Unknown Primary Cancer

Introduction

What is Unknown Primary Cancer?

Unknown Primary Cancer (also known as Cancer of Unknown Primary) in the head and neck region occurs when the origin of the cancer is unknown, but is found to have spread to the lymph nodes in the neck. If it's not the cancer type you're looking for, please explore the information about other types of Head and Neck Cancers.

Cancer of Unknown Primary accounts for 3–5% of all Head and Neck Cancers.

Cancer occurs when cells become abnormal and grow uncontrollably. These cells build-up to form a mass (or lump).

Most cancers that spread to the lymph nodes of the neck come from flat-shaped cells that line areas such as the inside of the mouth, nose and throat. These cancers are called squamous cell cancers (SCC).

Only a minority of cancer cases come from the salivary glands and other structures; another source are skin cancers, where squamous cells are also found.

What are lymph nodes?

Lymph nodes are bean shaped glands in the neck that are part of the immune system’s defence against infection. There are hundreds of lymph nodes in the head and neck area and the majority of these run down the sides of the neck and under the jaw. Lymph nodes are normally difficult to feel because they are soft and small (less than 1 cm). The lymph nodes may become swollen during infection or due to cancer.

Watch a 3D video explainer about Unknown Primary Cancer:

Unknown Primary Cancer

What Causes Cancer of an Unknown Primary?

Doctors often can't explain why a person gets cancer. However, the main causes of head and neck cancers and Cancer of Unknown Primary are:

Alcohol and smoking (cigarettes, cigars or pipes) or using ‘smokeless’ tobacco (snuff and chewing tobacco): significantly contribute to the development of Head and Neck Cancer. This is especially true for cancers of the mouth, throat and larynx (voice box). Those who smoke and drink a lot of alcohol are at a much higher risk compared with those who only use either alcohol or smoking alone. Get information about quitting smoking and reducing how much alcohol you drink.
Infection with HPV (human papillomavirus) may contribute to the development of Head and Neck Cancer, particularly those involving the tonsils or tongue base. The cancers in the tonsil and tongue base are usually small and difficult to detect, but have the ability to spread to enlarged lymph nodes in the neck and account for many cancers of unknown primary.
Sun exposure contributes to skin cancer, the most common type of cancer in Australia. Patients with Skin Cancer often have had many primary cancers treated making it difficult to know whether a cancer in a lymph node has come from a Skin Cancer or not.

Symptoms and Signs of Unknown Primary Cancer

Patients with Cancer of Unknown Primary usually notice a lump in their neck, which is usually painless. Most patients don’t have any other symptoms.

Swollen lymph nodes may be due to an infection, such as a cold or flu, but the swelling should subside after two weeks. Children and young adults may sometimes have persistently enlarged lymph nodes due to viruses such as glandular fever.

However, adults that notice a swollen lymph node that does not go away within four weeks should consult their doctor. Adults presenting with enlarged lymph nodes for a month or longer may be recommended a needle biopsy to check for cancer.

What are the Tests for Cancer of an Unknown Primary?

For diagnosis of Cancer of Unknown Primary, your doctor will need to do the following things:

talk with you about your medical history. This includes discussing symptoms that might point to the source of the cancer, risk factors (e.g. smoking or drinking), and any previous history of cancer
perform a physical examination by examining your nose, mouth, throat, thyroid gland and skin for any suspicious areas
arrange a referral to a head and neck or ear, nose and throat (ENT) specialist who may order diagnostic tests such as exams or scans for further assessment.

Common tests used include:

Examination Under Anaesthesia

In some patients, the primary cancer may grow slowly and be too small to be seen on examination and scans; the primary site may appear later during follow-up.

Sometimes, a biopsy of the primary site is needed to make sure there is no cancer within them, but examining these areas is often difficult when the patient is awake.

The doctor may suggest examining the areas under general anaesthesia (with you asleep) if the primary site of cancer hasn’t been identified. Whilst under anaesthesia, the doctor can perform a thorough examination of the mouth, throat, voice box and the back of the nose (nasopharynx).

Based on the examination, the doctor may recommend:

Needle biopsy (Fine Needle Aspiration or FNA biopsy): This is when a thin needle is inserted into the suspicious lymph node to remove a sample. Typically this is performed using ultrasound guidance with local anaesthetic to reduce your discomfort. The tissue is then examined under a microscope to look for cancer cells by a pathologist. This is the only sure way to know if you have cancer.
If a diagnosis cannot be made based on the FNA, it is either repeated or a core biopsy (a similar procedure with a larger needle) may be performed. If the diagnosis still remains uncertain, then a surgeon may perform an excisional lymph node biopsy to remove the suspicious lump under general anaesthesia and send the sample to the pathologist for review.

Ultrasound Scan

This is used to create a picture of the tissues in the neck, and is a very good way to assess the thyroid gland.

CT (Computed Tomography) Scan

This uses X-rays to take pictures of the inside of the body. Depending on the clinical situation, patients may require a CT scan of the head, neck, and possibly the chest. Often dye is injected into a vein during the procedure to give clearer images.

MRI (Magnetic Resonance Imaging) Scan

This uses magnetic fields to take pictures of the inside of the body, however this is less commonly used than CT scans.

PET (Positron Emission Tomography) Scan

As the cancerous lymph nodes are often too small to detect, PET scan is unable to show the cancer in the lymph nodes. However, using a radioactive form of sugar, PET shows if the cancer has spread elsewhere in the body and could help identify where the cancer has come from (the primary site).

X-Ray of Jaw Bone

This is part of the dental assessment, which may be needed before treatments.

Treatment Options for Unknown Primary Cancer

Your cancer care team will discuss the treatment options available for treating Cancer of Unknown Primary. This is also a good time to consider if you would like a second opinion.

The treatment most suited to each person depends on many factors, including:

the number and size of the lymph nodes that are affected
personal factors (e.g. age, general health and treatment history)
treatments available (and whether any clinical trials are available)
your preferences for treatment

The treatment options for Cancer of Unknown Primary are:

Surgery (often combined with radiotherapy and chemotherapy)
Radiation Therapy (often combined with chemotherapy)

Surgery for Unknown Primary Cancer

Some common types of surgery that can be used for Cancer of Unknown Primary in the head and neck area are:

Neck Dissection

Download PDF - Neck Dissection

Download PDF - Return to Activity Following Neck Dissection

This involves removing the enlarged cancerous lymph nodes, together with other lymph nodes in the same region of the neck.

Tonsillectomy

Download PDF - Tonsillectomy

This involves removing the tonsils, if there are signs of cancer in the tonsils or other lymph nodes in the neck. It can also help with diagnosing the type of cancer.

How Can I Prepare for the Surgery?

Your doctor will explain details of the surgery, general risks and side effects of surgery. Ask your doctor if you have questions. They may recommend:

stopping blood thinners (e.g. aspirin) before surgery to reduce the risk of bleeding
special stockings to reduce the risk of blood clots
early mobilisation (i.e not staying in bed) to reduce the risk of blood clots and chest infection
antibiotics to lower the risk of wound infection.

Before starting treatment, it is important that you consider stopping smoking to reduce the risk of infection and help you fully recovery after your treatment.

Side Effects of Surgery

Treatment for Cancer of Unknown Primary may lead to a number of side effects. You may not experience all of the side effects. Speak with your doctor if you have any questions or concerns about treatment side effects.

Radiation Therapy for Unknown Primary Cancer

For Cancer of Unknown Primary, radiation therapy may be used to treat the lymph nodes affected by cancer with or without the primary site(s) that it may likely have come from. The most common approach for cancer of unknown primary is called external beam radiation. This is where the radiation is applied from outside of the body.

Radiation therapy can be used in the following ways:

Definitive
This is when radiation therapy is used on its own without surgery. Definitive radiation therapy may be targeted to one side of the neck area (unilateral), containing the cancerous lymph nodes, or both sides of the throat (bilateral) to treat all possible areas of primary cancer. Typically, radiation therapy is delivered daily (but not on weekends) over 7 weeks. Chemotherapy may be added to the radiation therapy (chemoradiation)

Adjuvant
This is when radiation therapy is given after surgery and is used as an additional treatment to kill any cancer that may not have been removed during surgery. Adjuvant radiation therapy may also be given in combination with chemotherapy (called chemoradiation).

Palliative
In cases where a cure is not possible, radiation therapy is used to relieve symptoms of advanced cancer of unknown primary. Symptoms that may require palliative radiation therapy include pain, bleeding, breathing and swallowing difficulties.

How do I prepare for Radiation Therapy?

You will meet with many members of the cancer care team, who will help you learn how to look after yourself through radiation therapy, recovery and long term follow-up. They will also talk to you about side effects and how to manage them. It may be helpful to write down questions as they come up, so you can ask anyone in your cancer care team when you see them.

Radiation Therapy Mask-Making and Simulation

Radiation therapy is a precise treatment. In order to make sure, that the cancer is covered by the treatment, you will need to be very still during the treatment, usually for about five minutes. A radiation therapy mask that is made to fit perfectly to your shape, will be put on you during each treatment to help the machine target where the cancer is.
You will have a planning CT scan (and sometimes other scans) with the mask on. Your radiation oncologist and radiation therapists will use these scans with all your other clinical information to develop a radiation therapy plan just for you (a personalised plan). Your plan will be checked by the radiation therapy and radiation oncology physics team before it is ready to be used for your treatment. This whole process can take approximately 2-3 weeks.

Teeth and Mouth Care

You might need to have some of your teeth taken out, this will depend on the area being treated and the dose of radiation therapy. It is important to take out any broken or infected teeth before radiation therapy. Taking out unhealthy teeth after radiation therapy can cause problems with the jaw bone. Further information about removing teeth and what to expect before and after the operation is available here.

Diet and Nutrition

Your cancer and its treatment can make it hard to eat and drink. Your doctor will recommend you see a dietitian to maximise your nutrition during treatment as well as while you are recovering. Sometime feeding tubes may be recommended depending on the area being treated and the dose of radiation therapy.
There are two common types of feeding tubes:

Gastrostomy tube (sometimes called a PEG tube): this type of tube is inserted through your abdominal wall into your stomach, with part of the tube staying outside the stomach. A syringe can be attached to the tube to give you food this way if needed. The tube is inserted using a camera through the mouth into the stomach (gastroscopy) or using a CT scanner to guide insertion directly through the skin. If a PEG tube is needed, your doctor will organise this before starting your radiation therapy.
Nasogastric tube: this type of tube goes through the nose down into the stomach and is usually used for short periods (days or weeks). A nasogastric tube can be inserted at any time (before, during or after treatment).

Speech, Voice and Swallowing

Your cancer and its treatment can make swallowing and speech difficult. Your doctor will recommend you see a speech pathologist, who can help you with ways to manage swallowing and communication difficulties, during and after treatment.

There are many other aspects of supportive care that are available, ask your doctor if you have any specific needs.

Side Effects

The side-effects of radiation therapy start around two weeks into treatment and progress through treatment to peak in the last week or just after treatment ends. The side effects start to improve 2-3 weeks after the end of treatment.

Side effects associated with radiation therapy depend on:

the dose of radiation therapy
the area being treated
whether or not chemotherapy is added to the radiation

Each individual responds to radiation therapy differently. Some people may experience a few side effects while others may not experience any at all.

The following are some common side effects of radiation therapy:

tiredness
skin irritation in the treated area e.g. redness, dryness and itching, weeping skin, scaling or sometimes skin breakdown (sores)
dry mouth and throat due to lack of saliva (called xerostomia)
ulcers in the mouth or throat that make it painful or difficult to chew or swallow
altered taste, which is usually a loss of taste or sometimes an unpleasant taste in the mouth
pain on swallowing or difficulty with swallowing.

Most side effects are short lived and may go away within 4–6 weeks of finishing radiation therapy. Some side effects may last for months after you finish radiation therapy and some may be permanent.

Once your radiation therapy ends, you will have regular follow-up appointments so your cancer care team can check your recovery and monitor any side effects that you may have. Your doctor may recommend some specific supportive care options to help during your recovery, such as help with changes in diet, teeth and mouth care and speech or swallowing

Chemotherapy for Cancer of Unknown Primary

Chemotherapy works by destroying or damaging cancer cells. For head and neck cancers, chemotherapy is usually given into a vein through a needle with a catheter (tube) attached.

Usually chemotherapy is used in combination with radiation therapy to make the radiation therapy more effective. It is usually given once a week or once every 3 weeks throughout the duration of radiation therapy. Unlike chemotherapy for many other cancers, most patients do not lose their hair or have severe nausea and vomiting.

Side Effects

The side effects of chemotherapy depend on the medication used and how much you are given by your doctor (the dose). The most common medications used are called cisplatin, carboplatin and cetuximab.

Each person responds to chemotherapy differently. Some people may experience a few side effects while others may not experience any at all.
The following are common side effects of chemotherapy:

nausea and vomiting
loss of feeling in the fingers and toes
some medications may cause kidney damage
hearing loss/thinning
ringing in the ears
rash
higher risk of infection (if the chemotherapy reduces the number of white cells in the blood)

Most of these side effects are short lived and may go away once you finish chemotherapy. Some side effects can take months or years to improve or may be permanent.

Once your treatments end, you will have regular follow-up appointments so that your doctor can check your recovery, make sure the cancer has not returned and monitor and treat any side effects that you may have.

Questions to Ask

Exactly what type of cancer do I have? Where is it located?
Why did I get this cancer?
If I wanted to get a second opinion, can you provide all my medical details? Do you mind if I get a second opinion?
What stage is the cancer?
What are my treatment options? Which treatment do you recommend for me and why?
Have you discussed my case at a Multidisciplinary Team meeting and what were the recommendations?
Who will be part of the cancer care team, and what does each person do? Should I see another specialist before treatment, such as a radiation oncologist, medical oncologist, plastic surgeon, dentist, dietician or speech pathologist?
What are the possible side effects of treatment in the short- and long-term? How can they be prevented or managed?
Will the treatment affect my ability to eat, swallow, or speak? Will I need a feeding tube?
What will happen if I don't have any treatment?
How much will the treatment and/or operation cost? Will Medicare or my health insurance cover it?
What follow-up tests will I need? How often will they be?
Am I suitable for any clinical trials?
What lifestyle changes (diet, exercise) do you recommend I make?
Who can I call if I have any problems or questions?
Where can I find emotional support for me and my family? Is there a support group or psychologist you can recommend?

Follow-Up Care

For Cancers of Unknown Primary, in addition to making sure the cancer does not return in the lymph nodes, your doctor will also check whether the primary cancer has appeared. This will include a physical exam and checking your nose and throat using a thin, flexible tube with a light and camera (nasendoscopy).

Some people may also need imaging studies such asCT, MRIorPET scans during follow-up. It is important to keep up with follow-up to ensure that if the cancer comes back, it may be caught as early as possible and can be treated. If you have any concerns between visits you should contact your doctor or cancer care team.

Quitting smoking and drinking alcohol, in patients who do so, can help reduce the risk of a new head and neck cancer occurring. Ask your cancer care team for advice if this applies to you.

Mental Health for People with Cancer

Sometimes this is referred to as psychosocial aspects or survivorship.

Being diagnosed with cancer and having treatment can lead to extra worries or concerns for you and the people caring for you.

Depending on the treatment, you may experience any of the following: low mood or depression anxiety disfigurement difficulties with eating difficulties with speaking changes in sexual activity.

You may have got through the diagnosis and treatment for head and neck cancer, but you may be finding it difficult to deal with some of the side effects of treatment. Speak with you doctor about any difficulties you may be experiencing. Your doctor may give you a referral to a psychologist or another healthcare professional who can help you.

Speak with your family and friends too about any concerns you may have. You may find it helps to join a patient support group and speak with others who are having treatment for head and neck cancer. You can also find help and advice in online self-help resources such as beyondblue.

Further information about coping with cancer is available here.