Guideline Integration and the TOMR Paradigm

Dr. Raez addresses choosing between tumor-informed and tumor-naïve platforms, noting no formal prospective comparison exists.

Conceptually, tumor-informed testing should be more accurate since it identifies specific genomic aberrations from tissue, but tissue availability remains challenging given existing difficulties obtaining adequate tissue for diagnostic NGS.

In practice, research enrollment often determines test selection pragmatically: patients with available tissue receive tumor-informed testing, whereas those without adequate tissue receive tumor-naïve testing.

He emphasizes that ctDNA testing isn't currently recommended for widespread clinical use outside research contexts, given unresolved issues around patient anxiety, costs, billing, and accuracy, and that laboratory-approved tests don't automatically translate to guideline inclusion.

Dr. Teplinsky addresses guideline integration requirements, emphasizing the need to demonstrate that acting on ctDNA results improves meaningful outcomes including disease-free survival, distant recurrence-free survival, overall survival, and quality of life.

This requires prospective data showing management changes that help patients live longer, avoid recurrence, avoid unnecessary treatment, and optimize quality of life.

She emphasizes that simply mandating guideline inclusion isn't sufficient; clinicians need tangible, practical guidance regarding which specific test to order for which clinical scenario and resolution of coverage questions.

Dr. Grivas provides his honest assessment of TOMR readiness, emphasizing significant cancer-type-dependent variation in ctDNA detection ability and clinical setting relevance.

For bladder cancer specifically, he considers the IMvigor010/011, TOMBOLA, and CheckMate-274 data collectively make a strong case for serial ctDNA use in the adjuvant, immunotherapy-naïve setting, helping inform both the decision and timing of adjuvant checkpoint inhibitor initiation.

He acknowledges an "aura effect" where enthusiasm from bladder cancer success may drive broader application before adequate validation, emphasizing the need for honest patient discussions about test limitations including possible false-negatives, plus practical workflow considerations regarding result tracking and electronic medical record integration.

He notes emerging interest in renal cell carcinoma using more sensitive whole-genome-based assays in the adjuvant setting and anticipates future complementary use of plasma and urine tumor DNA for urinary tract cancers, though emphasizes that in metastatic disease, current data doesn't yet inform de-escalation or treatment discontinuation decisions.