Objective Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant syndrome which may cause early-onset cancers and entails a high risk of cancer in their lifetime. In 2017, American Association for Cancer Research(AACR) published the surveillance guidelines based on expert consensus. They recommend annual surveillance using whole-body MRI(WBMRI) and additional modalities referring to Toronto protocol. Whereas several study groups have reported high detection rates of malignant tumors, it might be likely to lead overdiagnosis rather than lead-time effects for surveillance. To consider the balance of benefits and harms of intensive surveillance for LFS patients, we performed a systematic review.

Methods We undertook systematically reviewed relavant articles on LFS surveillance which were published until the end of 2018 by searching Medline, Embase, and Igaku-Cyuo zasshi (for Japanese articles). The articles were original articles limited to English-language or Japanese-language publications. The results were compared among surveillance programs and modalities based on their reports.

Results Of 5,023 articles identified, 12 articles including one meta-analysis reported the results of LFS surveillance. Main modalities were 7 articles for WBMRI, 3 for brain MRI, 3 for breast MRI and 2 for PET/CT. Target patients and follow-up period were different. In WBRI, cumulative detection rates were from 4.31% to 13.56% and positive rates were 12.7% to 56.6%. Six institutions reported 71 patient lists which diagnosed by the surveillances. Among patients aged 20 years and over, 62.1% of malignant tumors were diagnosed by WBMRI and 44.4% for patients aged under 20 years. The proportion of detected malignant tumors increased to 80% when breast MRI added for patients aged 20 years and over and brain MRI for patients aged under 20 years. Even if other modalities were added, it did not contribute to an increase of the diagnosis of malignant tumors but showed a rise of low-malignant and benign tumors.

Conclusions AACR recommended intensive surveillance using complex modalities for LFS patients. However, they have also diagnosed many low-grade and benign tumors. Whereas LFS patients have a higher risk of cancer, it cannot be predicted when their cancer would occur in their lifetime. Although hereditary diseases can be detected relatively easily by dissemination of genetic testing, we have to carefully tackle the patient’s surveillance after genetic testing considering balance of benefits and harms.