Sasanlimab + BCG vs. BCG Alone in High-Risk NMIBC

Speaker - Dr. Neal Shore

Introduction:

The standard care for patients with high-risk non-muscle invasive bladder cancer (NMIBC) has traditionally involved transurethral resection of bladder tumor (TURBT) followed by induction and intravesical maintenance with BCG therapy. Despite the approach many patients still experience recurrence and disease progression leaving limited therapeutic options. The mechanism of action for combining BCG with a PD-1 blocker is well established, leveraging the upregulation of PD-L1 to enhance the immune response. A PD-1 inhibitor Sasanlimab, if delivered subcutaneously may offer practical advantages for the medical oncology and urology clinics that might potentially improve accessibility and patient compliance.

Methods:

1. It was a three-arm, randomized controlled trial that included 1055 patients. The study included BCG-naive patients with no prior exposure to PD-1/PD-L1 blockers.
2. The patients were stratified in the ratio 1:1:1 on the basis of presence or absence of carcinoma in situ (CIS). The study arms included the following:

• Arm A: Sasanlimab was administered subcutaneously every 4 weeks for 25 cycles. BCG induction and maintenance therapy was provided according to the Southwest Oncology Group (SWOG) protocol.
• Arm B: Only BCG induction therapy was given, with no maintenance phase.
• Arm C (Control Group): Standard BCG induction and maintenance therapy was administered.

3. Event-Free Survival (EFS) was used as the primary endpoint. EFS was defined by recurrence of high-grade disease, progression, persistence of CIS, or death from any cause.
4. The key secondary end points included factors like Overall Survival (OS), Complete Response (CR), safety, Quality of Life (QoL)
5. Appropriate statistical methods were applied to assess efficacy and safety across the trial arms.

Results:

• The demographics were very comparable between Arm A (Sasanlimab + BCG) and Arm C (BCG only).
• Categorization of patients based on disease stage:

1. 55% of patients had T1 stage bladder cancer.
2. 25% of the population had CIS.
3. 15% had CIS alone (isolated)

• The maintenance of BCG delivery was administered at similar rates across all arms. The discontinuation rates were also comparable. The addition of sasanlimab did not affect the delivery of BCG therapy.
• The Kaplan-Meier curves were observed to separate at 18 months, with sustained benefit favoring the combination arm (Arm A) confirmed at 2 and 3 years. A 32% reduction in the risk of EFS events was demonstrated in Arm A, with a hazard ratio of 0.68 and a p-value of 0.0095. Recurrence of high-grade disease was reduced by over 50% in Arm A compared to Arm C. In patients with CIS, a durable complete response at 36 months was achieved in 92% of those in Arm A, compared to 67.7% in Arm C.
• A reduction of over 50% in high-grade disease recurrence was observed in Arm A compared to Arm C. Subgroup analysis revealed a clear benefit of combination therapy in patients with CIS and T1 disease. No significant difference was noted between Arm B (induction-only sasanlimab) and Arm C, which indicated limited efficacy of induction-only therapy.
• Treatment-related adverse events were found to be consistent with the known profiles of BCG and checkpoint inhibitors. Immune-related adverse events, primarily low-grade thyroid abnormalities and rash, were reported in Arms A and B, with approximately 15% classified as Grade 3 or 4 and typically managed with thyroid supplementation. Serious immune-related events were observed in less than 1% of patients.
• No deterioration in quality of life was detected, and additional patient-reported outcomes and quality of life data are expected to be presented at ASCO and ESMO.

Conclusion:

The study was identified as the first among several that evaluated checkpoint blockade in BCG-naive patients to demonstrate a statistically significant prolongation of  event-free survival (EFS) when sasanlimab was combined with BCG. In patients with carcinoma in situ (CIS), a higher probability of sustained complete response at 36 months was observed with the combination therapy (92% vs. 68%).The safety profile was found to be consistent with expectations. The study has been accepted in principle for publication in Nature Medicine, which will recognize its contribution as a major global phase III trial.

Radical Cystectomy vs. Bladder-Sparing Therapy in Recurrent High-Grade NMIBC

Speaker - Dr. John Gore

Introduction:

The management of recurrent high-grade non-muscle invasive bladder cancer (NMIBC) poses a dilemma clinically that is particularly concerning with timing of radical cystectomy (RC). Prior systematic reviews had revealed a lack of robust comparative data, which portrayed the need for evidence to inform clinical and patient decision-making.

Recognizing the important role of patient-centered decision making, the CISTO study was designed in order to address the gap. The study compares outcomes between radical cystectomy and bladder-sparing therapy (BST) over a 12-month follow-up period. The study was motivated by patient advocacy findings in order to highlight the uncertainty and concern surrounding the cystectomy decisions.

Methods:

• The study was a pragmatic, prospective observational cohort study that included 570 patents that were recruited from 36 U.S. academic and community centres.
• The patients were divided into 2 groups: 371 patients were included in the BST arm and 199 patients were included in the RC arm.
• The inclusion criteria were based on the eligibility for both RC and BST, which was determined by the treating clinician. BST included salvage intravesical chemotherapy, re-induction BCG, systemic immunotherapy, etc.
• The researchers hypothesized that radical cystectomy (RC)—which involved surgical removal of the bladder and would result in worse physical functioning one year after treatment compared to bladder-sparing therapy (BST). This reflected concern that the more invasive nature of RC could impair long-term physical health and quality of life.
• Since this was not a randomized study, there could be selection bias—for example, healthier patients might be more likely to receive one treatment over another. To address this, the researchers used Targeted Maximum Likelihood Estimation (TMLE), which is a sophisticated statistical method that adjusts for confounding variables and helps estimate the true effect of treatment more accurately, improving the reliability of the findings.
• The primary outcomes included Physical Functioning (EORTC QLQ-C30 scale)
• The secondary outcomes included Global health (EQ-5D), Emotional well-being (PROMIS Anxiety/Depression), Bladder Cancer Index (urinary, bowel, and sexual domains), Financial toxicity (COST measure), Cancer-specific, recurrence-free, and progression-free survival

Results:

The following table shows the results of the study category wise when compared between both the arms.

Conclusion:

It was concluded that RC remains a crucial treatment option for recurrent high-grade NMIBC and it should not be dismissed based on assumptions about post-surgical quality of life. A majority of secondary outcomes—including mental health, recurrence-free survival, and financial health were seen to have favored radical cystectomy. Further follow-up and analysis are ongoing.

American Urological Association 2025, April 26-29, Las Vegas, NV