The continuing conundrum of feline injection-site sarcomas

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Veterinarians would much rather talk with cat owners about all the advantages of vaccination for cats rather than the extremely rare occurrence of feline injection-site sarcomas.

Estimates suggest that the risk of sarcoma development following vaccination is well below one per 10,000 doses of vaccine, according to the 2013 vaccination guidelines from the American Association of Feline Practitioners. The problem is, as noted by Dr. Apryl Steele, 2019 AAFP president, "There are currently no known management options to prevent or cure FISS."

Nevertheless, practitioners and researchers have continued working on answers for this aggressive form of cancer ever since a 1991 letter to the editor in the JAVMA suggested a potential association between vaccination of cats for rabies and development of sarcomas. Recent studies have examined areas such as incidence, pathophysiology, diagnostic imaging, prognostic markers, and treatment.

The AAFP guidelines recommend vaccination sites low on the legs rather than in the interscapular region "to facilitate complete tumor removal by limb amputation in the event that FISS develops." University of Florida researchers published a pilot study soon afterward suggesting that administering vaccines in the distal part of the tail is as effective as administering vaccinations at traditional sites (J Feline Med Surg 2014;16:275-280).

Cat being vaccinated between shoulder blades
According to 2013 guidelines from the American Association of Feline Practitioners on vaccination of cats: "The majority of safety and efficacy data comes from licensing studies in which vaccines are administered subcutaneously in the interscapular region. Due to concerns of potential sarcoma development, practitioners may consider giving vaccines in other locations."

Per the AAFP guidelines, "FISS risk following vaccination likely results from a complex interaction of multiple extrinsic (e.g., frequency and number of vaccines administered over time, composition of the injected product, etc) and intrinsic factors (e.g., genetic predisposition, tissue response following injection, etc)." Cornell University researchers published a study in 2017 finding that a feature of FISS is DNA damage, noting that response mechanisms to DNA damage can promote resistance to chemotherapy (Vet Comp Oncol 2017;15:518-524).

Dr. Karen Stasiak, veterinary medical lead for pet care biologicals at Zoetis Inc., said of FISS, "It is the topic in veterinary medicine that evokes the strongest emotion and opinion, yet the science of it remains muddled at best, and our understanding of even the pathophysiology of the disease state still eludes us."

Dr. Stasiak earned her veterinary degree and went into small animal practice in 2001, the year that the Vaccine-Associated Feline Sarcoma Task Force issued a groundbreaking report. The AVMA, American Animal Hospital Association, AAFP, and Veterinary Cancer Society had formed the task force in 1996. The report generated more questions than answers, Dr. Stasiak said, but research carried on after the dissolution of the task force, and injection sites became standardized to facilitate tumor removal.

The concerns started out with vaccines and expanded to all injections. Trying to tease out the causality of FISS is exceedingly difficult because the incidence is so rare. Dr. Stasiak said, "I do worry that this kind of makes people phobic of injecting things into cats."

Cat illustration showing injection sites
"Current research indicates that radical surgical resection of injection-site sarcomas, including margins of 5 cm when possible, is associated with the highest response rate and long-term survival," according to the 2013 AAFP vaccination guidelines. The guidelines recommend regions in green as injection sites for cats. "Those in red are key sites that should be avoided," according to the guidelines.

According to the AAFP guidelines, initial studies suggested a risk of sarcoma development of about two per 10,000 doses of vaccine, which increased to 13-36 per 10,000 doses in other studies. Estimates based on larger epidemiologic studies published between 2002 and 2007 suggest that the risk of sarcoma development following vaccination is actually very low, well below one per 10,000 doses of vaccine.

Dr. Stasiak said one recommendation for FISS prevention is to inject cats only as necessary, whether with a vaccine or a microchip. According to the AAFP vaccination guidelines: "The veterinarian should undertake a clinical risk/benefit assessment for each animal and discuss recommended vaccination schedules with the owner so that they can make an informed choice. The assessment should include discussion on the likelihood of exposure, the health and lifestyle of the animal, and the risks related to vaccination."

Also according to the guidelines, "Although initial reports linked development of sarcomas at vaccination sites with the use of inactivated rabies or FeLV vaccines, and aluminum-based adjuvants, more recent studies found no relationship between vaccine type, brand or use of inactivated versus modified-live vaccines and the risk of subsequent sarcoma formation."

The AAFP guidelines recommend instructing cat owners to monitor vaccine sites for any swelling or lumps, Dr. Steele said. The 3-2-1 rule is to perform an incisional biopsy if a lump persists for three months or longer after an injection, ever becomes larger than 2 centimeters in diameter, or continues to increase in size one month after an injection.

Dr. Stasiak said FISS treatment causes angst because the mainstay is aggressive surgery. Surgery must be planned carefully, using imaging to understand the full extent of the sarcoma. Treatment also may include radiation and chemotherapy.

Among current research efforts, a team at the University of Illinois is studying the approach of placing beads under cats' skin to administer carboplatin to tumors but not to other parts of the body. A team at Washington State University is studying placing radioactive material directly into tumors to shrink them for easier removal by surgery.

Stepping back to look at the big picture, Dr. Stasiak said the risk of FISS does not compare with the risk of many common diseases that are mostly preventable via vaccination.

Back in 2001, the Vaccine-Associated Feline Sarcoma Task Force concluded: "Vaccine-associated feline sarcomas are a conundrum for the veterinary medical profession. We do not understand the attributes of the feline immune system and genome that make cats susceptible to VAFS, yet we must continue to vaccinate cats against key infectious diseases."

See the 2013 vaccination guidelines from the American Association of Feline Practitioners and the 2001 report of the Vaccine Associated Feline Sarcoma Task Force.

Related JAVMA content:

Tail vaccination in cats effective, eases tumor removal (Dec. 15, 2013)

AAFP releases vaccination advisory panel report (Oct. 1, 2013)