Page 114 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 4 Epidemiology and the Evidence-Based Medicine Approach 93

A number of reports have linked the age of dogs at the time development, and coinfection with FIV and FeLV may have
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of neuter/spay to increased risk of developing hemangiosarcoma, synergistic effects on feline neoplasia risk.
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79–81
lymphoma, and MCTs in select breeds of dogs.
Using a retro-
VetBooks.ir spective analysis of medical records including dogs younger than Diagnosis and Screening
8 years of age from the Veterinary Medical Teaching Hospital at
the University of California, Davis, an increased risk of develop- As mentioned previously, numerous reporting guidelines have
ing hemangiosarcoma and MCTs was identified in female golden been produced for the human medical literature (e.g., http://meth-
retrievers neutered at 12 months of age or older compared with ods.cochrane.org/mecir). One of these describes an approach to
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intact female golden retrievers. The same analysis revealed an complete and accurate reporting of studies of diagnostic accuracy
increased risk of developing lymphoma in male golden retriev- (Standards for Reporting of Diagnostic Accuracy [STARD]). 97,98
ers neutered before 12 months of age compared with intact male The application of this and another instrument in the veterinary
99
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golden retrievers. A subsequent report that used a larger data set field has been discussed. Unfortunately, relatively few diagnos-
from the same location reported similar risks in golden retrievers, tic interventions in veterinary medicine have been examined or
but showed there was no difference in risk of cancer occurrence evaluated as fully, in terms of reliability, accuracy, efficacy, and
in Labrador retrievers associated with neuter status. Research effectiveness, as is needed to support EBM practices. Guidelines
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from the same institution that examined cancer-related mortality for prognostic studies in veterinary oncology have also been
in golden retrievers found that increasing age increased the odds reported. 100
of cancer-related mortality regardless of neuter status. Neutered It may also be appropriate to use clinical trial methodology to
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female golden retrievers were found to live statistically signifi- evaluate the outcomes of diagnostic tests, for example, whether
cantly longer than intact females and it was this increase in lon- the animal is better off for having had the test performed. 101 In
gevity that affected the rate of cancer occurrence rather than the addition, recommendations about diagnostic tests and screening
hormonal differences caused by neutering. This conflicting result programs may have both positive and negative effects beyond any
may be because of the fact that dogs of any age were included individual, on populations of animals and owners. Although new,
in this study whereas the previous reports limited results to dogs sophisticated diagnostic tests used in humans are being evaluated
aged 8 years or younger. 79,81,88 Results of a survey of Vizsla owners for use in companion animals, it is important to remember that
indicate that neutering at any age was associated with increased beyond the benefit in a specific case, efficacy and effectiveness
risk of developing lymphoma and MCTs regardless of sex. of tests should consider the broadest aspects of cost–benefit. In
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Increased risk associated with development of hemangiosarcoma human oncology, there has been much discussion about the prob-
was also indicated in both sexes regardless of the timing of neuter- lems inherent in certain widely applied screening processes and
ing with the exception of males neutered at less than 12 months of the consequences of false positives and negatives (e.g., prostate-
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age, which had no difference in risk compared with intact males. specific antigen test for prostate cancer 102 ). Owing to space con-
Prospective research conducted to examine associations between straints, we cannot expand on this crucially important area of
age at neutering and cancer outcomes is needed in a wider variety cancer epidemiology.
of dog breeds before current recommendations regarding spay/
neuter can be modified. Therapeutic Interventions
Risk Factors in Cats A review published in the Journal of Veterinary Internal Medicine
In cats, the epidemiology of injection-site sarcomas has been well highlighted that the quality of reporting of oncology studies in
studied. A review from 2011 provides information on the current dogs and cats has not improved appreciably over time and that
epidemiology, etiology, and clinical knowledge of feline injection- quality of reporting is highly correlated with the rate of positive
site sarcomas (FISSs). Kass et al conducted one of the first epi- outcomes (i.e., well-described studies are more likely to report
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demiologic studies investigating the hypothesis that vaccinations positive effects of a treatment). 103 This may also be exacerbated
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were related to feline fibrosarcoma risk in the early 1990s. A by the fact that the profession increasingly depends on corporate
main finding of this study was the shorter time interval from vac- contracts for funding of research, and, in addition to this having a
cination to FISS compared with the interval from vaccination to major effects on which treatments are investigated, there may also
non-FISSs. This finding was not supported by a second, larger be underreporting of studies in which either beneficial effects were
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case-control study. Although there is no doubt that the phenom- not seen or where there were deleterious side effects. As mentioned
enon of FISS exists, the administration of an injection itself is not previously, efforts are underway to produce reporting guidelines
sufficient to cause development of an FISS. The component causes for companion animal intervention studies. However, guidelines
(e.g., the nature of vaccines and adjuvants in the injected mate- for appropriate study design for clinical trials have been widely
rial and the role of the resulting inflammatory reaction), in addi- available for many decades, and the need for appropriate trials
tion to the physical injection that leads to the development of an in oncology has been specifically advocated (see Chapter 18). 104
FISS, are not well characterized. Further epidemiologic research Longer-term analyses of survival after diagnosis and treatment,
designed with due consideration of the challenging methodologi- including both outcome and cost–benefit analysis, are needed to
cal issues is needed to identify the various factors associated with provide the information that owners and veterinarians need to
FISSs. 92 choose the best options, with due consideration of quality-of-life
Cats infected with the feline immunodeficiency virus (FIV), issues.
the feline analog to the human immunodeficiency virus (HIV), Although there are good examples of randomized, controlled,
are at increased risk of certain cancers. FIV is a lentivirus typi- blinded trials in veterinary oncology, 105,106 essentially all studies have
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cally transmitted by biting. Lymphomas, particularly those some limitations in terms of either quality (validity) or relevance
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of B-cell origin, are the most commonly diagnosed neoplasia (extrapolation to other situations). For example, because many trials
among FIV-infected cats. Persistent feline leukemia virus (FeLV) are performed on clients at specialty practices or veterinary teach-
infection is also known to have a strong role in feline neoplasia ing hospitals, animals have passed through numerous filters to be