PROBLEM In bladder cancer we face relatively low response rates for immune checkpoint inhibitors (ICIs) with only 1 in 5 patients responding to treatment. Thereby 4 out of 5 patients do not benefit from ICIs, yet are exposed to unnecessary toxicity while their disease progresses, survival chances decrease, and unnecessary costs accumulate. Tailoring treatment to patient needs using biomarkers indicative of ICI response would prevent this overtreatment, though such biomarkers are currently unavailable. The BLINC SOLUTION is to use information generated by both WGS and RNA sequencing to unravel a biomarker profile with high predictive value for ICI efficacy in bladder cancer patients. WGS captures an accurate, complete view of genomic tumor characteristics and is unprecedented for providing an: 1) unbiased, 2) reliable, and 3) comprehensive inventory of all types of genetic variants thereby representing the most powerful technique for DNA-based biomarker discovery. Complementary to changes in DNA, RNA can disclose functional tumor characteristics and its microenvironment that may impact treatment responsiveness. By doing so BLINC aims to develop the first biomarker profile to accurately predict ICI responsiveness in patients with metastasized bladder cancer to reduce overtreatment, prevent side-effects, and enable personalized alternative treatment options for patients predicted not to respond.
Taken together, BLINC will improve cost-effectiveness of ICI treatment and will support the implementation of comprehensive genomic predictive diagnostics as an integral part of the Dutch health care system by presenting a use case focused on bladder cancer. BLINC will serve as example for using comprehensive genomic analysis as a reliable and economically attractive tool for biomarker discovery and personalized cancer care for other types of cancer and treatments.