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There are many factors that influence an individual animal’s prognosis after a diagnosis of cancer. Important factors include the tumour’s histopathological type, the stage and grade of the tumour and its likely response to treatment. Some of this information comes from the pathologist or clinical pathologist, some from signalment and a good clinical examination at the time of diagnosis and some from diagnostic imaging. The prognosis for an individual case comes from interpreting these findings against the literature and understanding the limitations of the literature.
Information from the pathologist
There are over 200 different types of cancer. Identification of the tissue of origin will give a broad idea of the tumour’s likely behaviour. The most important considerations are first, whether the tumour type has the potential to spread and secondly, how locally invasive the primary tumour is likely to be. A non-invasive tumour that has a very low risk of spread, and that can be removed easily with adequate surgical margins, has the potential to be cured. At the other end of the spectrum, a tumour that is known to be poorly sensitive to cytotoxic drugs, with a high risk of metastasis, would have a guarded prognosis even if the primary tumour was resectable.
Some common tumour types have a wide range of behaviour. For those tumours, grading can greatly help with prognostication.
The National Cancer Institute defines grade as ‘the description of a tumour based on how abnormal the tumour cells and the tumour tissue look under a microscope. It is an indicator of how quickly a tumour is likely to grow and spread’.
Histopathology is usually needed for grading. Grading can only reliably be performed on a reasonably sized biopsy, as small samples tend to underestimate the grade. Grading systems are used particularly to aid decision making for canine mast cell tumours and soft tissue sarcomas where there are significant variations in aggressiveness.
However, many of the grading systems rely on criteria that are subjective, leading to significant variations in grade assigned to the same tumour by different pathologists. Recently there has been a move towards more objective measurable markers of prognosis, which are often related to cell proliferation (eg, the mitotic index [MI]).
The MI is defined as the number of mitotic figures identified per 10 high-power fields. Very broadly speaking, the higher the MI, the more concern regarding prognosis.
Table 1 shows the link between MI and prognosis for some common tumours.
Stage is an assessment of the tumour burden at the moment of examination. The World Health Organization uses the TNM system, where T refers to the primary tumour, N to the presence or absence of nodal metastatic disease and M describes the presence or otherwise of distant metastasis. Knowledge of the stage not only allows a more informed prognosis but helps with planning treatment and provides a baseline to allow response to treatment to be assessed. If a tumour has already spread, the grade of the primary tumour or the presence or absence of other predictive indicators is largely irrelevant.
Staging a tumour involves assessing the size and invasiveness of the primary tumour and looking for any evidence of the tumour elsewhere. Different tumour types spread to different organs. Staging can be undertaken via a good clinical examination but usually involves diagnostic imaging. Sometimes cytology is needed (eg, for lymph node examination).
An example of how stage informs prognosis is given in Table 2. The size and appearance of the primary tumour can give useful information. Generally, large, ulcerated, inflamed, rapidly growing, fixed masses are associated with a poorer prognosis.
The site of the tumour also has prognostic significance. For common oral tumours, the further rostral a lesion is the better. Tonsillar tumours are associated with a more guarded prognosis, regardless of histologic subtype. Cutaneous and subcutaneous mast cell tumours have a much better prognosis than visceral ones. The outcome for canine melanoma is very site dependent. Cutaneous melanomas, on the whole, have a good prognosis, with the exception of those affecting the digit. Oral melanomas have a high risk of spread, with the exception of well-differentiated, deeply pigmented tumours of the lips.
The prognosis for many cancers is heavily influenced by treatment. Untreated, high-grade B cell canine multicentric lymphoma has a survival time of a matter of weeks, whereas the majority of dogs treated with CHOP (protocols involving cyclophosphamide, vincristine, doxorubicin and prednisolone) will survive with very good quality of life for months. Broadly speaking, those cats and dogs with lymphoma that have an early complete remission to the first cycle of treatment are likely to survive longer compared to those that don't. Once out of remission, animals can be then treated with rescue protocols. Thus, the prognosis is heavily influenced by the clinician’s knowledge and the owner’s willingness to treat.
This is also relevant for tumours where surgery is the mainstay of treatment. The surgical dose can influence prognosis. On the whole, a tumour taken off with incomplete margins will have a more guarded prognosis than one taken off with wide clean margins. A good example is feline injection site sarcomas, where studies have shown that a planned, radical first excision results in a longer median survival time of 901 days compared with marginal excision, where a median time to first recurrence of just 79 days was recorded.1
It is important to provide the client with as accurate a prognosis as possible, especially since many of the treatment modalities for cancer are expensive, time consuming and have the potential to cause side effects. Some prognostic indicators are more important than others and have more robust evidence associated with them. Arguably, the most useful information is the histological type and stage for solid tumours. For ‘liquid’ tumours (ie, leukaemia and lymphoma) the sub-type, grade and then response to treatment with chemotherapy gives the most useful information.
Although useful in terms of discussing the course of disease in a population of animals, most prognostic indicators do not provide a crystal ball for each individual case. They provide guidance at best and need interpreting in the light of other prognostic indicators and concurrent disease. Every oncologist knows cases that have either a considerably worse or better outcome than would be expected, and the element of uncertainty associated with any information also needs to be clearly explained to an owner before embarking on a definitive treatment.
In this series, Vet Record publishes advice from expert veterinary professionals on how to treat common conditions. All are summaries of articles that first appeared in our sister journal In Practice. The aim is to give readers concise, up to date practical information to optimise their care of patients.
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