New rectal cancer treatment may reduce risk of recurrence, help avoid surgery

• A new treatment for locally advanced rectal cancer (LARC) has proved successful enough to avoid surgery and reduce the risk of recurrence, according to a new study.
• Total neaoadjuvant treatment (TNT) involves bouts of short-course radiotherapy followed by different rounds of chemotherapy.
• Researchers in Sweden found that the treatment reduced the existence of tumors by twice the amount as previous approaches.
• The treatment could reduce the need for complicated bowel surgery and the subsequent complications that ensue.

A new treatment for locally advanced rectal cancer (LARC) has proved successful enough to avoid surgery and reduce the risk of recurrence, according to a new study conducted at Uppsala University in Sweden and published in eClinicalMedicine .

Total neoadjuvant treatment (TNT) involves bouts of short-course radiotherapy followed by different rounds of chemotherapy .

The researchers followed 273 patients with high risk LARC at 16 hospitals from July 2016 to June 2020, and another 189 patients at 18 hospitals (including the original 16) during the same period. The patients received TNT and researchers found that the rates of tumor disappearance doubled from previous treatment regimens (from 14% to 28%), but also that there was no increase in the rate of recurrence.

Sweden, which has a population of about 10.5 million people, has about 2,000 people diagnosed with rectal cancer every year, and one-third of those have a high risk of recurrence.

Initial treatment for rectal cancer is often more than a month of radiotherapy or a combination of radiotherapy and concurrent chemotherapy. Surgery involves removing part of the patient’s bowel, which creates problems with bowel control and the need to install a stoma .

Bengt Glimelius, PhD , lead author of the study and professor of oncology at Uppsala University and a senior consultant at Uppsala University Hospital in Sweden, said in a press release that TNT’s ability to attack tumors directly can provide relief from the invasive surgery and subsequent side effects.

“If the tumor disappears completely during treatment, surgery is not required. This means that the rectum is preserved and the need for a stoma and a new rectum is eliminated,” Dr. Glimelius said.

“When part of the rectum is surgically removed, the new rectum does not quite understand that it should be able to refrain from frequently sending a signal to the brain that you need to use the toilet,” he explained.

What sets TNT apart from other treatments for colorectal cancer?

Anne Mongiu, MD, PhD, FACS, FASCRS, co-director of the colorectal surgery program at Yale Cancer Center and Smilow Cancer Hospital and also an assistant professor of surgery (colon and rectal) at Yale School of Medicine, who was not involved in the study, told Medical News Today that rectal cancer treatment has been evolving since the 1980s, but that TNT’s approach changes the order of treatment.

“Total Neoadjuvant Therapy (TNT) refers to giving a full regimen of chemotherapy (FOLFOX, FOLFOXIRI, FOLFIRINOX, or CAPEOX most commonly) and chemoradiotherapy (radiation therapy in combination with Capecitabine) used in the treatment of rectal cancer prior to surgery. The treatment modalities used in TNT are relatively established; TNT simply shifts the entirety of the treatment prior to surgery,” Dr. Mongiu said.

“Chemotherapy was often given in the adjuvant (post-surgery) setting for those with positive lymph nodes to reduce the risk of metastatic disease. However, often patients did not get a full course of chemo or could not start it in a timely fashion after surgery if there were surgical complications,” she continued.

“Therefore, in the 2010s, there were a number of trials which moved chemotherapy to the neo-adjuvant (pre-surgical) time frame. This increased overall compliance with chemotherapy and was shown to have an increase in complete pathologic response (pCR) whereby no residual tumor was identified in post-surgical pathology specimens,” she said.

Nilesh Vora, MD , a board certified hematologist, medical oncologist, and medical director of the MemorialCare Todd Cancer Institute at Long Beach Medical Center in Long Beach, CA, who was also not involved in the study, told Medical News Today that TNT was a novel approach.

“The idea of giving neoadjuvant therapy means great compliance to the intended therapies and a greater chance of downstaging the tumor before surgery. This is novel compared with historical therapies for rectal cancer,” Dr. Vora said.

How accessible is TNT globally?

Glimelius, the study’s lead author, told MNT that total neoadjuvant treatment can be equally effective worldwide.

“The previous treatment was either radiotherapy alone or a combination with radiotherapy and chemotherapy simultaneously with chemotherapy, surgery, and postoperatively chemotherapy. TNT means all radiotherapy and chemotherapy before surgery and nothing afterwards,” Glimelius said.

“TNT is more or less taking over around the world. Could be provided worldwide. In the preceding randomized trial, seven countries, including the U.S. took part.  No difference between countries,” he added.

Mongiu emphasized that while the treatment is theoretically accessible to people around the world, economic disparities will prevent it from happening.

“The underlying healthcare infrastructure in each country impacts the availability of TNT. Most first-world countries, including the United States, Canada, Europe, many Asian countries, and Australia, offer TNT as evidenced by their participation in the large randomized clinical trials on TNT,” Mongiu said.

“Lower income countries and those with unstable infrastructure may struggle to purchase/maintain the specialized equipment, trained multidisciplinary teams, and chemotherapy agents needed to administer TNT,” she added.