Safety and preliminary efficacy of Disitamab Vedotin combined with Toripalimab and concurrent radiotherapy in bladder-preserving treatment for HER2-positive invasive bladder cancer.

AIMS: To explore the safety and preliminary efficacy of Disitamab Vedotin (DV) combined with Toripalimab (T) and concurrent radiotherapy regimen (DVTR) in the comprehensive bladder-preserving treatment for HER2-positive invasive bladder cancer patients.

MATERIAL: A total of 10 invasive bladder cancer patients who met the indication for radical cystectomy (RC) but refused the surgery were enrolled from January 2023 to Sep 2025, with follow-up extended until March 2026. All patients underwent maximum transurethral resection of bladder tumor (mTURBT)+/-neoadjuvant therapy with DV plus T after postoperative pathology confirmed HER2 positivity. Concurrent radiotherapy was administered combined with synchronous DV plus T treatment. Patients were followed up until March 2026 or death after the end of treatment.

RESULTS

The overall treatment completion rate was 90% (9/10), with 1 patient only receiving 46 Gy of radiotherapy due to personal reasons. The incidence of grade ≥3 adverse reactions during treatment was 10% (1/10), which was leukopenia. The common grade 1-2 adverse reactions were radiation cystitis (9/10) and hand-foot numbness (2/10); hemorrhagic cystitis caused by radiation occurred in 2 patients (2/10) at the 20th and 22nd months after treatment, respectively. At the last follow-up, the median follow-up time was 17.2 months (range, 6-31 months). The bladder preservation success rate was 90% (9/10); the patient who did not complete radiotherapy had T3 recurrence at 5 months, underwent salvage RC and recovered normally, however, died of intestinal obstruction complications 13 months later. The event-free survival rate was 80% (8/10); 1 patient had T1 recurrence at 7 months after treatment and continued bladder-preserving treatment for 31 months.

CONCLUSION

As a novel strategy for comprehensive bladder-preserving treatment, the DVTR regimen based on DV combined with T and concurrent radiotherapy has initially shown acceptable safety and preliminaryly reliable efficacy in this study. It provides a potential bladder-preserving option for patients with HER2-positive invasive bladder cancer regardless of PD-L1 status, though this conclusion requires validation in larger cohorts,which is worthy of further investigation with an expanded sample size.