One of the first papers evaluating transplant candidates with pre-existing malignancies was performed by Dr. Israel Penn in 1997.1 In this retrospective analysis of the recurrence rates of 1,297 preexisting tumors in renal transplant recipients, 1,137 neoplasms were treated prior to transplantation. The recurrence rate was 21%, and it was 33% in 99 cancers treated after transplantation. Fifty-four percent of recurrences in the pretransplant-treated group occurred among malignancies treated within two years of transplantation, 33% in those treated two to five years before transplantation, and 13% among those treated more than five years pretransplantation. Among those cancers treated pretransplantation the highest recurrence rates occurred with breast cancer (23%), symptomatic kidney cancers (27%), sarcomas (29%), bladder cancer (29%), nonmelanoma skin cancers (53%) and multiple myeloma (67%).
In a contemporary systematic review, Boissier et al.2 assessed the risk of tumor recurrence in patients undergoing renal transplantation after having a urologic malignancy. There were 32 retrospective studies enrolling 2,519 patients that were included in the analysis. For renal cell carcinomas, the risks of recurrence, cancer-specific, and overall survival were similar between transplantation and dialysis. For prostate cancer, most of the tumors had favorable prognoses consistent with prior nomograms. Studies dealing with urothelial carcinomas mainly included upper urinary tract urothelial carcinoma (UC) in the context of aristolochic acid nephropathy, for which the risks of synchronous bilateral tumor and recurrence were high. This study concluded that immunosuppression does not affect outcomes and natural history of low-risk renal cell carcinomas and prostate cancer.
Given the excellent cancer-specific and survival outcomes in patients with T1a renal cell carcinoma (RCC) (>90% for both metrics over three to five years of follow-up), there is no waiting time necessary for low stage (T1a, low grade) RCC. Among patients with higher risk disease (ie. Von Hippel-Lindau [VHL] patients), the three-year recurrence rate is 30-50% and thus a renal transplant waiting period of two to three years is recommended. Patients with symptomatic/locally advanced RCC should wait a minimum of five years prior to transplantation.
Following renal transplantation, the risk of renal cell carcinoma is higher than the general population. A recent population-level analysis identified 683 RCCs among 116,208 kidney transplant recipients.3 RCC risk was substantially elevated compared with the general population (standardized infection ratio [SIR] 5.68, 95% confidence interval [CI] 5.27-6.13), especially for papillary RCC (SIR 13.3 versus SIR 3.98 for clear cell RCC). Among kidney transplant recipients, RCC risk was significantly elevated for Black patients compared to Whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). A recent paper again assessed survival after a cancer diagnosis among solid organ transplant recipients.4 This study assessed cases in the US general population (n=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry from 1987 to 2014. Cancer-specific mortality was higher in transplant recipients compared with other patients with cancer, which was particularly pronounced for melanoma (adjusted hazard ratio [aHR] 2.59, 95% CI 2.18-3.00) and cancers of the breast (aHR 1.88, 95% CI 1.61-2.19), bladder (aHR 1.85, 95% CI, 1.58-2.17), and colorectum (aHR 1.77, 95% CI 1.60-1.96).
Dr. Krishnamurthi concluded his presentation with the following remarks:
- Low stage, low-grade RCC requires no waiting time prior to renal transplantation
- For patients with T2/3, Grade 3 RCC, the recommended waiting time is two to three years for transplantation
- Patients with N+/M+ RCC should wait for five years prior to renal transplant
- Patients should be advised that if they develop RCC following renal transplant, they are at a slightly decreased survival rate compared to patients with sporadic RCC
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, USA, Twitter: @zklaassen_md, at the Society of Urologic Oncology (SUO) - American Urologic Association (AUA) 2020 Summer Webcast Program, July 18, 2020
- Penn, I. "Evaluation of transplant candidates with pre-existing malignancies." Annals of Transplantation 2, no. 4 (1997): 14-17.
- Boissier, Romain, Vital Hevia, Harman Max Bruins, Klemens Budde, Arnaldo Figueiredo, Enrique Lledo-Garcia, Jonathon Olsburgh et al. "The risk of tumour recurrence in patients undergoing renal transplantation for end-stage renal disease after previous treatment for a urological cancer: A systematic review." European Urology 73, no. 1 (2018): 94-108.
- Karami, S., E. L. Yanik, L. E. Moore, R. M. Pfeiffer, G. Copeland, L. Gonsalves, B. Y. Hernandez, C. F. Lynch, K. Pawlish, and E. A. Engels. "Risk of renal cell carcinoma among kidney transplant recipients in the United States." American Journal of Transplantation 16, no. 12 (2016): 3479-3489.
- D’Arcy, Monica E., Anna E. Coghill, Charles F. Lynch, Lori A. Koch, Jie Li, Karen S. Pawlish, Cyllene R. Morris, Chandrika Rao, and Eric A. Engels. "Survival after a cancer diagnosis among solid organ transplant recipients in the United States." Cancer 125, no. 6 (2019): 933-942.