Eugene Pietzak, MD, on pembrolizumab plus BCG for BCG-naïve “very high risk” T1 NMIBC

In this video, Eugene Pietzak, MD, highlights results from a phase 2 study of pembrolizumab (Keytruda) in combination with BCG as a bladder-preserving option for patients with very high-risk, BCG-naive high-grade T1 non–muscle-invasive bladder cancer (NMIBC) with concomitant carcinoma in situ (CIS) who declined upfront radical cystectomy.¹ The results were presented at the 2026 American Urological Association Annual Meeting in Washington, DC.

Pietzak is a urologic surgeon at Memorial Sloan Kettering Cancer Center in New York, New York.

“We conducted a study specifically [looking] at that very high risk T1 cohort of patients, where we combined intravenous pembrolizumab with BCG,” Pietzak explained. “Most guidelines recommend these patients undergo upfront radical cystectomy. I will say, most patients have grown fond of their bladders and are looking for bladder-preserving options, so most of them are not so keen on proceeding directly to cystectomy without trying something first. Even as a clinician, [we may] feel very uncomfortable with the idea of these very high-risk patients receiving just BCG alone, because progression can be a life-threatening situation.”

The study used a Simon two-stage design and enrolled 37 adults who had BCG-naive HGT1 disease with concomitant CIS and at least 1 additional high-risk feature after declining radical cystectomy. Among the patients enrolled, 68% had tumors measuring at least 3 cm, 57% had extensive lamina propria invasion, and 43% had multifocal T1 disease. Nearly two-thirds (73%) of patients had at least 2 adverse-risk features, while more than half (51%) had 3 or more.

The primary end point—a 6-month complete response rate—was achieved in 92% of patients (34/37; 95% CI, 79 to 97), exceeding the prespecified threshold for clinical significance. At a median follow-up of 20.8 months, no patients had progressed to muscle-invasive disease, 4 experienced recurrence, and 2 underwent radical cystectomy. High-grade recurrence-free survival at 12 months was 88%, with median recurrence-free survival not reached.

Although the efficacy results were encouraging, Pietzak emphasized that treatment intensification came with increased toxicity. Grade 3 or higher immune-related adverse events (AEs) occurred in 21% of patients, and overall grade 3 treatment-related AEs were reported in approximately one-third of the cohort (32%). One death was considered possibly related to pembrolizumab. Pietzak stressed that these risks should be weighed against both the limitations of BCG alone and the morbidity associated with radical cystectomy. While longer follow-up is needed, he said the findings support pembrolizumab plus BCG as a potential bladder-preserving strategy for selected patients with the highest-risk NMIBC who decline or are unfit for cystectomy.

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