Abstract
PURPOSE: PTEN hamartoma tumor syndrome (PHTS) is an autosomal dominant cancer predisposition and overgrowth syndrome caused by pathogenic germline variants in the PTEN gene, with an increased risk of both benign and malignant tumors involving the breast, colon, endometrium, thyroid, skin, and kidney. The objective of these clinical guidelines was to use the latest knowledge to generate an international consensus resource for providers, researchers, and individuals with PHTS on the best practices in the surveillance and management of cancer and overgrowth in PHTS. EXPERIMENTAL DESIGN: The International PHTS Cancer and Overgrowth Guidelines Working Group was established, comprising a core group of six international experts in the diagnosis and management of PHTS. The working group held joint meetings with individuals with PHTS and their advocates. Informed by the literature, the working group met regularly between 2022 and 2024 to produce guideline statements, refined through iterative feedback. A modified Delphi approach was used with an independent external panel of PHTS, genetics, and cancer experts to establish final consensus guidelines. RESULTS: Clinical consensus recommendations for the surveillance and management of cancer and overgrowth in individuals with PHTS were formed. The guidelines encompass the recommended practices in cases of breast, colon, endometrial, thyroid, and kidney cancers, as well as overgrowths. CONCLUSIONS: The clinical management of individuals with PHTS is complex and necessitates a multidisciplinary approach. We generated international consensus guidelines for the surveillance and management of cancer and overgrowth in PHTS, aiming at improving care for affected individuals and families.