Diagnosis And Staging Of Metastasis 

  • Nour Asaad MSc Applied Biomolecular Technology, BSc Biochemistry and Molecular Medicine, The University of Nottingham
  • Ananthajith Rajesh BSc Hons Biomedical Science, University of Edinburgh

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Overview 

Metastasis is the process of spreading the cancerous cell by leaving the primary tumour to a distant location from its original site(the tumour in the original site is called the primary tumour and once it is spread to other locations and organs it is called metastatic or secondary tumour).1

The metastatic process consists of sequential steps, the primary tumour invades the deeper and adjacent or even the more distant tissue. It generates its blood vessels to grow and then spread through the blood, lymphatics or direct infiltration of the neighbouring tissues.1 Metastatic tumours may affect multiple organs together and affect their function.2 

The diagnosis and early detection of cancer will significantly affect the prognosis and increase the survival rate as metastasis is the most frequent reason for cancer's poor prognosis and deaths as it resists conventional therapies.1,4 This article will delve more into metastasis diagnosis and how staging affects treatment.

Signs and symptoms of cancer metastasis 

Proper understanding of the signs and symptoms of cancer metastasis plays a significant role in early detection and diagnosis. It will markedly affect the prognosis of the disease and improve the patient outcome by early interventions. 

Signs and symptoms vary depending on the site of the metastasis and the type of primary cancer. For example, bone metastasis is a common site for metastases and it affects many patients with advanced cancer. The patient will experience pain, and pathological fracture due to focal bone destruction also they may have a dense lesion due to excessive abnormal formation of bone. Spinal cord compression and hypercalcemia also occur in patients with bone metastasis.5

On the other hand, brain metastasis commonly arises in patients with breast cancer, lung cancer and melanoma causing headaches, neurological symptoms like seizures, weakness, balance changes, cognitive, and behavioural changes, and vision problems.6 

Finally, Liver metastasis may cause abdominal pain and jaundice. Abdominal swelling, nausea and vomiting and bowel obstruction are associated with abdominal metastasis.  

As we mentioned earlier, the signs and symptoms vary however, there are some that are common that occur in patients with different metastases: 

  • Weight loss
  • Loss of appetite
  • Fatigue
  • Recurrent or persistent low-grade fever

Diagnosis of metastasis

There are many systemic approaches available to diagnose and identify the primary site of the tumour such as imaging techniques, biopsy, histological tests, blood tests, and biomarkers.

Imaging

Imaging is the main technique used for diagnosis and staging of cancer and for monitoring and follow-up of tumours. Additionally, it plays a huge role in the discovery of cancer complications like compression of the adjacent structures.7 Imaging has multiple advantages by being minimal or non-invasive and ease of accessibility without tissue destruction, pain or discomfort.

There are different imaging techniques that can be applied during testing. 

PET scan

Positron emission tomography (PET) is a nuclear image that proved its effectiveness and power in detecting cancerous lesions. It is often used to differentiate between malignant and benign tumours. 

In PET scans fluorodeoxyglucose (FDG) a radioactive drug is used as a contrast agent during the procedure. It is given in small amounts making it safe. 

PET scans can localise the areas of high activity (such as tumours) and this helps identify the best places for biopsies or radiotherapies.9

CT scan

CT scan is a method effective in the detection and identification of the lesion and it forms an integral part in the follow-up process. It differentiates between benign and malignant tumours according to size, shape and density and provides a detailed image of the body structures. It is also useful in detecting cancer complications. 

One of the features of a CT scan is its ability to produce a 3D image of the body part helping in an accurate localisation of assessment of the lesions. 

Ultrasound

Ultrasound is one of the most common imaging techniques used in the detection of tumours, especially in breast, thyroid, kidney, liver, prostate, pancreatic uterine and ovarian cancer and more frequently it is used to guide the biopsy.  

MRI

The MRI has a large magnet that forms a strong magnetic field around the body of the patient absorbing energy and emitting waves that will be reconstructed as a 3D image. It is a non-invasive method that provides critical details regarding the tumour’s location, size, stage and grade.10

Biopsy and histology

Biopsy is one of the most essential diagnostic tools in the identification of cancer. It discovers the type of cancerous lesion based on the characteristics of the cell observed under the microscope.

Biopsy has different types and methods, whether diagnostic by removing a small part of the lesion (Incisional biopsy) or diagnostic and therapeutic by removing the entire lesion with a clear margin (Excisional biopsy).11

Additionally, fine needle aspiration (FNA) is a method of taking a biopsy by aspirating a small amount of tissue or fluid from the lesion using a small fine needle.  On the other hand, the process of using a large needle to remove the tissue is called a (core needle biopsy). 

Blood tests

Simple blood tests have an important role in identifying patients who require further investigations for cancer and those who are at risk. These diagnostic tests may give the practitioner an idea that cancer may be present and indicate an urgent referral which certainly may reduce the diagnostic delay. For example, high platelets count, low albumin, high calcium level and high inflammatory markers can be an indication of an underlying serious problem like cancer.12

Tumour markers

Tumour markers are substances produced by tumours or due to the body’s response to these tumours. There are hundreds of these markers, and they include substances like proteins, enzymes, hormones and others.3 They can be detected through body fluids like pleural fluid or serum or from the tissue itself such as solid tumours, and lymph nodes.13

Staging of metastasis

The degree of spreading of cancerous lesions is a key feature in determining the prognosis and the most appropriate treatment, hence identifying the overall outcome. There are multiple staging systems worldwide, but the most commonly used one was developed by the American Joint Committee on Cancer (AJCC), called the  TNM system:14 

  • T referred to primary tumour size and extent
  • N referred to Lymph node involvement
  • M referred to the presence of distant metastasis

T, N, and M are defined by numbers (eg.: T1, T2, N1), the combination of these numbers results in the stages of cancer that range between stage 1 to stage 4, the latter being the most aggressive.14

Furthermore, there is another form of TNM staging system described as pathological staging (pTNM staging) which is based on the examination of the tissues removed as a biopsy. 

Staging is a critical process to determine the appropriate treatment, the course and outcome of the disease and determine the patient's survival rate. 

FAQs 

What is metastasis?  

Metastasis is the process of spreading the cancerous cell by leaving the primary tumour to a distant site away from its original organ. 

How is metastasis diagnosed? 

Using multiple techniques including imaging (X-RAY, MRI, PET scan, and CT scan) and biopsy (Incisional and excisional biopsy)are helpful in the diagnosis of cancer besides blood tests and tumour markers. 

What is the TNM staging system?

  • T = Primary tumour size and extent
  • N = lymph node involvement
  • M = presence or absence of metastasis

How accurate staging could affect the treatment plan? 

  1. By determining the appropriate treatment options for the patient
  2. By predicting the patient's survival rate and the outcome of the treatment
  3. By tracking the effect of the treatment

Conclusion

There are many advancements that are every day being implemented and applied in the field of oncology, that aim to identify new effective ways for early detection and accurate diagnosis of cancerous lesions which lead to better outcomes and determine the people who are at risk of developing cancer from earlier in order to increase their chances and improve their quality of life. 

References

  1. Gerstberger S, Jiang Q, Ganesh K. Metastasis. Vol. 186, Cell. Elsevier B.V.; 2023. p. 1564–79.  
  2. ​Woodhouse EC, Chuaqui RF. Skeletal Complications of Malignancy mors-including breast, prostate, and lung-frequently metastasize. Cancer [Internet]. 1997 [cited 2024 Jun 19];80:1529–66. Available from: https://onlinelibrary.wiley.com/terms-and-conditions 
  3. ​Crosby D, Bhatia S, Brindle KM, Coussens LM, Dive C, Emberton M, et al. Early detection of cancer. Science (1979) [Internet]. 2022 Mar 18 [cited 2024 Jun 19];375(6586). Available from: https://doi.org/10.1126/science.aay9040 
  4. ​Fidler IJ. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nature Reviews Cancer. 2003 Jun;3(6):453–8.  
  5. ​Coleman RE, Croucher PI, Padhani AR, Clézardin P, Chow E, Fallon M, et al. Bone metastases. Vol. 6, Nature Reviews Disease Primers. Nature Research; 2020.  
  6. ​Boire A, Brastianos PK, Garzia L, Valiente M. Brain metastasis. Nat Rev Cancer. 2020 Jan 1;20(1):4–11.  
  7. ​Bansal A, Dhamija E, Chandrashekhara SH, Sahoo RK. Role of CT in the detection and management of cancer related complications: a study of 599 patients. Ecancermedicalscience. 2023 Apr 1;17.  
  8. ​Fass L. Imaging and cancer: A review. Vol. 2, Molecular Oncology. Elsevier; 2008. p. 115–52.  
  9. ​Griffeth LK. Use of Pet/Ct Scanning in Cancer Patients: Technical and Practical Considerations. Baylor University Medical Center Proceedings. 2005 Oct;18(4):321–30.  
  10. ​Thompson J, Lawrentschuk N, Frydenberg M, Thompson L, Stricker P. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. Vol. 112, BJU International. Blackwell Publishing Ltd; 2013. p. 6–20.  
  11. ​Rosai J. Rosai and Ackerman’s Surgical Pathology 10e E-Book. 2011 [cited 2024 Jun 21];2892. Available from: https://books.google.com/books/about/Rosai_and_Ackerman_s_Surgical_Pathology.html?id=1CKX7aGBbUsC 
  12. ​Virdee PS, Bankhead C, Koshiaris C, Wright Drakesmith C, Oke J, Withrow D, et al. BLOod Test Trend for cancEr Detection (BLOTTED): protocol for an observational and prediction model development study using English primary care electronic health record data. 2023 [cited 2024 Jun 21];7:1. Available from: http://creativecommons.org/licenses/by/4.0/
  13. ​Sharma S. Tumor markers in clinical practice: General principles and guidelines. Indian Journal of Medical and Paediatric Oncology. 2009 Jan;30(01):1–8.  
  14. Gress DM, Edge SB, Greene FL, Washington MK, Asare EA, Brierley JD, et al. Principles of Cancer Staging. 2017 [cited 2024 Jun 21]; Available from: www.asco.org.

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