The standard of care for MIBC remains radical cystectomy combined with neoadjuvant chemotherapy. However, approximately 50% of patients are ineligible for or refuse chemotherapy, and outcomes with RC alone are often dismal. Prior studies, PURE-01 and SURE-01, demonstrated activity with neoadjuvant pembrolizumab and TRODELVY, respectively. The ongoing Phase II SURE-02 study (NCT05535218) investigates the efficacy of perioperative TRODELVY + Pembro, incorporating a bladder-sparing approach based on clinical response. This report details the results of a prespecified interim analysis. From October 2023 to February 2025, 49 patients were treated and 36 were efficacy evaluable:

Key Findings (Interim Data on 36 were efficacy evaluable):

1. Compelling Clinical Complete Response (cCR) Rate: ~44% achieved cCR (confirmed by imaging + negative TURBT + biopsy)

2. Bladder Preservation: 23 patients chose bladder-sparing after cCR

3. 12 month bladder intact event free survival: 100% in cCR patients at last follow-up; 74% overall in the cohort

4. 12 month Event-Free Survival (EFS) rate: 71.3%

5. Disease Progression: Only 4 patients progressed during/soon after therapy; 1 progressed post-cystectomy

Regarding safety, Grade ≥3 treatment-related adverse events occurred only in 9 patients (18.4%). Serious treatment-related adverse events occurred in 8.2% (n = 4) of patients. Only 3 TRODELVY dose omissions and one dose delay (1 week) were recorded, and notably, no TRODELVY dose reduction was required, underscoring the regimen's manageable toxicity profile.  

KOL insights

"Perioperative SGP resulted in 44% cCR, allowing bladder preservation not just including these cCR patients, but in the rest of the patients undergoing reTURBT. The interim results from SURE-02 support further investigation into the sacituzumab govitecan/pembrolizumab combination in MIBC." –Expert Opinion

Conclusion 

Currently, the standard of care for muscle-invasive bladder cancer (MIBC) centers on radical cystectomy, often combined with neoadjuvant cisplatin-based chemotherapy for eligible patients. While adjuvant nivolumab is approved for high-risk patients post-cystectomy, many patients are ineligible for or decline neoadjuvant chemotherapy, leaving a significant unmet need for effective, bladder-sparing alternatives.

In this setting, the interim results from the SURE-02 study offer a potentially transformative option. Neoadjuvant TRODELVY  (an antibody-drug conjugate targeting TROP-2) combined with pembrolizumab The combination of perioperative TRODELVY and pembrolizumab demonstrated an impressive 44% clinical complete response rate, with a tolerable safety profile, enabling bladder preservation in 74% of patients who declined radical cystectomy. The study also provided crucial molecular insights. These findings support more refined patient selection and underscore the potential of biomarker-driven strategies. However, the study  has some limitations such as the interim nature of analysis and the relatively small sample size. 

Although not yet practice-changing, these promising results make a strong case for continued evaluation of TRODELVY plus pembrolizumab. If confirmed in the full cohort and future Phase III trials, this regimen could emerge as a much-needed, bladder-sparing alternative—broadening treatment options and potentially redefining the therapeutic approach for MIBC patients who cannot undergo standard chemotherapy.