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Article of the week: Prostate cancer in kidney transplant recipients – a nationwide register study

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is an editorial written by a prominent member of the urological community and a video produced by the authors. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Prostate cancer in kidney transplant recipients – a nationwide register study

Ola Bratt*, Linda Drevin, Karl-Göran Prütz§, Stefan Carlsson, Lars Wennberg** and Pär Stattin††

*Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, Gothenburg University, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Regional Cancer Centre, Uppsala-Orebro, Uppsala, §Swedish Renal Registry, Ryhov Hospital, Jönköping, Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, **Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, and ††Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

Abstract

Objective

To investigate whether post‐transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients.

Patients and Methods

We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998–2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case‐control study was designed to compare time period and risk category‐specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher’s exact test were used and 95% confidence intervals (CIs) calculated.

Prostate cancer‐specific and overall survival for all 133 Swedish men who were diagnosed with prostate cancer after kidney transplantation between 1998 and 2016, and a control group of 665 men with prostate cancer without a kidney transplant, matched for age, year of prostate cancer diagnosis, educational duration, and county of residence. The curves were constructed with the Kaplan–Meier method. There was no evidence for a difference in cancer‐specific survival (log‐rank test: P = 0.37), but overall survival was shorter (log‐rank test: P = 0.003). KT, kidney transplantation; PC, prostate cancer.

Results

Almost half of the 133 kidney transplantation recipients were transplanted before the mid‐1990s, when PSA testing became common. The transplant recipients were not more likely than age‐matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70–0.99) or high‐risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62–1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer‐specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant.

Conclusions

This Swedish nationwide, register‐based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low‐grade prostate cancer can be accepted for transplantation.

Editorial: Prostate cancer and kidney transplantation – exclusion or co‐existence?

Untreated prostate cancer is generally a contraindication to kidney transplantation. At our institution in Boston, we are often referred individuals with low‐volume low‐risk prostate cancer for treatment. For a cancer that would otherwise be managed with active surveillance, these kidney transplantation candidates will often be forced into some form of definitive therapy, generally radical prostatectomy, a procedure with a well‐known long‐term side‐effect profile, and then have to wait for a period of time, generally 2 years, before being considered for transplantation. The basis for this approach stems from the theoretical higher risk of disease progression and ultimately mortality on immunosuppression. In this issue of the BJU International, Bratt et al. [1] challenge these assumptions and report on the outcomes of kidney transplant recipients diagnosed with prostate cancer. First, they found no difference in prostate cancer incidence, suggesting that transplant recipients, despite being immunosuppressed, are not at higher risk of prostate cancer. Second, they found that the prostate cancer characteristics at diagnosis, overall and prostate cancer‐specific survival of kidney transplant recipients do not differ significantly from non‐transplant patients. Furthermore, the probability of developing advanced prostate cancer over time was not higher among transplant recipients on immunosuppression. Taken together, these findings show that transplant patients are not at a higher risk of poor prostate cancer outcomes.

Hypothesising that many of the transplant recipients in this study already had prostate cancer when they underwent transplantation (based on assumptions about cancer screening practices in Sweden and the time periods included), the authors aim to refute current transplantation guidelines contraindicating solid organ transplantation in those with a history of prostate cancer and requiring a minimum recurrence‐free period before placing these patients on the organ waiting list [23]. The findings of Bratt et al. [1] corroborate previous case series including the largest study of cancer incidence among transplant recipients and a meta‐analysis of six studies. Given the available data, is it still justifiable to deny patients with low‐risk prostate cancer life‐saving kidney transplantation? If the answer is ‘no’, what would be fair cutoffs in Gleason score, number of positive biopsy cores, PSA level, time from diagnosis, etc.? While this study does not definitely answer the question, it would seem reasonable that candidates for active surveillance, especially those with very low‐risk prostate cancer, should be eligible for kidney transplantation without prior definitive therapy. Denying immediate placement on the waiting list represents not only a significant reduction of quality of life, but also leads to reduced survival due to longer dialysis time.

Another concern often heard from those in favour of definitive therapy before transplantation is the added risks of prostatectomy in immunosuppressed individuals; this is understandable given that the incidence of definitive therapy on active surveillance is ~50% at 10 years after diagnosis [4]. However, the available data suggest that prostatectomy after transplantation is safe. For example, in a recent systematic review, only one of 35 patients had a Clavien ≥ 3 complication and graft function was maintained in all patients [5]

To summarise, this study [1], and others before that, suggests that immunosuppression after kidney transplantation is unlikely to adversely affect prostate cancer initiation or progression. Men with low‐risk prostate cancer should be considered for transplantation without first undergoing definitive therapy. There is evidence around the world, and at our institution, that transplant specialists are finally starting to accept this pathway. This study will further reinforce this concept.

by Lorine Haeuser, David‐Dan Nguyen Quoc‐Dien Trinh

References

  1. Bratt O, Drevin L, Prütz K‐G, Carlsson S, Wennberg L, Stattin P. Prostate cancer in kidney transplant recipients – a nationwide register study. BJU Int 2020; 125: 679– 85
  2. Murray KF, Carithers RL. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 2005; 41: 1407– 32
  3. Oechslin E, Kiowski W, Schneider J, Follath F, Turina M, Gallino A. Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation. Ann Oncol 1996; 7: 1059– 63
  4. Tosoian JJ, Mamawala M, Epstein JI et al. Intermediate and longer‐term outcomes from a prospective active‐surveillance program for favorable‐risk prostate cancer. J Clin Oncol 2015; 33: 3379– 85
  5. Zeng J, Christiansen A, Pooli A, Qiu F, LaGrange CA. Safety and clinical outcomes of robot‐assisted radical prostatectomy in kidney transplant patients: a systematic review. J Endourol 2018; 32: 935– 43

Video: Prostate cancer in kidney transplant recipients – a nationwide register study

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Prostate cancer in kidney transplant recipients – a nationwide register study

Abstract

Objective

To investigate whether post‐transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients.

Patients and Methods

We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998–2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case‐control study was designed to compare time period and risk category‐specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher’s exact test were used and 95% confidence intervals (CIs) calculated.

Results

Almost half of the 133 kidney transplantation recipients were transplanted before the mid‐1990s, when PSA testing became common. The transplant recipients were not more likely than age‐matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70–0.99) or high‐risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62–1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer‐specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant.

Conclusions

This Swedish nationwide, register‐based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low‐grade prostate cancer can be accepted for transplantation.

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