Assessment of colorectal cancer recurrence risk following solid organ transplantation

Introduction

Despite advancements in treatment, colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States, accounting for more than 50,000 deaths annually (1). Curative-intent treatment typically involves surgical excision with or without adjuvant systemic chemotherapy, depending on several factors including disease stage (2). While this approach has significantly improved outcomes, disease recurrence remains a prominent clinical challenge (3). Identifying groups of patients at increased risk for CRC recurrence is critical to improving their outcomes.

Prior solid organ transplant (SOT) is an established risk factor for CRC, with studies estimating a 2–4-fold higher risk of developing CRC compared to the general population (4-6). This represents an emerging challenge as the number of SOTs performed has increased by more than 70% in the past decade and it is estimated that there are currently over 400,000 SOT recipients living in the United States (7,8). Several factors contribute to the heightened risk of developing CRC in this population, with a leading hypothesis being that the chronic immunosuppressive requirements necessary to prevent organ rejection limit anti-tumor immune surveillance (9-11). We have previously reported how the molecular characteristics of SOT-associated CRC differ from those in the general population, including a higher proportion of mismatch repair deficient (MMRd) disease, supporting a role of increased immunosuppression contributing to this elevated incidence (12). Consequently, the increasing prevalence of SOT recipients combined with the necessity of immunosuppression presents a growing challenge to healthcare providers managing secondary malignancies following SOT, including CRC.

While the increased incidence of CRC in patients with prior SOT is well established, less is known about the risk of CRC recurrence following curative-intent CRC treatment in SOT recipients. Because immune surveillance is thought to influence the initial development of CRC and potentially relapse risk after curative-intent treatment, we predicted that SOT recipients would experience higher recurrence rates than the non-SOT CRC population. We also expected this risk to vary across individuals, shaped by patient-specific and tumor-specific factors rather than functioning as a uniform effect of transplantation alone. To address this gap, we evaluated molecular and clinical features associated with CRC relapse in a cohort of post-SOT patients to support more precise risk stratification, surveillance planning, and treatment decision-making for this growing population. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-970/rc).

Methods

We conducted a multi-institutional retrospective cohort study at The Johns Hopkins Hospital and the University of Wisconsin Hospitals and Clinics. We identified patients with a history of SOT who were subsequently diagnosed with CRC following their transplant between the years 2016 and 2025. Patients were eligible if they were ≥18 years of age at the time of CRC diagnosis and had undergone SOT prior to this diagnosis. All SOT patients at both institutions were screened via electronic medical record search functions, and further manual chart review was conducted to ensure patients met inclusion criteria for the study cohort.

Data were extracted via chart review using electronic medical record search functions. Variables collected included patient demographics, transplant type and date, CRC staging and date of diagnosis, tumor location, evidence of disease recurrence (defined by radiographic or histopathologic evidence of recurrence), induction and maintenance immunosuppression data, tumor genomic data, and clinical outcomes. Primary CRC treatment types were collected including surgical approaches, receipt of adjuvant therapies, and receipt of neoadjuvant therapy in subjects with rectal cancer. Additionally, intra-operative transfusion status at the time of organ transplant was collected and compared to recurrence status. Recurrence patterns were characterized as local recurrence (at the anastomotic site or primary tumor bed) or distant metastasis which was further stratified into liver versus non-liver metastases. Recurrence pattern classification was determined by review of imaging, histopathology, and clinical documentation.

The primary objective was to compare the rate of CRC recurrence in the study cohort to that of the general population. Observed CRC recurrence rates, both overall and stratified by stage, were compared to pooled benchmark recurrence rates derived from published population-based studies (13-16). This approach was utilized given the absence of a matched non-SOT comparator cohort. Standardized incidence ratios (SIRs) were calculated to compare observed recurrence rates to expected rates for the study cohort based on these pooled benchmarks. SIRs served as an indirect standardization between observed and pooled population recurrence rates to measure the incidence of recurrence between the two groups. Given this approach, it must be acknowledged that the analyses rely on the assumptions that published recurrence estimates provide a reasonable comparator reference and therefore should be interpreted as exploratory and hypothesis generating rather than definitive measure of CRC recurrence risk. Subjects noted to have stage IV disease at initial CRC diagnosis were excluded from recurrence analyses given the presence of pre-existing disseminated disease. Additionally, we compared demographic, clinical, pathologic staging, and molecular characteristics of patients with and without recurrence and assessed the impact of immunosuppression on study cohort variables.

Within the subgroup analysis, we evaluated both induction immunosuppression as well as maintenance immunosuppression. To compare the influence of various induction immunosuppression regimens on recurrence risk in the study cohort, we compared subjects who had received lymphocyte depleting regimens (i.e., ATG, alemtuzumab) versus those that received alternative non-depleting regimens (i.e., basiliximab, corticosteroids). For maintenance immunosuppression, we compared subjects actively receiving calcineurin inhibitor (CNI) alone based regimens (tacrolimus or cyclosporine +/− corticosteroids, azathioprine, etc.) versus CNI plus mycophenolate mofetil (MMF) based regimens at the time of CRC diagnosis.

Further subgroup analysis focused on tumor genomic differences between cohort subjects with or without evidence of disease recurrence. Tumor genomics were determined via next-generation sequencing (NGS) testing and were identified during manual chart review. Not all patients had undergone NGS testing, and those without such testing were excluded from recurrence analysis of tumor molecular profiles.

Statistical analysis

Descriptive statistics were used to summarize baseline demographic and clinical characteristics of the study cohort. Categorical variables were reported as frequencies and percentages, while continuous variables were reported as medians with interquartile ranges (IQRs). The Mann-Whitney U test was used to compare continuous variables and Fisher’s exact test to compare categorical variables across groups. Kaplan-Meier survival curves and Cox proportional hazards models were employed to assess recurrence-free survival (RFS) and overall survival (OS). Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. A P value of <0.05 was considered statistically significant. Statistical analyses were conducted using Jamovi (version 2.6.26).

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Boards of the Johns Hopkins Hospital (No. IRB00309275) and the University of Wisconsin Hospitals and Clinics (No. 2024-1092). Informed consent was waived due to the retrospective nature of this study and the minimal risk to patients.

Results

A total of 53 patients diagnosed with CRC following SOT were included in this study. The median age at CRC diagnosis was 59 years (IQR, 47.0–70.0 years), and the cohort included 29 males (55%) and 24 females (45%). The racial distribution of this study cohort included 12 African American (23%), 39 Caucasian (73%), 1 Asian (2%), and 1 Pacific Islander (2%) patients. Multiple transplant types were represented in this cohort including 26 kidney, 12 liver, 5 combined liver-kidney, 5 combined pancreas-kidney, 4 lung, and 1 heart transplant. At the time of CRC diagnosis, the disease stage distribution was as follows: stage 0 (n=1), stage I (n=9), stage II (n=14), stage III (n=18), and stage IV (n=11). The location of the primary tumor was right-sided colon in 33 patients (62%), left-sided colon in 8 patients (15%), and rectum in 12 patients (23%). The median time interval from SOT to CRC diagnosis was 138.1 months (IQR, 72.1–221.7 months). CRC recurrence occurred in 14 patients (33%). Among the 14 patients who demonstrated recurrence, 13 (93%) were found to have distant metastases and 1 (7%) patient was found to have local recurrence. Liver metastases were identified in 6 of the 13 subjects noted to have distant metastases. Of note, this single local recurrence was in a patient with right-sided CRC. The median RFS was 41.4 months (IQR, 21.9–57.9 months) with calculated RFS rates at 1, 3, and 5 years of 87%, 68%, and 64% respectively. The median OS of the study cohort was 41.7 months (IQR, 20.7–68.0 months) with OS rates at 1, 3, and 5 years of 88%, 73%, and 54% respectively. Baseline characteristics of the study cohort are summarized in Table 1.

To evaluate the influence of prior SOT on CRC recurrence, we compared observed recurrence to population benchmarks as outlined in Table 2. Recurrence was observed in 22.2% of stage I patients, 42.9% of stage II patients, and 33.3% of stage III patients. The overall SIR for CRC recurrence within the study cohort was 1.69 (95% CI: 0.84–2.84). The SIR was 3.66 (95% CI: 0.44–11.45) for stage I disease, 2.55 (95% CI: 0.93–5.02) for stage II disease, and 1.12 (95% CI: 0.41–2.20) for stage III disease (Figure 1). Notably, recurrence estimates in early-stage disease carry wide CIs with associated SIR calculations and therefore should be interpreted cautiously with consideration for sparse-event bias.

Figure 1 Forest plot representation of calculated SIRs of observed disease recurrence compared to population benchmarks by stage and overall cohort recurrence. The cohort demonstrated heightened recurrence risk with an SIR 1.69 (95% CI: 0.84–2.84). Stage specific SIRs demonstrated the highest relative recurrence risk in stage I (SIR 3.66; 95% CI: 0.44–11.45) and stage II (SIR 2.55; 95% CI: 0.93–5.02) disease. Stage III disease also demonstrated a more modest trend towards increased recurrence risk (SIR 1.12; 95% CI: 0.41–2.20). Error bars represent the 95% CI. CI, confidence interval; CRC, colorectal cancer; SIR, standardized incidence ratio.

Patients with CRC recurrence were compared to those without recurrence within the study cohort. All 5 patients with KRAS mutant disease in this cohort relapsed (P=0.01). Conversely, none of the 8 patients with BRAF mutant disease relapsed (P≤0.001). Furthermore, Kaplan-Meier survival analysis between recurrence and non-recurrence groups yielded a thirteen-fold increased risk of recurrence associated with KRAS mutations (HR =13.58, 95% CI: 2.56–72.00; P=0.002) (Figure 2) and a five-fold increased risk of recurrence associated with APC mutations (HR =5.03, 95% CI: 1.18–21.47; P=0.02). Given the previously reported increased prevalence of MMRd disease in post-SOT CRC and established lower CRC recurrence rates in MMRd disease in the general population, we evaluated recurrence risk between MMRd and mismatch repair proficient (MMRp) cases within this cohort. Four (30.8%) of the 13 patients with MMRd CRC relapsed compared to 9 (42.9%) of the 21 patients with MMRp disease. This difference was not statistically significant (P=0.72). Looking at differences in the molecular background by MMR status, BRAF positivity was only observed in the MMRd disease group (n=7) (P=0.001) (Figure 3). Similarly, PIK3CA mutations were strongly associated with MMRd disease (P=0.02). While not statistically significant, APC (42.9%) and KRAS (55.6%) mutant disease were more common in patients with MMRp disease. Finally, patients with MMRd disease were older (P=0.001). It should be noted that molecular testing was more frequently performed in patients with advanced disease at initial CRC diagnosis and in those who went on to recur (Table 3). To further characterize differences between patients who demonstrated recurrence versus those patients who did not, we examined recurrence status by pathologic T and N staging within the cohort. Patients with higher T-stage (T3–T4) disease at diagnosis were more likely to exhibit disease recurrence compared to those with lower T-stage (T1–T2) disease. Nodal involvement is shown for both recurrent and non-recurrent cases. These results are descriptive in nature, and the distribution of pathologic stages is shown in Table 4. We additionally evaluated the association between intraoperative blood transfusion requirements at the time of transplant and CRC recurrence. Recurrence was noted in two subjects that received intraoperative transfusions, with the remaining cases of recurrence not requiring intraoperative transfusion. Given the small number of transfusions identified, formal statistical analysis was not performed.

Figure 2 Kaplan-Meier curve stratified KRAS mutational status and associated risk of recurrence of CRC following SOT. KRAS positive mutation tumors demonstrated significantly greater rates of disease recurrence than those without KRAS mutations. The hazard ratio was 13.58 with an associated P value of 0.002. Censoring events are denoted by vertical ticks. The X-axis represents time to recurrence in months, and the Y-axis represents the proportion of patients with recurrence. CRC, colorectal cancer; SOT, solid organ transplant.

Figure 3 Bar plot representation of BRAF mutational status based on patient cohort tumor mismatch repair status. BRAF positive disease was exclusively observed in the MMRd group (P=0.001). The bars represent the number of patients within the study cohort that demonstrated either MMRp or MMRd disease and the associated BRAF mutational status within those disease groups. MMRd, mismatch repair deficient; MMRp, mismatch repair proficient.

All patients with stage I–III disease underwent curative-intent resection. Among stage 0/I patients (n=10), 4 (40%) were managed with endoscopic resection alone while the remainder received complete mesocolic excision (CME) or total mesorectal excision (TME). All stage II and III patients underwent CME or TME resection. Among the 12 patients with rectal cancer, 3 (25%) received standard-of-care neoadjuvant chemoradiation, while 1 (8%) received total neoadjuvant therapy (TNT) with the remainder proceeding to surgery without neoadjuvant therapy. Adjuvant therapies varied by stage. No stage I patients received adjuvant therapy and were maintained in surveillance. Three subjects with high-risk stage II disease received adjuvant therapy with Xeloda or 5-fluorouracil (5-FU) alone; whereas stage II subjects without high-risk features were maintained in surveillance without receiving adjuvant therapies. Among patients with stage III disease, 11 (61%) received adjuvant treatment (4 received Xeloda or 5-FU and 7 received oxaliplatin based regimens), while 7 (39%) were managed with a surveillance strategy.

African American patients had higher rates of CRC recurrence (P=0.04). However, no statistically significant differences were identified between recurrent and non-recurrent groups for age at diagnosis, sex, transplant type, tumor location, time from transplant to CRC diagnosis, induction or maintenance immunosuppression regimens, or other mutational subgroups (P>0.05).

When comparing induction immunosuppression regimens, there were no statistically significant differences in relapse risk. However, we found more Caucasian patients received non-depleting agents than patients of other races (P=0.008). Additionally, cases of liver transplantation predominantly received non-depleting agents, whereas renal transplants received more lymphocyte depleting induction regimens (P≤0.001). It is worth noting that 11 Caucasian patients had been recipients of liver transplants in comparison to one African American patient.

Cohort subjects were also stratified into high versus low absolute lymphocyte count (ALC) levels utilizing a median split (ALC median, 1.18). Several statistically significant findings were identified including evidence of lower ALC levels at the time of CRC diagnosis in women compared to men (P=0.046). Additionally, the lower ALC level group was noted to have more right-sided CRC disease, while the higher ALC level group demonstrated a higher proportion of rectal disease (P=0.041). Finally, those subjects in the higher ALC level group were more likely to have MMRp disease (P=0.03).

When comparing maintenance immunosuppression regimens, the only significant difference between these groups was higher tumor mutational burden (TMB) levels in the CNI alone group (P=0.03). There was notably no significant difference in disease relapse when comparing these two groups at the time of CRC diagnosis.

Discussion

This novel investigation of CRC recurrence risk in SOT recipients provides valuable knowledge on the interplay of tumor genomic characteristics, and immunosuppression on CRC tumor biology and relapse risk in a unique patient population. We report on 53 patients treated at The Johns Hopkins Hospital and the University of Wisconsin Hospitals and Clinics who were diagnosed with CRC following SOT. Our study demonstrates a trend towards increased recurrence risk in patients with post-SOT CRC and provides insight into genomic and immunosuppression factors contributing to this heightened recurrence risk.

Although not reaching the level of statistical significance, we observed higher rates of recurrence for this post-SOT cohort across all stages of disease in comparison to population benchmarks. These findings align with our original hypothesis that SOT recipients may be at heightened risk for CRC recurrence, which we hypothesize may relate to diminished immune surveillance from chronic immunosuppression. Of interest, the SIRs for early stage I–II disease are particularly increased when compared to stage III disease. As prior literature suggests, immunogenic MMRd tumors are enriched in earlier stages of disease, with a plausible explanation being that intact immune surveillance reduces the risk of early disseminated tumor cells establishing metastatic foci. Therefore, we speculate it is possible that the effect of SOT-associated impaired immune surveillance may be more pronounced in early-stage disease (17). We hypothesize that the near universal use of adjuvant treatment in patients with stage III disease may limit the impact of immunosuppression on relapse risk (18,19).

Today, there are no globally accepted management guidelines for CRC that take into account SOT status. While our study does not directly evaluate surveillance strategies or adjuvant treatment decisions, our findings suggest that this population may have unique disease characteristics that warrant consideration of a personalized management approach. For example, the potentially elevated relapse risk in early-stage disease might warrant consideration of more intensive screening or a lower threshold for using adjuvant treatment in this group (20-22). However, future prospective evaluation of modified surveillance and/or adjuvant treatment approaches in this patient population are vital to guide clinicians on how to approach these cases.

We report on several molecular features that are associated with disease relapse. We observed a marked increase in CRC recurrence risk in patients with KRAS and APC mutant disease. This association between KRAS mutations and relapse is consistent with current literature reporting that KRAS mutated CRC in the general population is associated with more aggressive disease biology and increased recurrence risk (23). There is limited literature supporting an increased prevalence of KRAS mutations in post-SOT CRC; however, KRAS mutated CRC has previously been associated with CNI use in chronic immunosuppressive regimens (24,25). KRAS mutations may serve as a useful prognostic marker for recurrence in post-SOT CRC. Emerging use of KRAS targeted therapies might prove valuable in this patient population and could be explored in future studies.

Current literature comparing APC mutational status and CRC prognosis is mixed with some studies suggesting APC mutations are a poor prognostic marker and others suggesting a protective effect (26,27). Within our cohort there is evidence of increased CRC recurrence risk in APC mutated disease, in the post-SOT setting. This observed association is likely driven by co-mutations and interplay with MMR status as we observed a higher frequency of both APC and KRAS mutations in MMRp disease, which generally carry higher relapse rates for a given stage than MMRd counterparts (28).

BRAF-mutations conferred a positive prognosis in our study cohort. Furthermore, all BRAF positive cases were also MMRd tumors as consistent with established BRAF-mutation and MMRd associations (29). Notably while none of the patients with BRAF mutant MMRd disease (n=7) relapsed, 4 of the 6 patients with MMRd disease but lacking BRAF mutations relapsed.

Within our study cohort we sought to evaluate potential factors related to immunosuppression requirements and CRC recurrence as well as other disease factors. There was no evidence that the type of induction immunosuppression impacted recurrence of CRC in SOT recipients, nor did it have a significant impact on tumor biology. These findings are not overly surprising as we hypothesize that it is the chronicity of immunosuppression that negatively impacts immune surveillance, predisposing this population to heightened recurrence and induction alone would not contribute to such mechanisms.

Notably when comparing chronic immunosuppression regimens within our study cohort, there was no evidence that the choice of immunosuppression regimen modified CRC recurrence risk. Current literature demonstrates mixed evidence of whether a mTOR inhibitor-based regimen may reduce malignancy risk and for immunosuppression reduction following evidence of graft stability, although the data remains insufficient for establishment of clear guidelines (30,31). Our cohort has few cases of regimens consisting of mTOR inhibitors such as sirolimus, thus limiting these observations. Future studies should focus on comparing mTOR inhibitors versus CNI and evaluate chronic immunosuppression over the course of transplantation.

In addition to chronic immunosuppression, it is possible acute management of graft rejection with more intensive pulse dose glucocorticoids or further lymphocyte depleting agents might have significant impacts on immune surveillance of tumors. While the retrospective nature of this investigation made identifying these interventions challenging, we believe this represents an important area of future investigation to understand the relationship between these immunosuppressive exposures and SOT-associated CRC relapse risk.

This study has several limitations that warrant consideration when interpreting the observations and results outlined. First, the retrospective design of the study creates inherent biases, and the small cohort size limits statistical power, reducing the ability to definitively draw conclusions. Furthermore, we utilized pooled population data for comparison of CRC recurrence rates in our SOT population compared to that of the general population. As such, it should be acknowledged that potential confounding variables exist that were not matched or controlled given the limitations of the comparator group used in this study. Furthermore, molecular testing was not available on all study cohort patients, potentiating risk of bias in the tumor genomic results. Most patients with more aggressive/advanced disease underwent genomic diagnostic testing, and most that did not receive such testing were predominantly early-stage disease. Finally, although this was a multi-institutional study, the findings of this cohort may not be generalizable to other patient settings, particularly centers with differing demographic and socioeconomic patient profiles. Additionally, given this study was conducted at tertiary-care academic centers, referral bias and center-specific practice patterns may have influenced patient selection, treatment approaches, and observed outcomes, potentially limiting the generalizability of this study’s findings to other practice settings.

Conclusions

In summary, this multi-institutional retrospective cohort study assessed CRC recurrence risk following SOT and demonstrated a trend toward increased recurrence risk across all disease stages when compared to population benchmarks. We identified key tumor genomic features that may be associated with recurrence risk and serve as potential prognostic markers. The findings of this study should be interpreted as exploratory, and highlight the need for further prospective studies to validate and expand on these observations. It is our hope that our study provides rationale for future prospective investigations aimed at evaluating whether increased surveillance strategies and/or modified adjuvant treatment approaches may improve outcomes in SOT recipients with CRC.

Acknowledgments

We would like to thank Swim Across America (E.S.C.), ASCO Conquer Cancer Foundation (E.S.C.), Colorectal Cancer Alliance (E.S.C.), Bloomberg Kimmel Institute for Cancer Immunotherapy (all authors), and Cancer Convergence Institute (all authors) for their generous support of this work.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-970/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-970/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-970/prf

Funding: This study was supported by Swim Across America (to E.S.C.), MD Anderson-Johns Hopkins GI Spore (No. P50CA221707, to E.S.C.), ASCO Conquer Cancer Foundation (to E.S.C.), Colorectal Cancer Alliance (to E.S.C.), Bloomberg-Kimmel Institute for Cancer Immunotherapy, and Cancer Convergence Institute.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-970/coif). K.B. reports research funding from Merck and BMS, and that spouse is an employee of AstraZeneca. D.T.L. has received consulting fees from Merck, Bristol Myers Squibb, Nouscoum, G1 Therapeutics, Janssen, Regeneron, Tavotek Biotherapeutics, Janssen, Sirtex, Tango Therapeutics, and Merus; Contracts from Merck, Bristol Myers Squibb, Curegenix, Nouscom, Medivir, and Abbvie and Honoraria from Merck. E.S.C. reports research funding from Affimed GMBH, Parabilis, Haystack, Incyte, NextCure, Pfizer, Regeneron, is a paid consultant for Boston Scientific, Parabilis, Roche, Seres Therapeutics, SirTex, Tatum Biosciences, and Urogen, and received travel support from NextCure. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Boards of the Johns Hopkins Hospital (No. IRB00309275) and the University of Wisconsin Hospitals and Clinics (No. 2024-1092). Informed consent was waived due to the retrospective nature of this study and the minimal risk to patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Siegel RL, Wagle NS, Cercek A, et al. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023;73:233-54. [Crossref] [PubMed]
2. Engstrom PF, Benson AB 3rd, Saltz L, et al. Colon cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2003;1:40-53. [Crossref] [PubMed]
3. Dougaz W, Bouasker I, Gouta EL, et al. Predictive factor of recurrence after curative resection for stage I-II colon cancer. Tunis Med 2019;97:685-91. [PubMed]
4. Engels EA, Pfeiffer RM, Fraumeni JF Jr, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011;306:1891-901. [Crossref] [PubMed]
5. Kasiske BL, Snyder JJ, Gilbertson DT, et al. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905-13. [Crossref] [PubMed]
6. Adami J, Gäbel H, Lindelöf B, et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer 2003;89:1221-7. [Crossref] [PubMed]
7. Spardy J, Concepcion J, Yeager M, et al. National Analysis of Recent Trends in Organ Donation and Transplantation in the United States: Toward Optimizing Care Delivery and Patient Outcomes. Am Surg 2023;89:5201-9. [Crossref] [PubMed]
8. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2023 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration. Published February 12, 2025 (covering data 2012–2023). Available online: https://srtr.transplant.hrsa.gov/adr/adr2023
9. Safaeian M, Robbins HA, Berndt SI, et al. Risk of Colorectal Cancer After Solid Organ Transplantation in the United States. Am J Transplant 2016;16:960-7. [Crossref] [PubMed]
10. Prenner S, Levitsky J. Comprehensive Review on Colorectal Cancer and Transplant. Am J Transplant 2017;17:2761-74. [Crossref] [PubMed]
11. Merchea A, Shahjehan F, Croome KP, et al. Colorectal Cancer Characteristics and Outcomes after Solid Organ Transplantation. J Oncol 2019;2019:5796108. [Crossref] [PubMed]
12. Christenson ES, Lee V, Wang H, et al. Solid Organ Transplantation Is Associated with an Increased Rate of Mismatch Repair Deficiency and PIK3CA Mutations in Colorectal Cancer. Curr Oncol 2022;30:75-84. [Crossref] [PubMed]
13. Qaderi SM, Galjart B, Verhoef C, et al. Disease recurrence after colorectal cancer surgery in the modern era: a population-based study. Int J Colorectal Dis 2021;36:2399-410. [Crossref] [PubMed]
14. Boute TC, Swartjes H, Greuter MJE, et al. Cumulative Incidence, Risk Factors, and Overall Survival of Disease Recurrence after Curative Resection of Stage II-III Colorectal Cancer: A Population-based Study. Cancer Res Commun 2024;4:607-16. [Crossref] [PubMed]
15. Nors J, Iversen LH, Erichsen R, et al. Incidence of Recurrence and Time to Recurrence in Stage I to III Colorectal Cancer: A Nationwide Danish Cohort Study. JAMA Oncol 2024;10:54-62. [Crossref] [PubMed]
16. Kim C, Kim WR, Kim KY, et al. Predictive Nomogram for Recurrence of Stage I Colorectal Cancer After Curative Resection. Clin Colorectal Cancer 2018;17:e513-8. [Crossref] [PubMed]
17. Schaller J, Agudo J. Metastatic Colonization: Escaping Immune Surveillance. Cancers (Basel) 2020;12:3385. [Crossref] [PubMed]
18. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 3.2025. National Comprehensive Cancer Network; 2025. Available online: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
19. Baxter NN, Kennedy EB, Bergsland E, et al. Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update. J Clin Oncol 2022;40:892-910. [Crossref] [PubMed]
20. Dharia A, Boulet J, Sridhar VS, et al. Cancer Screening in Solid Organ Transplant Recipients: A Focus on Screening Liver, Lung, and Kidney Recipients for Cancers Related to the Transplanted Organ. Transplantation 2022;106:e64-5. [Crossref] [PubMed]
21. Benoni H, Nordenvall C, Hellström V, et al. Previous Solid Organ Transplantation Influences Both Cancer Treatment and Survival Among Colorectal Cancer Patients. Transpl Int 2024;37:13173. [Crossref] [PubMed]
22. Kim JY, Ju MK, Kim MS, et al. Clinical characteristics and treatment outcomes of colorectal cancer in renal transplant recipients in Korea. Yonsei Med J 2011;52:454-62. [Crossref] [PubMed]
23. Bonnot PE, Passot G. RAS mutation: site of disease and recurrence pattern in colorectal cancer. Chin Clin Oncol 2019;8:55. [Crossref] [PubMed]
24. Hasjim BJ, Ostowari A, Gandawidjaja M, et al. De novo colorectal cancer after kidney transplantation: a systematic review and meta-analysis. Br J Cancer 2025;132:1010-8. [Crossref] [PubMed]
25. Revuelta I, Moya-Rull D, García-Herrera A, et al. Role of oncogenic pathways and KRAS/BRAF mutations in the behavior of colon adenocarcinoma in renal transplant patients. Transplantation 2012;93:509-17. [Crossref] [PubMed]
26. Corsini EM, Mitchell KG, Mehran RJ, et al. Colorectal cancer mutations are associated with survival and recurrence after pulmonary metastasectomy. J Surg Oncol 2019;120:729-35. [Crossref] [PubMed]
27. van den Broek E, Krijgsman O, Sie D, et al. Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients. Oncotarget 2016;7:73876-87. [Crossref] [PubMed]
28. Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247-57. [Crossref] [PubMed]
29. Domingo E, Espín E, Armengol M, et al. Activated BRAF targets proximal colon tumors with mismatch repair deficiency and MLH1 inactivation. Genes Chromosomes Cancer 2004;39:138-42. [Crossref] [PubMed]
30. Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002;3:991-8. [Crossref] [PubMed]
31. Hellemans R, Pengel LHM, Choquet S, et al. Managing immunosuppressive therapy in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer): an overview of the available evidence and guidance for shared decision-making. Transpl Int 2021;34:1789-800. [Crossref] [PubMed]