Donor Cancer Transmission: Focusing on the Evidence

Physicians have long been aware that the use of donor organs to alleviate suffering and extend life could on occasion be accompanied by the unintended transfer of donor disease. Dr Israel Penn was the first to draw attention to the problem of cancer transmission,¹ and he consolidated the ongoing experience into a central database based on voluntary reporting. His efforts over a 31-y period (1969–2000) led to a number of insights, and the Israel Penn International Tumor Transplant Registry (https://ipittr.uc.edu/) remains an active source of consultation.

Further progress developed with the onset of mandatory reporting of suspected tumor transmission events to national agencies. Comparison to the total number of transplant patients led to estimates of cancer transmission risk for various tumor types. Several classification systems for assessment of donor tumor transmission risk, all very similar, have evolved based on these data, on literature reports, and on expert opinion.² However, the information base is largely driven by recipient events and does not take into account donors who may have had cancer but never transmitted it to a recipient.

In the current issue of Transplantation, Mahillo et al³ present a prospectively gathered data set of outcomes from deceased donors with malignancies from the Spanish experience for the 2013 to 2018 period, based on national data gathered by the Organizacion Nacional de Traspantes. This study incorporates information from a nonstandard risk donor program on the donor side and a biovigilance system that follows recipient complications, to provide a best effort assessment to date of the actual results of transplant outcomes performed from donors with active or historical malignancies.

The study followed 275 donors with cancer known before transplant (107 with cancer at time of transplant and 168 with historical cancer) and 74 donors who had cancer diagnosed after transplant. Of those with cancer known before transplant, no cases of transmission were documented despite the fact that 10 donors had tumors considered high risk for transmission by current criteria.

In the case of 74 donors with cancer diagnosed following transplant, 10 transmitted disease to 64% of recipients (16 of 25), leading to death in 56% of affected individuals with a median 14 mo survival after diagnosis. The other 64 donors did not transmit cancer, although 22 in this group also had tumors that would fall into the high risk transmission category.

The data should be interpreted in light of current practice, which is associated with an extremely low rate of tumor transmission, estimated at 6 per 10 000 transplants. The most conspicuous finding is that all reported transmissions occurred when donor tumor was diagnosed following transplant. What circumstances can cause this, and what tumors in particular should be searched for? Conversely, are there donor tumors that inappropriately preclude transplantation because of an overestimate of transmission risk?

Four scenarios associated with delayed donor tumor diagnosis are uncovered. Most frequently (56%), a renal cell carcinoma was discovered during back table examination while organ transplantation was occurring elsewhere. This relates to the local practice of performing this procedure at the transplant center rather than the donor center. The second circumstance (19%) was that of carcinoma discovered during donor autopsy. This speaks to the utility of donor autopsy when feasible and to the need to expedite important information transfer (1 autopsy diagnosis of lung cancer was communicated 6 mo posttransplant). The third circumstance (19%) entailed suspicious lesions found at time of donation and diagnosed as benign on frozen section but subsequently found to be malignant on permanent section. Expert pathology consultation is always mentioned, but the limitations of hematoxylin and eosin frozen section should be kept in mind and access to the final report expedited. Finally, (6%) additional information from the donor history later became available in some cases, reflecting the urgent circumstances under which organ transplantation is usually performed.

Of those tumors that were transmitted, lung cancer represented 56%, highlighting the need for particular vigilance, especially in donors at increased risk for such tumors. No standardized approach for radiologic assessment exists but could be considered in individual cases, balancing transmission risk against time delay, costs, and the possibility of false positive results.

Regarding donor cancers that were not transmitted, the data support other studies that lower the historical estimates of transmission risk for central nervous system tumors.⁴ The authors also appropriately conclude that the diagnosis of prostate cancer does not automatically disqualify a potential organ donor, again in keeping with current thought.⁵ Remarkably, however, the series includes only the second reported case of prostate cancer transmission.

An additional important point concerns the time of tumor onset. Many transmitted donor tumors arise within the first 2 posttransplant years, and this is informally used as a cutoff to separate “donor-transmitted” from “donor-derived” tumors, the latter arising from donor cells but not present at the time of transplant. However, 31% of donor-transmitted tumors in this series arose after 24 mo, emphasizing the need for continued surveillance for this possibility beyond an arbitrary 2-y cutoff time.

The authors suggest that their report serves to support or potentially modify current guidelines regarding risk of donor tumor transmission. The most current general guide to assessment of donor disease transmission risk is the Council of Europe’s Guide to the Quality and Safety of Organs for Transplantation² (available at https://www.edqm.eu/en/organs-tissues-and-cells-technical-guides) and information from the current report will undoubtedly be incorporated into future editions. A curated library of donor disease transmission reports is also available at https://www.notifylibrary.org/ and provides a window into experience with tumor transmission and management.

Mahillo et al appropriately recognize the limitations of their study. Regardless, this represents a valuable addition to the growing body of evidence upon which time-constrained decision making at the time of organ donation and transplant can be based and also contains suggestions to address weak points in current practice. Continued accrual of such information, as well as appropriate use of currently available information,⁶ will enable increased donor organ utilization without an increased risk of malignancy transmission.