SUO 2023: Long-term Outcomes of Bladder-Sparing Therapy Compared to Upfront Radical Cystectomy in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer in an International Cohort

(UroToday.com) The 2023 Society of Urologic Oncology (SUO) annual meeting held in Washington, D.C. between November 28^th and December 1^st, 2023, was host to the Young Urologic Oncologists (YUO) program. Dr. Jacob Taylor presented the long-term results of a comparative analysis of bladder-sparing therapy versus upfront radical cystectomy in an international cohort of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).

Over the past few decades, we have witnessed the emergence of bladder-sparing treatment approaches for localized, muscle invasive bladder cancer. Published recently in The Lancet Oncology, Zlotta et al. demonstrated that trimodality therapy was oncologically equivalent to radical cystectomy in well-selected patients with muscle invasive disease.¹ To this end, Dr. Taylor and colleagues sought to evaluate similar bladder-sparing approaches in NMIBC patients.

This was a multi-center, retrospective cohort analysis of patients with BCG-unresponsive bladder cancer diagnosed between 2005 and 2023. BCG-unresponsive disease as defined using the FDA criteria:

1. High-grade T1 on first assessment following induction BCG therapy
2. Any high-grade NMIBC within 6 months of adequate BCG therapy (≥5 induction + ≥2 maintenance)
3. CIS with or without Ta/T1 within 12 months of adequate BCG therapy

Treatments at time of diagnosis of BCG-unresponsive disease were collected, The primary endpoint was overall survival in patients undergoing upfront radical cystectomy compared to bladder-sparing therapy. Secondary endpoints included:

• Rates of recurrence/progression
• Metastasis-free survival
• Cancer-specific survival
• Cystectomy-free survival

This analysis included a total of 578 patients, of whom 70% were recruited between 2013 and 2020.
Of the 578 patients, 162 underwent an immediate cystectomy and 416 opted for bladder-sparing therapy. The median length of follow-up was 50 months (IQR: 29 – 69; radical cystectomy: 60 months and bladder-sparing therapy: 47 months). Radical cystectomy patients were slightly younger (70 versus 72 years, p=0.01), but otherwise, there were no differences with regards to sex, body mass index, or comorbidity scores.

With regards to initial disease characteristics, patients who underwent radical cystectomy were significantly more likely to have had T1 disease after induction (54% versus 33%). Conversely, bladder-sparing treated patients were significantly more likely to have CIS ≤12 months after last maintenance (38% versus 26%). Bladder-sparing treated patients received a higher median number of BCG instillations (total + maintenance: 11 versus 9).
Summarized in the table below are the bladder sparing treatments that were administered at the time of development of BCG unresponsive disease (only 1^st line treatments). The most common treatments were re-induction with or additional maintenance with continued BCG (38.5%) or intravesical gemcitabine + docetaxel (22.8%).
The second through fourth line bladder-sparing treatment modalities in patients with failure of an initial course of bladder-sparing therapy are as follows:

To date, no significant differences have been observed with regards to overall survival:
Metastasis-free survival:

Cancer-specific survival:

Looking at the data from the bladder-sparing therapy group in further detail, Taylor and colleagues noted that the rate of undergoing cystectomy at 12 months was 12%, 25% at 24 months, and 40% at 60 months. The 12-, 24-, and 60-months rates of metastases were 2%, 7%, and 14% respectively. The corresponding bladder-cancer specific mortality rates were 1%, 5%, and 14%, respectively.

The pathologic outcomes of patients undergoing either upfront or delayed radical cystectomy are summarized below. Notably, the incidence of pN+ disease was significantly higher in patients undergoing radical cystectomy after one (13.4%) or ≥2 lines (12.2%) of bladder-sparing treatment, compared to those undergoing upfront cystectomy (4.4%, p=0.030).
Dr. Taylor concluded that:

• No statistically significant difference in overall, cancer-specific, or metastasis-free survival could be demonstrated between upfront radical cystectomy and bladder-sparing treatment for patients with BCG unresponsive NMIBC.
• There needs to be close surveillance given the high risk of disease recurrence and progression.
• The initial rates of metastasis and death are low but increase significantly after 12 months.
• Approximately 32% of patients who undergo bladder-sparing therapy will eventually undergo radical cystectomy, and they have higher rates of node positivity and increasing rates of non-organ confined disease.
• Further prospective evaluation is needed.

Presented by: Jacob Taylor, MD, MPH, SUO Clinical Fellow, University of Texas Southwestern Medical Center, Dallas, TX

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Society of Urologic Oncology (SUO) annual meeting held in Washington, D.C. between November 28^th and December 1^st, 2023

1. Zlotta AR, Ballas LK, Niemierko A, et al. Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis. Lancet Oncol. 2023;24(6):669-681.