Recurrent & Advanced Cancer

Michele, USNot only was I diagnosed with a rare form of cancer, I had a rare form of metastasis located in my bone. After surgery to remove the sacral tumor I received simultaneous chemotherapy and radiation; 2 rounds of chemo lasting 96 hours each and 7 weeks of radiation that resulted in my hospitalization for the last 2 weeks of treatment for pain control. I baffled them all when I went into remission last year; I have just passed my 1 year anniversary.

Stage IV

We have grouped our discussion of stage IV and recurrent anal cancer together as they often utilize similar treatment approaches and usually indicate metastatic disease. Similar treatment avenues may also be explored in each case. Some doctors may refer to both stage IV and recurrent cancers as ‘advanced cancer’. This section also explores clinical trials and genome research

Metastatic anal cancer is when cancer has spread from the part of the body where it started, i.e. the anus, to other parts of the body. This happens because the cancerous cells have travelled either through the lymph nodes or bloodstream and have begun to grow and form new tumours. Your cancer may be metastatic when you are diagnosed or it may spread after initial treatment.


Stage IV anal cancer is when the cancer has metastasised or spread to distant lymph nodes, tissues or organs such as the lungs, liver, brain or bones. Chemotherapy is the standard treatment, although sometimes radiation is also used.

The initial chemotherapy treatment regimen for stage IV anal cancer generally involves 5-FU and cisplatin. Other initial treatment approaches may include paclitaxel and/or carboplatin. For more detailed information on treatment for stage IV anal cancer, please see Treatment for Anal Cancer. For more information on side effect management, please see our Chemotherapy page.

The treatment for stage IV cancer has remained essentially the same since the 1970s. We are working to bring more attention to the issue of anal cancer so that research will advance treatment far beyond its current state.

There is currently an international clinical trial underway to investigate the most effective chemotherapy regimen for inoperable locally recurrent or metastatic anal cancer from the drugs that are currently commonly used to treat advanced disease. One arm consists of cisplatin and 5-FU and the other consists of carboplatin and paclitaxel.

Clinical trials may also provide you access to newer treatments that can help you in managing your advanced cancer. See our section on clinical trials below. While the numbers are still too small, in the last few years we have also seen more clinical trials exploring different treatments for anal cancer. We continue to work for more options for people with stage IV and recurrent anal cancer.


Cancer is called ‘recurrent’ when it comes back after being treated. It can come back in or near the same place as before, or it can spread to other organs such as the lungs, liver or bones.

  • A local recurrence comes back in the same place.
  • A regional recurrence comes back nearby.
  • A distant recurrence comes back in another place not near the original tumour.

Once you have been diagnosed with recurrent anal cancer your doctor will restart the cycle of testing to learn as much as possible about the recurrence, including staging. This will help determine treatment.

Treatment largely depends on where the cancer has recurred, and what type of treatment you had last time.

  • The American Cancer Society states that if the cancer returns in the anus or in nearby lymph nodes and you were initially treated with radiation and chemotherapy (the Nigro Protocol), surgery and/or chemotherapy may be your new treatment option. Recurrent anal cancer in or near the anus may involve an abdominoperineal resection (APR).
  • If you initially had surgery alone, you may be placed on a chemotherapy and radiation regimen.
  • If you were initially diagnosed with stage IV anal cancer, then additional rounds of chemotherapy, with the possible addition of radiation, may be the next step.

Please see Living with the Side Effects for information on what side effects to expect from treatment and how to manage them.

Clinical trials are currently exploring the combination of radiation with chemotherapy and radiosensitisers (used to make tumours more sensitive to radiation) as treatment for recurrent anal cancer. See our section on clinical trials, next.

Peer to Peer Support Program

Looking for someone to talk to about your anal cancer diagnosis? We are here to help.


Doctor showing patient something on a laptop

Your care team may suggest exploring clinical trials as an option for your recurrent or advanced cancer treatment. The purpose of clinical trials is often to evaluate whether new treatments work and whether they are more effective than, and as safe as, existing treatments. Patients who participate in clinical trials are able to access new potential treatments before they are widely available, but are not guaranteed that these treatments are safer or even better than the standard treatment.

When the Foundation first started, there were very few clinical trials that involved anal cancer. Fortunately, the interest in and attention to anal cancer has increased in the past few years. That being said, we continue to work to create even more treatment options for people living with anal cancer and other HPV-associated diseases.

Clinical trials for anal cancer treatment may be studying:

Radiosensitising agents: these are drugs that increase the sensitivity of tumors to radiation, making radiotherapy more effective. The hope is that lower doses of radiation and chemotherapy will be the result.

Surgery improvements: researchers are looking at the effectiveness of artificial bowel sphincters in people with APR. The goal is to avoid the need for a permanent ostomy.

Targeted drugs: researchers are studying drugs that target specific changes within cancer cells. These drugs may work even when chemotherapy does not, and may have less severe side effects. One example of targeted drugs are those targeting a protein found in the cells for multiple cancers called EGFR. EGFR helps cells grow, and tumours tend to have too much of it on their surface. Targeting this protein may help slow cancer growth. Targeted drugs are still in development and need a platform of solid genetic research, which remains an emerging field for general cancer research.

Immunotherapy: this is treatment that boosts the body’s immune system in the hope that it will be able to combat cancerous cells on its own. There are different types of immunotherapies under study.

Vaccines designed to be administered after a cancer diagnosis to boost the immune system are also under study. The Anal Cancer Foundation is currently supporting research studying vaccine-based immunotherapy treatments for patients with recurrent HPV-related cancers. The goals of this research are to identify targets on HPV-related cancers, including anal cancer, and to activate and train specific immune cells to selectively attack these targets on the cancer cells.

Another type of immunotherapy to treat anal cancer approaches treatment from another angle; through the use of antibodies called checkpoint inhibitors. Cancer cells can set up a defense system that blocks the immune system from recognising and attacking abnormal cells. This type of research explores antibodies that block this interaction and allow the immune system to recognise and target the cancer cells. In addition to the vaccine study mentioned above, the Foundation supports a clinical trial that is looking at a checkpoint inhibitor, nivolumab. The study will assess if nivolumab promotes an immune response against anal cancer tumours which have not responded to other types of treatment, or are metastasised.

Another avenue of immunotherapy research is looking at specialised creams to treat anal neoplasia (AIN)/genital warts. One such cream is called imiquimod, which works by boosting the body’s immune response against the wart or area of AIN.

Research at NIH is currently exploring therapies that make use of large quantities of tumour-specific lymphocytes grown in the lab. Tumour-specific lymphocytes are the white blood cells your body makes to attack tumours. The white blood cells are taken from the tumour site, multiplied in the lab, then put back into the patient with the hope that the cells destroy the tumour.

This is an early area of research, and these are just some of the immunotherapy studies that are ongoing.

These are just some of the available clinical trials. To find the best study for you, and other clinical studies underway, speak to your doctor, and check clinical trial finders, below.


The National Cancer Institute has the US database of open and completed clinical trials, as well as useful information about participation.

National Cancer Institute (NCI) provides an online search tool for cancer clinical trials at You can ask for help with a search by calling 1-800-4-CANCER (1-800-422-6237). They have also created a document Clinical Trials: What you Need to Know, which may prove useful as well.


The NHS has a useful information page about what you need to know about finding and participating in a clinical trial in the UK.


Genome research is a fast-growing and relatively new area of study in the cancer research world. Cancer genome research compares genes in tumours to genes in healthy, noncancerous tissues in order to understand important differences between the two. The term ‘cancer genome’ refers to all the genes in a cancerous cell. These are similar to healthy cells but specific mutations, or changes, are responsible for making these formerly healthy cells cancerous. For example, researchers are learning that the same type of cancer in two different people can have different mutations.

The research goal is to provide insight into what drives cancer development. Ultimately, if we understand how a healthy cell’s DNA has changed to become cancerous, it may indicate areas of the genome that can be targeted by specific drugs. In the future this may mean that each individual has ‘personalised’ medicine where people are no longer treated by the anatomical site but by the genetic mutations in their tumour.

Genome research has advanced to the point that doctors can now test the biopsy sample from your tumour to see if it has specific mutations that could affect your treatment options. Many insurance companies do not cover this testing. For most cancers, this research is in its early stages – and in clinical trials — without comprehensive data that can be applied across the population.

One of the biggest genome research projects is The Cancer Genome Atlas (TCGA) project, which is currently trying to map cancer genomes using tissue from cancer patients across the US. The ultimate goal of the project is to better understand what turns a normal healthy cell cancerous, and how the various tumours differ from one another. Most recently, TCGA unveiled research that detailed possibly important differences in the genome of head and neck cancers that have been caused by HPV. This may have important treatment and prevention implications for HPV-related cancers.

In the UK, the 100,000 Genomes project aims to sequence 100,000 genomes from NHS patients by 2017. The NHS is able to link a lifetime of medical records to the results of genomic sequencing and more clearly understand the relationship between genes, other lifespan factors and illness. The 100,000 Genomes project will focus on patients of rare diseases, patients with certain types of cancers, and the family members of these patients. This will help improve understanding about the genomics and genomic changes behind rare diseases and cancer, and point the way toward the most effective therapies. Unfortunately, HPV-related cancers are not yet on the list of cancers being studied at the moment, but your provider can apply to nominate the cancer for inclusion with a scientific case.

While some of the results of today’s genome research may not be available for use in treatment for a while, discoveries will lead to improved testing and treatment in the future. Talk to your doctor to learn more about how genes play a role in cancer, and if your tumour should be tested for mutations.

roadmap-main-e1445292160202For more information on our vision for the future of HPV and anal cancer research, check out our Research Roadmap. Also check out Our Story to read more about what drives us to put an end to HPV and associated diseases.


We’re here to empower thrivers and the anal cancer community. But we can’t do it without your support.