The role of localised prostate cancer treatment in renal transplant patients: A systematic review

Abstract Objective To systematically review and critically appraise all treatment options for localised prostate cancer in renal transplant candidates and recipients. Method A systematic review was conducted adhering to PRISMA guidelines. Searches were performed in the Cochrane Library, Embase, Medline, the Transplant Library and Trip database for studies published up to September 2022. Risk of bias was assessed with the Cochrane Risk of Bias in Non‐Randomised Studies of Interventions for non‐randomised studies tool. Results A total of 60 studies were identified describing 525 patients. The majority of studies were either retrospective non‐randomised comparative or case series/reports of poor quality. The vast majority of studies were focussed on prostate cancer after renal transplantation. Overall, 410 (78%) patients underwent surgery, 93 (18%) patients underwent radiation therapy or brachytherapy, one patient underwent focal therapy (high‐intensity frequency ultrasound) and 21 patients were placed on active surveillance. The mean age was 61 years old, the mean PSA level at diagnosis was 9.6 ng/mL and the mean follow‐up time was 31 months. The majority of patients had low‐risk disease with 261 patients having Gleason 6 prostate cancer (50%), followed by 220 Gleason 7 patients (42%). All prostate cancer mortality cases were in high‐risk prostate cancer (≥Gleason 8). The cancer‐specific survival results were similar between surgery and radiotherapy at 1 and 3 years. Conclusion Localised prostate cancer treatment in renal transplant patients should be risk stratified. Surgery and radiation treatment for localised prostate cancer in renal transplant patients appear equally efficacious. Given the limitations of this study, future research should concentrate on developing a multicentre RCT with long‐term registry follow‐up.


| INTRODUCTION
Prostate cancer has an increasing incidence in renal transplant recipients (RTRs) because of a variety of factors including pre-transplant screening, increasing age of recipients and prolonged survival after transplantation.The incidence of kidney transplants has increased with the highest surge in those aged 45 to 65 years old, corresponding to the index group for prostate cancer screening. 1Although it is undeniable that renal transplantation has improved life expectancy in chronic renal disease patients, the management of prostate cancer in this group is controversial.Multiple unknowns include the impact of immunosuppression, the role of cancer screening and the timing and type of prostate cancer treatment.Recent studies suggest that prostate cancer outcomes are no worse in RTR compared with their non-transplant counterparts. 2,3The aim of this study was to review and critically appraise all treatment options for localised prostate cancer in renal transplant candidates and recipients.

| Study design
The study was a systematic review reported according to PRISMA 2020 standards. 4A study protocol was registered with PROSPERO (CRD42022311393).

| Eligibility criteria
Eligible participants included adult patients with a diagnosis of localised prostate cancer pre-or post-renal transplantation.Patients with metastatic disease at time of diagnosis were excluded.Interventions included active surveillance, surgery, radiation ± androgen deprivation therapy and focal therapies.All prospective and retrospective comparative and non-comparative studies were included.

• Cochrane Library
• The Transplant Library

| Search strategy
OVID MEDLINE and OVID EMBASE were searched using the search string found in Table A1.This strategy was adapted to search the Cochrane Library, the Transplant Library and the Trip database.Full articles with relevant clinical information were retrieved and reviewed.The bibliographies of all retrieved and relevant publications identified by the above strategies were searched for further studies.
The above strategy was also used to search abstract proceedings for major urological conferences including EAU, AUA, BAUS and USANZ.
There was no language restriction.

| Selection process
Two reviewers (AD and GW) searched the above information sources independently and assessed identified studies for inclusion.The full study text was reviewed when it could not be clearly excluded on the basis of its title and abstract.A study was included when both reviewers independently assess it as satisfying the eligibility criteria from the full text.A third reviewer (WR) mediated in the event of a disagreement following discussion.

| Data management
Data extraction was processed onto a data extraction form.Duplicate studies were only included once.

| Data collection process
Authors independently extracted data on the trial inclusion criteria using standardised forms.The following data were extracted: author, year of publication, country, study period, inclusion criteria, total number of people and cancer treatment modality.

| Data items
Data extracted included sample size, baseline patient characteristics including age, baseline immunosuppression, PSA level, cancer grade and stage.Surgical data included approach, estimated blood loss, length of stay and presence of pelvic lymph node dissection.Radiation data included total dose and presence of neoadjuvant ADT.

| Primary outcomes
• The primary outcome was survival (prostate cancer-specific survival and overall survival).Cancer-specific survival was defined as deaths identified as being due to prostate cancer.Overall survival was defined as death due to any cause.The time points for survival were at 1 and 3 years.

| Secondary outcomes
• Prostate cancer treatment complications were collated according to the Clavien Dindo Classification. 5Short-term complications include organ injury and bleeding.Long-term complications include urinary incontinence, urethral stricture, erectile dysfunction, radiation cystitis and proctitis.
• Renal graft complications were collated according to the Clavien Dindo Classification for surgical complications and Common Terminology Criteria for Adverse Events (CTCAE) for radiation complications. 6Biochemical recurrence rate and positive margin rate

| Risk of bias in individual studies
Risk of bias for each included trial was assessed by the same initial reviewers.Risk of bias was assessed using the Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-1) for non-randomised studies. 7Case series were assessed using the Canada Institute of Health Economics Quality Appraisal Tool for case series. 89 | Data synthesis Data summary was provided with tables and graphs.A narrative synthesis explored the relationship and findings of the included studies.

| Dichotomous and continuous outcomes
Dichotomous data (e.g.survival at 1 and 3 years) were pooled with a single-arm meta-analysis with weighting according to inverse variance using a random effects model.Key continuous outcomes (e.g.PSA) were analysed using mean.Considering there was a lack of similar comparative studies, a double-arm meta-analysis was not performed.

| Dealing with missing data
Attempts were made to make contact with individual study authors when missing data were identified.

| Assessment of heterogeneity
The extent and impact of between-study heterogeneity were assessed by inspecting the forest plots and by calculating the tausquared and I-squared statistics respectively.The 95% confidence intervals around tau-squared and I-squared were calculated to judge our confidence about these metrics.We adopted the following I-squared thresholds to assess heterogeneity 9 : • 0 to 40%: heterogeneity may not be important A subgroup analysis was performed according to treatment type.A sensitivity analysis examining quality components and risk of bias was not possible because of the lack of randomised controlled trials.

| Meta-bias (es)
Considering the lack of RCTs, it was not possible to perform a funnel plot.Selection and publication bias was discussed in a narrative fashion as part of the critical appraisal process.

| Confidence in cumulative evidence
Strength of body of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). 10ch rating addresses key elements including the overall quality of evidence, magnitude of the effect, certainty of the results, the impact of patient values and preferences and certainty of these values and preferences.

| Study characteristics and results of individual studies
The 60 studies included a total of 525 patients.Table 1 lists all included studies.All studies were either retrospective nonrandomised comparative or case series/reports.Four studies were published in the 1990s, the remaining were published in the 21st Century. 11,12,28,37Studies recruited patients between 1980 and 2021.
The vast majority of studies were focussed on prostate cancer after renal transplantation.PSA screening for renal transplant patients prior to prostate cancer diagnosis was mentioned in only seven studies with the most common protocol being yearly PSA and digital rectal examination from the age of 50. 12,16,26,63,64,67,68erall, 410 (78%) patients underwent surgery, 93 (18%) patients underwent radiation therapy or brachytherapy, one patient underwent focal therapy (HIFU) and 21 patients were placed on active surveillance.The mean age was 61 years old, the mean PSA level at diagnosis was 9.6 ng/mL and the mean follow-up time was 31 months.The majority of patients had low-risk disease with 261 patients having Gleason 6 prostate cancer (50%), followed by 220 Gleason 7 patients (42%).All prostate cancer mortality cases were in high-risk prostate cancer (≥Gleason 8).Thirty-three (8%) patients had high-risk prostate cancer (Gleason 8 or higher).The vast majority of patients (n = 415 patients, 80%) had pathologically or clinically organ-confined localised disease (pT2 or cT2 or less).This was followed by 85 patients (16%) with extraprostatic extension or seminal vesicle invasion (pT3).

| Quality assessment
The quality of the included studies was generally low.Eight retrospective comparative papers had level of evidence III with control groups, and the remaining 52 case series and case report studies had level IV evidence.Using the ROBINS-1 tool, all studies were classified as critical risk of bias. 7Table A3 summarises the risk of bias quality in the retrospective comparative studies.Considering the retrospective nature of these trials, there were global concerns with serious and critical risk of bias with confounding, patient selection and outcome measurement.All studies did not have an objective measure of functional outcomes such as continence or erectile function.The case report and case series were assessed using the Canada Institute of Health Economics Quality Appraisal Tool. 8The quality of the studies was generally poor.Table A4 summarises the risk of bias quality assessment.

| Results of syntheses
The outcome results were broken down by treatment group and timing of prostate cancer treatment (pre-transplant vs. post-transplant).

| Surgery post-transplant primary outcomes
Using a single-arm random effects model, the overall survival rates at 1 and 3 years were 100% and 99%.The prostate cancer-specific survival at 1 and 3 years was 100% (Figure 2A,B).There was one prostate cancer-specific mortality that was in a Gleason 8 prostate cancer patient who eventually developed castrate-resistant metastatic disease. 26There was a higher positive margin (24.7%) in the robotic group.Subgroup survival analysis by Gleason grading was unable to be performed because of the lack of clear reporting in the included studies.

| Surgery post-transplant secondary outcomes
The surgical complication rate was 14.5% with the vast majority of these being minor (Clavien Dindo Classification Grade 2 or less).Major complications included rectal injury and rectourethral fistula requiring colostomy, 17 postoperative lymphocoele requiring percutaneous drainage or marsupialisation, 15,27,50 postoperative bleeding requiring pelvic vessel angioembolisation 53 and pelvic abscess requiring open drainage. 48The renal graft-specific complication rate was 3% with the main cause being transplant ureteric injury during dissection. 15,27Others included iliac vein thrombosis 6 months post-surgery, 17 pelvic haematoma resorting in renal graft hydronephrosis 70 and ureteric stricture requiring subsequent reconstruction. 52stoperative

| Surgery pre-transplant
7][68] The majority of patients had an open prostatectomy (64%).There were no studies examining robotic surgery in the pre-transplant setting.Of the 66 patients, 54 (82%) had low-risk prostate cancer (Gleason 6) and 12 (18%) patients had intermediate-risk prostate cancer (Gleason 3 + 4).The mean time was 28.6 months between surgery treatment and renal transplantation. 69Mean operating time was 170 min.Length of stay, continence and erectile dysfunction rates were not recorded.These studies reported a 100% overall survival and 100% cancer-specific survival at the last follow-up.neoadjuvant ADT was poorly reported with only one study listing the reason, for example cT3 disease. 26

| Radiation primary outcome (oncological)
The overall survival rate at 1 and 3 years was 100% and 83%.The prostate cancer-specific survival at 1 and 3 years was 100% and 99% (Figure 3A,B).The prostate cancer deaths were in high-risk Gleason 8 prostate cancer patients. 3,26,54,60Subgroup analysis by Gleason grading again was unable to be performed because of the lack of clear reporting in the included studies.

| Radiation secondary outcome (functional)
Only half of the radiation patients included had complications specifically stated.The majority of complications were minor grade 1 cystitis and proctitis.There was one major complication-one patient who had a grade 3 proctitis requiring a diverting colostomy. 6012 | Radiotherapy pre-transplant Overall, there were two studies that examined radiotherapy treatment for prostate cancer before renal transplantation.67,69 There were a total of seven patients with a mean age of 63.5 and PSA of 6.7.Of the seven patients, three had low-risk prostate cancer (Gleason 6) and four patients had intermediate-risk prostate cancer (Gleason 3 + 4).
Only one study listed the mean time (19 months) between radiotherapy treatment cessation and renal transplantation. 69These studies reported a 100% overall survival and 100% cancer-specific survival at the last follow-up.Radiation complications were not recorded.

| Active surveillance
There were two studies that included active surveillance with a total of 21 cases. 3,26The surveillance protocol was not stated.There was no prostate cancer-specific death recorded.Five out of the 21 cases

| Focal therapy
There was only one focal therapy study included. 65This case report examined a 62-year-old male with a PSA 6 and Gleason 7 prostate cancer who underwent high-intensity frequency ultrasound (HIFU) treatment.The patient was still alive with no recurrence at a followup of 42 months.No complications were recorded.

| Surgical comparison with non-renal transplant cohorts with prostate cancer
In total, there were eight retrospective comparative studies.Of these, six studies compared oncological outcomes of radical prostatectomy in RTRs with standard non-RTR prostate cancer control groups. 15,17,19,26,47,50One study compared open retropubic radical prostatectomy versus open perineal radical prostatectomy amongst RTRs. 22One study compared prostate cancer outcomes in renal transplant patients with non-transplant patients however did not report subgroup analysis based on treatment type, for example surgery and radiotherapy. 3ongst the studies comparing the oncological outcomes of radical prostatectomy in RTRs with standard non-RTR control groups, the surgical margin, biochemical recurrence, cancer-specific survival and overall survival rates were similar in both the cases and control.The blood loss, hospital length of stay and surgery duration were similar in all comparative studies.Functional outcomes were poorly reported with only three studies reporting continence with no difference between the transplant and control groups.

| Heterogeneity assessment
There was a low risk of heterogeneity with all survival outcomes being <20% on the I-squared test.

| Certainty of evidence
Recommendations for clinical practice were graded by the modified GRADE methodology. 10The rating strength was low based on the poor overall quality of the evidence and the certainty of the results from retrospective studies.With regard to the primary outcome, there was high overall and cancer-specific survival amongst the RTRs who underwent prostate cancer surgery and radiotherapy comparable with the general nontransplant population.These findings are in keeping with survival rates in other reviews in this field. 71,72 3 years, the cancer-specific survival was similar between both groups (99% in radiation group and 100% in surgery group).The overall survival was higher in the surgery group (99% vs. 83%).Although patient comorbidities were not collected because of poor reporting amongst included studies, this may be related to radiation patients being generally less fit and older.Despite data showing equivalence between surgery and radiation for localised prostate cancer, this selection bias is well known in contemporary prostate cancer management with surgery preferred for younger, less co-morbid patients. 73This bias may also explain the reason why the majority of studies published had patients treated with surgery (86%).Any future research must ensure a higher proportion of non-surgical treatment options.
All prostate cancer-specific mortality cases were in high-risk prostate cancer patients.High-risk prostate cancer should be treated regardless if it is found pre-or post-renal transplant.This finding highlights the importance of a risk-based model, such as the American Society of Transplantation recommended wait time guideline, 74 to guide prostate cancer management in the renal transplant patient.
Graft complications were higher in the surgery group although the lack of complications reported in the radiation group may be due to the short follow-up period.The main graft complication was graft ureteric injury in four patients.Transplant ureteric stenting placed prior to prostatectomy may aid in ureter identification preventing injury, especially during the endopelvic fascia dissection and PLND. 75ere was one graft loss recorded that was a case of late deep vein thrombosis affecting the iliac vessels leading to graft loss. 17 prophylaxis.Although that patient did not undergo a PLND, this case also highlights the importance of selective PLND based on nomograms or radiological pelvic lymph node involvement considering the higher risk of DVT with PLND. 76ostate cancer treatment complications were similar in the radiation and surgery groups.Serious complications (Clavien Dindo Grade 3 or higher) occurred in 6% of surgery patients with no perioperative deaths recorded.The radiation complications were mainly related to cystitis and proctitis with the most severe case being a patient with Gleason 6 prostate cancer who underwent EBRT and developed colitis requiring a diverting colostomy. 60

| Implications of surgical approach in renal transplant patients
The kidney graft location within the iliac fossa provides unique anatomical challenges and technical modifications including laparoscopic port placement and dissection.Suggested modifications for RARP include placement of all ports on the opposite side to the graft, emphasis on placing ports under direct vision because of previous abdominal surgery and initiation of bladder mobilisation and space of retzius development from the contralateral side to the graft. 21Other modifications include using one instead of two assistant ports and not using the fourth robotic arm. 24,25For open radical prostatectomy, Heidenreich recommended the blade of the self-retained to be placed above the rectus muscle to avoid pressure injury to the graft. 22e vast majority of robotic cases were conducted in the standard manner with only seven patients across three studies reporting the retzius sparing approach. 34,44,46There was no difference between the standard and retzius sparing approaches.The shortened length of stay and lower blood loss associated with robotic surgery in this review is in keeping with the reported literature. 77The finding of interest however is the high positive margin rate in prostatectomy cases in RTRs (21%) with the highest rate in the robotic arm (25%).Contributing factors may include the fact that the robotic arm had a higher proportion of intermediate-risk prostate cancer (57%) compared with the open arm, which had a higher proportion of indolent Gleason 6 low-risk disease (60%).In addition to the modifications listed above, a smaller pelvic space and altered tissue planes from prior renal transplant can lead to a more challenging dissection.Careful meticulous dissection combined with an experienced surgical team and a general or transplant surgeon on standby is helpful to prevent the previously listed complications.
The vast majority of studies did not list the indication for a PLND.
When it was performed, the vast majority were conducted on the contralateral side only.This is not particularly surprising considering the risks of an ipsilateral lymph node dissection including transplant ureteric and vascular injury resulting in graft loss.Unless there is preoperative imaging suggestive of ipsilateral pelvic lymph node metastases, it is recommended that dissection is avoided on that side.

| Implications of radiotherapy approach in renal transplant patients
The location of the renal graft within the iliac fossa impacts radiotherapy planning considering its close proximity to the prostate.Kidneys are radiosensitive with radiation nephritis and ureteric stricture potential long-term risks especially if the ipsilateral iliac lymph nodes are part of the treatment field.The pathogenesis is progressive microvascular injury and stromal fibrosis leading to relative ischaemia and stricture formation. 59Measures to decrease the complication risk revolve around decreasing the dose to surrounding organs such as irradiation when the bladder is full or decreasing the planning target volume specifically to avoid the upper pelvic areas. 36

| Lack of active surveillance and focal therapy papers
Despite the widespread contemporary use of active surveillance for low-grade prostate cancer in non-transplant patients, there were only two studies that described its use. 3,26The majority of included studies were in the pre-active surveillance era.As such, a large proportion of included patients with low-grade disease (Gleason 6) had treatment.
Active surveillance in renal transplant patients appears to be safe.
A large Swedish registry found that immunosuppression in renal transplant patients did not increase the risk of prostate cancer progression. 3They also found that transplant recipients were not more likely than age-matched non-transplant men to be diagnosed with any high-risk or metastatic prostate cancer.This suggests that active surveillance is an appropriate option in immunosuppressed patients.

| Prostate cancer screening
The reporting of PSA screening for prostate cancer renal transplant patients was limited.In a survey of US transplant centres, 89% routinely screen for prostate cancer in renal transplant candidates and patients with the most common starting age being 50 years old. 78The concern of routine pre-transplant screening is the impact of overscreening and overtreatment.This review found that half of treated localised prostate cancer patients had low-grade Gleason 6 disease with only a small portion (21 patients) placed on active surveillance.This would indicate a significant degree of overtreatment for these patients.
The practice of subjecting men with low-grade prostate cancer to treatment and prolonged subsequent follow-up before they can be accepted for an organ transplantation can therefore be questioned, not least as longer time on dialysis is associated with worse outcomes after kidney transplantation. 79It is suggested that the decision to transplant or not should take into account the comparison between prostate cancer mortality versus dialysis mortality.The overall 5-year survival for renal dialysis varies between 35.8% and 50% dependent on age and comorbidities. 80Renal transplantation has shown to significantly improve overall mortality by up to 86% at 5 years. 80It is noted that the vast majority of localised prostate cancers have 5-year cancer-specific survival rates in excess of 90%. 81

| Limitations of research
Overall included studies were limited to retrospective comparative and case series.Most studies had a serious to critical risk of bias during analysis.The majority of studies were from one centre with participants entering at different stages of disease with short follow-up to detect any clinically relevant oncological outcome.There was significant heterogeneity with regard to inclusion criteria, outcome measures and prostate cancer-specific mortality definitions amongst studies.Most studies did not report outcome measures a priori.In particular, functional outcomes including quality of life measures for continence and erectile function were not measured with standardised tools.

| Limitation of review processes
All Gleason 7 intermediate-risk cases were grouped together as the majority of studies did not separately report ISUP Grade Group 2 to Grade Group 3. Based on population-based active surveillance data, it would be inferred that certain favourable intermediate-risk prostate cancer would be amenable to active surveillance; however, no strong conclusion can be made with this data set. 82Any future papers in this field must clearly differentiate the different grade subgroups.In addition, the survival time points included were short considering the decades-long duration required to assess long-term prostate cancer survival. 73The 3-year survival data presented were directly related to the lack of long-term follow-up in the included studies.

| Implications for future research
As there are relatively low numbers of renal transplant patients who have prostate cancer, recruitment for an adequately powered future RCT may be problematic.Bratt reported a prevalence of 0.07% of prostate cancer patients with a prior renal transplant in Sweden. 3actically, a well-designed prospectively collated registry study crosslinking renal transplant and prostate cancer data would be the ideal study type.
Future research needs to be multicentred encompassing multiple national and international renal transplant centres with subgroup analysis by treatment type.There should be more emphasis on recruiting patients undergoing active surveillance, radiotherapy and focal therapy.Future reporting of functional and complication outcomes such as continence would benefit from standardised measures such as the validated Incontinence Questionnaire-Urinary Incontinence Short Form. 83Any future research should also examine the impact of different immunosuppression regimes specifically a comparison between mTOR inhibitors (with reported anti-neoplastic properties) versus calcineurin inhibitors (with reported pro-neoplastic properties).From an oncological-specific perspective, the grading and staging should be uniform with long-term follow-up (10 years or more).

| Implications of results for practice and policy
Prostate cancer management in RTRs should be conducted in tertiary renal transplant centres with specialised uro-oncology expertise.The results indicate that future studies require a uniform prostate cancer screening program for renal transplant candidates and recipients to be reported as part of their trial.Although there are numerous criteria available, a commonly accepted one from the American Society of Transplantation would involve biennial PSA screening from the age of 50 with a life expectancy of 10 years or more before and after renal transplantation. 84The results of this systematic review suggest that the majority of localised prostate cancer diagnosed in RTRs are low grade.Active surveillance should be the primary management option in this group considering the financial and public health medical implications of overtreatment.

| CONCLUSIONS
Localised prostate cancer treatment in renal transplant patients should be risk stratified according to cancer risk nomograms.Surgery or radiation treatment for localised prostate cancer in renal transplant patients appears equally efficacious.Given the limitations of this study, there is a trend that low and favourable intermediate-risk prostate cancer patients may proceed to renal transplantation without cancer treatment.High-risk prostate cancer should be treated prior to renal transplantation if detected pre-transplant.

AUTHOR CONTRIBUTIONS
Anthony Dat, Gavin Wei, Simon Knight and Weranja Ranasinghe contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript.

APP E NDIX A: APPENDICES
T A B L E A 1 Search string.

Figure 1
Figure 1 details the search selection process.The search of listed databases identified 302 studies using a combination of search terms 'renal transplant' AND 'prostate cancer' or their medical subject ureteric injuries repaired intraoperatively 1 patient sustained graft failure due to pelvic haematoma needing nephrostomy, balloon dilatation, ureteropelvic reanastomosis due to Acute transient renal failure requiring nephrostomy secondary to retropubic haematoma T A B L E 2 (Continued) 85%) had organ-confined localised prostate cancer and six patients (7%) had cT3 disease.The range of doses for external beam radiotherapy was between 60 and 78 Gy.The dose for brachytherapy was 145 Gy.The mean time between renal transplant to radiotherapy was 94 months with a mean follow-up period of 43 months.A total of 23 (26%) patients underwent either adjuvant or neoadjuvant androgen deprivation therapy (ADT) ranging from 6 months to 3 years duration.The criteria for undergoing adjuvant or

(
25%) died of non-prostate cancer causes specifically myocardial infarction, chronic kidney disease, leukaemia and renal abscess.Two patients had Gleason 4 + 3, which does not fit into contemporary active surveillance guidelines.The surveillance follow-up duration was between 1 and 9 years for included patients.T A B L E 2 (Continued) as median.b Gleason score on biopsy.c Side of PLND not specified.
This case highlights the importance of prophylactic postoperative DVT F I G U R E 2 (A) Pooled analysis with random effects modeloverall survival post-transplant surgery 3 years.(B) Pooled analysis with random effects model-prostate cancer-specific survival posttransplant surgery 3 years.T A B L E 4 Included radiotherapy studies.
Pooled analysis with random effects modeloverall survival post-transplant radiation therapy 3 years.(B) Pooled analysis with random effects model-prostate cancer-specific survival post-transplant radiation therapy 3 years.
L E A 5 Further included surgery studies characteristics.

2 T
A B L E A 6 Further included radiotherapy studies characteristics.

Table A2
lists the reasons for exclusion.A total of 60 studies were included in the systematic review.

Table 4
in TableA6.There was a total of 86 post-transplant radiotherapy patients consisting of 54 external beam radiotherapy patients and 32 brachytherapy patients.The mean PSA was 11 ng/mL, and the mean patient age was 64 years.Gleason 6 patients contributed to 45% of cases, whereas Gleason 7 patients contributed to 42% of radiotherapy cases.Of the studies that listed the clinical staging, T A B L E 2 Included surgical studies.
Comparison of different radical prostatectomy approaches.
study cohort, whereas other studies reported according to specific combination therapy.Steroids were the most commonly reported immunosuppressant followed by calcineurin inhibitors.A comparison between calcineurin inhibitors versus mTOR inhibitors was unable to be conducted because of variations in immunosuppression drug reporting across all studies.T A B L E 3 Excluded studies.