Renal Transplant Risks With Prostate Cancer
Overview
Renal transplant candidates are recommended to undergo a systematic screening for prostate cancer at the time of listing. It is a growing concern that low-risk prostate cancer diagnosis may lead to reduced access to renal transplant services without any significant oncological benefit.
The aim of this study was to evaluate the outcomes of renal transplant candidates who were newly diagnosed with prostate cancer at the time of listing and its effect on the candidate’s accessibility to renal transplant and transplant outcomes in association with their treatment options.
This study, being a retrospective study, was carried out in twelve French renal transplant centers over a period of 10 years. Patients who were included into the study were renal transplant candidates who were newly diagnosed with prostate cancer at the time.
Data on the candidate’s demographic information and clinical details of prostate cancer, renal disease and renal transplant surgeries were collected.
The principal outcome of this study was to assess the time interval between active renal transplant listing and prostate cancer diagnosis in renal transplant candidates.
The total median time interval between diagnosis of prostate cancer and active listing for renal transplant was 25 months. There were statistically significant differences in the time intervals between the active surveillance and the radiotherapy groups. Treatment modalities for prostate cancer were seen to have a limited effect on the accessibility of renal transplant, the outcomes of renal transplant and oncological outcomes of the patients.
Introduction
Prostate cancer is cancer originating from the prostate gland. It causes the gland to enlarge in size due to excessive replication of cancer cells. Despite the fact that the prostate cancer incidence in patients suffering from end-stage renal disease (ESRD) is identical to the incidence seen in the general population, systematic prostate cancer screening using the prostate specific antigen (PSA) levels measurement and digital rectal examination (DRE) is still recommended in renal transplant candidates at the time of listing. It has been seen that decreased or delayed access to renal transplant leads to a decreased quality of life and life expectancy in renal patients who are undergoing dialysis. There are also concerns that low-risk prostatic cancer over-diagnosis may lead to a reduction in the accessibility of renal transplant with no significant oncologic benefit. The aim of this study was to evaluate the outcomes of renal transplant candidates who were newly diagnosed with prostate cancer at the time of listing and its effect on the candidate’s accessibility to renal transplant and transplant outcomes in association with their treatment options.
Method
This study was given approval by the French National Urology Ethics Committee and involved 12 transplant centers. Demographic data, clinical data, end-stage renal disease data, renal transplant data, data on the diagnosis and treatment of prostatic cancer and follow-up data were obtained using the patient’s medical files. Data was obtained from the 1st of March 2021 to the 1st of June 2021. The screening for prostate cancer was carried out in accordance with the recommendations given by the Renal Transplantation Committee of the French Urological Association (CTAFU). Prostate cancer screening was done via the measurement of prostatic specific antigen (PSA) and direct rectal examination (DRE) in patients aged >50 years at the time of renal transplant listing. Progression of prostate cancer in patients who had initial active surveillance was determined by rising prostate specific antigen levels and high grade tumors seen on biopsies. However, in patients who had curative treatment such as surgery, radiotherapy or both, progression of prostate cancer was determined by rising levels of prostatic antigen levels and extension of cancer to the lymph nodes. Duration of contra-indications were described as the time interval between prostate cancer diagnosis and active transplant listing or last follow-up if the patient is not yet actively listed.
The delay to actively list patients till after treatment of prostatic cancer was decided based on the guidelines provided by the French Association of Urology (AFU).
The principal outcome of this study was to assess the time interval between the new diagnosis of prostate cancer and active listing of the patient for renal transplant according to specific treatment modalities. The secondary outcome of this study was to assess the time delay between the diagnosis of prostate cancer and renal transplantation, also, the time span of contra-indications and time delay from active renal transplant listing to renal transplant based on treatment modalities. Additionally, the study aimed to demonstrate the variations in accessibility to renal transplant services based on prostate cancer treatment choices. Oncological outcomes, epidemiological factors, anatomical and pathological features and clinical presentations were put into consideration.
Inclusion Criteria
This study was an observational retrospective study which included patients who were just diagnosed with prostate cancer at the time of listing for renal transplant from 1st January 2010 to 31st December 2020.
Exclusion Criteria
Patients who had a previous history of prostatic cancer before renal transplant listing were not included in the study.
Statistical Analysis
Median and interquartile range or standard deviation and mean were used to report quantitative variables. Number and percentage were used to report qualitative variables. A p value of <0.05 was used alongside bilateral testing in the statistical analysis.For quantitative data, ANOVA and student tests were utilized following the verification of normality, otherwise, the Kruskal-Wallis tests or Wilcoxon tests were used as alternatives. Chi-square test was used for qualitative data to compare percentages. Incomplete or missing data were skipped if it represented only a fraction (<5%) of the total data of the variables involved, while statistical analysis was carried out on the remaining complete data.
Results
216 out of 9700 male renal transplant candidates in the 12 renal transplant centers were newly diagnosed with prostate cancer at the time of evaluation. The 216 men diagnosed with prostate cancer were included into the study and were followed up from the time of first contact with the renal transplant team to the last follow-up visit for a median duration of 50.6 months.
131 (60.6%) of the 216 patients with an early diagnosis of prostate cancer during the last follow-up were eventually actively listed, while 63 (29.2%) of the 216 patients underwent a renal transplant from living donors (57 patients) or deceased donors (6 patients).
69 (31.9%) out of the 216 patients were not actively listed and put on an inactive list while waiting for the temporary contra-indications related to prostate cancer (in 64 candidates) or other causes such as obesity and cardiovascular pathologies ( in 5 candidates) to be lifted. 12 (5.6%) patients had definite contra-indications to renal transplant while 4 (1.9%) patients refused renal transplant.
The median time interval from the diagnosis of prostate cancer to active transplant listing was seen to be 25 months. 63 (48.1%) out of the 131 actively listed patients received a renal transplant after a median time duration of 8 months after being actively listed.
131 (60.6%) out of the 216 patients underwent primary radical prostatectomy with or without salvage therapy. 39 (18.1%) out of the 216 patients underwent radiotherapy via external beam radiation with or without androgen deprivation therapy (ADT). 46 (21.3%) out of the 216 patients were given other treatment with either active surveillance (24 patients),watchful waiting (8 patients) and androgen deprivation therapy or focal therapy such as brachytherapy alone (14 patients).
Based on treatment modality, the median time interval between the diagnosis of prostatic cancer and active listing was 24.8 months for the primary surgery group, 14.4 months for the active surveillance group and 39.9 months for the primary radiotherapy group. There were significant statistical differences in the median time intervals between the active surveillance group and the primary radiotherapy group with a p value of 0.03.
The time duration between active listing and renal transplant surgery was seen to be significantly shorter in the primary radiotherapy groups (1.4 months) when compared with the time duration of the active surveillance groups (8.9 months) and primary surgery group (9 months). The temporary contra-indication duration was seen to be longest in the radiotherapy groups (39.9 months), when compared with the duration seen in the active surveillance groups (18.8 months) and primary surgery groups (24 months).
A total of 212 (98.1%) patients had a diagnosis of localized prostatic cancer. 84 (39.6%) patients were seen to have low risk prostate cancer, 114 (53.8%) patients were seen to have intermediate risk prostate cancer, while 14 (6.6%) patients were seen to have high risk prostate cancer according to the updated d’Amico prostate cancer classification system.
95 (47%) patients were assessed for distant staging using PET scans or bone scans, with positive staging showing either 3 lymph node metastases or 1 bone metastasis on PET scan identified in 4 patients. A patient was given a diagnosis of synchronous primary lung cancer via imaging from a CT-scan.
18 (8.3%) patients reported a recurrence of prostate cancer following treatment. Three out of the 18 patients underwent salvage radiation therapy for biological prostate cancer recurrence following radical prostatectomy. One out of the 18 patients had a prostatectomy for prostate cancer progression following initial active surveillance. Four (22.2%) out of the 18 patients underwent renal transplant after salvage treatment of prostate cancer recurrence with a mean time duration of 32.5 months.
43 (68.3%) out of the 63 patients who received renal transplants had previously undergone primary surgery for prostate cancer, 5 (7.9%) out of the 63 patients who received renal transplants had previously undergone radiotherapy, while 10 (15.9%) out of the 63 patients who received renal transplants had previously undergone focal ablation or brachytherapy for prostate cancer. The median follow-up duration following renal transplant was 35.4 months, while the 5-year renal transplant survival rate was 70.3%.
A total of 36 (16.7%) deaths was reported among patients included in this study. Eleven deaths were recorded among patients who were on the renal transplant waitlist, nine deaths occurred among patients who underwent renal transplant following prostatectomy, while twelve patients died while waiting for the temporary contra-indications to be lifted. The remaining deaths were recorded among those who declined renal transplant and those who were definitely contra-indicated for renal transplant. The overall 5-year survival rate after prostate cancer diagnosis was 79.6% while the cancer-specific 5-year survival rate following diagnosis was 99.1%.
Conclusion
This study gave a detailed assessment of patients who were diagnosed with prostate cancer during evaluation for renal transplant listing compared to the registry studies which mixed all patients with prostate cancer despite the time at diagnosis. Data gotten from this study has shown that the treatment modalities for prostate cancer had only a limited effect on the access and outcomes of renal transplant. Radiation therapy led to a significantly increased delay to active transplant listing with no significant increase in the median time delay to undergo renal transplant. Data obtained from this study also suggests that the use of active surveillance at the time of listing for patients low-risk prostate cancer is a valid strategy which does not hinder access to renal transplant nor worsen oncological outcomes.
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