Bladder-sparing regimen for MIBC shows promising antitumour activity

In the treatment of patients with muscle-invasive bladder cancer (MIBC), a perioperative regimen of the antibody–drug conjugate sacituzumab govitecan plus pembrolizumab yields a promising clinical complete response rate without eliciting grade ≥4 adverse events (AEs), allowing bladder preservation without further therapy in some patients, according to the phase II SURE-02 trial.

“The primary analysis results from the SURE-02 trial show, for the first time, a benefit of using a perioperative antibody–drug conjugate plus immune-checkpoint inhibitor combination in a bladder-sparing approach for patients with MIBC,” said lead author Prof Andrea Necchi from Vita-Salute San Raffaele University in Milan, Italy.

SURE-02 included 49 MIBC patients (median age 66 years, 84 percent male, 98 percent White) who were deemed ineligible for or declined cisplatin-based neoadjuvant chemotherapy and were scheduled for radical cystectomy.

All patients received four cycles of intravenous pembrolizumab 200 mg on day 1 and intravenous sacituzumab govitecan 7.5 mg/kg on day 1 and day 8, every 3 weeks. This was followed by radical cystectomy or redo-transurethral resection of the bladder tumour (re-TURBT) in patients who refused to undergo radical cystectomy and then 13 cycles of postsurgical pembrolizumab 200 mg, every 3 weeks.

Over a median follow-up of 14 months, 19 patients (39 percent) achieved the primary endpoint of a clinical complete response, defined as negative imaging and no viable tumour at re-TURBT. Clinical complete response rate was higher among patients with luminal vs nonluminal subtypes (57 percent vs 33 percent; p=0.073). [Lancet Oncol 2026;doi:10.1016/S1470-2045(26)00050-1]

Among patients with complete clinical response, the 12-month event-free survival and bladder-intact-event-free survival rates were both 91 percent. All of them were metastasis-free, and two had an intravesical relapse.

In the entire intention-to-treat population, a total of 25 patients (51 percent) achieved an overall pathological response (pathological downstaging to ypT≤1N0-x stage). The 12-month event-free survival rate was 71 percent, the 12-month metastasis-free survival rate was 74 percent, and the 12-month bladder-intact-event-free survival rate was 38 percent.

As for safety, grade 3 treatment-related AEs occurred in eight patients (16 percent), with the most common being diarrhoea (8 percent). There were no treatment-related deaths. Three patients (6 percent) had serious treatment-related AEs, including bullous pemphigoid in two patients and colitis in one.

Moving beyond radical surgery

Radical cystectomy with neoadjuvant cisplatin-based chemotherapy is the standard-of-care treatment for MIBC. However, up to 50 percent of patients are ineligible for or refuse neoadjuvant chemotherapy, and there are still others who decline surgery after completion of a neoadjuvant therapy. There are several reasons for this, Necchi noted.

“The improvements of therapeutic efficacy of novel neoadjuvant therapies leading to more patients achieving a complete response, the noteworthy advances in the management of urothelial carcinoma in terms of staging, quality of TURBT, and tolerability of novel therapies compared with platinum-based chemotherapy … are making patients increasingly confident that they could be cured without the need to perform an impactful radical surgery,” Necchi said.

Indeed, data from practice-changing trials such as the NIAGARA trial and the more recent KEYNOTE-905/EV-303 trial, both relying on radical cystectomy as backbone treatment, showed the possibility of omitting surgery with high proportions of pathological complete responses.

“Overall, antibody–drug conjugates are reshaping the standard for neoadjuvant therapy, signalling a departure from cisplatin dependence… SURE-02 suggests a future path for bladder preservation in selected patients with systemic therapy alone,” wrote Dr Kriti Mittal from the University of Massachusetts Chan Medical School Worcester, Worcester, Massachusetts, US, and Dr Monika Joshi from the Penn State Cancer Institute, Hershey, Philadelphia, US, in an accompanying editorial. [Lancet Oncol 2026;doi:10.1016/S1470-2045(26)00073-2]

“Highly active regimens such as antibody–drug conjugates plus immune checkpoint inhibitors, regardless of cisplatin eligibility, when guided by biomarkers, have the potential to minimize the need for consolidative therapy in MIBC, improve the overall outcome, and help rewrite patients’ cancer journey,” Mittal and Joshi concluded.