Kaasinen and colleagues are to be congratulated for contributing one of the best descriptions of the long-term, treatment-modified history of carcinoma in situ (CIS) of the bladder. The primary outcome of the study of BCG versus BCG alternating with mitomycin C (MMC) reported a 10% higher recurrence rate in the BCG/MMC arm. This finding could plausibly be attributed to the known poorer efficacy for CIS of MMC compared to BCG, as the treatment schedule provided 11 MMC instillations and just five BCG instillations over a period of 1 year in one arm compared to 16 BCG instillations in the other arm. What is noteworthy is that, first, even the predominantly MMC arm achieved a marked improvement over the expected natural history of (untreated) CIS. Secondly, while the Kaplan–Meier curves for progression separate, albeit non-significantly, in the two arms, the curves for disease-specific mortality and overall survival intertwine, even for patients followed up for as long as 20 years. Does this imply that chemotherapy may be good enough for some patients with CIS, i.e. those who are unable to tolerate BCG? Thirdly, on the issue of risk of progression, this article suggests that younger patients (< 65 years) and those with exophytic tumour and concomitant CIS (vs primary or secondary CIS) are at higher risk. Lastly, Kaasinen et al. report a 5.7% incidence of usually fatal progressions in patients who remain at risk beyond 10 years, raising a debate on long-term surveillance strategies.
