Abstract
Background/Aim: Occasionally, candidate renal transplant recipients (RTRs) are incidentally diagnosed with prostate cancer (PCa) during pre-transplant screening examinations; however, their clinical course remains unclear. This study aimed to clarify the clinical course of RTR diagnosed with PCa during pre-transplant screening tests. Patients and Methods: Between April 2008 and April 2022, 15 candidates for RTRs were newly diagnosed with PCa during the screening test. We analyzed the patients’ treatment choices, initial treatment results, waiting duration for renal transplantation, and whether they finally underwent transplantation. Results: The median patient age was 64 years (range=52-75 years). The median prostate-specific antigen level was 6.9 ng/ml (5.2-56.9 ng/ml). According to D’Amico risk stratification, one, 10, and four patients were at low, intermediate, and high risk, respectively. As for treatment choice, 13 patients chose surgery. Moreover, intensity-modulated radiotherapy and hormone therapy were chosen by one patient each. Of these, seven patients underwent transplantation, with a median waiting time from initial treatment to transplantation of 20.3 months (9.2-40.0 months). One patient discontinued transplantation owing to poor cancer control, four patients had donor issues (change in mind, aging, or disease), and one patient waited because pathological findings revealed locally invasive cancer. Conclusion: PCa diagnosis in candidate RTRs during the pre-transplant screening test impacts the candidate’s clinical course.
As of June 2019, the Organ Procurement and Transplantation Network reported that 47.8% of kidney recipients were over 50 years of age (1). Therefore, men who are candidates for or have undergone kidney transplantation may need to address issues related to prostate cancer (PCa) screening, detection, and management. In most cases, including cancers with an extremely low risk of recurrence, such as ductal carcinoma in situ of the breast (2), a two-year wait period is the minimum recommended time between cancer treatment and solid organ transplantation. In case of PCa, renal transplant recipients (RTRs) require no waiting time, even if PCa poses a high risk; this is because the majority of PCa cases are indolent. Moreover, there is no evidence that immunosuppression increases the risk of development or progression of PCa following renal transplantation (3-6). However, the clinical course of RTR candidates diagnosed with PCa during screening remains unclear. This study aimed to elucidate the clinical course of these patients.
Patients and Methods
From April 2008 to April 2022, 15 candidates for RTRs were newly diagnosed with PCa during the pre-transplant screening test at Tokyo Women’s Medical University, Tokyo, Japan. We followed up these patients and retrospectively analyzed their medical data: age, initial prostate-specific antigen (PSA), prostate volume, Gleason scores (GS), clinical T stage, D’Amico risk stratification, duration of dialysis, etiology of chronic kidney disease (CKD), treatment choices for PCa, and recurrence of PCa after initial treatment. The primary outcome of the present study was whether kidney transplantation actually occurs after PCa treatment. The secondary outcome was to check the reason why these patients could not undergo transplantation.
The Internal Ethics Review Board of Tokyo Women’s Medical University approved our retrospective study (Institutional Review Board approval no.382F). It was carried out in accordance with the principles outlined in the Declaration of Helsinki. The requirement for written informed consent was waived due to the retrospective nature of the study.
Results
Table I summarizes patient characteristics. The patients’ median age was 64 years (range=52-75 years), and the median hemodialysis duration was 19 months (range=0-204 months). CKD was caused by diabetes mellitus, chronic glomerulo-nephritis, membranous nephropathy, autosomal dominant polycystic kidney disease, and unknown reasons in seven, two, one, two, and two patients, respectively. The median PSA level and prostate volume were 6.9 ng/ml (5.2-56.9 ng/ml) and 34.3 ml (17.1-51 ml), respectively. One, 10 and four patients had GS of six, seven, and eight, respectively. The clinical stage was T3b, T2, and T1c, in 1, 2, and 12 patients, respectively. None of the patients had metastatic disease. According to the D’Amico risk stratification, one, 10, and four patients were at low, intermediate, and high risk, respectively.
Patient characteristics.
The clinical courses of the patients are summarized in Table II. Thirteen patients chose surgery (retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robot-assisted radical prostatectomy in one, four, and eight patients, respectively). One patient opted for intensity-modulated radiotherapy (IMRT). Additionally, case 10 was hopeful and opted for hormone therapy.
Clinical courses.
Seven patients underwent transplantation after PCa treatment without reduction or discontinuation of immunosuppressive drugs. The median waiting time from initial treatment and from diagnosis of PCa to transplantation was 20.3 months (9.2-40.0 months) and 27.2 months (15.2-67.3 months), respectively. Although using immunosuppressive drugs, none of the RTRs experienced PCa recurrence. Eight patients did not undergo kidney transplantation. Case 2 did not undergo transplantation owing to poor cancer control. Four patients (cases 4, 6, 7, and 12) could not receive transplantation owing to donor-related issues. The living donor for case 4 turned 80 years old during the waiting period to achieve good PSA control after IMRT, and was subsequently excluded from donor adaptation. The living donor for case 6 suffered from CKD due to urethral stone. Two living donors (cases 7 and 12) lost the intention of donating their kidneys to their recipients. Case 9 waited for two years after surgery, as pathological findings revealed a locally invasive cancer. Case 10 lost the intention to undergo renal transplantation during PCa treatment. Case 11 was waiting for a kidney donor.
Discussion
This study showed that seven of 15 (47%) patients were able to receive renal transplantation after diagnosis and treatment for PCa, with a median waiting time of 20.3 months after treatment. However, eight patients could not receive transplantation owing to recipients’ clinical issues and donor-related issues.
PCa is the most common malignant tumor in men (2, 7). Therefore, during the screening process prior to transplantation, occasionally, these candidates may be incidentally diagnosed with PCa. Although many studies have described treatment modalities and subsequent waiting times for PCa diagnosed before transplantation, few have reported whether transplantation was performed after PCa treatment.
RTRs are three times more likely to develop malignancies than the general population; moreover, the risk of renal cell carcinoma is 15-100 times higher (3, 8-10). Therefore, transplant candidates are actively screened for occult malignancies to ensure appropriate allocation of limited organs (11). Mostly, a minimum gap of two years is advised between cancer treatment and solid organ transplantation. For cancers with an increased risk of recurrence, wait times of 2-5 or >5 years are recommended (2). However, a greater risk of developing PCa is not indicated in any prior research (3, 8, 12). During the first five years after radical prostatectomy for low-risk prostate cancer, the possibility of recurrence is low (13). Thus, candidates for renal transplantation with localized PCa should be immediately considered for transplantation after radical prostatectomy, as patients face a risk of dying on dialysis during the five-year period. Several reports have shown that even for candidates with intermediate-risk PCa, the likelihood of cancer-specific death within 15 years of treatment is <5% (4, 14). Therefore, RTRs with PCa can receive transplantation with no waiting time, even with factors, such as PSA >20 ng/ml, Gleason score 8-10, and T3 after treatment initiation that increase risk of PCa. Moreover, the nomogram predicts <10% risk of cancer-specific death over the next 15 years (2).
In Western countries, cadaveric kidney transplantation accounts for the majority of cases. However, in Japan, living-donor kidney transplantation accounts for 80% of cases. Therefore, if a living donor is identified, transplantation can be performed relatively quickly. Nevertheless, in our study, only two of the seven patients received transplantation within one year, and the median waiting time after initial treatment was 20.3 months. In actual clinical practice, at least one to two years are required to prepare for kidney transplantation after confirming stabilization of PSA after prostatectomy. In many cases, donor-related problems arose during preparation, making it impossible to obtain a transplant. Our study showed that of the eight patients who were unable to receive transplantation, four cases occurred due to donor-related issues. Two living donors lost their intention to offer their kidneys to their recipients while waiting for PCa treatment. Andersen et al. (15) reported that becoming a donor was a complex experience, and donors felt a strong sense of responsibility and obligation toward the recipient and took an active stance in donating. Moreover, despite having intentions to donate, donors were often uncertain prior to transplantation. Edwards et al. (16) reported that donors felt strong conflict and anxiety before and after being asked to make an important decision, indicating that emotional turmoil is a natural reaction in donors who donate living kidneys. Therefore, it is likely that donors, who are often unsure until the last minute, may change their minds if something happens to the recipient.
Study limitations. This study was carried out at a single center with a relatively small number of cohorts with inherent biases, and was limited by the retrospective design. Therefore, further prospective studies with a large sample size of cohorts are required to confirm the present findings in the future.
Conclusion
Our study revealed that seven of 15 patients were able to receive renal transplantation after diagnosis and treatment for PCa, with a median waiting time of 20.3 months after treatment. In cases of PCa in candidate RTRs during the pre-transplant screening test in the future, we have to consider not only recipient-related issues but also donor related-issues.
Footnotes
Authors’ Contributions
YK wrote the manuscript and prepared the tables. YK, JI, CN, RM, KU, KY, TH, TS, HI, and TT performed prostate cancer surgeries and kidney transplantation. All the Authors have read and approved the final manuscript.
Conflicts of Interest
All Authors declare that they have no conflicts of interest in relation to this study.
- Received September 15, 2023.
- Revision received September 27, 2023.
- Accepted September 28, 2023.
- Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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