Presented by: BORIVOJ GOLIJANIN
Minimally Invasive Urology Institute of the Miriam Hospital and Warren Alpert Medical School of Brown University

Introduction

Pembrolizumab was approved in January 2020 for treatment of patients with high-risk, BCG refractory non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy. This study reports our single institutional experience using pembrolizumab for this indication.

Materials

Records of patients with NMIBC treated by pembrolizumab from 01/2020-01/2023 were retrospectively reviewed for key demographic and clinical information. Kaplan-Meier curves were used to calculate progression free (PFS) and treatment specific survival (TSS), and combined positivity score (CPS) of PD-L1 on immunochemistry was assessed.

Results

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Out of 250 screened records of NMIBC, 18 records with median age of 74.1, male to female ratio of 3.5:1, and a median follow-up of 17.5 months (IQR= 8.1 – 22.5) were included. All had a history of CIS and were treated with intravesical chemotherapy after they became BCG refractory. At start of pembrolizumab, 1/18 (5.6%) was cTa, 6/18 (33.3%) had CIS, and 11/18 (61.1%) had cT1. After an average of 8.9 cycles (SD=6.3), 72.2% of patients (13/18) discontinued. Five patients (38.5%) are still in treatment with an average of 12.6 cycles (SD=10.4 cycles). One patient out of thirteen who stopped treatment had a sustained complete response at 19 cycles. Discontinuations were due to: Grade 2 or higher toxicity in 7/13 (53.8%), disease progression in 4/13 (30.8%), , and 1/13 stopped due to disease recurrence. Recurrence-free survival rates at 3-, 6-, and 12-months were 16.7%,  11.1%, and 5.6%, respectively. 6- and 12-month PFS rates were 94% and 77.7%, respectively. Kaplan-Meier revealed a PFS of 19.5 months (SD=2.4) and a TSS of 26.5months (SD=2.9).  Four patients required radical cystectomy and were pTa (n=1), pTis (n=1), pT1 (n=1), and pT4 (n=1). PD-L1 positivity, defined as CPS > 10, was noted for only one patient.

Conclusion

High toxicity leading to early withdrawal from treatment was common in this cohort. This study does not confirm previously reported high response rates beyond one year. Early discussion on radical surgery remains an important part of our guidelines for treatment of BCG refractory NMIBC. Additional research is warranted to better identify patients who are likely to benefit from this agent.

Funding

None

Lead Authors

Vikas Bhatt,
Minimally Invasive Urology Institute of the Miriam Hospital and Warren Alpert Medical School of Brown University

Co-Authors

Galina Lagos,
Lifespan Cancer Institute at the Miriam Hospital and Warren Alpert Medical School of Brown University

Kamil Malshy,
Minimally Invasive Urology Institute of the Miriam Hospital and Warren Alpert Medical School of Brown University

Ali Amin,
Department of Pathology and Laboratory Medicine at the Miriam Hospital and Warren Alpert Medical School of Brown University

Anthony Mega,
Lifespan Cancer Institute at the Miriam Hospital and Warren Alpert Medical School of Brown University

Dragan Golijanin,
Minimally Invasive Urology Institute of the Miriam Hospital and Warren Alpert Medical School of Brown University