Jonathan Anker, MD, highlights response-guided bladder preservation strategy in MIBC

At the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California, Jonathan F. Anker, MD, PhD, discussed findings from the phase 2 HCRN GU 20-444 trial (NCT05406713). The study is evaluating a response-adapted, bladder-sparing approach using pembrolizumab (Keytruda) monotherapy in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or declined cisplatin chemotherapy.

Anker is an instructor of medicine (hematology and medical oncology) at the Icahn School of Medicine at Mount Sinai in New York, New York.

Anker explained that radical cystectomy remains the standard of care for MIBC but is associated with substantial morbidity, mortality risk in older populations, and permanent urinary diversion. Given that a subset of patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR) and experience durable disease control, investigators have sought to identify strategies to safely omit surgery in select patients. Prior HCRN work combining cisplatin-based chemotherapy with immunotherapy demonstrated that approximately 43% of patients achieved a stringent clinical complete response (cCR), with favorable long-term outcomes in those who deferred cystectomy. However, because up to half of patients with MIBC are cisplatin-ineligible, HCRN GU 20-444 was designed to evaluate whether pembrolizumab monotherapy could achieve similar response rates in a bladder-sparing paradigm without chemotherapy.

The study enrolled 46 patients with cT2-3N0M0 urothelial carcinoma who were cisplatin-ineligible or declined chemotherapy. Following maximal transurethral resection of bladder tumor (TURBT), patients received 2 cycles of pembrolizumab (400 mg every 6 weeks), followed by rigorous restaging including cystoscopy with biopsies, urine cytology, and MRI. Patients who achieved a cCR—defined by no evidence of disease across all modalities—continued pembrolizumab for up to 7 additional cycles and omitted definitive local therapy, while those without a cCR proceeded to radical cystectomy or chemoradiation.

At a median follow-up of approximately 11 months, 43% of patients achieved a cCR, mirroring results from prior combination therapy studies. Among the 20 patients with a cCR, all initially avoided cystectomy, with no metastatic recurrences observed to date; 1 patient underwent delayed cystoprostatectomy for a new prostate cancer diagnosis (with no residual bladder tumor).

According to the authors, these findings suggest that pembrolizumab monotherapy with response-guided management may offer a feasible bladder-sparing strategy in selected patients with MIBC.

REFERENCE

1. Anker JF, King J, Tripathi A, et al. Phase 2 trial of pembrolizumab (P) with response-guided bladder-sparing in patients with muscle-invasive bladder cancer (MIBC; HCRN GU 20-444). J Clin Oncol. 2026;44(suppl 7; abstr 737). doi:10.1200/JCO.2026.44.7_suppl.737