Oncological diagnostics and screening tests: What's the evidence?

By Erica Tramuta-Drobnis, VMD, MPH, CPH

If only we could detect cancer before it becomes clinical in all patients, wouldn't that be fabulous?

Let's use the example of a hemoabdomen in a large to giant breed dog that has collapsed and is pale and weak: a classic presentation for an emergency visit. The dog presents as tachycardic, with pale to muddy oral mucous membranes, poor pulses, and with or without an obvious fluid wave in the abdomen. Abdominocentesis finds frank blood, and a splenic mass is identified on point-of-care ultrasound (POCUS). Wouldn't it be fantastic if a simple blood test with excellent specificity and sensitivity could screen at-risk dogs for this condition as they age, before the acute bleed occurs? What about breeds at risk for lymphoma, mast cell tumors, and other commonly seen neoplasias? Can they be identified before the dog presents with grave clinical signs?

Possible diagnostics for cancer screening

New cancer screening methods have the potential to greatly benefit animals, improve the diagnostic capabilities of the humans who take care of them, as well as clinical outcomes. Emerging methods include:

1. Liquid biopsies. These are primarily blood or urine-based assays that identify cancer-related biomarkers or genetic alterations in an animal's blood. However, to date, these tests are not standardized and should be confirmed with tissue-based samples.^1–6 Further, these tests have variable sensitivity and specificity, making their validity and utility questionable at best, based on current evidence and available diagnostics.
2. Molecular diagnostics. Some examples are next-generation sequencing [NGS], a form of DNA/RNA sequencing that detects mutations or variations that suggest the presence of cancer.^6,7 (e.g. BRAF mutations found in urine samples of those with bladder tumors^8,9)
3. Nematode Scent Detection Test (NSDT) via Caenorhabditis elegans. Several pilot and early studies in humans and very early studies in animals suggest the chemotactic analysis of urine samples via this nematode can detect certain cancers based on olfactory detection of volatile organic compounds (VOCs) within the urine.^10–17 In people, research has evaluated prostate, mammary, and pancreatic cancers, among others.

   Evaluations in dogs have suggested effectiveness in correctly identifying animals with mast cells, hemangiosarcoma, lymphoma, melanoma, and soft tissue sarcomas. However, the study design, inclusion/exclusion criteria, grade of evidence, and study publication location are of low grade and thus require further evaluation. This test may provide a cost-effective screening modality for those at risk of cancer in the future.

4. Urine VOCs detection. VOCs are being further researched for use via canine scent detection, gas chromatography, or other modalities not associated with a nematode.^18–20
5. Nu.Q Vet Cancer Test. This in-house diagnostic test uses a blood sample. Early research suggests it can evaluate concentrations of canine plasma nucleosomes via antibodies specifically designed for nucleosomes. Initial research has shown evidence suggesting early diagnosis of lymphoma and hemangiosarcoma may be possible.

   Current company research is evaluating other cancers, including mast cell tumors. Elevated cell death, which increases the presence of plasma nucleosomes, may indicate neoplasia, and a positive result indicates further testing is warranted.^21–23 The initial report's sensitivity rates suggested a sensitivity of 49.8 percent for cancer findings in all dogs and a specificity level of 97 percent. However, mast cell tumors, osteosarcomas, and soft tissue sarcomas were the least likely to be identified, but often of key concern.^24,25

   To date, additional supporting literature and research not affiliated with the founding company is warranted.^22,23 Studies in humans suggest that nucleosomes may be used in cancer identification; thus, it is reasonable to assume that this diagnostic may ultimately benefit animals.

Diagnostic aids to help in grading, staging, and therapeutic planning, once neoplasia has definitively been identified, include:

1. Advanced imaging, including those using AI-enhanced imaging (e.g. MRI, CT, and PET scans).^6,26,27
2. Precision veterinary medicine techniques, including:^6,28,29
   1. SearchLight DNA™. This is a tumor genetic diagnostic test that utilizes predictive biomarkers to aid in treatment and prognosis guidance. This diagnostic test evaluates for 120 genetic mutations within the animal's DNA and then recommends therapy based on the genetic findings.^6,30–32 The significance of all 120 mutations is still not fully understood. Independent research validating the utility of this test is still ongoing, and additional information is warranted.
   2. FidoCure® identifies numerous mutations within a tissue sample of a cancerous lesion. A veterinarian submits a cancerous tissue sample, and the company develops a DNA report personalized to that patient's tumor, identifying any key genetic mutations that may impact treatment modalities. Then they assist in prescribing or recommending oral therapies for at-home administration.^33–35 However, additional mutations may be identified in addition to known cancer mutations that can help guide evidence-based therapeutic practices. To date, no further information has been gleaned. Additional studies are warranted.
3. Personalized Prediction Profiles (PPP). This utilizes artificial intelligence modalities to enhance therapy (e.g. ImpriMed™, which was the first available option).^36–39 This, too, is a form of precision veterinary medicine, also known as "functional" precision medicine.⁴⁰ This program aims to enhance treatment protocols based on pre-established evidence-based practices using AI learning and methodologies. Additional high-quality independent research studies, with publications in highly reputable journals, are justified.
   

What's the evidence?

Can or should minimally invasive or noninvasive methods be routinely used to identify neoplasias in time to treat and even cure patients before they reach critical or terminal states? Novel diagnostics are becoming more visible in the veterinary field. However, is there sufficient evidence to support current or soon-to-be-released diagnostics and screening tests touted as lifesaving to employ them confidently in practice?

A commonly promoted concept in human medicine is "precision medicine," which uses lifestyle, environmental factors, and genetics to personalize care. The goal of many of the diagnostics being developed in veterinary medicine revolves around this concept. However, precision medicine focuses on the gene side while considering environmental and lifestyle factors.^41,42

Currently, most uses of precision medicine in veterinary medicine are more targeted toward treatment as part of a multi-modal approach.⁴⁰ Still, the use of genetics in early cancer diagnosis is promising, and research is ongoing in veterinary and human medicine. Additional work in this field is merited. In addition, research and refinements in techniques must continue in the currently available methods and programs to improve the sensitivity and specificity of various tests.

Knowledge gaps and uncertainty

Research in cats and other species is very limited. To fill the gaps, further research to evaluate non-invasive diagnostic means in other species is warranted. Studies in other species must be vigorous, generalizable, and well-designed.

Unfortunately, much of the current body of evidence (including that utilized in this article) that supports newer screening and diagnostic tools appears in journals with questionable publication practices. The fact the bulk of supporting evidence for these cancer screening tests appears in such predatory journals, in addition to small sample sizes, retrospective studies, a lack of comparable studies, and a lack of independent research, is a concern. Nevertheless, further research is justified to support or refute accuracy claims and to provide recommendations that can be adopted in practice.

Take-home points

Human studies and some early animal research suggest liquid biopsies (blood samples with genetic markers, biomarker evaluation, or related tests) could be utilized for early cancer detection, but only in combination with physical exams, routine diagnostics, and medical history and findings. Further research is paramount to ensure the sensitivity and specificity of these tests and to confirm that such tests do not simply create undue stress in pet-parents by screening for mutations and other parameters that are not understood and cannot be reliably interpreted and translated into clinical practice.

While some of the aforementioned screening and diagnostic/precision medicine modalities have variable degrees of evidence supporting use, if a clinician chooses to adopt these types of diagnostics, clients should be informed they are not the only means of diagnostics or treatment, and they are not necessarily reliable. If employed, these tests should be used as part of a multimodal toolset in diagnosing and treating cancer. Clinicians should be aware clients may start asking for these screening tests. They should be knowledgeable about their pros and cons before offering them, and consultation with outside experts (e.g. oncologists) may be advisable.

Erica Tramuta-Drobnis, VMD, MPH, CPH, is the CEO and founder of ELTD One Health Consulting, LLC. Dr. Tramuta-Drobnis works as a public health professional, emergency veterinarian, freelance writer, consultant, and researcher. She is a member of the Evidence-Based Veterinary Medical Association (EBVMA). For information about the association or to join, visit the EBVMA website. While all articles are reviewed for content, the opinions and conclusions of the author(s) do not necessarily reflect the views of the EBVMA or Veterinary Practice News.

References

1. O'Kell AL, Lytle KM, Cohen TA, et al. Clinical experience with next-generation sequening–based liquid biopsy testing for cancer detection in dogs: a review of 1,500 consecutive clinical cases. Published online June 1, 2023. doi:10.2460/javma.22.11.0526
2. Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238. doi:10.1038/nrc.2017.7
3. Chibuk J, Flory A, Kruglyak KM, et al. Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs. Front Vet Sci. 2021;8. doi:10.3389/fvets.2021.664718
4. Flory A, McLennan L, Peet B, et al. Cancer detection in clinical practice and using blood-based liquid biopsy: A retrospective audit of over 350 dogs. J Vet Intern Med. 2023;37(1):258-267. doi:10.1111/jvim.16616
5. Flory A, Kruglyak KM, Tynan JA, et al. Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study. PLOS ONE. 2022;17(4):e0266623. doi:10.1371/journal.pone.0266623
6. Burgess K. Veterinary Oncology Diagnostic Testing: Advances and Clinical Applications. MSPCA-Angell. June 2024. Accessed April 25, 2025. https://www.mspca.org/angell_services/veterinary-oncology-diagnostic-testing-advances-and-clinical-applications/
7. Qin D. Next-generation sequencing and its clinical application. Cancer Biol Med. 2019;16(1):4-10. doi:10.20892/j.issn.2095-3941.2018.0055
8. Decker B, Parker HG, Dhawan D, et al. Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test. Mol Cancer Res. 2015;13(6):993-1002. doi:10.1158/1541-7786.MCR-14-0689
9. Kehl A, Aupperle-Lellbach H, de Brot S, van der Weyden L. Review of Molecular Technologies for Investigating Canine Cancer. Animals. 2024;14(5):769. doi:10.3390/ani14050769
10. Hirotsu T, Sonoda H, Uozumi T, et al. A highly accurate inclusive cancer screening test using Caenorhabditis elegans scent detection. PloS One. 2015;10(3):e0118699. doi:10.1371/journal.pone.0118699
11. Namgong C, Kim JH, Lee MH, Midkiff D. Non-invasive cancer detection in canine urine through Caenorhabditis elegans chemotaxis. Front Vet Sci. 2022;9. doi:10.3389/fvets.2022.932474
12. Lanza E, Di Rocco M, Schwartz S, et al. C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples. Sci Rep. 2021;11(1):17133. doi:10.1038/s41598-021-96613-z
13. Thompson M, Sarabia Feria N, Yoshioka A, et al. A Caenorhabditis elegans behavioral assay distinguishes early stage prostate cancer patient urine from controls. Biol Open. 2021;10(3):bio057398. doi:10.1242/bio.057398
14. Ueda Y, Kawamoto K, Konno M, et al. Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice. Oncotarget. 2019;10(52):5412-5418. doi:10.18632/oncotarget.27124
15. Sugimoto T, Okuda Y, Shima A, et al. A new detection method for canine and feline cancer using the olfactory system of nematodes. Biochem Biophys Rep. 2022;32:101332. doi:10.1016/j.bbrep.2022.101332
16. Asai A, Konno M, Ozaki M, et al. Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer. Oncotarget. 2021;12(17):1687-1696. doi:10.18632/oncotarget.28035
17. Kusumoto H, Tashiro K, Shimaoka S, et al. Efficiency of Gastrointestinal Cancer Detection by Nematode-NOSE (N-NOSE). In Vivo. 2020;34(1):73-80. doi:10.21873/invivo.11747
18. Suthat Na Ayutaya V, Tantisatirapoon C, Aekgawong S, Anakkamatee W, Danjittrong T, Kreepala C. Urinary cancer detection by the target urine volatile organic compounds biosensor platform. Sci Rep. 2024;14(1):3551. doi:10.1038/s41598-024-54138-1
19. Matsumura K, Opiekun M, Oka H, et al. Urinary volatile compounds as biomarkers for lung cancer: a proof of principle study using odor signatures in mouse models of lung cancer. PloS One. 2010;5(1):e8819. doi:10.1371/journal.pone.0008819
20. Silva CL, Passos M, Câmara JS. Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry. Br J Cancer. 2011;105(12):1894-1904. doi:10.1038/bjc.2011.437
21. Volition. Nu.Q Vet. Volition. 2025. Accessed April 26, 2025. https://volition.com/nu-q-vet/
22. Bremer HD, Lattwein E, Renneker S, Lilliehöök I, Rönnelid J, Hansson-Hamlin H. Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay. Vet Immunol Immunopathol. 2015;168(3):233-241. doi:10.1016/j.vetimm.2015.10.002
23. Rahier JF, Druez A, Faugeras L, et al. Circulating nucleosomes as new blood-based biomarkers for detection of colorectal cancer. Clin Epigenetics. 2017;9(1):53. doi:10.1186/s13148-017-0351-5
24. Wilson-Robles HM, Bygott T, Kelly TK, et al. Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs. BMC Vet Res. 2022;18(1):329. doi:10.1186/s12917-022-03429-8
25. Wilson-Robles H, Miller T, Jarvis J, et al. Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer. PLoS ONE. 2020;15(8):e0236228. doi:10.1371/journal.pone.0236228
26.  Burti S, Banzato T, Coghlan S, Wodzinski M, Bendazzoli M, Zotti A. Artificial intelligence in veterinary diagnostic imaging: Perspectives and limitations. Res Vet Sci. 2024;175:105317. doi:10.1016/j.rvsc.2024.105317
27. Banzato T, Bernardini M, Cherubini GB, Zotti A. A methodological approach for deep learning to distinguish between meningiomas and gliomas on canine MR-images. BMC Vet Res. 2018;14(1):317. doi:10.1186/s12917-018-1638-2
28. Chon E, Hendricks W, White M, Rodrigues L, Haworth D, Post G. Precision Medicine in Veterinary Science. Vet Clin North Am Small Anim Pract. 2024;54(3):501-521. doi:10.1016/j.cvsm.2023.12.006
29. Lloyd KCK, Khanna C, Hendricks W, Trent J, Kotlikoff M. Precision medicine: an opportunity for a paradigm shift in veterinary medicine. J Am Vet Med Assoc. 2016;248(1):45-48. doi:10.2460/javma.248.1.45
30. Vidium Animal Health. SearchLight DNA. Vidium Animal Health. 2024. Accessed April 26, 2025. https://vidiumah.com/searchlight-dna/
31. Chon E, Wang G, Whitley D, et al. Genomic tumor analysis provides clinical guidance for the management of diagnostically challenging cancers in dogs. J Am Vet Med Assoc. 2023;261(5):668-677. doi:10.2460/javma.22.11.0489
32. Chon E, Sakthikumar S, Tang M, et al. Novel genomic prognostic biomarkers for dogs with cancer. J Vet Intern Med. 2023;37(6):2410-2421. doi:10.1111/jvim.16893
33. Thrive Pet Healthcare. Thrive Pet Healthcare and FidoCure Report on One Year of Groundbreaking, Personalized Cancer Care for Hundreds of Dogs. Thrive Pet Healthcare. July 19, 2023. Accessed April 26, 2025. https://www.thrivepetcare.com/thrive-guide/thrive-and-fidocure-report-on-one-year-of-groundbreaking-cancer-care
34. FidoCure®. How it Works. FidoCure®. 2025. Accessed April 26, 2025. https://fidocure.com/how-it-works/
35. Business Wire. FidoCure To Unveil Breakthrough in Canine Hemangiosarcoma at 2024 Veterinary Cancer Society Annual Conference. Business Wire. October 15, 2024. Accessed April 26, 2025. https://www.businesswire.com/news/home/20241015518943/en/FidoCure-To-Unveil-Breakthrough-in-Canine-Hemangiosarcoma-at-2024-Veterinary-Cancer-Society-Annual-Conference
36. Colombe P, Béguin J, Benchekroun G, Le Roux D. Blood biomarkers for canine cancer, from human to veterinary oncology. Vet Comp Oncol. 2022;20(4):767-777. doi:10.1111/vco.12848
37. Koo J, Choi K, Lee P, et al. Predicting Dynamic Clinical Outcomes of the Chemotherapy for Canine Lymphoma Patients Using a Machine Learning Model. Vet Sci. 2021;8(12):301. doi:10.3390/vetsci8120301
38. Callegari AJ, Tsang J, Park S, et al. Multimodal machine learning models identify chemotherapy drugs with prospective clinical efficacy in dogs with relapsed B-cell lymphoma. Front Oncol. 2024;14:1304144. doi:10.3389/fonc.2024.1304144
39. Bohannan Z, Pudupakam RS, Koo J, et al. Predicting likelihood of in vivo chemotherapy response in canine lymphoma using ex vivo drug sensitivity and immunophenotyping data in a machine learning model. Vet Comp Oncol. 2021;19(1):160-171. doi:10.1111/vco.12656
40. ImpriMed, Inc. ImpriMed's Science: Live Cancer Cells + Artificial Intelligence. ImpriMed. Accessed April 26, 2025. https://www.imprimedicine.com/science
41. FDA's Center for Devices and Radiological Health. Precision Medicine. FDA. August 18, 2023. Accessed April 25, 2025. https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine
42. Chon E, Hendricks W, White M, Rodrigues L, Haworth D, Post G. Precision Medicine in Veterinary Science. Vet Clin North Am Small Anim Pract. 2024;54(3):501-521. doi:10.1016/j.cvsm.2023.12.006