1963O - JCOG1019: An open-label, non-inferiority, randomised phase III study comparing the effectiveness of watchful waiting (WW) and intravesical Bacillus Calmette-Guérin (BCG) in patients (Pts) with high-grade pT1 (HGT1) bladder cancer with pT0 on the second transurethral resection (TUR) specimen

Background

Intravesical BCG is the standard of care (SOC) for HGT1 bladder cancer. However, whether intravesical BCG is necessary for pts with HGT1 bladder cancer with pT0 histology on the 2nd TUR specimen remains unclear. This study aimed to confirm the non-inferiority of WW to intravesical BCG in pts with HGT1 bladder cancer with pT0 on the 2nd TUR.

Methods

JCOG1019 is an open-label, randomised, phase 3 study that included pts who underwent complete eradication of all visible bladder tumours using TUR and had a histopathological diagnosis of HGT1 bladder cancer. After the 1st registration, pts underwent the 2nd TUR and were enrolled in the 2nd registration if the specimens showed pT0. These pts were randomised in a 1:1 ratio to undergo WW or receive intravesical BCG for 8 weeks. The primary endpoint was relapse-free survival (RFS), excluding the Tis and Ta intravesical recurrences. Non-inferiority was shown if the upper limit of the two-sided 90% confidence interval (CI) of the hazard ratio (HR) was <1.60. Select secondary endpoints included overall survival (OS) and safety.

Results

513 pts were enrolled at the 1st registration. A total of 263 pts were enrolled in the 2nd registration and randomised (BCG: 133; WW: 130); patient characteristics were balanced between the arms. At the data cutoff, the median follow-up was 7.02 years. WW was non-inferior to BCG with respect to RFS (HR 0.692 [90% CI: 0.443-1.082 (<1.60)]; one-sided p=0.001 for non-inferiority by a stratified Cox regression). OS was similar (HR 0.640 [95% CI: 0.334-1.228]) in both the groups. Pts treated with BCG had a higher incidence of adverse events during the entire period, including follow-up, than those who underwent WW (90.2% vs. 50.0% in all grades; 3.8% vs. 3.1% in grade ≥3).

Conclusions

For pts with bladder cancer with HGT1 at the initial TUR and pT0 at the 2nd TUR, WW was non-inferior to intravesical BCG in terms of RFS, excluding Tis and Ta intravesical recurrences. The safety profile of WW was better than that of BCG. These results support WW as a new SOC for pts with HGT1 bladder cancer and no residual tumour at the 2nd TUR.

Clinical trial identification

UMIN000006390.

Editorial acknowledgement

Legal entity responsible for the study

Urologic Oncology Study Group of the Japan Clinical Oncology Group.

Funding

Health and Labour Sciences Research Grant for Clinical Research (H22-67) from the Ministry of Health, Labour and Welfare, Japan; National Cancer Centre Research and Development Funds (23-A-16, 23-A-20, 26-A-4, 29-A-3, 2020-J-3, 2023-J-03).

Disclosure

H. Kitamura: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, MSD, Sanofi, Bristol Myers Squibb, Merck Biopharma, Takeda, Janssen; Financial Interests, Personal, Advisory Board: Kissei; Financial Interests, Institutional, Trial Chair: AstraZeneca; Financial Interests, Institutional, Local PI: MSD, Bristol Myers Squibb. K. Hashimoto: Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K., Bayer Holding Ltd., Astellas Pharma Inc., AstraZeneca. T. Kobayashi: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, Bayer, MSD; Financial Interests, Personal, Advisory Board: Janssen, Astellas; Financial Interests, Institutional, Research Grant: Chugai. S. Narita: Financial Interests, Personal, Invited Speaker: Bayer, Janssen, AstraZeneca, Chugai, Kyowa Kirin, Nippon Shinyaku, Sanofi; Financial Interests, Personal, Advisory Board: Takeda. T. Kimura: Financial Interests, Personal, Invited Speaker: Bayer, Astellas, Sanofi, AstraZeneca, Takeda, Janssen, MSD, Pfizer. All other authors have declared no conflicts of interest.