≤1N0) after receiving NST. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between treatment type and downstaging.

Among stage II patients (n=89), the downstaging rate was highest in the immunotherapy group (86.7%), followed by immunotherapy plus chemotherapy group (82.6%) and chemotherapy group (60.8%). Logistic regression demonstrated that the combination therapy significantly increased the odds of downstaging compared to chemotherapy alone (OR = 3.13; 95% CI: 1.04–9.42; p = 0.043). Immunotherapy alone was also associated with higher odds of downstaging (OR = 4.97; 95% CI: 1.10–22.43; p = 0.037). In stage IIIA (n=91), downstaging rates were 52.9% (combination therapy), 53.2% (chemotherapy), and 40.0% (immunotherapy), with no significant differences between regimens. Bladder recurrence was highest in the Immunotherapy group, particularly in stage IIIA (80.0%), and lowest in the combination therapy group (stage IIIA: 64.7%). Partial cystectomy was more frequently performed in the combination group (stage II: 39.1%; stage IIIA: 29.4%), while radical cystectomy was least frequent in this group (stage II: 13.0%) compared to chemotherapy alone (stage II: 60.8%).

Both immunotherapy alone and in combination with cisplatin-based chemotherapy were associated with significantly improved downstaging rates compared to chemotherapy alone in stage II MIBC. Notably, the combination therapy demonstrated a favorable surgical outcomes, with the highest rates of partial cystectomy and the lowest rates of radical cystectomy, suggesting a potential benefit for bladder preservation. However, bladder recurrence was highest in the immunotherapy group, especially in stage IIIA (80.0%), indicating a potential trade-off between early response and long-term control. These findings suggest that immunotherapy-based NST—particularly combination regimens—may offer improved oncologic and functional outcomes in selected patients and merit further prospective validation.