In this issueof JAMAOncology,Acunaet al1 examine theassociationbetweensolid-organtransplantationandcancermortality inapopulation-basedsetting.By relyingon robustmethodologyandlinkeddatafromthe CanadianOrganReplacement Register, the Ontario Cancer Registry, and theOffice of the RegistrarGeneralofOntario, theywereable tocircumventcommon limitations of past population-level analyses on the same topic.2,3 Forone, thecauseofdeathwas reliablyobtained forall transplantrecipients.Apaststudymayhaveunderestimatedcancer as a causeof deathgiven thehighnumberof caseswithunknown cause of death.3 Second, the ability to ascertain for the typeofcancerdeathallowsustodifferentiatebetween(1) recurrence and death from a pretransplant neoplasm and (2) death fromadenovomalignantneoplasm.This isanimportantdistinctionbecausemanyliverandlungtransplantrecipientsultimately die of the samedisease thatwas the indication for transplantation.Third,competingriskmethodologyiselegantlyusedtoconclude that the riskof cancerdeath isnot restricted to long-term survivors and increases steadily over time. From their analysis, the authors found that solid-organ transplant recipients are at increased risk of cancer-specific death, regardless of age, sex, organ transplanted, and transplant period. The outcomes of transplantation have improveddramatically over time—a corollary of advances in immunosuppression,patient selection,andperhapsevensurgical technique.Thishas led toadecline innoncancermortality and a proportional upward shift in cancer mortality, now the second leading cause of death among transplant recipients.1,4 Theprovocative reportbyAcunaandcolleagues1 raisesseveral important questions,which remain unanswered.While it establishes anassociationbetween transplantationandcancer death, itdoesnotprovideanexplanationfor thesefindings.Several investigators havehypothesized thatmalignant lesions in transplant recipientsare inherentlymoreaggressive than in the generalpopulation;whether it is relatedtothe immunosuppressive regimen remainsunknown. Indeed, immunosuppression inducesa chronic immunedisturbance,whichpredisposes the patient to infectionsand inflammation.Thismaybe important, as certainvirusesareknowntobe involved in thedevelopment ofmalignantneoplasms.2,4Alternatively, transplant recipients, once diagnosedwith cancer,may not receive the optimal care fromclinicians,whether justifiedornot. Insomecircumstances, the benefits of “standard of care”multimodal treatment need tobeweighedagainst the riskof graft loss andother complications. For example, many clinicians would be hesitant to give neoadjuvant chemotherapyprior to surgery for invasive bladdercancer toagraft recipient,despite thesurvivalbenefits supported by level 1 evidence. More importantly, this studydoesnotestablishwhatneeds tobedone for transplant recipients at riskof cancerdeath.The most sensible approach would be to promote better preventive care, which would include lifestyle recommendations (suchasdiscontinuingtobaccosmoking)andcancerscreening.5 Although posttransplant care guidelines establish clear recommendations for preventive care including cancer screening, the effectiveness and adherence to these recommendations remain unmeasured.6 Moreover, the role of cancer screening in thegeneral population,particularly forbreast and prostate cancer, has comeunder scrutiny.7 Given themost recentUnited States Preventive ServicesTaskForce recommendations against prostate-specific antigen–based screening for prostate cancer in all men, it may be even harder to justify screening in transplant recipientswhohaveamore limited life expectancy than their general-population counterparts. Conversely, given the findingsof thestudybyAcunaetal,1 onemay argue that this subset of patients is at increased risk of cancer mortality, which could serve to justify pursuing “targeted” cancer screening.