Pretransplant Solid Organ Malignancy and Organ Transplant Candidacy

A Consensus Expert Opinion Statement

David P. Al-Adra; Laura Hammel; John Roberts; E. Steve Woodle; Deborah Levine; Didier Mandelbrot; Elizabeth Verna; Jayme Locke; Jonathan D'Cunha; Maryjane Farr; Deirdre Sawinski; Piyush K. Agarwal; Jennifer Plichta; Sandhya Pruthi; Deborah Farr; Richard Carvajal; John Walker; Fiona Zwald; Thomas Habermann; Morie Gertz; Philip Bierman; Don S. Dizon; Carrie Langstraat; Talal Al-Qaoud; Scott Eggener; John P. Richgels; George J. Chang; Cristina Geltzeiler; Gonzalo Sapisochin; Rocco Ricciardi; Alexander S. Krupnick; Cassie Kennedy; Nisha Mohindra; David P. Foley; Kymberly D. Watt

Disclosures

American Journal of Transplantation. 2021;21(2):460-474. 

In This Article

Abstract and Introduction

Abstract

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Introduction

The primary barrier for consideration of solid organ transplantation (SOT) in patients with pretransplant malignancy (PTM) is the concern that immunosuppression amplifies the risk of cancer recurrence, potentially impacting posttransplant mortality. While it is clear that immunosuppression administered to SOT recipients is associated with an increased likelihood of de novo cancer,[1] clinical evidence on the safety of immunosuppression in the circumstance of PTM is limited.

The most utilized guidelines for the selection of patients with PTM for SOT were extrapolated from recommendations made for potential renal transplant recipients.[2] In most cases, a minimum of 2 years between cancer treatment and SOT was advised. Two-year waiting times were recommended even for cancers with extremely low or zero risk of recurrence, such as ductal carcinoma in situ of the breast. For cancers at increased risk of recurrence, even longer wait times of 2 to 5 or greater than 5 years were recommended, with little or no supporting data. Historical data on transplant recipients with PTM obtained from the Israel Penn International Transplant Tumor Registry reported a 21% overall risk of cancer recurrence following SOT, and higher rates in certain, high-risk malignancies.[3] This information formed the basis for previous recommendations.

Contemporary, population-based studies have reported lower cancer recurrence rates than the original registry provided,[4] although poorer outcomes persist in those with PTM.[5,6] Recent studies also indicate a higher incidence of all-cause mortality in SOT recipients with PTM than those without, but the cause of mortality is not entirely linked to recurrence of the cancer.[5,7] However, despite these increased risks, overall patient survival may still be superior to what would be anticipated without transplantation and may approach acceptable transplant-specific outcomes. In addition, newer therapies may improve outcomes for recurrences.

As improvements in cancer therapies result in better prognosis and survival, more individuals with a history of cancer are likely to present with a need for SOT. In fact, SOT in patients with PTM has increased substantially in recent decades (<1% in 1994 to 8.3% in 2016 for kidney transplant recipients).[7] The risk of cancer recurrence and the possibility for worse outcome following SOT must be weighed against the benefit the patient will receive from the transplant (life-saving vs. life-prolonging), while also considering the potential alternatives (eg, dialysis and ventricular assist devices) (Figure 1).

Figure 1.

Potential factors to consider when evaluating a patient with a PTM for transplantation

The risk of cancer recurrence may also vary depending on the organ transplanted and the immunosuppression regimen used. For example, lung recipients historically carry the greatest risk as they are often under the influence of the highest immunosuppression. Transplantation of a patient who later dies of cancer recurrence, rather than a patient without cancer, may result in loss of an organ. Therefore, it is imperative to establish reasonable and updated recommendations to assist practitioners in selecting the appropriate transplant candidates with PTM in a safe and consistent manner.

Purpose and Scope of Consensus

Our goal is to assist transplant practitioners in determining suitability and timing of transplantation after a successfully treated malignancy. The recommendations presented here are limited to commonly encountered solid organ cancers, including breast, colorectal, anal, urological, gynecological, nonsmall cell lung cancers. Hematological cancers and melanoma are discussed in a separate manuscript. The type of solid organ transplant needed may significantly affect recipient candidacy, due to both variability in waitlist mortality and degree of immunosuppression expected posttransplant. Furthermore, it is important to consider the limitations of this document; while comprehensive, the recommendations cannot account for every clinical situation or the needs of each individual patient.

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