<Table Of Contents

Oncology and Transplant Candidacy

by Laura E. Flores, 2024 Medical Fellow, Reshma Jagsi, and Michael Baine

Demand for solid organs far exceeds the limited supply available for transplant. As a result, the question of how to ensure a fair and justifiable distribution remains challenging. Active malignancy has historically barred patients from transplant candidacy until at least two years of remission has been achieved. The decision to include active malignancy as a contraindication is based primarily on two concepts: safety and the prospect of success.

Beginning with an illustrative vignette of a patient with low-risk prostate cancer, we will argue that active malignancy may not be a suitable contraindication to transplantation in all cases and that it constitutes a criterion that merits reconsideration in existing policies and practices. We will further argue that oncologists, as consultants with specialized knowledge, must play a more active role in determining and communicating transplant eligibility for their patients while also reflecting on the themes of advocacy and role conflict that arise in this context.

Vignette

R.H. is a 64-year-old African American male with a late diagnosis of congenitally corrected transposition of the great arteries. Upon persistent and worsening cardiac symptoms, he was referred to the cardiac transplant clinic for initial evaluation for cardiac transplantation. As a result of usual screening for a transplant, his prostate specific antigen was found to be elevated. Following MRI-guided biopsy, he was diagnosed by a genitourinary-trained pathologist with Gleason 3+4, favorable-intermediate risk prostate cancer. Prior to the American Society of Transplant Surgeons’ 2020 guidelines,1 active malignancy was an absolute contraindication to continued transplant eligibility, and thus the patient and physicians chose to pursue prostate cancer treatment prior to further pursuit of cardiac transplantation. Though the guidelines addressing the intersection of transplantation and malignancy are sparse, this topic remains controversial, with many patients like R.H. denied care due to active malignancy. The treating radiation oncologist wrote in her consultation note that under normal circumstances, pursuit of active surveillance instead of active treatment could be considered; however, due to the patient's circumstances, only active treatment could be pursued. R.H. received definitive external beam radiotherapy but died of complications from his underlying cardiac condition before reaching the two years of “remission” that the transplant team stated was necessary to make him eligible for transplant. The radiation oncologist wondered if she could or should have done more.

Ethical Issues in This Case

Any commodity that can be in short supply relative to the need for it, as with solid organs, raises the issue of fair and justified distribution. Given the salience of the ethical dilemmas inherent in allocation of scarce organs for transplantation, organizations have developed robust guidelines to determine how best to screen, list, and ultimately choose patients suitable for solid organ transplant.2 These determining factors include medical conditions and psychosocial elements. Processes for each organ having slightly different considerations.3

Among medical considerations, age-appropriate and disease-specific cancer screening is a necessary facet of pre-transplant evaluation.4 Cancer screenings are important for identifying patients with a prior history of malignancy and those who may harbor an active one. In those with a history of cancer, it is generally recommended that potential candidates achieve at least two years of remission from their cancer before pursuit of transplant.1,5 Guidelines for each organ and recommendations for wait times for patients with treated malignancies are available. These standards also acknowledge that not all malignancies are created equal in terms of recurrence risk and response to post-transplant immunosuppression.5

Active malignancy is used in the initial screening phase as an eliminating factor, narrowing down potential candidates en bloc. Active malignancy is a relative contraindication for solid organ transplant,6 and the guidelines mention active malignancy “with high risk of recurrence or death” as an absolute contraindication to the listing for specific solid organs, including lung transplant.2 Specifically, the decision to exclude those with active malignancy or to wait out the necessary cancer-free period prior to listing is based on two main principles: 1) safety and 2) prospect of success.

In addition to the risks inherent in the surgical procedure itself, transplant recipients are committed to a lifetime of taking immunosuppressant medications— medications that may increase risk of recurrence, cause development of de novo malignancies, or, in the case of active malignancy, hasten and/or worsen cancer growth.7,8 The necessary use of immunosuppressant medications represents a real conflict with respect to safety in those with active malignancy, possibly worsening their cancer, leading to suffering and premature death.9,10

Prioritizing the success of an organ transplantation ensures that organs are allocated to patients who are most likely to benefit from the transplant, thereby maximizing the overall success rates and effective use of this scarce resource. By carefully considering guidelines, the organ allocation process aims to ensure that each donation has the highest chance of success, ultimately improving outcomes for recipients and optimizing the use of donated organs.3 Cancer can markedly influence the prospect of success in organ transplantation due to the complexities it introduces into patient management and post-transplant outcomes. The presence of cancer, particularly if it is aggressive or has a high risk of recurrence, can diminish the likelihood of long-term survival. It can also reduce the chance of successful graft function. A single cancer diagnosis also raises the possibility of needing further cancer treatment in the event of recurrence, which may have direct or indirect impact on the life of the transplanted organ. For example, cytotoxic chemotherapeutic agents can have significant toxicity for each of the solid organs transplanted, and immunotherapy may significantly increase risk of rejection.

The Question—Prostate Cancer with Active Surveillance

Here, we will focus on low-risk and favorable-intermediate risk prostate cancer, collectively referred to as “lower-risk” prostate cancer. Consider our patient, R.H, and his diagnosis of Gleason 3+4 prostate cancer in the setting of a transplant workup. Generally, patients diagnosed with this form of lower-risk prostate cancer have four major treatment options: active surveillance, radical prostatectomy, radiation therapy (RT), or observation.11 The choice of treatment is a collaborative decision involving the patient, their urologist, and their radiation oncologist. It is personalized based on factors such as side-effect profile, age, performance status, current health, and the stage of the cancer.

Active surveillance involves regular laboratory and imaging-based monitoring without immediate treatment of the cancer with the expectation that intervention may be necessary if the cancer progresses. For patients with low-grade prostate cancer, active surveillance is often considered and even preferred.11 The evidence supporting the safety and efficacy of active surveillance is strong. For newly diagnosed low- or intermediate-risk prostate cancer, active surveillance without immediate treatment is associated with a 10-year cancer-specific survival rate of over 95%. Approximately half of men remain free of progression or needing treatment after 10 years.12

In the context of potential solid organ transplantation in a patient with active malignancy, current guidelines for those eligible for active surveillance are sparse at best.13 The American Society of Transplantation’s guidelines are the most comprehensive, allowing for patients undergoing active surveillance in specific prostate cancer groups to initiate kidney transplant without a wait period.1 The Kidney Disease: Improving Global Outcomes guidelines specify that those with a Gleason score ≤ 6 can be listed for transplantation and state that no wait time is needed for those curatively treated for prostate cancer with a Gleason score of ≤ 6. However, the guidelines do not make mention of active surveillance.14 The European Association of Urology specifies that there is to be no wait time in listing those with “appropriately treated” low-stage/grade prostate cancer, though they similarly do not make mention of active surveillance.15 The European Renal Best Practices note that wait time should be determined through a discussion with the treating oncologist, taking into account patient factors such as potential for progression or recurrence, comorbid conditions, and age.16

Regarding R.H., we must consider the aforementioned reasons for exclusion: safety and the prospect of success. Beginning with safety,there is little evidence to suggest immunosuppression increases the risk of a clinically meaningful prostate cancer or the risk of recurrence of prostate cancer following previous treatment. A recent meta-analysis evaluating the risk of prostate cancer in immunocompromised solid organ transplant recipients found there to be no significant elevation in risk compared with the general population.17 Further, there seems to be no major difference in prostate cancer-specific mortality in patients who have received a kidney transplant, suggesting the immunosuppression associated with transplants may not impact prostate cancer progression.18

When it comes to the patient’s prospect of success, we must consider the potential benefit R.H. would achieve from a transplant, weighing it against the risk his active malignancy poses to the success of the graft and his overall survival. Prostate cancer is generally characterized by its slow growth, particularly in cases of low-risk and favorable-intermediate-risk disease. Many patients with lower-risk prostate cancer live for many years without the cancer progressing to a life-threatening stage.19 As a result, the likelihood of dying from prostate cancer is relatively low compared to the risk of mortality from other causes. This fact is especially relevant when considering patients for organ transplantation. Given the slow progression of prostate cancer, patients with lower-risk disease are more likely to succumb to other health conditions rather than prostate cancer itself. Consequently, these patients should still be considered eligible for organ transplants for unrelated conditions, because the potential benefits of the transplant for the unrelated comorbid condition can significantly outweigh the risks associated with their prostate cancer. It bears noting, however, that there is sparse data on survival and progression in rarer organ transplants, such as heart and lung, as most of the literature focuses on renal procedures.

An Argument for Equity

Exclusion from consideration for transplant based on active-malignancy criteria has important consequences when applied to the population as a whole, inequitably disadvantaging large minoritized groups. Take for example, R.H., an African American male. African American men have a higher incidence of prostate cancer compared to the general population. Similarly, people who are African American are four times more likely to develop kidney failure than those who are white. Over one-third of those on the transplant list are African American.20 Given this information and if prostate cancer is a contraindication to transplant, the policy decision to reject any person with active malignancy, though seemingly even-handed, will actually have disproportionate consequences for African American men, violating a fundamental principle of ethics regarding distributive justice.

Decision-Making Standards–Role Responsibility

Given the multifaceted role of oncologists, the responsibility to consider ethics spans various dimensions, including individual patient care, societal health benefits, and policy reforms within the field. Above all, each oncologist must advocate for the best interests of their individual patients, ensuring that each one receives tailored, evidence-based treatments that optimize individual outcomes. This goal may mean balancing considerations. For example, an oncologist may need to weigh shorter-course RT to expedite the process of listing a patient for transplant against the risk of greater harm to the patient. Oncologists likewise must consider the greater good of society. They must convey information about prognosis fairly and with equanimity to help determine the best allocation of scarce transplantable organs. In doing so, they should try to maximize the chance of success with these scarce resources. Oncologists’ roles in population health also include promoting practices that are effective, equitable, accessible, and committed to reducing disparities in cancer care. Finally, oncologists must play a critical role in advocating for policy changes that advance the field. This pursuit means ensuring the observation of ethical standards and policies that may impact their patients. To this end, they might for instance, advocate for expanding transplant eligibility criteria to include certain currently excluded patient populations or participate actively in hospital ethics boards. Ethical considerations for the oncologist in transplant eligibility are expanded upon in Table 1.

Discussion:

Pretransplant malignancy is increasingly common in patients undergoing evaluation for transplant adequacy,4 and, as such, guidelines governing the distribution of organs in this group should be assessed by the physicians intimately involved in relevant care. This piece aimed to investigate the role of the treating radiation oncologist in advocating for transplant candidacy in the case of low- to intermediate-risk prostate cancer and the consequences of her potential silence. We propose that incidentally discovered low- or intermediate-risk prostate cancer during transplant screening should not disqualify patients from receiving a solid organ transplant, even if they do not immediately seek treatment for their prostate cancer. Being overly cautious and excluding such patients from transplant eligibility deprives them of potentially life-saving treatments based on what may well be an overestimated risk of prostate cancer progression or recurrence in the context of immunosuppression. Though we chose to focus on lower-risk prostate cancer in this case, other low-risk cancer conditions like ductal carcinoma in situ and localized skin cancers may be worthy of similar consideration.

Knowing the data on whether immunosuppression is really expected to compromise patient outcomes and ensuring that they are appropriately considered for eligibility for a potentially lifesaving organ transplant is a core ethical obligation of every oncologist. This approach ensures that patients receive comprehensive care that addresses all their health needs, promoting overall survival and quality of life while also ensuring that procedures for allocation of scarce organs are informed by realistic information about what a particular cancer diagnosis actually means for the safety and likelihood of success of a transplant. Only by serving as informed intermediaries—acknowledging the inherent conflict of interest present when advocating for one’s own patient—can oncologists fulfill their ethical obligations to both the patients before them and all of society.

Table 1. Ethical Considerations in Transplant Eligibility and Malignancy

Laura E. Flores was a 2024 FASPE Medical Fellow. She is a radiation oncology resident at the University of Nebraska Medical Center.

Notes

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  4. Acuna SA, Huang JW, Scott AL, et al: Cancer Screening Recommendations for Solid Organ Transplant Recipients: A Systematic Review of Clinical Practice Guidelines. American Journal of Transplantation 17:103-114, 2017
  5. Watschinger B, Budde K, Crespo M, et al: Pre-existing malignancies in renal transplant candidates—time to reconsider waiting times. Nephrology Dialysis Transplantation 34:1292-1300, 2019
  6. Chapman JR, Webster AC, Wong G: Cancer in the transplant recipient. Cold Spring Harb Perspect Med 3, 2013
  7. Vajdic CM, McDonald SP, McCredie MR, et al: Cancer incidence before and after kidney transplantation. Jama 296:2823-31, 2006
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  9. Moutinho BD, de Barros JR, Baima JP, et al: Immunosuppression and Malignant Neoplasms: Risk-Benefit Assessment in Patients with Inflammatory Bowel Disease. Am J Case Rep 21:e920949, 2020
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  11. Schaeffer EM SS, Adra N, et al. : NCCN Guidelines Version 4.2024, in Network NCC (ed): NCCN Guidelines. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf, 2024, pp PROS 2-PROS 5
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  17. Bao JM, Zhu HL, Yang GS, et al: No significant association between immunosuppression in solid organ transplantation and prostate cancer risk: a meta-analysis of cohort studies. Transl Cancer Res 8:939-949, 2019
  18. Liauw SL, Ham SA, Das LC, et al: Prostate Cancer Outcomes Following Solid-Organ Transplantation: A SEER-Medicare Analysis. J Natl Cancer Inst 112:847-854, 2020
  19. Albertsen PC, Hanley JA, Fine J: 20-year outcomes following conservative management of clinically localized prostate cancer. Jama 293:2095-101, 2005
  20. Harding K, Mersha TB, Pham PT, et al: Health Disparities in Kidney Transplantation for African Americans. Am J Nephrol 46:165-175, 2017