Our Results With Intra-Arterial Chemotherapy in Rectal Cancer

In this article, we will discuss a study we presented as a poster at the 21st National Cancer Congress and briefly describe rectal cancer treatment. Our study included rectal cancer patients who received intra-arterial chemotherapy at our clinic between 2012 - 2014. Its aim is to share our results with "chemotherapy administered through an artery via the groin (transarterial - intra-arterial)" before curative treatment in these patients.

The rectum is the final part of the digestive system, formed by a widening of the large bowel and averaging 15 cm in length. Rectal cancer follows a different disease course from other large bowel tumors. Although it shares characteristics with other colon cancers, unlike colon cancer treatment, it carries a higher risk of locoregional recurrence after surgery if the tumor involves all bowel wall layers and/or nearby lymph nodes. This is because, unlike the colon, it lacks an outer membrane called the serosa and has a much richer lymphatic flow.

Furthermore, surgery for a tumor in the middle or lower rectum may expose the patient to the risk of losing the anus and requiring a lifelong colostomy. In these patients, radiotherapy and chemotherapy before surgery (neoadjuvant treatment) can increase the rate of anal preservation and reduce the likelihood of living with a bag (colostomy). Preoperative radiotherapy also avoids exposure to the increased side effects of postoperative radiotherapy.

Comprehensive assessment after a rectal cancer diagnosis and consideration of available preoperative treatments are extremely important because they may reduce the likelihood of losing the anus. After adequate imaging, such patients should be evaluated jointly by a radiologist, surgeon, medical oncologist, and radiation oncologist working with a shared approach, and the final medical treatment plan should be made together.

Rectal Cancers Are Staged as Early, Local (Regional), Locally Advanced, and Metastatic (Spread to Distant Sites)

Surgery and oncological treatments (chemotherapy and radiotherapy) for rectal cancer vary according to disease stage and tumor location. Surgery is the cornerstone of early-stage treatment. The rectum consists roughly of three sections, considered the upper, middle, and lower rectum. Although surgery is a cornerstone in this cancer, it is not chosen as the first treatment in certain circumstances. If the tumor exceeds a certain size, reaching what we call a locally advanced stage, or lies in the middle or lower rectum, surgery is not preferred initially because the anus would be lost.

Some rectal tumors may extend beyond bowel wall layers into surrounding tissue and/or involve lymph nodes around the bowel. This is defined as locally advanced rectal cancer.

Particularly for tumors near the end of the middle rectum and/or in the lower rectum, surgery requires removal of both the rectum and the muscles enabling defecation, called the anal canal. This surgical method necessarily results in a colostomy (a bag attached to the abdomen for passing stool). This is an undesirable, distressing outcome for patients and their families.

When we encounter a rectal cancer patient, we first use PET-CT to determine whether it has spread to other organs such as the liver. If there are no distant metastases, we also perform MRI of the rectal region. Together with PET-CT, this allows us to assess how far the tumor extends beyond bowel layers, whether lymph nodes are involved, and its location, and then decide.

In both situations described above, starting treatment with surgery is inappropriate. Operating directly on these patients without preliminary treatment (neoadjuvant chemotherapy/radiotherapy) will adversely affect treatment success.

Conventional neoadjuvant chemotherapy in locally advanced rectal cancer involves administering chemotherapy drugs through a vein in the arm. Our study instead concerns administration through an artery to kill tumor cells. This requires first identifying the tumor-feeding vessels with angiography, then advancing a very thin tube called a catheter through the groin into those vessels (selective catheterization). The chemotherapy drug is thus delivered directly into the vessels feeding the tumor.

How Is It Performed?

For intra-arterial treatments, the patient is first placed on the angiography table, and the groin artery is accessed under local anesthesia (numbing through the skin). Thin tubes called catheters are then advanced to the tumor region, and angiography (DSA) images are obtained by injecting medication into the vessels. These images seek to identify vessels feeding the tumor or tumors. Some interventional radiology centers, including ours, have special angiography devices capable of simultaneous angiography and computed tomography. With "cone beam CT," tumors invisible on conventional angiography devices can be visualized with their feeding vessels in 3 dimensions. Once the tumor-feeding arteries are identified, special catheters reach them and transarterial treatments are administered.

When a chemotherapy drug is given conventionally through an arm vein, it reaches the tumor only after passing through the heart and lungs and being distributed throughout the body. Its concentration is therefore reduced by the time it reaches the tumor. In intra-arterial chemotherapy, the drug is delivered directly into the tumor without losing concentration. A greater effect can therefore be achieved with the same dose, or less drug can be used for the same effect. This may increase its effect on the tumor while reducing side effects. This method increases intratumoral drug concentration 3-7 times. Interest in intra-arterial chemotherapy for cancer treatment has increased particularly over the last 10 years.

Our study analyzed data from a total of 13 patients diagnosed with locally advanced rectal cancer. Their median age was 57.

In patients receiving intra-arterial chemotherapy (IACT), the rate of marked disease regression, or downstaging, was %84,6, and the pathological complete response rate was %30,7. Compared with the initial tumor burden, all but 1 patient responded.

Of the patients receiving IACT, 12 (%92,3) were considered suitable for surgery, but 1 declined it. Among those operated on, no colostomy was required except in one patient whose mass was very close to the anal canal (1 cm). The 1 (%7,7) patient declining surgery received chemoradiotherapy and achieved a complete response.

In conclusion, although patient numbers are small compared with chemoradiotherapy data, objective and complete response rates with IACT are quite high. This alternative to standard treatment methods could introduce an innovation in locally advanced rectal cancer treatment if these results are supported by well-designed studies involving large patient numbers and comparisons with chemoradiotherapy.