Imagine this clinical scenario: you are presented with a 10-year-old neutered female cat that was brought to the clinic after her owners noticed a mass on her abdomen, but otherwise seems healthy. On examination, you identify a well-defined 4cm mildly ulcerated mass on the right inguinal mammary gland. Diagnostic tests confirm that the patient has a mammary adenocarcinoma that has spread to her inguinal lymph nodes, which you score as stage III on the modified World Health Organization (WHO) staging system. This leads to a difficult conversation with the client who wants to do everything they can to prolong their cat’s life.
You identify a staged bilateral mastectomy as the best course of action, but note that even with surgery, the prognosis and survival time could be poor. You consider using adjuvant chemotherapy and consult the evidence to find out if this could positively impact survival time.
The evidence
Five studies were found that relate to the PICO question, all of them retrospective cohort studies: De Campos et al. (2014), Gemignani et al. (2018), Ito et al. (1996), McNeill et al. (2009) and Petrucci et al. (2021).
De Campos et al. (2014) retrospectively studied the cases of 16 cats treated in a veterinary hospital. These were split into two groups: one group (nine cats) receiving a unilateral radical mastectomy and no chemotherapy, and the other group (seven cats) being treated with conventional surgical excision and four cycles of intravenous carboplatin. The primary outcome studied was the overall survival of each animal following treatment.
Gemignani et al. (2018) retrospectively studied 105 cats that underwent unilateral or bilateral mastectomy of mammary adenocarcinomas in nine veterinary hospitals in various countries. These were split into two groups: group one (52 patients) which received surgical treatment alone, and group two (53 patients) which received surgical treatment as well as adjuvant chemotherapy. The outcomes studied were progression-free survival time, disease-specific survival time and post-operative complications.
Ito et al. (1996) retrospectively studied 32 cats with malignant mammary tumours at a university veterinary hospital. These were split into two groups: group one (16 patients) was treated with surgical intervention alone, while group two (16 patients) was treated with surgery and adjuvant chemotherapy. The outcomes studied were survival time and remission length.
McNeill et al. (2009) retrospectively studied the cases of 73 cats with feline mammary carcinomas. These were split into two groups: group one (37 patients) was treated with surgery alone, while group two (36 patients) was treated with surgery and adjuvant chemotherapy. The outcomes studied were disease-free survival time and overall survival time.
Petrucci et al. (2021) retrospectively studied 137 cats with mammary carcinomas that were treated in eight veterinary teaching and private hospitals. These were split into three groups: group one (80 patients) was treated with surgical intervention only, while groups two (34 patients) and three (23 patients) were treated with both surgical intervention and chemotherapy medications. Group two was treated with doxorubicin, and group three was treated with cyclophosphamide. The outcomes studied were disease-free interval, overall survival, and toxicity and side effects of the treatment.
Limitations of the evidence
Most of the data across all five studies was taken from veterinary hospitals – including teaching hospitals – which limits the applicability of the evidence to first opinion practices
All five of the studies were limited by their retrospective nature, which meant that there was a variability in the disease stage of patients, a lack of standardisation of surgical and chemotherapeutic protocols, and the absence of placebo groups.
There were also limitations in the retrospective determination of disease-specific causes of death and survival times. For example, both Ito et al. (1996) and De Campos et al. (2016) determined the cause of death via owner phone calls.
Most of the data across all five studies was taken from veterinary hospitals – including teaching hospitals – which limits the applicability of the evidence to first opinion practices. All of the studies drew on data that was from outside of the UK, which may limit the applicability of the findings as they may not represent the UK feline population and the feline populations of other nations that aren’t represented in the data. For example, Petrucci et al. (2021) reviewed cases treated in Portugal, and McNeill et al. (2009) studied cases treated in the USA.
Summary of findings
Only one of the papers reviewed, Gemignani et al. (2018), had results that were statistically significant in comparing the use of chemotherapy versus surgery alone in cats with mammary carcinomas. This study found that the use of chemotherapy was significantly associated with prolonging disease-specific survival time, and was considered protective using a Cox multivariate analysis. However, the strength of evidence in this paper was weak, limiting the overall reliability of its findings.
Cats that underwent a radical unilateral mastectomy (rather than conventional surgical excision) and also underwent chemotherapy had significantly longer survival times than those who only had surgery
Additionally, McNeill et al. (2009) had one statistically significant finding: cats that underwent a radical unilateral mastectomy (rather than conventional surgical excision) and also underwent chemotherapy had significantly longer survival times than those who only had surgery. This paper also found that overall, the median survival time was shorter in cats that had received chemotherapy versus cats that had received surgical intervention alone. However, these results are not statistically significant.
None of the findings of the other papers reviewed had statistical significance one way or another. De Campos et al. (2014) found that the treatment group that received chemotherapy had a higher median average survival time than the treatment group that did not, but that the difference was not statistically significant. Ito et al. (1996) found that the median rate of remission and median survival time were higher in treatment groups that did not receive chemotherapy. Petrucci et al. (2021) found that cats treated with two different types of chemotherapy medication had a longer median survival time than cats treated with surgical intervention alone.
Conclusion
While one paper […] does provide statistically significant findings that suggest chemotherapy can prolong the survival rate of cats with mammary carcinoma, the strength of this evidence is poor, and its findings are not backed up by other studies
There are few studies on the use of adjuvant chemotherapy to prolong the survival time of cats with mammary carcinomas, and those that do exist don’t offer enough strength of evidence to draw any conclusion one way or another. While one paper (Gemignani et al., 2018) does provide statistically significant findings that suggest chemotherapy can prolong the survival rate of cats with mammary carcinoma, the strength of this evidence is poor, and its findings are not backed up by other studies. There is a need for further studies with a robust study design to grow the strength of evidence. Specifically, larger prospective double-blinded randomised studies would provide a high strength of evidence.
| The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence. |
Disclaimer
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise; patient’s circumstances and owner’s values; country, location or clinic where you work; the individual case in front of you; and the availability of therapies and resources.
