Within urology, kidney transplantation is an established standard of care. Few reports of penile transplantation exist. However, complete human urinary bladder transplantation has not been reported clinically to date. Transplantation of an analogous organ, the uterus, has been performed for primary uterine infertility, with successful live births. Bladder replacement using the patient’s bowel is an established standard of care with a long track record, yet it is not without risks. These include, but are not limited to, reoperation for bowel/urinary leaks; electrolyte, nutritional, and metabolic derangements; weight loss; gastrointestinal dysfunction; urinary tract infections; and stone formation. Reported 90-day readmission rates following cystectomy and urinary diversion are 40% or higher. Bladder transplantation, if technically feasible, and in the highly selected patient, could provide a more normal-looking reservoir while evading some of these issues.

At the 2023 AUA Annual Meeting in Chicago, we presented a video titled “Robotic Bladder Auto-transplantation in a Brain-dead Heart-beating Deceased Donor” and a podium presentation detailing our team’s preclinical work in preparation for a UNOS (United Network for Organ Sharing)–approved “first-in-human” bladder transplant trial. Through preclinical studies spanning over 2 years, using animal and perfused cadaver models and ultimately brain-dead, heart-beating human research donors, we developed robotic bladder transplantation. This included robotic recovery of the vascularized composite bladder allograft, back-table vascular reconstruction, robotic vascular reanastomosis, and auto-transplantation. Direct visual inspection in these studies revealed a healthy, well-perfused bladder after transplantation, with strong uptake of indocyanine green immunofluorescence (see Figure).

Figure. Evaluation of a vascularized composite bladder allograft after auto-transplantation. Vascular viability is demonstrated through (A) direct robotic visual inspection, and (B) indocyanine green immunofluorescence.

To be sure, bladder transplantation brings its own set of issues, which will need to be addressed:

1. Broad application to the entire population of bladder cancer patients requiring cystectomy is a nonstarter due to the need for de novo immunosuppression posttransplantation.
2. The denervated bladder will serve as a urinary storage vessel and is not likely to have any contractile function. If the initial trial is successful, future studies would be focused on methods to restore emptying function of the transplanted bladder.
3. In the brain-dead heart-beating human research donor model, only immediate vascular perfusion can be assessed. Given the sensitivities around donor family informed consent, the longest time interval we were able to study in a brain-dead human research donor was 12 hours after auto-transplantation.
4. The inherent immunogenicity and immunological burden of the native bladder is not well understood. Based on multidisciplinary discussions, standard triple-therapy immunosuppression, such as that employed after uterine transplantation, will be utilized in the inaugural case. Any impact of rejection episode(s) on ultimate bladder capacity is uncertain. Protocol cystoscopy and biopsies will be obtained as part of our research protocol.
5. In the candidate patient with a benign etiology for their terminal bladder, it is unclear if the disease initially causing the cystopathy would return. After kidney transplantation, certain disease states can recur in the allograft. Though less likely given the paucity of known medical diseases that cause end-stage bladders, disease recurrence would need to be kept in mind.

At this time, only a highly selected set of patients, who are fully informed about the pros and cons, might be considered as potential candidates who may benefit more from a bladder transplant than the standard bowel-based urinary reconstruction. Initially, suitable candidates would be those with an end-stage bladder, in whom immunosuppression is already preexisting or imminent. The ideal inaugural patient would be one with end-stage renal disease secondary to bladder dysfunction, who is awaiting kidney transplantation wherein the bladder transplant would be performed concomitantly. Another scenario would be a patient with a preexisting functioning solid organ transplant who develops a terminal bladder from a benign etiology (neurogenic or chronic inflammatory). Finally, a functioning posttransplant patient currently on immunosuppression who has subsequently developed organ-confined bladder cancer could be considered.

We have opened a phase 0 clinical trial to determine the feasibility of bladder transplantation under a UNOS-approved Genitourinary Vascularized Composite Bladder Allograft Transplantation (NCT No. 05462561). If successful, bladder transplantation may offer a highly select population an alternative option to standard urinary diversion that more closely mimics the normal anatomy for urinary storage.