Introduction

What is Unknown Primary Cancer?

Cancer occurs when cells become abnormal and grow uncontrollably. These cells buildup to form a mass (in other words, a lump). Cancer of unknown primary in the head and neck region occurs when the origin of the cancer is not found but has spread to the lymph nodes in the neck. It accounts for 5% of all head and neck cancers.

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 few of cancer cases come from the salivary glands, skin or other places.

What are lymph nodes?

Lymph nodes are bean-shaped glands located throughout the body that are part of the immune system’s defence against infection. There are hundreds of lymph nodes in the head and neck area and most 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 with cancer.

Watch a 3D video explainer about Unknown Primary Cancer:

Unknown Primary Cancer

What Causes Cancer of an Unknown Primary?

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): increases risk of developing of head and neck cancer. Those who smoke and drink a lot of alcohol are at a much higher risk compared with those who only use alcohol alone.
Exposure to HPV (human papillomavirus): may contribute to the development of head and neck cancer involving the tonsils or back of the tongue (tongue base). The cancers in the tonsil and tongue base are usually small and difficult to detect but can spread to lymph nodes in the neck and account for many head and neck cancers classified as from an 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.

What are the Signs and Symptoms of Unknown Primary Cancer

Patients with cancer of unknown primary usually notice a lump in their neck, which is often 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 in this situation 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 three weeks should consult their doctor. Adults presenting with enlarged lymph nodes for longer than three weeks may be recommended to have a needle biopsy to check for cancer.

How is Cancer of Unknown Primary Diagnosed?

For a 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 perform a nasoendoscopy (a flexible camera that passes through the nose to better examine the back of the nose, throat and voice box), order diagnostic tests such as a biopsy of the lymph node (external needle biopsy under local anaesthetic) and scans for further assessment. An examination under anaesthetic may be required if these tests do not reveal an obvious source of the cancer.

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 in the clinic or on scans. Sometimes, a biopsy of the most likely primary site is needed to confirm there is no cancer there, 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 most 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 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

Gel is applied to the neck, and a hand-held device is rolled over the gel to create a picture of the tissues in the neck. It is painless and is a very good way to assess the thyroid gland.

CT (Computed Tomography) Scan

This uses X-rays to take 3D pictures inside 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 inside the body. An MRI scan may be used with, or instead of a CT scan to help with diagnosis. Dye may be injected into a vein during the procedure to make certain structures and blood vessels show up more clearly.

PET (Positron Emission Tomography) Scan

Using a radioactive form of sugar, a PET scan can show a cluster of cancer cells and check if the cancer has spread elsewhere in the body. This scan may help identify where the cancer has come from (the primary site). There are some instructions to follow for the next few hours after the scan while the radioactive dye is leaving your system.

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 the time to ask any questions you may have and a good time to consider if you would like further information, or a second opinion.

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

the number and size of 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 node(s), 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
staying active straight after surgery to reduce the risk of blood clots and chest infection
antibiotics to reduce to 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 several side effects. You may not experience all the side effects. Speak with your doctor if you have any questions or concerns about treatment side effects.

Possible side effects depend on the surgical approach that best suits your individual cancer. This includes whether you need to have lymph nodes removed from the neck and whether you need tissue taken from another part of your body to fix the area where the cancer was taken out. Your treating team will talk about the type of surgery they will do in more detail and the specific risks that apply to you.

Your doctor may recommend that you receive supportive care to help during your recovery. Further information about supportive care is available on the website.

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 and is non-invasive.

Definitive radiation therapy: This is when radiation therapy is used on its own to clear the cancer without surgery. Definitive radiation therapy is targeted to one side of the neck area (unilateral), containing the cancerous lymph nodes, and one side (unilateral) 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 given at the same time as the radiation therapy (concurrent chemoradiation), sometimes once per week or once every few weeks during the 7 weeks of radiotherapy.
Adjuvant radiation therapy: This is when radiation therapy is given after surgery and is used as an additional treatment to clear any cancer that may not have been removed during surgery. Adjuvant radiation therapy may also be given in combination with chemotherapy (concurrent chemoradiation).
Palliative radiation therapy: In cases where a cure is not possible, a lower dose of radiation therapy is used to relieve symptoms of advanced or metastatic cancer. Symptoms that may require palliative radiation therapy include pain, bleeding, breathing and swallowing difficulties.This is given over a shorter number of treatments, not 7 weeks.

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.

Mask-making and simulation: Radiation therapy is a precise treatment. To make sure, that the cancer is covered by the treatment and to minimise dose to normal structures, 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 minimise movement while the treatment machine targets 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) based on your own internal anatomy and cancer size and location. Your individual plan will go through several quality checks by the radiation therapy and radiation oncology physicist 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 jawbone.
Diet, nutrition and the role of your dietitian: 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. Sometimes 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 or RIG 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 and medications 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 (radiologically inserted gastrostomy, RIG). If a PEG or RIG tube is needed, your doctor will organise this before or close to the start of 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.
Once the treatment machine has turned off, you are not radioactive and can go about your day as normal after leaving the treatment room.

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 3-4 weeks after the end of treatment.

Side effects of radiation therapy depend on:

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

Each individual responds to radiation therapy differently. Some people may experience a few side effects while others may not experience many at all. The following are some common side effects of radiation therapy.

Common side effects of radiation therapy include:

tiredness
skin irritation in the treated area (e.g. redness, dryness and itching, peeling skin and some areas of skin breakdown (sores))
dry mouth and throat due to loss of saliva (called xerostomia)
changed taste (usually a loss of taste or sometimes an unpleasant taste in the mouth)
pain on swallowing or difficulty with swallowing, managed with pain relief
hair loss directly in the treatment area (for example, beard or sideburns, but not the top of the head)
losing weight

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 will usually order a PET scan, timed for you to have done about 12 weeks after your last radiation therapy session, to make sure the cancer has completely gone. If the cancer has not gone away after radiation therapy, or comes back in the future, you may still be able to have surgery to try to remove the cancer.

Your doctor may recommend some specific supportive care options to help you during your treatment and recovery. Further information about supportive care is available on the website.

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 individual responds to chemotherapy 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 chemotherapy:

a feeling of wanting to vomit (nausea) or vomiting
increased side effects of radiation, if you have chemotherapy at the same time as radiation
loss of feeling in the fingers and toes
kidney damage (caused by some medications)
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 treatment ends, 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.

Your doctor may recommend that you receive supportive care to help during your recovery. Further information about supportive care is available on the website.

Questions to Ask

What type of cancer do I have? Where is it located?
What are the risk factors?
What lifestyle changes (diet, exercise) do you recommend I make?
What are the chances that the treatment (surgery or radiotherapy or both, with or without chemotherapy) will cure the cancer?
How long will it take before I can eat again and what sort of food?
Will I need a feeding tube? How long will I need the feeding tube for?
What will happen if I don't have the treatment?
How much will the treatment cost? Will my health insurance cover it?
What are the possible side effects of treatment? How can they be prevented or controlled?
Will I have a scar?
Will I be able to lead a normal life?
Will I need follow-up treatment? What follow-up tests will I need after the operation?
What are the chances that the cancer will return?
Am I suitable for any clinical trials?

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 the likely sites of primary cancer as part of your monitoring. This will include a physical exam and checking your nose and throat using a thin, flexible tube with a light and camera (nasoendoscopy) in the clinic every few months. The timing of your follow up appointments may extend to twice a year or once a year after a suitable period without evidence of the cancer on examination in the clinic.

Some people may also need imaging studies such as CT, MRI or PET 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 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. Maintaining your overall health and fitness with the aid of your general practitioner can help reduce the risk of separate new cancers or other health impacts developing.

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 your 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 contact the Head and Neck Cancer Helpline (Head and Neck Cancer Helpline | Head and Neck Cancer Australia) and find help and advice in online self-help resources such as Beyond Blue.