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Delaying postradiotherapy surgery provides ‘useful alternative’ for rectal cancer
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Delaying surgery for 4 to 8 weeks after short-course radiotherapy conferred similar oncologic outcomes as immediate surgery among patients with rectal cancer, according to a randomized, nonblinded, phase 3 trial conducted in Sweden and published in The Lancet Oncology.
Patients who underwent delayed surgery had significantly fewer postoperative complications; however, 7% required hospital admission because of radiation toxicity.
“Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy with immediate surgery,” Johan Erlandsson, MD, of the department of molecular medicine and surgery at Karolinska University Hospital in Stockholm, and colleagues wrote. “Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.”
Preoperative radiotherapy reduces the risk for local recurrence after surgery for rectal cancer by more than 50%.
Typical treatment in most countries consists of conventionally fractionated long-course radiotherapy at five fractions of 1.8 Gy to 2 Gy per week for 5 to 6 weeks, usually in combination with chemotherapy. Common treatment in Sweden consists of short-course radiotherapy at five fractions of 5 Gy in 1 week followed by surgery within the following week. Fractionation and timing of surgery in relation to radiotherapy remain controversial.
In this noninferiority trial, called Stockholm III, researchers enrolled 840 patients with a biopsy-proven adenocarcinoma of the rectum from 18 hospitals in Sweden from Oct. 5, 1998, through Jan. 31, 2013.
Researchers randomly assigned 385 of those patients to one of three arms: short-course radiotherapy with surgery within 1 week (5 x 5 Gy radiation dose, n = 129; 63% men; median age, 67 years); short-course radiotherapy with surgery after 4 to 8 weeks (n = 128; 62% men; median age, 67 years); or long-course radiotherapy with surgery after 4 to 6 weeks (25 x 2 Gy radiation dose, n = 128, 57% male, median age, 66 years).
The remaining 455 patients were randomly assigned to one of the two short-course radiotherapy arms after a protocol amendment: short-course radiotherapy with immediate surgery (n = 228; 60% men; median age, 67 years) and short-course radiotherapy with delayed surgery (n = 227; 59% men; median age, 67 years).
Time to local recurrence calculated from the date of randomization to the date of local recurrence served as the study’s primary endpoint.
Median time to any local recurrence was 33.4 months (range, 18.2-62.2) among patients assigned short-course radiotherapy with immediate surgery, 19.3 months (range, 8.5-39.5) for patients assigned short-course radiotherapy with delayed surgery, and 33.3 months (range 17.8-114.3) for patients assigned long-course radiotherapy with delayed surgery.
Cumulative incidence of local recurrence was eight of 357 patients who received short-course radiotherapy with immediate surgery, 10 of 355 who received short-course radiotherapy with surgery delay, and seven of 128 who received long-course radiotherapy.
Compared with short-course radiation with immediate surgery, the HR for local recurrence was noninferior for short-course radiotherapy with a delay (HR = 1.44; 95% CI, 0.41-5.11) and long-course radiotherapy with a delay (HR = 2.24; 95% CI, 0.71-7.1).
Acute radiation-induced toxicity was recorded in one patient (< 1%) after short-course radiotherapy with immediate surgery; 23 patients (7%) after short-course radiotherapy with delay; and six patients (5%) after long-course radiotherapy with delay.
Frequency of postoperative complications was similar between all arms. Such complications occurred in 65 patients (50%) in the short-course radiotherapy group with immediate surgery, 48 patients (38%) in the short-course radiotherapy with delay (OR = 0.59; 95% CI, 0.36-0.97) and 50 (39%) in the long-course radiotherapy with delay (OR = 0.63; 95% CI, 0.39-1.04).
However, in a pooled analysis of the two short-course radiotherapy regimens, the risk for postoperative complications was significantly lower after short-course radiotherapy with delay than with immediate surgery (41% vs. 53%; OR = 0.61; 95% CI, 0.45-0.83).
Researchers noted that, due to insufficient resources for radiotherapy at certain hospitals, fewer patients were enrolled in the long-course radiotherapy with delay group than in the other two groups.
“Short-course radiotherapy with surgery delayed for 4 to 8 weeks might have certain advantages over immediate surgery in rectal cancer treatment,” Erlandsson and colleagues wrote. “Oncological outcomes seem similar to short-course radiotherapy with surgery within 1 week; acute radiation toxicity is observed but the postoperative complications are significantly fewer.”
d that short-course radiotherapy with delay provides the opportunity to advise patients on blood pressure adjustment, smoking cessation, nutrition and individualized training programs, and to plan surgery well in advance.
Short-course radiotherapy with immediate surgery remains a “valuable option” because the rectum is removed before symptoms of radiation damage appear, and because patients generally prefer shorter treatments, Krzysztof Bujko, MD, and Rafal Sopylo, MD, professors in the department of radiotherapy and surgery at Maria Sklodowska-Curie Memorial Cancer Centre in Warsaw, Poland, wrote in an accompanying editorial. They also noted that short-course radiotherapy with delay might be better suited for patients aged older than 75 years, although only one-fourth of those included in this trial fit that criteria.
“Because short-course radiotherapy with delayed surgery might be better tolerated than chemoradiation, short-course radiotherapy with delay might be especially useful in elderly fragile patients either with small tumors before local excision or in those with locally advanced tumors that need shrinkage before abdominal surgery,” Bujko and Sopylo wrote. “Interim analysis of the Stockholm III trial showed that 11.8% of patients achieved a pathological complete response after the short-course radiotherapy with delayed surgery. Thus, that watch-and-wait policy after such treatments is worthy of investigation.” – by Chuck Gormley
Disclosure: The researchers, Bujko and Sopylo report no relevant financial disclosures.
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