Fig. 1: Study design and primary objectives of HCRN GU16-257.

a, CONSORT diagram outlining disposition of patients enrolled on HCRN GU16-257 and demonstrating co-primary objective of estimating the cCR rate. b, Contingency table informing co-primary objective of assessing the positive predictive value of cCR for the composite outcome measure of 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients undergoing immediate cystectomy (n = 69 of 76 total patients). Seven patients were excluded for the following reasons: four patients who did not undergo clinical response assessment; two patients who did not achieve a cCR, who did not pursue cystectomy and who were lost to follow-up before 2 years; and one patient who achieved a cCR and without evidence of local or distant recurrence at 18 months and who was subsequently lost to follow-up. c, Metastasis-free survival according to cCR versus no cCR using landmark timepoint of post-cycle 4 restaging (n = 72; four patients were excluded who did not undergo clinical response assessment). Estimating metastasis-free survival was a secondary objective of the study. d, Overall survival according to cCR versus no cCR using landmark timepoint of post-cycle 4 restaging (n = 72; four patients were excluded who did not undergo clinical response assessment). Estimating overall survival was a secondary objective of the study. a and b were created with BioRender. *Composite outcome measure: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients undergoing immediate cystectomy.