There are limited data on the effectiveness of cancer screening in germline TP53 mutation carriers. Data about the utility of screening programs is mostly extrapolated from cancer screening studies in other groups at increased risk of specific cancers.
At present there is insufficient evidence for (or against) routine screening for the core cancers in children with LFS. Improved survival and less virilisation have been reported after early detection and screening for adrenocortical carcinoma (ACC) in Brazilian children with a specific TP53 mutation detected by newborn screen.r The prognosis of several types of sarcomas is associated with the ability to obtain clear surgical margins facilitated by early detection. A recent prospective study of biochemical and imaging surveillance, including whole-body magnetic resonance imaging (WB-MRI), in germline TP53 mutation carriers (both children and adults), showed that a comprehensive surveillance protocol is feasible, and that early tumour detection through surveillance is associated with improved survival: 5-year overall survival of 88.8% (95% CI, 78.7-100) in the surveillance group vs 59.6% (47.2-75.2) in the non-surveillance group (p=0.0132).r False-positive rate associated with WB-MRI in this study was <5%, however only biopsies that were pathologically non-neoplastic were considered. The number of follow-up investigations prompted by imaging results was not reported. Another study, albeit with small sample size, evaluated the diagnostic performance of WB-MRI as a cancer screening tool for children with genetic cancer predisposing conditions. It showed that WB-MRI had high sensitivity (100%), specificity (94%), as well as negative predictive value (100%); although the positive-predictive value was 25%.r
Several other centres worldwide are currently evaluating screening protocols using WB-MRI.rr Further data are needed before a comprehensive screening protocol can be recommended routinely in the management of families with TP53 mutations.
TP53 mutations are believed to cause radiation sensitivity, due to impaired recognition and repair of DNA damage and there are numerous reports of second primary malignancies developing in areas previously treated with radiation therapy. Minimising radiation therapy is recommended where possible, especially if other treatment modalities with comparable cure rates are available. Similarly tests using ionising radiation should be avoided if other effective modalities are available.r
There is evidence that smoking increases the risk of lung cancers in TP53 mutation carriers by 3 fold.r