Cancer Surveillance After Transplantation: An Evidence-free Zone?

The problem with cancer after transplantation is that despite cancer being an important cause of mortality after transplantation of any solid organ, there are very few trials of any nature and no randomized controlled trials. The number and diversity of cases simply preclude powering any such trial. The exception perhaps is a study of screening for bowel cancer in patients with kidney transplants.1 There are multiple domains of interaction of cancer and transplantation to be considered. The most frequent clinical problem is the development of de novo cancer after a transplant.2 However, clinicians must also carefully weigh risks of transmission of cancer through donation from a person who has had a cancer in the past and evaluate the risks for a recipient who has been treated for cancer before transplantation. It is in this latter area that a multidisciplinary group has come together to work out how to follow patients after transplant when they have had a pretransplant cancer.3 Terminology is important—this is not "screening" which implies searching for early development of a de novo cancer—it is surveillance designed to identify early, the return of the previously treated cancer. Of course this is, in one sense, merely an extension of the standard of care oncological clinical follow-up of a patient with a cancer. The catch is that we have little or no evidence on which to base any change in standard of care just because the patient has been immunosuppressed and has received a transplant. All our knowledge and our senses tell us that the increased incidence of de novo cancers because of immunosuppression may well augment return of a dormant or subclinical cancer. This justifies an expert consensus amongst both oncologists and transplant physicians to provide guidance to the field. The first principle espoused by this expert group is that all patients are individuals and that collaboration between their oncology team and their transplant team is essential to individualize the approach, based on the known type and stage of the treated cancer, as well as more general knowledge about the impact of immunosuppression on that cancer. Detailed recommendations are provided for a number of the more common cancers including: nonmelanoma skin cancer; melanoma; colon and anal carcinoma; prostate; lung; and renal cell and bladder cancers. Female-specific breast, endometrial, cervical, vulvo/vaginal, and ovarian cancers are considered in detail and advice provided on surveillance. Finally, the complex area of plasma cell dyscrasias and lymphomas is also addressed, and there is a plea not to forget that the patient is also subject to developing a second, de novo, cancer as well. What do we get from this advice? For the cancers known to be increased in incidence after commencement of immunosuppression, there is advice on how to augment follow-up surveillance testing and clinical examination. The point is made that for both breast and prostate cancer, though there is scant evidence of any impact of immunosuppression on incidence, thus favoring no change to general population surveillance strategies, mortality is probably higher than in the general population if there is recurrence. The message with respect to a prior lymphoma is to be very careful in selection of patients for transplantation who have had a prior lymphoma, especially given the very high relative risk of lymphoma in immunosuppressed patients.1 Personally, and from practicing in Australia, I would add that caution for patients with multiple pretransplant skin cancers, which can break out of control like wildfire after transplantation and kill the patient quite quickly. Is there much to criticize in the advice from this US-based expert group working in 15 major academic and clinical centers? There are 2 issues for those who seek to implement the guidance: first, it is rather first world centric with respect to cost, with advice on quite frequent expensive imaging using computerized tomography and magnetic resonance imaging; and second, there are rather frequent specialist visits required, which would overwhelm the workforces, especially of dermatology, in many countries. Understanding what to aspire to does, however, give important guidance. One might hope that technological development in many areas across oncological follow-up will rescue us and our patients from the current tyranny of tests and visits defined in this guidance document. Whole skin imaging with artificial intelligence review may help with skin cancer surveillance, for example, and there are novel biomarkers that need to be evaluated in many, if not most, of the cancers discussed.4 There is one more issue for our field to address—how should we gain better data and how should we keep track of this fast moving field? The call for "more studies" must now be backed by a consolidated and multinational effort to create the academic infrastructure for the prospective data collection we will need to better serve the transplant population into the future, rather than leave them hanging onto the coat tails of general population-based studies we know miss the point for our patients.