🚨 Perioperative immunotherapy in MIBC at #ESMO2026. Three phase III trials, three different answers, and one uncomfortable lesson for those of us who report pCR. 🔬

📊 NIAGARA (durvalumab + GC, n=1,063): pCR 37.3%, EFS HR 0.68 (0.56–0.82), OS HR 0.75 (0.59–0.95) ✅

📊 KEYNOTE-866 (pembrolizumab + GC, n=907): pCR 44.4%, EFS HR 0.88 (0.71–1.10), OS HR 1.00 (0.76–1.27) ❌

📊 CA017-078 (nivolumab + GC, n=653): pCR 39.1%, EFS HR 0.94 (0.71–1.25), OS HR 0.88 (0.64–1.21), OS immature ❌

Cross-trial, not head to head. Populations, schedules, follow-up (34 to 55 months) and statistical design all differ, so the ranking is exploratory.
But look at the direction. The trial with the highest pCR returned an OS hazard ratio of exactly 1.00. 🧠
Three points from the pathology side:
1️⃣ pCR is a response marker, not a surrogate. Comparable absolute pCR gains of roughly 9 to 10 points across all three, divergent survival. If pCR tracked cure, that pattern should not be possible. pCR remains elusive at least for standard chemotherapy plus IO.
2. And pCR itself is not standardised across trials. ypT0N0 depends on sampling protocol, block numbers, regression assessment and whether review is central or local. The NIAGARA figure quoted here comes from a reanalysis, which tells you the endpoint moved on re-review. A 9-point difference is not comfortably above that measurement noise.
Also worth noting: NIAGARA and KEYNOTE-866 both gave adjuvant IO, CA017-078 did not. So adjuvant continuation alone does not explain the split either. We genuinely do not know why these diverged. 🎯
Which is the real message. We are comparing trials on an endpoint we produce, that is not validated, not standardised, and not stratified by biology. Fixing that is a pathology job, and it is overdue. We need that now more than ever with neoadjuvant systemic phase becoming SOC.
@OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot
#Uropathology #BladderCancer #blcsm #MIBC #pathtwitter
Great summary below from Niklas Klümper.