Genomic’s Eleven.

Top Line: Bladder preserving therapy for muscle-invasive bladder cancer (MIBC) is a category 1 strategy per NCCN, but we all learned selecting ideal candidates is key.

The Study: Things such as hydronephrosis and carcinoma-in-situ have long been taught as features that do poorly with non-cystectomy management. Can we do better in 2022? High levels of MRE11, a DNA nuclease that helps coordinate DNA damage repair, is seen as a harbinger of intrinsic cellular deficiencies in DNA damage repair. In other words, more and more MRE11 is expressed in the presence of persistent DNA damage–think hyperinsulinemia in the presence of type 2 diabetes. This pooled analysis of six prospective trials of bladder-preserving therapy for MIBC retrospectively measured MRE11 expression in 135 analyzable pretreatment tumor tissues. As compared to those with expression levels in the lowest quartile, those with higher levels had half the risk of bladder cancer mortality following the bladder preserving approach of TURBT followed by definitive chemoradiation (HR 0.50, 41% v 21% at 4 years).

TBL: With further validation, tumor expression of MRE11 may prove a biologic predictor of who is more or less likely to do well with a bladder conservation approach for MIBC. | Magliocco, JAMA Netw Open 2022