Trial Outcomes & Findings for The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer (NCT NCT00904813)
NCT ID: NCT00904813
Last Updated: 2021-05-07
Results Overview
Local recurrence was defined as tumour growth below the level of the sacral promontory, related to the previous rectal cancer, and diagnosed radiographically with MRI, CT, or both, or clinically (preferably with histological confirmation). A diagnosis of local recurrence was confirmed and reported by the patient-responsible physician to the Swedish ColoRectal Cancer Registry (SCRCR), a nationwide validated national registry. Local recurrence was measured both as first and any event occurring during follow-up (censoring date March 30 2015), when all patients had been followed for at least 2 years.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
840 participants
Primary outcome timeframe
From date of randomisation until date of local recurrence or date of death from any cause, whichever came first, assessed up to end of follow-up.
Results posted on
2021-05-07
Participant Flow
Patients were recruited from 18 hospitals in Sweden between 1998-2013 and initially randomly assigned (1:1:1) to three different arms; Short-course radiotherapy with surgery within 1 week (SRT) or after 4-8 weeks (SRT-delay), or Long-course radiotherapy with surgery after 4-8 weeks (LRT-delay). After a protocol amendment in 1999 hospitals could choose to randomise patients to all three arms or only short-course treatment arms (SRT or SRT-delay, 1:1). Patients could only be randomised to one arm.
Of 8122 eligible patients, 385 were assigned to the three-armed randomisation and 455 to the two-armed randomisation, resulting in 840 participants included in the study.
Participant milestones
| Measure |
Three-arm Randomisation: SRT
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Two-arm Randomisation: SRT
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Two-arm Randomisation: SRT-delay
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
129
|
128
|
128
|
228
|
227
|
|
Overall Study
COMPLETED
|
129
|
128
|
128
|
228
|
227
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer
Baseline characteristics by cohort
| Measure |
Three-arm Randomisation: SRT
n=129 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
n=128 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
n=128 Participants
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Two-arm Randomisation: SRT
n=228 Participants
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Two-arm Randomisation: SRT-delay
n=227 Participants
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Total
n=840 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
67 years
n=5 Participants
|
67 years
n=7 Participants
|
66 years
n=5 Participants
|
67 years
n=4 Participants
|
67 years
n=21 Participants
|
67 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
93 Participants
n=21 Participants
|
336 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
81 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
137 Participants
n=4 Participants
|
134 Participants
n=21 Participants
|
504 Participants
n=8 Participants
|
|
Tumour height from anal verge
0-5 centimeter
|
50 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
78 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
284 Participants
n=8 Participants
|
|
Tumour height from anal verge
6-10 centimeter
|
49 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
95 Participants
n=21 Participants
|
344 Participants
n=8 Participants
|
|
Tumour height from anal verge
11-15 centimeter
|
30 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
63 Participants
n=21 Participants
|
207 Participants
n=8 Participants
|
|
Tumour height from anal verge
Missing
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
|
Type of Surgery
Anterior Resection
|
79 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
139 Participants
n=4 Participants
|
136 Participants
n=21 Participants
|
515 Participants
n=8 Participants
|
|
Type of Surgery
Abdominal perineal excision
|
47 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
79 Participants
n=21 Participants
|
278 Participants
n=8 Participants
|
|
Type of Surgery
Hartmann's
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
43 Participants
n=8 Participants
|
|
Type of Surgery
Local excision
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Type of Surgery
No resection
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
|
ypStage
I
|
38 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
83 Participants
n=21 Participants
|
271 Participants
n=8 Participants
|
|
ypStage
II
|
43 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
55 Participants
n=21 Participants
|
250 Participants
n=8 Participants
|
|
ypStage
III
|
48 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
86 Participants
n=4 Participants
|
76 Participants
n=21 Participants
|
278 Participants
n=8 Participants
|
|
ypStage
IV
|
0 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
25 Participants
n=8 Participants
|
|
ypStage
Stage x
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
|
ypStage
Missing
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: From date of randomisation until date of local recurrence or date of death from any cause, whichever came first, assessed up to end of follow-up.Population: Participants were analysed according to intention to treat.
Local recurrence was defined as tumour growth below the level of the sacral promontory, related to the previous rectal cancer, and diagnosed radiographically with MRI, CT, or both, or clinically (preferably with histological confirmation). A diagnosis of local recurrence was confirmed and reported by the patient-responsible physician to the Swedish ColoRectal Cancer Registry (SCRCR), a nationwide validated national registry. Local recurrence was measured both as first and any event occurring during follow-up (censoring date March 30 2015), when all patients had been followed for at least 2 years.
Outcome measures
| Measure |
Three-arm Randomisation: SRT
n=129 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
n=128 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
n=128 Participants
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Two-arm Randomisation: SRT
n=228 Participants
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Two-arm Randomisation: SRT-delay
n=227 Participants
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Pooled Short-course RT: SRT
n=357 Participants
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from the three-armed and two-armed randomisation.
|
Pooled Short-course RT: SRT-delay
n=355 Participants
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from the three-armed and two-armed randomisation.
|
|---|---|---|---|---|---|---|---|
|
Time to Local Recurrence.
|
28.3 months
Interval 20.7 to 62.2
|
22.1 months
Interval 15.5 to 34.3
|
33.3 months
Interval 17.8 to 114.3
|
35.1 months
Interval 18.2 to 59.9
|
17.2 months
Interval 8.5 to 39.5
|
33.4 months
Interval 18.2 to 62.2
|
19.3 months
Interval 8.5 to 39.5
|
SECONDARY outcome
Timeframe: From surgery until 30 days postoperatively.Population: Participants were analysed as treated and grouped based on type of preoperative radiotherapy (RT) and overall treatment time (OTT).
Postoperative complications was defined as any cardiovascular event, infectious, neurological or surgical complications occurring within 30 days after surgery, or during the same hospital admission, validated from medial records. Overall postoperative complication was defined as having at least one postoperative complication. Participants were grouped based on type of preoperative radiotherapy (RT) regimen (eg short- or long course) and overall treatment time (OTT), defined as time between start of RT and surgery. Participants receiving short-course RT were categorised into four different groups; Group A: OTT 7 days, Group B: OTT 8-13 days, Group C: OTT 5-7 weeks, Group D: OTT 8-13 weeks. Participants receiving long-course RT were categorised into two different groups; Group E: OTT 9-11 weeks, Groups F: OTT 12-14 weeks.
Outcome measures
| Measure |
Three-arm Randomisation: SRT
n=100 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
n=247 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
n=192 Participants
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Two-arm Randomisation: SRT
n=160 Participants
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Two-arm Randomisation: SRT-delay
n=52 Participants
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Pooled Short-course RT: SRT
n=59 Participants
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from the three-armed and two-armed randomisation.
|
Pooled Short-course RT: SRT-delay
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from the three-armed and two-armed randomisation.
|
|---|---|---|---|---|---|---|---|
|
Number of Participants With Postoperative Complications in Relation to Preoperative Radiotherapy Regimen and Overall Treatment Time.
Overall postoperative complications
|
45 Participants
|
138 Participants
|
82 Participants
|
63 Participants
|
16 Participants
|
28 Participants
|
—
|
|
Number of Participants With Postoperative Complications in Relation to Preoperative Radiotherapy Regimen and Overall Treatment Time.
No postoperative complication
|
55 Participants
|
109 Participants
|
110 Participants
|
97 Participants
|
36 Participants
|
31 Participants
|
—
|
SECONDARY outcome
Timeframe: At the time of surgery.Population: Participants grouped based on allocated treatment and analysed as-treated. Only participants with available microscopy slides were included in the analysis.
Tumour regression (TRG) was assessed using the Dworak grading scoring system, ranging from scores 0 to 4 with higher scores indicating better tumour regression. Definition of scores; 0 = no regression, 1 = dominant tumour mass with obvious fibrosis and/or vasculopathy, 2 = dominantly fibrotic changes with few tumour cells or groups (easy to find), 3 = very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucous substance, 4 = no tumour cells, only fibrotic mass (total regression or complete response). All available microscopy slides were assessed by one pathologist, blinded to treatment.
Outcome measures
| Measure |
Three-arm Randomisation: SRT
n=318 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
n=285 Participants
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
n=94 Participants
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Two-arm Randomisation: SRT
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Two-arm Randomisation: SRT-delay
Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Pooled Short-course RT: SRT
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from the three-armed and two-armed randomisation.
|
Pooled Short-course RT: SRT-delay
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from the three-armed and two-armed randomisation.
|
|---|---|---|---|---|---|---|---|
|
Tumour Regression Based on the Dworak Grading Scoring System
TRG 0
|
29 Participants
|
20 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
|
Tumour Regression Based on the Dworak Grading Scoring System
TRG 1
|
233 Participants
|
124 Participants
|
42 Participants
|
—
|
—
|
—
|
—
|
|
Tumour Regression Based on the Dworak Grading Scoring System
TRG 2
|
50 Participants
|
92 Participants
|
37 Participants
|
—
|
—
|
—
|
—
|
|
Tumour Regression Based on the Dworak Grading Scoring System
TRG 3
|
2 Participants
|
16 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
|
Tumour Regression Based on the Dworak Grading Scoring System
TRG 4
|
4 Participants
|
29 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
|
Tumour Regression Based on the Dworak Grading Scoring System
Not assessable
|
0 Participants
|
4 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
Adverse Events
Three-arm Randomisation: SRT
Serious events: 0 serious events
Other events: 65 other events
Deaths: 51 deaths
Three-arm Randomisation: SRT-delay
Serious events: 7 serious events
Other events: 48 other events
Deaths: 43 deaths
Three-arm Randomisation: LRT-delay
Serious events: 6 serious events
Other events: 50 other events
Deaths: 49 deaths
Pooled Short-course RT: SRT
Serious events: 1 serious events
Other events: 188 other events
Deaths: 110 deaths
Pooled Short-course RT: SRT-delay
Serious events: 23 serious events
Other events: 144 other events
Deaths: 108 deaths
Serious adverse events
| Measure |
Three-arm Randomisation: SRT
n=129 participants at risk
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
n=128 participants at risk
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
n=128 participants at risk
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Pooled Short-course RT: SRT
n=357 participants at risk
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from both three-armed and two-armed randomisation.
|
Pooled Short-course RT: SRT-delay
n=355 participants at risk
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from both three-armed and two-armed randomisation.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Acute radiation-induced toxicity
|
0.00%
0/129
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
5.5%
7/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
4.7%
6/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
0.28%
1/357
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
6.5%
23/355
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
Other adverse events
| Measure |
Three-arm Randomisation: SRT
n=129 participants at risk
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.
|
Three-arm Randomisation: SRT-delay
n=128 participants at risk
Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.
|
Three-arm Randomisation: LRT-delay
n=128 participants at risk
Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.
|
Pooled Short-course RT: SRT
n=357 participants at risk
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from both three-armed and two-armed randomisation.
|
Pooled Short-course RT: SRT-delay
n=355 participants at risk
Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from both three-armed and two-armed randomisation.
|
|---|---|---|---|---|---|
|
Surgical and medical procedures
Reoperation
|
8.5%
11/129
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
5.5%
7/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
5.5%
7/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
12.0%
43/357
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
10.4%
37/355
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
|
Surgical and medical procedures
Any postoperative complication
|
50.4%
65/129
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
37.5%
48/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
39.1%
50/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
52.7%
188/357
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
40.6%
144/355
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
|
Surgical and medical procedures
Any surgical complication
|
31.0%
40/129
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
25.8%
33/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
23.4%
30/128
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
35.9%
128/357
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
28.2%
100/355
Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place