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Rectal Cancer: Pre-surgery Radiotherapy Cuts 10-Year Recurrence by Half, in ASTRO Plenary Study

Samson, Kurt

doi: 10.1097/01.COT.0000392889.90335.fd
ASTRO Annual Meeting

ASTRO Annual Meeting

A short course of radiation before patients undergo surgery for colorectal cancer appears to more than double the odds of being cancer-free after 10 years, according to a randomized study presented during the plenary session of the ASTRO Annual Meeting.

Lead investigator Corrie Marijnen, MD, a radiation oncologist at Leiden University Medical Center in The Netherlands, said at a news briefing that the findings demonstrate that radiation prior to surgery offers significant benefits. For patients who received radiation before surgical resection, the 10-year local recurrence rate was 6.4%, versus 13.3% for patients who underwent surgery alone.

“In 805 patients, the incidence of recurrence was reduced from 30 percent to just five percent when pre-op radiation was administered for five days, followed by surgery,” she reported.

“Preoperative radiation is convenient for patients, since it requires only one week of daily radiation treatments. It is a safe and effective treatment that is typically painless, like receiving an x-ray. This study shows that Stage II and III rectal cancer patients should receive radiation therapy before surgery to prevent recurrence and preserve quality of life.”

Total mesorectal excision (TME) for rectal cancer has become the standard surgical treatment for rectal cancer, and it is believed that the technique has reduced pelvic recurrence rates to around 7%. Preoperative and postoperative radiation can further decrease the local regional recurrence rate, but the reduction in risk is counterbalanced by increased short- and long-term toxicity.

CORRIE MARIJNEN, MD: “Preoperative radiation is convenient for patients, since it requires only one week of daily radiation treatments

CORRIE MARIJNEN, MD: “Preoperative radiation is convenient for patients, since it requires only one week of daily radiation treatments

The TME trial investigated the value of this regimen in combination with total mesorectal excision. Long-term results were reported after a median follow-up of 11 years.

The study involved more than 1,800 patients who were eligible for TME and whose cancer had spread outside of its original location, but not to other parts of the body. Patients were randomly selected to receive either short-term radiation before surgery or surgery alone. Chemotherapy was not permitted.

Patients who underwent radiation before surgery had a significant decrease (6%) in their chances of local recurrence after 10 years when compared with those who did not receive radiation (11%). Overall recurrence was significantly lower in the irradiated group, 28.8% vs 33.6%, but this difference did not translate into improvement in overall survival, the researchers found.

“This study shows that patients with Stage II and III disease should receive radiation therapy before surgery to prevent recurrence and preserve quality of life,” said Dr. Marijnen. “We have advised that in all our Nordic countries, patients with Stage II and III rectal cancer will get this short course of preoperative radiotherapy before their TME surgery.”

A subgroup analysis showed that reduced local recurrence was reduced only in patients with a negative circumferential resection margin, in patients with positive lymph nodes, and in those with tumors more than 5 cm from the verge.

“These results demonstrate that good surgery absolutely is necessary and that radiotherapy can definitely add to the prevention of local recurrence,” she said.

“Our study suggests that tumors in the middle rectum and Stage III rectal cancer patients will most greatly benefit from receiving radiation before surgery. We believe that this short course of radiation will open a new window of opportunities in the treatment of rectal cancer coming back to its original tumor site and surrounding area.”

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Earlier Data

The findings are similar to two major studies published last year in Lancet (2009;373:811-820 and 821-828). One showed better local control and disease-free survival with preoperative radiotherapy than with selective postoperative chemoradiotherapy, while the second found that for any plane of surgery, a short-course of radiation reduced local recurrence by more than half.

Moreover, in patients who had a mesorectal plane resection, local recurrence was almost completely eliminated.

The data came from the Medical Research Council CR07 and National Cancer Institute of Canada Clinical Trials Group C016 trials.

Several previous randomized trials have provided similar evidence and confirm well-accepted observations, noted Robert D. Madoff, MD, from the University of Minnesota, in an accompanying editorial (Lancet 2009; 373:790-792).

“Preoperative radiation can mitigate, but not eliminate, the adverse effects of imperfect surgery. The best outcomes occurred when preoperative radiation was followed by optimum surgery, but conversely, optimum surgery alone was not the complete answer to local recurrence.”

Nader Hanna, MD, Head of Surgical Oncology at the University of Maryland Greenebaum Cancer Center, also noted that although the findings are encouraging, the study confirms that radiation is not a substitute for total resection. Complete resection remains the usual approach, but the study raises questions about the possibility of removing distal tumors to safe sphincter function, he said.

It also confirms that radiation alone is not a substitute for total mesorectal resection.

“Should patients just undergo surgery of just the lateral margins of the tumor? If so, that would be prac tice changing, but we do not know,” he said in a telephone interview. “Remember that even with radiation and surgery, recurrence in these patients is quite high. The numbers speak for themselves.”

© 2010 Lippincott Williams & Wilkins, Inc.
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