I'm extremely happy to have received the @Uroweb Hans Marberger Award at #EAU22 Also great to see friends f2f again #MedTwitter #UroSoMe

Special thanks to all coauthors and especially @DRobesti @GPloussard @GFallara_MD @PGrivasMDPhD

📈 The CHT outcomes in EV-302 were consistent or superior to those in other phase III trials. Despite higher non-progression-related discontinuation and a PFS follow-up protocol that potentially disadvantaged chemotherapy, the OS benefit of EVP remains robust and unbiased.

Key findings: ✅No imbalance in censoring for OS (p=0.7) ⚠️Significant imbalance in PFS censoring (p<0.01) reflecting premature censoring of non-progressors starting maintenance Even assuming all censored CHT pts were “immortalized”, EVP had a clear OS advantage (HR 0.63, p<0.01

We applied a multi-step strategy: 🔹 Reconstructed KM curves 🔹 Reverse KM analysis to evaluate censoring balance 🔹 Simulation modeling to test extreme scenarios of informative censoring 🔹 Cross-trial comparisons with KEYNOTE-361, DANUBE, IMvigor130, and CheckMate-901

1. A high discontinuation % in the chemo arm: ~45% of patients discontinued treatment for reasons unrelated to progression or toxicity (vs 10% EVP) 2. Protocol for PFS follow-up, which initially censored patients at the start of subsequent therapy— including maintenance avelumab

EV-302 reshaped the landscape of metastatic urothelial carcinoma. However, two critical methodological aspects warranted deeper scrutiny and were addressed in our recent paper: https://t.co/nR2JD6RRE4

Huge thanks to #prostatectomy mentors @GPloussard @AmbroiseSalin @AshTewariMD @jdhdavis - trying to make the most of what I learned from each of you!

Anastomosis as per Van Velthoven with a 3-0 strata fix marked in the middle by my amazing surgical team, beginning on the BN side

Hood #robotic #prostatectomy with maximal bladder neck preservation ↙️ Although I mostly trained with a non-BN approach, I switched to BN preservation whenever feasible and do not perform posterior reconstruction/Rocco stitch

Thank you @OncLive for having organized a symposium with @uofcincycancer and for the interview More on Gene therapy for #NMIBC: https://t.co/Irnt2d9V30 Tune in for more @DRobesti

A great honor to be part of this group! Thank you @UroDocAsh !

Navigating the non-muscle-invasive bladder cancer space can be challenging. Thank you @UroDocAsh and @urotoday for the great discussion and the invite. @uc_health @uofcincycancer

Finally: After correcting for IC, RC outcomes were still superior to TMT Our data underline the complexity of comparing outcomes between TMT and RC, and challenge the acceptance of TMT based on retrospective comparison in spite of randomization. Follow @DRobesti for more 🥇

For OS, the minimum proportion of events required compensate for the potential effect of IC ranged from 16 % to 33 %. After adjusting for potential presence of IC, RC was still superior in terms of OS relative to TMT (5-year OS: 42 % vs. 30 %; p < 0.001).

Additionally, we simulated different dropout rates, due to theoretical frailty, and classified them as competing events in the Fine & Gray competing risks model (1999), rather than treating them as censored events ( https://t.co/ZWhe2sPEXT)

Ok, an imbalance in censoring can happen in RCTs ( https://t.co/7Z7COvYzcu) or retrospective studies - what did we do next? We performed a simulation analysis to assess the minimum proportion of events required among censored patients to compensate for the potential effect of IC.

What did we find? - Across 6 studies, an imbalance in censoring was present for ten time-dependent outcomes, favoring RC in OS, MFS, and DFS. These findings were consistent after stratifying for propensity score matching and neoadjuvant chemotherapy (see sensitivity analysis).

Quick digression: We relied on the method by Gilboa #EJC https://t.co/1mlXt3cZBf In brief: more censoring somewhere = less events = better observed outcomes on KM analysis

We performed a meta-analysis of 6 retrospective studies comparing TMT vs RC (n=8,594) and reconstructed individual KM data. We assessed the imbalance in censoring by using the reverse KM function, for which 1⃣original event ≡ censoring 2⃣original censoring ≡ event

An imbalance in the censoring pattern may represent loss of unaccounted information, or informative censoring (IC). IC occurs when dropout rates between study arms are imbalanced in a non-random manner due to unaccounted factors, resulting in loss of information.