- •Li-Fraumeni syndrome is a rare genetic disease that is associated with an increased rate of certain cancers in patients, including prostate cancer.
- •Early diagnostic management of prostate cancer is recommended. Screening should start before the age of 40 and aggressive treatment should be applied due to the nature of the disease.
- •The preferred therapeutic option is surgery because of the high rate of resistance to radiotherapy and to certain cytotoxic agents, as well as the increased risk of secondary tumors.
- •The effectiveness of hormone therapy in Li-Fraumeni syndrome is uncertain due to the lack of current evidence.
Clinical Practice Points
- •The present article treats about Li-Fraumeni syndrome (LFS), a genetic disease with autosomal dominant transmission which is associated with an increased predisposition to suffer certain cancers. However, prostate cancer has not been recognized as one of the main neoplasms associated with LFS, and so its diagnosis is not included in LFS screening programs.
- •Urologists should make a prompt identification of patients or relatives at risk of suffering Li- Fraumeni syndrome, and referral to a genetic counseling unit. Prompt diagnosis and treatment of prostate cancer is important.
- •Given the aggressive nature of the condition in carriers of a PT53 gene mutation, radical surgery is the first option in localized disease. As this condition confers higher risk of developing secondary tumors, radiotherapy and chemotherapy should be avoided. There is no clear evidence regarding the usefulness of hormone therapy in these patients.
- •We consider that the recommendations set out in the article can help urologist in the management of patients diagnosed with LFS and suspected prostate cancer.
Abbreviations:LFS (Li-Fraumeni syndrome), ADT (Androgen deprivation therapy), MDS (Myelodysplastic syndrome), NGS (Next generation sequencing), mHSPC (Metastatic hormone-sensitive prostate cancer)
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- GeneReviews®. 1999; (editors)
- Risks of first and subsequent cancers among TP53 mutation-carriers in the NCI LFS cohort.Cancer. 2016; 122 (1st december): 3673-3681
- Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome.Curr Opin Oncol. 2018; 30: 23-29
- Hereditary urological cancer syndromes.Nat Clin Pract Urol. 2007; 4: 218-226
- Inherited TP53 variants and risk of prostate cancer.Eur Urol. marzo de. 2022; 81: 243-250
- A cancer family syndrome in twenty-four kindreds.Cancer Res. 15 de septiembre de. 1988; 48: 5358-5362
- Sensitivity and predictive value of criteria for p53 germline mutation screening.J Med Genet. enero de. 2001; 38: 43-47
- Revisiting Li-Fraumeni syndrome from TP53 mutation carriers.J Clin Oncol. 2015; 33 (20 de julio de): 2345-2352
- Germline mutations in the TP53 gene.Cancer Surv. 1995; 25: 101-124
- Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.Cancer Res. 1 de marzo de. 1994; 54: 1298-1304
- Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012: Globocan 2012.Int J Cancer. 2015; 136: E359-E386
- Prostate cancer and Li-Fraumeni syndrome: implications for screening and therapy.Urol Case Rep. 2015; 3: 21-23
- American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility.J Clin Oncol. 2015; 33: 3660-3667
- Principles of genetic counseling in the era of next-generation sequencing.Ann Lab Med. 2018; 38: 291-295
- Clinical utility of the immunocytochemical detection of p53 protein in cytological specimens.Cancer Res. 1994; 54: 2914-2918
- Assessing TP53 status in human tumours to evaluate clinical outcome.Nat Rev Cancer. 2001; 1: 233-240
The TP53 Database [Internet]. Isb-cgc.org. [Retrieved November 11 2021 ]. Available from: https://tp53.isb-cgc.org/
- Contribution of inherited DNA-repair gene mutations to hormone-sensitive and castrate-resistant metastatic prostate cancer and implications for clinical outcome.JCO Precis Oncol. 17 de septiembre de. 2019; 3 (PO.19.00067): 1-12
- Germline mutations in ATM and BRCA1/2 Distinguish risk for lethal and indolent prostate cancer and are associated with early age at death.Eur Urol. 2017; 71: 740-747
- Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer.J Clin Oncol. 2013; 31: 1748-1757
- Germline and somatic mutations in prostate cancer for the clinician.J Natl Compr Canc Netw. 1 de mayo de. 2019; 17: 515-521
- members of the EAU – ESTRO – ESUR –SIOG prostate cancer guidelines panel. EAU – ESTRO – ESUR – SIOG guidelines on prostate cancer.EAU Guidelines Office, Arnhem, The Netherlands2021 (978-94-92671-13-4PublisherPlace published)
- p53 mutations increase resistance to ionizing radiation.PNAS. 1993; 90 (15th June): 5742-5746
- Effects of p53 mutations on cellular sensitivity to ionizing radiation.Am J Clin Oncol. 2001; 24: 486-490
- Contribution of genotoxic anticancer treatments to the development of multiple primary tumours in the context of germline TP53 mutations.Eur J Cancer. 2018; 101: 254-262
- Inherited mutations in cancer susceptibility genes are common among breast cancer survivors who develop therapy-related leukemia.Cancer. 2016; 122 (15th January): 304-311
- Genetic testing in Li-Fraumeni syndrome: uptake and psychosocial consequences.J Clin Oncol. 2010; 28: 3008-3014