Anal Cancer Metastatic

Metastatic anal cancer, where the disease has spread to other organs, presents significant treatment challenges and requires careful coordination of care strategies.

Table of contents

• What Is Metastatic Anal Cancer
• Where Anal Cancer Can Spread
• Initial Presentation
• Treatment Approaches
• Chemotherapy for Metastatic Disease
• Combined Treatment Strategies
• Treatment Challenges and Limited Options

What Is Metastatic Anal Cancer

Metastatic anal cancer, also called Stage IV anal cancer, means the cancer has spread from the anus to other parts of the body^[4]. The cancer can be any size and may or may not have spread to nearby lymph nodes (small bean-shaped structures that help fight infection)^[4]. Unfortunately, cancer that has spread elsewhere in the body is considered advanced cancer^[4].

Anal cancer is a relatively rare gastrointestinal tumor with roughly 7,000 new cases per year^[3]. The anus is the end of the large intestine where stool (solid waste) leaves the body^[1]. It is connected to the rectum by the anal canal, which is about 1 to 1½ inches long and is controlled by two ring-like sphincter muscles that contract to hold stool in and relax to allow its passage out of the body^[1].

Where Anal Cancer Can Spread

If anal cancer spreads, it can spread to several different areas of the body. The most common sites include lymph nodes around the rectum, groin, and pelvis^[7]. From there, the cancer can spread to other organs including the rectum, bladder, urethra, vagina or prostate, liver, lungs, and bone^[7].

The liver is a particularly common site for metastatic spread^[4][9]. When cancer has spread to these distant locations, treatment approaches must address not only the original tumor site but also the metastatic disease.

Initial Presentation

Metastatic anal cancer as an initial presentation occurs in 10-20% of patients^[3][9]. This means that some people are first diagnosed when the cancer has already spread to other parts of the body. The signs and symptoms that may prompt someone to seek medical care include bleeding from the anus or rectum, a lump near the anus, pain or pressure in the area around the anus, itching or discharge from the anus, and changes in bowel habits^[1].

Some people may experience symptoms related to where the cancer has spread. For example, a person with liver metastases might experience abdominal pressure or other symptoms related to the affected organ^[3].

Treatment Approaches

The aim of treatment for Stage IV anal cancer is to slow down the growth of the cancer^[4]. Treatment decisions depend on several factors including where the cancer is in the anus, the patient’s general health, and where the cancer has spread^[4].

While treatment for localized disease is well established with concurrent chemoradiation (chemotherapy and radiation given at the same time) as the standard of care, metastatic anal cancer remains a therapeutic challenge^[3]. National Comprehensive Cancer Network (NCCN) guidelines recommend systemic chemotherapy as the initial choice of treatment for metastatic anal disease^[3].

If a person is not fit enough for chemotherapy, doctors might suggest best supportive care, also called palliative care. This aims to relieve the symptoms of the cancer and improve quality of life^[4]. Treatments may include radiotherapy and surgery focused on symptom relief^[4].

Chemotherapy for Metastatic Disease

Chemotherapy is the main treatment for advanced anal cancer^[4]. It uses anti-cancer drugs to destroy cancer cells. These drugs are also called cytotoxic drugs^[4]. They circulate throughout the body in the bloodstream, which allows them to reach cancer cells wherever they may be.

The NCCN recognizes that there are limited data to influence the management of metastatic anal cancer, but some evidence suggests fluoropyrimidine (a type of chemotherapy drug) and cisplatin (a platinum-based drug) as the initial choice of treatment outside the setting of clinical trials^[3]. Common treatment combinations include cisplatin with 5-fluorouracil (5-FU)^[11].

Other chemotherapy regimens that may be used for metastatic disease include combinations with drugs like oxaliplatin, carboplatin, and paclitaxel^[11]. For subsequent therapy after failure of more standard treatments, newer drugs such as nivolumab or pembrolizumab may be considered^[11].

Combined Treatment Strategies

Some patients with metastatic anal cancer have been successfully treated with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site^[14]. This approach is similar to strategies used in metastatic colorectal cancer, where resection of isolated liver metastases is increasingly utilized as an effective treatment strategy in select patients^[14].

For example, some patients have been treated with induction chemotherapy (initial chemotherapy to shrink tumors) followed by surgical removal of isolated liver metastases and then radiation to the anal primary tumor with concurrent chemotherapy^[3][14]. This combined approach can result in control of disease without evidence of recurrence in carefully selected patients^[3].

A combined strategy of systemic and local therapies may prove beneficial in selected cases^[14]. Control of the primary tumor is important as local failure patterns may result in significant problems for the patient^[14]. However, this approach requires careful patient selection and coordination between different treatment specialists.

Treatment Challenges and Limited Options

Management of metastatic anal cancer is challenging as treatment options are limited^[9]. Chemotherapy with cisplatin is generally used as the first-line agent, but patients may progress or relapse even after achieving complete remission^[9].

If the patient fails the initial treatment regimen, options become limited with no strong level I evidence available to guide the treatment^[3]. Treatment of recurrent disease is difficult due to lack of published data^[9]. Management of these patients is largely based on case reports and case series studies, but large randomized studies are lacking^[9].

Recent reports of treating metastatic anal cancer patients with newer agents such as EGFR inhibitors (drugs that target a specific protein on cancer cells) were encouraging^[9]. There is ongoing research to identify better treatment options for patients whose cancer does not respond to standard therapies or who experience disease progression after initial treatment.