ABSTRACT
Introduction: Advanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations ("as is" scenario) and recommend future actions ("to be" scenario). Methods: Twenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts. Results: Recommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies. Discussion: While the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease.
ABSTRACT
INTRODUCTION: Preemptive surgery is the prophylactic removal of an organ at high risk for malignant transformation or the resection of a precancerous or "early" malignant neoplasm in an individual with a hereditary predisposition to cancer. Recent advances in molecular diagnostic techniques have improved our understanding of the biologic behavior of these conditions. Predictive testing is an emerging field that attempts to assess the potential risk of cancer development in predisposed individuals. Despite substantial improvement in these forms of testing, all results are imperfect. This information often becomes an important tool that is used by healthcare providers to evaluate the risk-benefit ratio of various risk modifying strategies (i.e., intensive surveillance or preemptive surgery). METHODS: A systematic literature review was performed using Medline and the bibliographies of all referenced publications to identify articles relating to preemptive surgery for premalignant foregut lesions. RESULTS AND DISCUSSION: In this review, we outline the controversies surrounding predictive risk assessment, surveillance strategies, and preemptive surgery in the management of high-grade dysplasia (HGD) in Barrett's esophagus (BE), hereditary diffuse gastric cancer (HDGC), bile duct cysts, primary sclerosing cholangitis (PSC), and pancreatic cystic neoplasms. Resection of BE is supported by the progressive nature of the disease, the risk of occult carcinoma, and the lethality of esophageal cancer. Prophylactic total gastrectomy for HDGC appears reasonable in the absence of accurate screening tests but must be balanced by the impact of surgical complications and altered quality of life. Surgical resection of biliary cysts theoretically eliminates the exposed epithelium to decrease the lifetime risk of cholangiocarcinoma. Liver transplantation for PSC remains controversial given the scarcity of donor organs and inability to accurately identify high-risk individuals. Given the uncertain natural history of pancreatic cystic neoplasms, the merits of selective versus obligatory resection will continue to be debated. CONCLUSIONS: Preemptive operations require optimal judgment and surgical precision to maximize function and enhance survival. Ultimately, balancing the risk of surgical intervention with less invasive interventions or observation must be individualized on a case-by-case basis.
