In Some Rectal Cancers, 5 Days of Radiation as Good as 5 Weeks

Nick Mulcahy

January 20, 2016

Patients undergoing preoperative radiation for locally advanced rectal cancer and their clinicians now have a choice about the length of that treatment.

In a phase 3 trial, the effectiveness of an experimental short-course of radiation (5 days) was similar to that of long-course radiation (28 days), which is currently the standard of care. And the short course was less toxic.

Both schedules were combined with chemotherapy in the trial, known as Polish-II.

The results make the short-course option a new standard of care for these patients, said study investigator Lucjan Wyrwicz, MD, PhD, head of the medical oncology unit in Department of Gastrointestinal Cancer at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw, Poland.

"Having two standards is better than having one standard," said Dr Wyrwicz. "If we say, in 2016, there should be one kind of treatment for rectal cancer, it sounds stupid," he told reporters during a press briefing held in advance of the Gastrointestinal Cancers Symposium 2016 in San Francisco.

"It does give patients another choice," said press briefing moderator Smitha Krishnamurthi, MD, a medical oncologist at Case Western Reserve University in Cleveland, who is an American Society of Clinical Oncology expert. The experimental approach provides "shorter, more convenient, and less expensive" radiation that, along with chemotherapy, "appears equally active to standard chemoradiation," she summarized.

Dr Wyrwicz pointed out that the convenience of the short-course partially results from the fact that after the 5 days of radiation, patients can go home and receive their remaining chemotherapy on an outpatient basis.

Rectal cancers can be divided into "the good, the bad, and the ugly," he said, noting that locally advanced disease is "the ugly" because it has a "threatened resection margin" and, thus, is either unresectable or on the verge of being so. Preoperative therapy has the goal of reducing the size of the tumor in the hope of improving radical resection rates and other outcomes.

In their trial, Dr Wyrwicz and colleagues randomized half of the 515 patients with unresectable, locally advanced rectal cancer (stage cT3 or cT4) to standard chemoradiation (the control group) and half to short-course radiation (the experimental group). All patients also received chemotherapy.

The standard chemoradiation consisted of 50.4 Gy delivered in 28 fractions, administered simultaneously with a fluorouracil (5-FU) bolus, leucovorin, and oxaliplatin (the FOLFOX4 regimen).

The experimental group received the same FOLFOX4 regimen after the short-course radiation (5 days x 500 cGy for the pelvis).

Both groups underwent surgery about 12 weeks after starting radiation and about 6 weeks after neoadjuvant treatment.

The radical resection rate — the study's primary end point — favored the experimental group over the control group, but was not significant (77% vs 71%; P = .081).

At 3 years, the rate of disease-free survival was similar in the experimental and control groups (53% vs 52%; P = .74), as was the cumulative incidence of local failure (22% vs 21%; P = .82). However, there was a trend toward superior overall survival at 3 years in the experimental group (73% vs. 65%; P = .046).

Median follow-up was 35 months.

The "early observation" that there might be an overall survival benefit with the short course of radiation warrants further investigation in resectable rectal cancer, Dr Wyrwicz said.

There are, in fact, two independent trials (Polish-I and Trans-Tasman) in the setting of resectable rectal cancer that show that the short-course and standard chemoradiotherapy are equally effective.

There was significantly less acute toxicity of neoadjuvant treatment in the experimental group than in the control group (75% vs 83%; P = .006), but the rate of patients with grade 3+ toxicity was similar in the two groups (23% vs 21%).

Dr Wyrwicz pointed out that the addition of oxaliplatin to 5-FU and radiation is no longer considered standard therapy and is known to be more toxic than 5-FU with radiation. In 2012, after reports that the addition of oxaliplatin provided no advantage, it was determined that investigators at the trial's 40 sites could use their discretion when deciding whether to administer it. In total, 70% of the patients in the experimental group and 66% in the control group received oxaliplatin.

Dr Krishnamurthi observed that the use of short-course radiation in locally advanced rectal cancer varies by region, and is "more popular" in Europe than in the United States.

She also contends that results of an Australian study comparing short- and long-course radiotherapy in this setting might have been off-putting to some clinicians because there was a "slightly higher recurrence rate in low-lying rectal cancers" with the short course. But Dr Wyrwicz noted that this finding was "very weakly supported" as it was not statistically significant.

This study was conducted by the Polish Colorectal Study Group and received funding from the Polish Ministry of Science and Higher Education. Dr Wyrwicz and Dr Krishnamurthi have disclosed no relevant financial relationships.

Gastrointestinal Cancers Symposium (GICS) 2016: Abstract 489. To be presented January 23, 2016.

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