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RAPIDO Results Offer New Standard of Care for Rectal Cancer

Washington University colon and rectal surgeons are committed to providing patients the best possible care for sensitive, serious conditions, including colorectal cancers. Surgeons at the School of Medicine and Siteman Cancer Center are experts in treating colorectal cancer using laparoscopic surgical techniques. The Section of Colon and Rectal Surgery is home to leaders in the specialization of colorectal surgery, internationally recognized and at the forefront of research, education and patient care.

The treatment of colorectal cancer requires a collaborative approach, including experts in surgery, radiation and medical oncology. At the School of Medicine, surgeons, radiologists and oncologists take a truly multidisciplinary approach to managing these serious conditions, ensuring the most effective diagnosis, staging and treatment of colon and rectal cancers.

Results of a clinical trial identify a new standard of care for patients with locally advanced rectal cancer. Surgeons from the Section of Colon and Rectal Surgery, alongside radiologists from the Mallinckrodt Institute of Radiology and oncologists from the Department of Medicine participated in this study, advancing patient care both locally and internationally through their contributions.

The results, published in the Journal of Clinical Oncology in May 2020, compare the conventional treatment of rectal cancer with an experimental treatment involving more pre-operative (neoadjuvant) therapy and a shorter overall treatment time.

Rectal cancer is a disease in which cancer cells form in the tissues of the rectum—the last 6-8 inches of the colon. These cells form in the innermost layer of the rectum, and have the potential to spread to other layers, lymph nodes or nearby organs, which determines the stage of cancer. If the cells have spread to nearby tissues or lymph nodes, the cancer is described as locally advanced rectal cancer (LARC).

According to the American Cancer Society, colorectal cancer is the third most common cancer diagnosed in men and women in the United States, and the third leading cause of cancer-related death. Despite these statistics, death rates from colorectal cancer have been on the decline in recent years, thanks to advances in screening and early detection and removal. The results of this trial have the potential to improve patient outcomes and reduce colorectal cancer death rates even further.

TNT Makes an Impact

In 2011, researchers at Washington University School of Medicine in St. Louis and Siteman Cancer Center joined an international multicenter clinical trial to study the impact of neoadjuvant therapies on disease-free survival of patients with LARC.

The objective of the trial—called the Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) Trial—was to decrease Disease-related Treatment Failure (DrTF) in patients with LARC. DrTF includes locoregional failure, distant metastasis, a new primary colon tumor or treatment-related death—outcomes where the treatment does not leave the patient cancer-free.

The current standard treatment for patients whose cancer puts them at high risk of DrTF includes 5 weeks of preoperative, long course radiotherapy in combination with chemotherapy. This treatment, called neoadjuvant chemoradiotherapy, is followed by surgery to remove the tumor. Then, based on a combination of the clinical and pathologic stage, the treatment may include postoperative systemic chemotherapy. This treatment regimen is effective at preventing the tumor from returning in the pelvis, but does not decrease the risk of the tumor showing up somewhere outside of the rectum. It is also a long and difficult treatment process, lasting up to 44 weeks for some patients.

This treatment regimen is widely accepted as the standard in the United States.

Photo by National Cancer Institute

The RAPIDO trial included 56 study locations, 55 of them in Europe. Researchers from Washington University School of Medicine at Siteman Cancer Center were the only participants from North America involved in this phase 3 clinical trial.

The new treatment, tested in the RAPIDO trial, administers 5 days of short course radiotherapy. Delivering the same biologic dose of radiation in a shorter time, this treatment then administers systemic chemotherapy pre-operatively, followed by surgery. All of the chemoradiotherapy occurs before surgery, making this a total neoadjuvant therapy (TNT).

There are several benefits to this treatment regimen, including the shorter duration: TNT typically lasts 31 weeks rather than 44.

“Short course radiation is accepted in Europe, but not in the US,” says Matthew Mutch, MD, Section Chief of Colon and Rectal Surgery. “This study demonstrates some of the benefits of short course radiation compared to long course radiation.”

RAPIDO trial results also found a lower rate of distant metastases in high-risk LARC patients, meaning the new treatment regimen reduced the rate of DrTF. Colorectal surgeons in the Department of Surgery have found that systemic chemotherapy is better tolerated before surgery than after, patients receive more systemic chemotherapy when given before than after surgery, and more total patients receive systemic chemotherapy—and their rectal cancers are more likely to shrink—with TNT.

“I want to thank all of the colorectal surgeons who braved ‘conventional wisdom,’” says Parag Jitendra Parikh, BSE, MD, Director of MR-Guided Radiation Therapy and GI Radiation Oncology at Henry Ford Cancer Instititue. Parikh, who was a member of the Department of Radiation Oncology during the RAPIDO trial, hopes to see more physicians offer this treatment option to their patients.

Surgeons in the Section of Colon and Rectal Surgery at Washington University School of Medicine provide up-to-the-minute care in all aspects of colon and rectal surgery, striving to advance treatment options to achieve optimal patient outcomes.

“At the School of Medicine,” says Steven Hunt, MD, Associate Professor of Colon and Rectal Surgery, “the experts and leaders in every field come together for the patient. We are proud to work closely with radiologists and oncologists in this trial and every day for our patients. That collaborative environment allows us to provide care unlike any other cancer center in the region or nation.”