Bladder and Urethral Cancer - Any New Ideas?
World Small Animal Veterinary Association World Congress Proceedings, 2011
Nicholas Bacon, MA, VetMB, CertVR, CertSAS, DECVS, DACVS, MRCVS
College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

Most urinary neoplasia is epithelial in origin and displays aggressive malignant behaviour. The majority of tumours are transitional cell carcinoma (TCC) and these typically present due to stranguria or urinary obstruction due to advanced tumor stage, late in the course of the disease. In the bladder, surgery is the only treatment that offers a potential cure, provided the neoplasm can be completely excised and metastasis has not occurred.

A large volume of bladder (commonly reported to be 70%) can be resected with no lasting effect on urinary storage and voiding. It is common however for the animal to have transient urinary incontinence following large partial cystectomies. This should not need treating and tends to improve over a few weeks. When the tumour is surrounding one or both ureteric openings and the rest of the bladder mucosa appears unaffected, then vesico-ureteric resection and neoureterostomy can be performed. The terminal ureter/s is resected with at least 1–2 cm of palpably normal margin, and re-implanted in a grossly normal area, usually the bladder apex. The dogs are monitoring by ultrasound initially every month for signs of hydronephrosis and tumour recurrence, and after 3 rechecks, this can become every 3 months.

Total cystectomy, partial urethrectomy, and ureter re-implantation into the vaginal remnant is possible for advanced diffuse cases of bladder neoplasia. Technically very demanding to achieve clean tumour free margins and ensure ureteric patency, the unavoidable complication is urinary incontinence. Techniques of total cystectomy and prostatectomy also exist with re-implantation of the ureters into the urethral remnant, or the prepuce.

A technique for resection of the trigone and cranial urethra has recently been described in two dogs (Saulnier-Troff, et al., Veterinary Surgery, 2008), one with TCC, one with rhabdomyosarcoma. The technique involved elevating the serosa off the bladder neck and with it preserving the vascular supply of the caudal vesical artery and the nervous plexus to the bladder and urethral remnant, and then circumferentially resecting en bloc the bladder neck and proximal urethra. This is clearly a technically advanced procedure and cannot be recommended as a treatment option until more than 2 cases are described unless no other options exist to the owner. It clearly caries high risks of local recurrence, bladder necrosis and urinary incontinence.

Surgical options for urethral neoplasia depend entirely on case selection and presentation. Diffuse disease extending from the urethral papilla through to the trigone are not surgical candidates. Options for localized small volume disease include:

Caudal:

 Vagino-urethroplasty. Following a pubic symphysiotomy, the caudal urethra is resected and re-anastomosed (end-to-side) to the vagina.

 Urethral pull-through. Similar in concept to a rectal pull-through. Following an episiotomy, the vaginal wall is incised circumferentially around the papilla and the terminal urethra tractioned caudally, and repaired mucosa-mucosa.

 Urethral resection; plus prepubic urethrostomy.

Central:

 Partial urethrectomy. End-to-end anastomosis.

 Urethral repair. Autogenous sublingual mucosal free graft recently described in experimental dogs as pre-clinical study for urethral defects in humans. Free mucosal graft inverted and sutured into a tube, and placed across the urethral defect.

Diffuse:

 Trans-urethral resection (TUR). Adapted from the treatment for BPH in men. A TUR device is inserted into the urethra and diffuse proliferative neoplastic tissue is shaved off the walls. Risks include full thickness urethral tears/perforations. Only been described in one case series.

 Tube cystostomy. Foley or low-profile catheter inserted at laparotomy for bladder decompression. Is a treatment option for any level of urethral obstruction. Is fast and easy to insert, suitable for both cats and dogs, and is remarkably well tolerated.

Radiation

Radiation therapy (XRT) as a treatment option for lower urinary tract carcinomas poses several unique challenges, including the difficulty in tumor localization and the proximity of the tumor to dose limiting structures such as the ureters and colon. Complications of therapy include cystitis and fibrosis as well as irritation to surrounding organs. These sequelae can significantly detract from the patients' quality of life and successful use of XRT for the treatment of canine carcinoma requires careful delivery of the radiation dose.

To date, two different methods of delivering the prescribed radiation dose have been described; intra-operative radiotherapy (IORT), in which the bladder and/or prostate is exteriorized and single large doses (10–40 Gy) are given; or fractionated treatments where multiple smaller doses (3–5.75 Gy) in 6 to 12 fractions are given to total doses of 30–48 Gy. These studies have shown tumor responses, but treatment-related toxicity including colon perforation and stenosis of the ureters has been reported with IORT. New applications of stereotactic radiosurgery (SRS) currently under investigation at the University of Florida include the treatment of urethral TCC. CT in conjunction with SRS allows precise lesion localization followed by a highly conformal dose delivery to the tumor with minimal exposure to surrounding tissues. Our group is currently targeting urethral tumors and to date 10 female dogs with urethral TCC have been treated with promising results - most dogs are dying of tumour growth outside the radiation field, or distant metastasis. Obstruction was relieved in all dogs. It is important to note that SRS, like any radiation, is a local treatment, and so patients will require systemic chemotherapy, for example mitoxantrone q3 weeks and a daily COX-2 inhibitor (piroxicam, meloxicam). The goal of SRS, fundamentally, is to offer local disease control in the urethra and move the emphasis of survival onto the chemotherapy.

Interventional Oncology

Palliative urethral stenting offers relief to dogs with urinary obstruction due to neoplastic infiltrative disease. It does not address local disease as such, only the symptoms, and the gold-standard therapies for urethral neoplasia should still be discussed, including systemic chemotherapy. The stents used commonly are self-expanding and made of nitinol (VetStent - Urethra, Infiniti Medical) and are laser cut from a single piece of material. Deployment requires fluoroscopic imaging to ensure accurate positioning, as in contrast to the tracheal stents which can be re-constrained mid deployment if the position is sub-optimal and the stent re-positioned, once deployment has started with a urethral stent it cannot be reversed.

Recently intra-arterial chemotherapy has been described for management of bladder and prostate tumours in dogs (Weisse et al., 2008). The advantage of intra-arterial delivery of chemotherapy is that by carefully selecting a major contributing artery to the tumour, the drug is delivered at a high dose to the target tissue, without the dilutional effect of intravenous administration, which is followed by cardiac, then pulmonary bed, then cardiac, then arterial dispersion before reaching the tumour. All data for this procedure are immature. Numbers of dogs treated are small, and through case-selection, many had failed conventional intravenous chemotherapy, further worsening likely outcome and response. The potential however is high and it offers a minimally invasive therapy for unresectable bladder, urethral or prostate cancer.

  

Speaker Information
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Nicholas Bacon, MA, VetMB, CertVR, CertSAS, DECVS, DACVS, MRCVS
College of Veterinary Medicine
University of Florida
Gainesville, FL, USA


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