Society of Urologic Oncology (SUO) 21st Annual Meeting

SUO 2020: Next Generation Clinical Trial Design BCG-Unresponsive NMIBC

( There have been several recent single-arm trials in the Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) setting (Table 1).

The first question that arises is whether these single-arm trials are enough or do we need to randomize patients for our future trials. As seen in Table 1, these treatments are given for a minimum of two years, requiring a high number of physician visits during these treatment years. To get more accurate information, we may need to consider randomizing these patients in the long run and compare these treatments head to head before making any informed decisions.

We also need to consider that the approved treatment of pembrolizumab for BCG unresponsive NMIBC has a relatively low complete response rate of 19% after 12 months with grade a 3-5 adverse events rate of 13%.

Table 1 – Recent single-arm trials in the BCG unresponsive NMIBC:


Aside from the single-arm trial technique, there are additional trial pathways to assess the efficacy of the studied drug with:

  • Randomized simple 1:1
  • Randomized combination
  • Sequential

Only pembrolizumab has been approved for the treatment of NMIBC as previously stated, but other treatments are being used despite having not being evaluated in a randomized prospective trial and despite having not received Federal Drug Administration (FDA) approval (Table 2).

Table 2 – Current proposed treatments for BCG unresponsive NMIBC:


The next decision needed to be made is whether BCG unresponsive NMIBC trials need to be powered separately for carcinoma in situ (CIS) and papillary disease. Table 1 demonstrates that the complete response rates for the available treatments were significantly higher for papillary disease than for CIS.

The third important decision that needs to be made is what should be our primary outcome and how should we determine it. It is not clear if there is any clinical meaning to the endpoint of complete response rate at three months and whether we should rely only on the complete response rate at 12 months. Additionally, it is still ambiguous whether we need to perform a follow-up biopsy to determine the response.

In conclusion, Dr. Kates believes that the next BCG unresponsive NMIBC trial should be randomized, powered enough for both CIS and papillary disease, with the main outcome being 12 months complete response rate. A Follow-up biopsy should probably not be needed if enhanced cystoscopy is used for follow-up.

Presented by: Max Kates, MD, Director, Bladder Cancer Program Assistant Professor of Urology, Department of Urology and Oncology, Brady Urological Institute, Johns Hopkins Hospital

Written by: Hanan Goldberg, MD, MSc, Assistant Professor, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, @GoldbergHanan during the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC

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