Staging Tests and Their Prognostic Significance in Dogs with Lymphoma
Lymphoma is one of the most common cancers in dogs, accounting for 80% or more of hematopoietic tumors and nearly a quarter of all cancer diagnoses.1 A biopsy and histopathology remain excellent ways to diagnose lymphoma, but a number of other diagnostic tests are available to establish the diagnosis including cytology, PCR for antigen receptor rearrangements, flow cytometry, and a new lymphoma-specific biomarker blood test.1
After establishing a diagnosis of cancer, the next step is to perform a litany of tests referred to as staging tests to determine the extent of the disease. Staging tests are recommended based on patterns of spread for particular cancers and typically include lab work, imaging, and collecting cytology samples from places cancer might spread (often lymph nodes or other organs).
Why Are Staging Tests Critical?
Since lymphoma is typically a systemic disease and is therefore treated with chemotherapy, the primary aim of staging tests is to document the disease present at the time of diagnosis in order to:
- Determine the most appropriate treatment options.
- Establish baseline measurements that can be re-evaluated to confirm response to treatment.
- Identify prognostic factors that may influence patient outcomes.
Staging tests also have a secondary aim—to identify comorbid conditions that might impact the patient or treatment. Examples include organ dysfunction, other cancers, and non-cancerous conditions. Organ dysfunction may influence the choice of chemotherapy drugs (e.g., kidney or liver dysfunction may increase the risks of side effects or prevent the use of some drugs). Other cancers may be more immediately life-threatening than the original cancer that was detected (e.g., an incidental invasive adrenal tumor may be more concerning than a modestly sized soft tissue sarcoma on a limb). Non-cancerous conditions might also be immediately life-threatening or may need to be treated (e.g., obstructive GI foreign bodies or cystoliths).
Staging Lymphoma in Dogs
In addition to tests to confirm the diagnosis and determine immunophenotype, complete staging tests would include complete blood count, chemistry panel (+/- ionized Ca), urinalysis, thoracic radiographs, abdominal ultrasound, cytology of the liver and spleen, and bone marrow aspirate.1,2 For very large patients, a CT scan may be used over radiographs and ultrasound.
Based on the results of these tests, the stage of lymphoma is classified according to the World Health Organization's staging system:1
|
Stage |
Substage |
||
|
I |
Involves a single lymph node |
a |
No clinical signs present (feeling good) |
|
II |
Involves regional lymph nodes (typically confined to one side of the diaphragm) |
b |
Clinical signs present (feeling sick) |
|
III |
Involves all lymph nodes (generalized) |
||
|
IV |
Involves the liver or spleen (+/- stage I, II, or III) |
||
|
V |
Involves the bone marrow, blood or non-lymphoid organs (e.g., eyes, brain, kidneys, skin, gastrointestinal tract, lungs, etc.) |
||
Significance Of Staging Tests Results in Dogs with Lymphoma
At diagnosis, most dogs are at least stage III (meaning all of their peripheral lymph nodes will be enlarged) and substage a (meaning they are not feeling sick). Dogs with stage IV, stage V, or substage b lymphoma are less likely to respond to treatment as well or as long as dogs with stage III, or substage a disease.1,3
Other negative prognostic indicators for survival include:3
- Immunophenotype (T-cell lymphomas are typically worse than B-cell lymphoma)
- Hypercalcemia (more frequent in dogs with T-cell lymphoma and substage b)
- Presence of anemia
- Presence of thrombocytopenia
- Older age at the time of diagnosis
- Higher serum globulin concentration
- Treatment with prednisone/prednisolone prior to chemotherapy
- Achieving complete remission
- Low MHC II expression (on flow cytometry)4
What Tests Should Be Performed for Dogs with Lymphoma?
A survey of veterinary oncologists reported that tests like abdominal ultrasound, bone marrow aspirate, and immunophenotyping are offered at higher rates at academic institutions compared to private practices. This may reflect different approaches related to teaching and research versus clinical practice, availability of personnel or time for diagnostics, and costs to pet owners.2 In my clinical experience in both academia and private practice, cost is a major factor in what staging tests are elected. Full staging may be important for owners who would like as much information as possible before committing to chemotherapy, but results may not change the initial recommendation for chemotherapy. Full staging tests and establishing a histologic diagnosis are most important in research evaluating treatments or trying to identify prognostic factors.
When funds are limited, the financial toxicity associated with staging tests must be considered—the costs of staging tests could prevent some owners from affording treatment. In these instances, I typically prioritize treatment over extensive diagnostics. At a minimum, I recommend a cytological diagnosis, CBC, chemistry panel, and urinalysis to screen for organ dysfunction, hypercalcemia (suggestive of T-cell immunophenotype), abnormal cells in circulation (suggestive of stage V disease), and cytopenias (suggestive of V disease) prior to chemotherapy. I also prefer to include thoracic radiographs to screen for heart enlargement (which may deter use of doxorubicin due to its cardiotoxicity), pleural effusion (which may need to be drained), and mediastinal masses (suggestive of T-cell immunophenotype).
Leveraging Staging Tests To Improve Prognosis
Staging tests are an important part of a cancer work-up that allows you to document the extent of disease present and identify prognostic factors and comorbid conditions that could impact treatment-related decisions.1,2 A number of negative prognostic factors have been identified in dogs with lymphoma, and many can be readily detected through routine lab tests and imaging used in staging.1,3,4 While no veterinarian can predict the future for an individual patient, staging tests can help guide conversations with owners about treatment-related outcomes and create realistic expectations. In many cases, owners may feel more comfortable proceeding with chemotherapy when staging tests have been performed and negative prognostic indicators are not identified.
References:
- Vail DM, Pinkerton M, Young KM. "Hematopoietic Neoplasia." Withrow and MacEwen's Small Animal Clinical Oncology 6th Edition. Edited by Vail DM, Thamm DH, Liptak JM. Elsevier, 2019, pp 688-772.
- Regan RC, Kaplan MSW, Bailey DB. Diagnostic evaluation and treatment recommendations for dogs with substage-a high-grade multicentric lymphoma: results of a survey of veterinarians. Vet Comp Oncol 2013; 11(4):287-295. doi: 10.1111/j.1476-5829.2012.00318
- Bennett P, Williamson P, Taylor R. Review of canine lymphoma treated with chemotherapy—outcomes and prognostic factors. Vet Sci 2023; 10(5):342. doi: 10.3390/vetsci10050342
- Rao S et al. Class II major histocompatibility complex expression and cell size independently predict survival in canine B-cell lymphoma. J Vet Intern Med 2011; 25(5):1097-105. doi: 10.1111/j.1939-1676.2011.0767
