Watchful waiting vs intravesical BCG in high grade pT1 bladder cancer
Dr Hiroshi Kitamura - University of Toyama, Toyama, Japan
High grade T1 bladder cancer comprises 20% of non-muscle invasive bladder cancer. It has malignant potential of progression to muscle invasive disease and metastatic disease too. We need intentional treatment for such cancers but, in fact, high grade T1 bladder cancer is heterogeneous. So we focussed on the patients with high grade T1 bladder cancers whose second TUR specimen showed now residual tumour. The standard treatment for high grade T1 bladder cancer is initial TURBT followed by second TUR and intravesical BCG. But for such patients it means no residual tumour on the second TUR specimen, they might skip intravesical BCG because BCG is toxic and there are problems with BCG shortages in many countries. That’s the background of our trial.
What was the study design?
JCOG1019 was a phase III multi-institutional novel randomised controlled trial powered for no inferiority. The participants who underwent TURBT and had a histopathological diagnosis of high grade T1 bladder cancer were ineligible for primary registration. The participants then underwent a second TUR and were enrolled into the secondary registration if they had pathologically confirmed pT0 histology.
The participants were randomised in a 1:1 ratio to undergo watchful waiting or to receive intravesical BCG for eight courses.
What were your findings?
Finally, watchful waiting demonstrated no inferiority to intravesical BCG. In fact, the hazard ratio for the primary endpoint, the primary endpoint was relapse free survival, excluding Ta or Tis intravesical recurrence, the hazard ratio was 0.69 and the upper limit of 90% CI was 1.08 which was lower than 1.6. So it means the non-inferiority was statistically significant.
Toxicity, in terms of toxicity, of course the participants in the intravesical BCG group had a lot of side effects, treatment related adverse events, for example fever, fatigue, emission pain, urinal frequency and so on. But the frequency was similar to that of previously reported.
In any case, the non-inferiority was proved so we believe that watchful waiting is the new standard of care for patients with high grade T1 bladder cancer who have no residual tumour on the second TUR specimen.
