A multi-institutional, open-label, randomized phase 3 trial, JCOG1019, has found that watchful waiting is non-inferior to intravesical Bacillus Calmette-Guérin (BCG) therapy in patients with high-grade T1 bladder cancer who have no residual tumor (pT0) following a second transurethral resection (TUR). The study, presented at the ESMO Congress 2024, suggests a potential shift in the standard of care for this specific patient population, especially considering the global BCG shortage and treatment-related adverse events.
The JCOG1019 trial enrolled 263 patients with high-grade T1 bladder cancer who achieved pT0 status after a second TUR. Participants were randomized to either a watchful waiting arm or an intravesical BCG arm, receiving eight courses of BCG weekly. The primary endpoint was relapse-free survival (RFS) for T1 or deeper intravesical and/or extravesical recurrence or death. Non-inferiority was defined as the upper limit of the two-sided 90% confidence interval of the hazard ratio being less than 1.6.
Key Findings
Results indicated that watchful waiting was indeed non-inferior to intravesical BCG with respect to RFS (HR 0.69, upper limit 1.08). The five-year RFS rate was 86.5% in the watchful waiting group and 81.8% in the BCG group. Overall survival (OS) and metastasis-free survival (MFS) with bladder preservation were also similar between the two groups. The five-year OS rate was 92.0% in the watchful waiting group and 91.7% in the BCG group. The five-year MFS rates were 89.7% and 86.4%, respectively.
However, intravesical recurrence-free survival, including Ta or Tis intravesical recurrence, was slightly better in the BCG arm (3-year rate of 80%) compared to the watchful waiting arm (3-year rate of 70%), although this difference was not statistically significant (HR 1.33).
Safety Profile
The safety profile favored watchful waiting, with a lower incidence of adverse events compared to the BCG arm (50.0% vs. 90.2%). Grade 3 or higher adverse events were also less frequent in the watchful waiting group (3.1% vs. 3.8%). Adverse events associated with BCG treatment included fever, fatigue, hematuria, urinary frequency, and urinary tract pain.
Clinical Implications
Dr. Hiroshi Kitamura, MD, PhD, of the University of Toyama in Japan, who presented the data, suggested that these results support watchful waiting as a potential new standard of care for patients with high-grade T1 bladder cancer without residual tumors at the second TUR. He noted that 90% of patients in the watchful waiting arm avoided BCG during the follow-up period.
"From the point of view of cancer death, metastasis and radical cystectomy, we strongly recommend watchful waiting if the second TUR specimen shows no residual tumor," Dr. Kitamura stated. However, he also acknowledged that for patients who want to avoid Ta or Tis intravesical recurrence, intravesical BCG may still be recommended.
The study authors suggest that older, more comorbid patients might be particularly suitable candidates for watchful waiting, while younger patients may still benefit from BCG therapy. The findings also have implications for addressing the ongoing BCG shortage, as watchful waiting can reduce the demand for BCG in this specific patient population.
