Bladder-Sparing Therapies for Bacillus Calmette-Guérin-Unresponsive Carcinoma In Situ: An Upper and a Lower Response Group With an Unstable Boundary

Objectives: The objectives of this study are to determine which orderings among five bladder-sparing therapies for Bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ are supported by the published response data, and which depend on how response is defined and analysed.Methods: The pivotal cohorts of the five regimens approved or in rolling application were identified, and counts derived from the published data were analysed with independent binomial models and Beta(1,1) priors.Papillary-only cohorts were not eligible.Complete response, as each trial defined it, and a 12-month response-related quantity were examined, with all comparisons repeated across 10 specifications of the response definition, the analysis population and the anchor.Results: Five cohorts of 82 to 110 patients were included.Complete response estimates were 81.9%, 75.1%, 70.4%, 53.4% and 40.8% for TAR-200, cretostimogene, nogapendekin alfa inbakicept plus bacillus Calmette-Guérin (NAI plus BCG), nadofaragene firadenovec and pembrolizumab.The corresponding 12-month quantities were 45.9%, 46.4%, 45.2%, 24.6% and 19.2%, which differ in anchor, population and construct.All six comparisons between the higher three and the lower two excluded zero by 20.5 to 27.2 percentage points, whereas none within the higher three did so under any 12-month specification.Of the 100 comparisons, 44 included zero, and no comparison excluded zero in the opposite direction.Two of the 10 specifications depend on a three-month cretostimogene count that has not been published and was bounded rather than observed.Restricting the analysis to the four approved agents, excluding cretostimogene, left these findings unchanged.Conclusions: The published response quantities form an upper and a lower group rather than a stable ranking of five.TAR-200 and cretostimogene remained above the lower two agents in 8 to 10 specifications, whereas the separation of NAI plus BCG was less stable.Within the upper group, the agents could not be ordered.