Transitional Cell Carcinoma: What’s new

The past few years have seen tremendous progress in the treatment of this disease and based upon some very interesting early research, the next few years look bright as well.

Transitional cell carcinomas (TCC) are the most common tumor of the urinary system in dogs. The triad of hematuria, stranguria and pollakiuria are the cardinal clinical signs associated with this tumor. It is the progression of these signs by the local tumor that causes most of the morbidity and ultimate mortality from TCCs. Metastatic disease is uncommon at presentation but becomes increasingly common as the pet lives longer. The most common metastatic sites are the iliac / sublumbar nodes, liver, lungs and vertebrae.

The advances for the treatment of TCC have been in two major areas, chemotherapy and interventional surgery.

Historically, the three most common chemotherapeutic agents used for TCCs are mitoxantrone, doxorubicin, and carboplatin. Within the past few years two others have been added to this armamentarium, vinblastine and chlorambucil. In, 2011, Arnold et al [1]published a paper showing that vinblastine was an effective agent in the treatment of TCCs in dogs. The median survival time reported was approximately 150 days with some of the dogs surviving for over 900 hundred days after diagnosis. This research and our own experience with this protocol caused some of our oncologists to switch from mitoxantrone to vinblastine as their first-line treatment for TCCs. The other major advance in medical oncology is the use of chlorambucil in the management of this disease. Unlike the prior injectable chemotherapeutics, Schrempp et al[2] used chlorambucil in a metronomic setting-daily low dose of a chemotherapeutic agent. The median survival time of dogs from the beginning of treatment was over 200 days with some dogs surviving over 700 days. As you can see, these survival times can be considerable and the addition of two new chemotherapy options is significant.

Interventional surgery, in the form of both stenting and laser ablation has given veterinarians two additional options to discuss with their clients. Stenting is a palliative procedure designed to address the local complications of TCC either in the trigone/urethra or ureters.  The placement of these stents is usually a rapid and safe procedure and is typically effective at restoring luminal patency. In addition, there were no major complications reported[3]. Quality of life is restored and pets can survive for a significant amount of time after stent placement[4]. Laser ablation therapy has already been reported both as a palliative single therapy[5] as well as in conjunction with chemotherapy[6].  Here too, survival times and quality of life can be significantly improved, with some pets living for over 1500 days.

More options are not always better options.  However, for TCCs, the four developments of vinblastine, chlorambucil, stenting and laser ablation have indeed given veterinarians both more and effective alternatives to traditional therapies.

Ultrasound image of Transitional Cell Carcinoma

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Ultrasound Image of Transitional Cell Carcinoma

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(Fluoroscopic image after urethral stent placement from  http://www.viries.org/portfolio-item/urethral-stenting-for-malignant-obstruction/)

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Submitted by Gerald Post, DVM, MEM, DACVIM (Oncology)

The Veterinary Cancer Center

References:

  1. Arnold, E.J., M.O. Childress, L.M. Fourez, K.M. Tan, J.C. Stewart, P.L. Bonney, and D.W. Knapp. “Clinical Trial of Vinblastine in Dogs with Transitional Cell Carcinoma of the Urinary Bladder.” Journal of Veterinary Internal Medicine 25, no. 6 (November 2011): 1385–90. doi:10.1111/j.1939-1676.2011.00796.x.(http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2011.00796.x/epdf)
  1. Schrempp, Diane R., Michael O. Childress, Jane C. Stewart, Tiffany N. Leach, Kean Ming Tan, Andrew H. Abbo, Amalia E. de Gortari, Patty L. Bonney, and Deborah W. Knapp. “Metronomic Administration of Chlorambucil for Treatment of Dogs with Urinary Bladder Transitional Cell Carcinoma.” Journal of the American Veterinary Medical Association 242, no. 11 (2013): 1534–38. (http://www.ncbi.nlm.nih.gov/pubmed/23683018)
  1. Weisse, Chick, Allyson Berent, Kim Todd, Craig Clifford, and Jeffrey Solomon. “Evaluation of Palliative Stenting for Management of Malignant Urethral Obstructions in Dogs.” Journal of the American Veterinary Medical Association 229, no. 2 (2006): 226–34. (http://avmajournals.avma.org/doi/abs/10.2460/javma.229.2.226).
  1. McMillan, Sarah K., Deborah W. Knapp, José A. Ramos-Vara, Patty L. Bonney, and Larry G. Adams. “Outcome of Urethral Stent Placement for Management of Urethral Obstruction Secondary to Transitional Cell Carcinoma in Dogs: 19 Cases (2007–2010).” Journal of the American Veterinary Medical Association 241, no. 12 (2012): 1627–32. (http://avmajournals.avma.org/doi/abs/10.2460/javma.241.12.1627)
  1. Cerf, Dean J., and Eric C. Lindquist. “Palliative Ultrasound-guided Endoscopic Diode Laser Ablation of Transitional Cell Carcinomas of the Lower Urinary Tract in Dogs.” Journal of the American Veterinary Medical Association 240, no. 1 (2012): 51–60. (http://avmajournals.avma.org/doi/abs/10.2460/javma.240.1.51)
  1. Upton, Melinda L., C. H. Tangner, and Mark E. Payton. “Evaluation of Carbon Dioxide Laser Ablation Combined with Mitoxantrone and Piroxicam Treatment in Dogs with Transitional Cell Carcinoma.” Journal of the American Veterinary Medical Association 228, no. 4 (2006): 549–52. (http://avmajournals.avma.org/doi/abs/10.2460/javma.228.4.549)

 

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