De novo malignancies following liver transplantation: a case-control study with long-term follow-up

Abstract

Background: Long-term survival data on de novo malignancy are limited following orthotopic liver transplantation (OLT) when compared with controls without malignancies.

Methods: Over a 12 yr period at our institution, 50 of 1043 patients (4.8%) who underwent OLT were identified to have 53 de novo malignancies. The clinical characteristics and survival of these patients were retrospectively reviewed and compared with a control cohort of 50 OLT recipients without malignancy matched with the incidence cases by age, year of OLT, sex, and type of liver disease.

Results: Chronic hepatitis C, alcohol and primary sclerosing cholangitis were the three leading causes of liver disease. Skin cancer was the most common malignancy (32%), followed by gastrointestinal (21%), including five small bowel tumors, and hematologic malignancies (17%). The cases and controls were not significantly different in the immunosuppressive regimen (p = 0.42) or the number of rejection episodes (p = 0.92). The five- and 10-year Kaplan-Meier survival rates for the cases were 77% and 34%, respectively, vs. 84% and 70%, respectively, for the controls (p = 0.02 by log-rank test). Patients with skin cancers had survival similar to the controls, but significantly better than non-skin cancers (p = 0.0001). The prognosis for patients with gastrointestinal tumors was poor, with a median survival of 8.5 months after the diagnosis.

Conclusion: In this single institutional study, de novo malignancies after OLT were uncommon. Patients with non-skin cancer after OLT had diminished long-term survival compared with the controls. Our results differ from other reports in the high incidence of gastrointestinal malignancies with attendant poor prognosis.

Fig. 1

Time to development of de novo malignancy after orthotopic liver transplantation (OLT) according to tumor type. *Others include three patients with ENT and four patients with urogenital tumors.

Fig. 2

Kaplan–Meier survival curve for 50 patients with de novo malignancy (cases) and 50 patients without de novo malignancy (controls) after orthotopic liver transplantation (OLT). Time zero represents the date of liver transplantation. The difference in survival between cases and controls was statistically significant by log-rank test (p = 0.02).

Fig. 3

Kaplan–Meier survival curve for patients with non-skin cancer vs. skin cancer and controls after orthotopic liver transplantation (OLT). Time zero represents the date of liver transplantation. The 33 patients with non-skin had significantly worse survival than the 17 patients with skin cancer (p = 0.0001 by log-rank test; hazard ratio 4.9, 95% CI 1.67–14.2, p = 0.004).

Fig. 4

Kaplan–Meier survival curve after tumor diagnosis for patients with de novo malignancy after orthotopic liver transplantation (OLT) according to tumor type. Time zero represents the date of tumor diagnosis. A statistically significant difference was found in survival between different tumor types and skin cancer (p = 0.003 by log-rank test).