Can Immunotherapy Plus Radiotherapy Replace Surgery for Bladder Cancer?

Muscle-invasive bladder cancer (MIBC) can behave very aggressively when not detected early and seriously affect patients' quality of life. Radical cystectomy (surgical removal of the bladder) has long been the standard treatment for localized MIBC. However, this surgery can carry a high risk of complications and substantially impair quality of life. Research into organ-preserving treatment strategies is therefore very important.

A Bladder-Preserving Approach

Preclinical studies have shown that combining radiotherapy with immunotherapies targeting different immune checkpoints (such as CTLA-4 and PD-L1) may increase antitumor activity. The Phase II IMMUNOPRESERVE clinical trial explored this approach and found that durvalumab and tremelimumab given with concurrent radiotherapy could improve bladder preservation. Garcia-del-Muro and colleagues published the results on February 15, 2025, in Clinical Cancer Research .

Design of the IMMUNOPRESERVE Trial

The study enrolled 32 patients with clinical stages T2 to T4a and no metastases or lymph node involvement. Patients were selected who had received only Bacillus Calmette–Guérin (BCG) immunotherapy previously and had not undergone bladder radiotherapy. Treatment proceeded as follows:

1. Patients underwent transurethral resection (TUR).
2. Durvalumab (1500 mg) and tremelimumab (75 mg) were given every 4 weeks for a total of three doses.
3. During the same period, the bladder received a total radiotherapy dose of 64–66 Gy.
4. Patients with residual or recurrent MIBC after treatment underwent salvage cystectomy.

The primary endpoint was complete disappearance of MIBC (complete response) on post-treatment biopsies. Secondary endpoints included bladder-intact disease-free survival, distant metastasis-free survival, and overall survival.

Results

The study results showed high activity of combined immunotherapy and radiotherapy:

• Complete response rate: 81% (26 patients)
• Patients with residual MIBC: 2
• Patients who could not be evaluated: 4
• Median follow-up: 27 months
• Patients undergoing salvage cystectomy: 2
• 2-year survival rates:
  • Bladder-intact disease-free survival: 65%
  • Distant metastasis-free survival: 83%
  • Overall survival: 84%
• Recurrence rates:
  • Non-MIBC recurrence: 3%
  • MIBC recurrence: 19%
  • Development of distant metastases: 16%

Regarding side effects , Grade 3 and 4 events occurred in 31% of patients. The most common adverse events were:

• Diarrhea (6%)
• Acute kidney failure (6%)

These data suggest that radiotherapy combined with durvalumab and tremelimumab may be a safe and effective treatment option. The researchers noted that larger clinical trials are needed to determine whether this approach could offer an alternative to radical cystectomy.

Importance of the Study and Future Prospects

This is an important clinical study demonstrating synergistic effects of immunotherapy and radiotherapy in muscle-invasive bladder cancer. This early-stage study is promising because it suggests that combining the two may improve survival without compromising quality of life.

The researchers emphasize the need for studies involving more patients, longer follow-up, and direct comparison with chemoradiotherapy to confirm these positive findings. If later-phase trials achieve similar success rates, combined immunotherapy and radiotherapy could become an alternative to radical cystectomy, potentially improving quality of life by preserving patients' bladders.