Genetic Testing and Surveillance Cuts Costs and Improves Survival in Li-Fraumeni Syndrome

Balancing timely identification with sustainable care pathways remains a persistent challenge for health systems. A pan-European analysis has examined the clinical course and financial burden among individuals with TP53 alterations associated with LFS. New findings show that proactive carrier identification and structured surveillance can yield substantial cost benefits.

At the European Society of Human Genetics annual conference, investigators within the EU PREVENTABLE project presented a Europe-wide evaluation of surveillance for TP53 carriers with LFS. The approach combines early identification, often through family history or very early tumor onset, with presymptomatic genetic testing and enrollment in routine screening protocols. Surveillance includes whole-body MRI, brain MRI and, for adults, breast MRI, ultrasound examination of the abdomen, and clinical examination by a specialist.

Retrospective clinical data were compiled by the Rouen joint oncogenetics team from the University Hospital and the Henri Becquerel Center, spanning 505 TP53 carriers and 361 noncarrier relatives across seven European countries via nine European Reference Network (ERN) expert centers. Costs were calculated for each individual’s care pathway using standardized French hospital prices. Two cohorts were compared: individuals under proactive surveillance and those treated after a cancer diagnosis.

Among 155 TP53 carriers without prior cancer in the preventive cohort (median age 28 years), 18 developed one or more cancers during follow-up. The analysis found significantly improved survival in the preventive group, with a mean prevention cost of €6,046.80 per patient. In the treatment cohort of 273 patients who had already developed cancer before genetic testing (median age 33 years), mean treatment cost was €53,906 per patient, including 109 early-stage and 164 advanced-stage cases.

The European Reference Network GENTURIS is developing consensus clinical guidelines for LFS and other tumor risk syndromes that prioritize early risk identification, genetic testing before symptoms, and structured surveillance. The research team plans further analyses and publication of the multicountry dataset, and they hope the results will inform prevention strategies at the health authority level. This work is presented as the first Europe-wide evidence linking preventive surveillance in LFS to both clinical benefit and substantial cost savings.

“From a clinical perspective, our results were not surprising, since intensive screening should enable earlier cancer detection, generally associated with better clinical outcomes. But what is particularly noteworthy is that we have been able to see this reflected in real-world data across several European countries. And we were also struck by the dramatic difference between prevention and treatment costs,” said Marion Rolain, biomedical researcher and engineer in the genetics department at the Center Hospitalier Universitaire Rouen.

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