The Spectrum of De Novo Malignancies After Liver Transplantation: A Review on Current Trends and Surveillance

Abstract: Over the last few decades, advances in liver transplantation (LT) have consistently improved patient survival, providing recipients with longer life expectancy and better quality of life. However, patients undergoing prolonged immunosuppression face an increased risk of de novo malignancies (DNMs) due to the oncogenic effects of immunosuppressive drugs and other established risk factors. These include chronic viral infections, sun exposure, smoking, the underlying etiology of liver disease (such as alcoholic liver disease and primary sclerosing cholangitis), and various biodemographic factors, including age, body weight, lifestyle choices, and ethnicity. As a result, DNMs have become one of the leading causes of late mortality among LT recipients, accounting for 20– 25% of post-transplant deaths. Nonmelanoma skin cancers are the most common DNMs, representing 35–40% of cases, with a cumulative risk 10–20 times higher than that of age- and sex-matched individuals in the general population. Post-transplant lymphoproliferative disorders (PTLD) are the second most frequent DNMs, particularly prevalent in pediatric recipients (5–20% of total DNMs), and are associated with significantly lower survival rates. Solid organ tumors, which account for 40–50% of DNMs, primarily involve the lung, head and neck, and colorectal sites, and demonstrate a two- to threefold higher incidence and more aggressive progression compared to the general population. The development of solid organ DNMs has a major impact on long-term outcomes following LT, highlighting the need for updated reviews focused on prevention and management. The increased incidence of DNMs in LT recipients underscores the importance of minimizing immunosuppressive therapy, stratifying patients according to cancer risk, implementing early protective strategies (such as reducing exposure to known risk factors), and establishing tailored, costeffective long-term screening protocols to detect malignancies at an early stage. Early detection enables timely treatment, ultimately improving long-term survival and quality of life. Future prospective studies are needed to optimize and validate surveillance strategies for this high-risk population.