Article Text

Download PDFPDF

443 Pembrolizumab for BCG refractory non-muscle invasive bladder cancer yields poor recurrence-free survival and high toxicity in patients
  1. Borivoj Golijanin1,
  2. Vikas Bhatt1,
  3. Ali Amin2,
  4. Galina Lagos3,
  5. Andre De Souza3,
  6. Anthony E Mega3 and
  7. Dragan Golijanin1
  1. 1The Minimally Invasive Urology Institute at the Miriam Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
  2. 2Department of Pathology and Laboratory Medicine at the Miriam Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
  3. 3Lifespan Cancer Institute at the Miriam Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background High-grade non-muscle-invasive-bladder-cancer (NMIBC) has high recurrence rates and potential resistance to intravesical therapies. Anti-PD-L1 immunotherapy with pembrolizumab was approved in January 2020 for treatment of patients with high-risk, BCG refractory 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. In this study we report on our single institutional experience using pembrolizumab in BCG refractory patients.

Methods Records of patients with NMIBC treated by pembrolizumab from 01/2020–01/2023 at a single institution 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 Out of 250 screened records of NMIBC in this time period, 18 records with median age of 74.1 (IQR=67.8 – 81.4), male to female ratio of 3.5:1, and a median follow-up of 17.5 months (IQR= 8.1 – 22.5) met the inclusion criteria. All patients had 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) stopped treatment. Only five patients (38.5%) are still undergoing treatment with an average of 12.6 cycles (SD=10.4 cycles). Only one patient out of thirteen who stopped treatment had a sustained complete response at 19 cycles. Reasons for discontinuation included: 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 methods showed a PFS of 19.5 months (SD=2.4) and a TSS of 26.5months (SD=2.9). Four patients ultimately required radical cystectomy with pathologies showing 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.

Conclusions Our institutional experience using pembrolizumab in the treatment of high risk BCG refractory NMIBC suggests high toxicity leading to early withdrawal from treatment. Similarly, our experience did not confirm previously reported high response rates beyond one year. Additional research is warranted to better identify patients who are likely to benefit from this agent.

Ethics Approval This study was approved by institutional review board of the The Miriam Hospital and Lifespan Hospital System in Providence, RI. Study ID: 1047794. All required consents were acquired prior to data collection.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.