Dissecting metastatic cancer
Dr Daleen Geldenhuys helps us understand what metastatic cancer is and how it may respond to treatment.
What is metastatic cancer?
The word metastatic originates from a Greek word that means: to change. It’s a dreaded word to patients and doctors alike, which indicates that the cancer has left the organ of origin. The cancer is now Stage 4 (IV) and, in most instances, not curable.
Some patients present with Stage 4 disease at the time of diagnosis and others may have a recurrence of a cancer that was previously treated.
Oligometastases refers to a limited number of metastases (usually less than 3-5 tumours in one or two organs) and a possible better outcome.
The metastatic tumour
The metastatic tumour is the same type of cancer as the primary tumour (original tumour in the body), but it may differ in clonality (same family but cousins). The cancer cells may leave the primary organ and travel through the blood and/or lymphatic system but may also involve another organ by direct extension into that organ. For example, colon cancer can attach itself to the ovary and is then called a Krukenberg tumour, or breast cancer can grow in the skin.
It stays the same cancer. For example, it may start as breast cancer and spread to the liver, but it doesn’t become liver cancer, it’s breast cancer in the liver. When a doctor takes a biopsy and sends it to the pathologist for review, the same cells will be seen as on the original breast biopsy. It will stain with the same biological markers and will even physically try and resemble breast ducts or lobules.
It’s possible that this may happen during the early stages of cancer before the patient is even aware of the cancer and the cells may enter a latency period (time that passes between being exposed to something that can cause disease and having symptoms). The cancer cells only start multiplying much later sometimes even years later.
Disseminated (spread) tumour cells can survive for decades after surgical resection of a primary tumor and even after chemotherapy, radiation, and hormonal therapy. The therapy markedly reduces the possibility, but it may still occur.
The disseminated cancer cells may initiate new tumours at distant organ sites. It’s a multi-step process and may even potentially seed to tertiary sites in time.
Common sites of spread
Some cancer types predominantly spread to one organ. For example, pancreatic cancer to liver, and prostate cancer to bone. Others show sequential organ colonisation, such as colon cancer first to liver then later to the lungs (tertiary site). Others, such as breast or lung cancer may colonise many different organ sites, either sequentially or synchronously (at the same time).
The liver, lungs, bone, and brain are frequently involved by a variety of cancer types, where the skin, ovaries, and spleen are less common sites.
De novo metastatic disease
When a patient presents with de novo metastatic disease (first diagnosed when it has already spread) and was not treated before, many factors are considered when deciding on treatment, such as removing the primary tumour, treating with systemic therapy (chemo, hormonal, or immunotherapy), and depending on the response, attempt to remove the metastases (metastasectomy). Such treatment is individualised and needs a multi-disciplinary team.
It may still be necessary to remove the primary cancer. For example, in a patient with colon cancer and liver metastases, the colon cancer may cause obstruction and need to be removed before or sandwiched during chemotherapy.
It’s possible that metastases in one organ may respond to chemo or hormone therapy whilst metastases in another organ may grow. The clonality of the tumours may differ. In other words, the cancer cells may have looked the same when they metastasised but with time
the ongoing mutations in different sites will result in genetically different looking and behaving tumours. It may be necessary to biopsy the metastasis to determine its characteristics.
Patients who present with oligometastases at the time of initial cancer diagnosis may be considered for metastasectomy (surgical removal of the metastatic lesions) or other ablative therapies, such as chemo embolization and microwave ablation. This may lead to potential cure of Stage 4 disease.
Oligorecurrence may occur in patients who have undergone curative-intent treatment to locoregional disease that remains controlled (primary colon cancer has no relapse) in the setting of new metastatic disease, like two or three liver metastases in colon cancer.
Patients with multiple metastases can be rendered oligometastatic from an effective response to systemic treatment that eradicated most metastases but failed to destroy one or a limited of resistant tumours.
Oligoprogression occurs when one or a limited number of metastases recur or progress while systemic therapy continues to control the primary site and most areas of metastatic disease. Some tumours may be resistant to treatment as the clonality differ.
Patients with oligometastatic cancer don’t always develop progression to widespread metastases. Therefore, there may be appropriately selected patients, with respect to disease bulk/burden and number of metastases, who can be treated with metastasis-directed surgical or ablative procedures. Locally ablative treatment directed to known metastases may render a patient disease-free, possibly for a protracted interval.
Certain Stage 4 cancers can expect a cure from the onset, such as testicular cancer. Even after a relapse, a cure can still be achieved with an autologous bone marrow transplant and high-dose chemotherapy.
Metastatic cancer is not a single disease and may even be different in the same person. It requires individualised treatment and a committed multi-disciplinary team. Nowadays, with many new modalities of treatment, we consider most metastatic cancers as chronic disorders and no longer rapidly fatal events.
MEET THE EXPERT – Dr Daleen Geldenhuys
Dr Daleen Geldenhuys is a specialist physician and medical oncologist who works at West Rand Oncology Centre at Flora Clinic. She treats patients with all types of cancer and enjoys clinical research, and is a member of SASMO, SASTECS, ESMO and ENETS.
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