Intervention Review

You have free access to this content

Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer

  1. Laura De Caluwé,
  2. Yves Van Nieuwenhove,
  3. Wim P Ceelen*

Editorial Group: Cochrane Colorectal Cancer Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 16 JUL 2012

DOI: 10.1002/14651858.CD006041.pub3


How to Cite

De Caluwé L, Van Nieuwenhove Y, Ceelen WP. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD006041. DOI: 10.1002/14651858.CD006041.pub3.

Author Information

  1. Ghent University Hospital, Department of GI Surgery, Ghent, Belgium

*Wim P Ceelen, Department of GI Surgery, Ghent University Hospital, De Pintelaan 185, Ghent, B-9000, Belgium. wim.ceelen@ugent.be.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Bosset 2006

Methods1.Randomization method: telephone to central office (assumed)
2. Abdominal imaging: CT
3. Chest imaging: CXR
4. 4 arm study: Arm 1 preop RT + S; Arm 2 preop XRT + concurrent 5FU LV + S;Arm 3 preop RT + S + post op 5FU LV ; Arm 4 preop RTCT+ S + postop 5FU LV
5. Total randomized 1011


Participants1. Rectal Cancer
2. Location: within 15 cm from anal verge
3. Resectability: locally resectable
4. T3 or resectable T4 (defined by clinical criteria or endoscopic ultrasound)
5. WHO PS 0-1
6. </=80yr


Interventions1.Surgery: AP/anterior resection or Hartman with TME
2. RT : 45 Gy in 25fr.
3. RT volume: 5cm above and below tumour and perirectal nodes below S2-3. If tumour above 10cm, include
only 3 cm above tumour. If tumour in low rectum, S2-3 to perineum. Posteriorly to include entire sacrum with 3cm beyond macroscopic extension
4. RT-S: within 3-10 weeks of completing neoadjuvant therapy
5. 3 or 4 field
6. Chemotherapy: 5FU 325mg/m2/d; Leucovorin 20mg/m2/day Dy1-5 & 28-32 for arms 2 and 4, and
postoperative for arms 3 and 4


Outcomes1. Duration of FU: 5.4 yrs
2. Perioperative mortality: CRTS 2.4 % (12/506) RTS 1.2% (6/505)
3. Mets (liver) @ lap: Y
4. Curative resection: not stated
5. Overall resection: 94.5 %
6. Compliance to radiotherapy: CRTS 483/506 (95.5%) RTS 495/505 (98.0%)
7. OAS: Y
8. CSS?
9. Tox post RT: Y
10. Acute tox post S: Y
11. Late tox post S: Y
12. LR: Y
13. QOL: N
14. Proportion sfincter sparing: CRTS 267/506 (52.8%) RTS 255/505 (50.5%)
15. Proportion downstaging: Y


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Boulis-Wassif 1984

Methods1.Randomization method: not stated. conducted by cooperative group. Likely via central office
2. Abdominal imaging: Not stated
3. Chest imaging: Not stated
4. Study arm (Preop chemoradiotherapy arm) : 171randomized, 45 excluded.
5. Control arm (Preop radiotherapy arm): 168 randomized , 47 excluded


Participants1. Rectal Cancer
2. Location: below within 15cm anal verge
3. Resectability: fit for surgery


Interventions1.Surgery: AP/anterior resection
2. RT : 3450 cGy in 15fr. (for both arms)
3. BED: 35.2Gy1
4. RT volume: ''chimney and diamond fields" paraaortic and pelvis.
5. RT-S: within 2 wk
6. 2 field
7. Cointervention: none
8. 2 arms, control (Radiotherapy followed by surgery), Study (Chemoradiotherapy followed by surgery)
9.Chemotherapy: 5FU 10mg/kg/d day 1-4


Outcomes1.Duration of FU: mean 5.2yrs
2. Perioperative mortality: CRTS 19/126 RTS 11/121
3. Mets @ lap: CRTS 13/126 RTS 15/121
4. Curative resection: Not stated
5. Overall resection: CRTS 121, RTS 124
6. Compliance to radiotherapy: not given
7. OAS: Y
8. CSS: N
9. Tox post RT: not given
10: Acute tox post S: not given
No complication not given
11. Late tox post S: not given
12: LR: N
13. QoL:N


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Bujko 2006

Methods1.Randomization method: telephone to central office
2. Abdominal imaging: ultrasound or CT
3. Chest imaging: CXR
4. XRT + S arm : (short XRT)155 randomized, 0 excluded.
5. Arm B: (Long XRT+CT): 157 randomized , 0 excluded


Participants1. Rectal Cancer
2. Location: inferior edge palpable of digital exam
3. Resectability: locally resectable
4. T3 or resectable T4
5. not involving sphincter


Interventions1.Surgery: AP/anterior resection or Hartman with TME
2. RT : XRT +S arm: 2500cGy cGy in 5fr. ; Arm B: 50.4Gy in 28 fr with concomitant CT weeks 1 & 5
3. BED: Arm A 38.7Gy10, Arm B 40.9Gy10
4. RT volume: Not stated
5. RT-S: XRT+S within 7 days; Arm B: within 4-6 weeks
6. 3 or 4 field
7. Arm B chemotherapy: 5FU 325mg/m2/d; Leucovorin 20mg/m2/day Dy1-5 & 28-32


Outcomes1.Duration of FU: not stated
2. Perioperative mortality: XRT+S 0/155 Arm B 0/157
3. Mets @ lap: not stated
4. Curative resection: not stated
5. Overall resection: XRT+S 145/155 Arm B 147/157
6. Compliance to radiotherapy: XRT+S 152/155 Arm B 141/157
7. OAS: N
8. CSS: N
9. Tox post RT: no complications XRT+S 118/155 Arm B 24/157 Any complications XRT+S 37/155 Arm
B 133/157 Gd 3-4 XRT + S 5/155 Arm B 26/157 Gd 5 (Death) XRT +S 0/155 Arm B 2/157
10: Acute tox post S: Not stated
11. Late tox post S: not given
12: LR: N
13. QoL:N
14. Proportion sphincter sparing
15. Proportion downstaged (by T stage, N stage, Tumor size)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Gerard 2006

Methods1.Randomization method: not stated
2. Abdominal imaging: liver sonography - CT scan
3. Chest imaging: CXR
4. Study arm: CRT 375
5. Control arm: RT 367


Participants1. Rectal Cancer
2. Location: accessible by digital examination
3. Resectability: locally resectable


Interventions2 arms: preop XRT vs preop CRT
1.Surgery: TME recommended
2. RT 45Gy in 25 fr for both arms
3. BED: 32.5Gy10
4. RT volume: NA
5. RT-S: NA
6. NA
7. Cointervention: postoperative CT (5FU FA) x 4 cycles


Outcomes1.Duration of FU: 81m
2. Perioperative mortality (60 days): 2% for both arms
3. Mets @ lap: not stated
4. Curative resection: not stated
5. Overall resection: not stated
6. Compliance to radiotherapy: not stated
7. OAS: Y
8. CSS: Y
9. Tox (gr 3-4) post RT: Preop RT arm: 10/367 CRT arm: 55/375
10: Acute tox post S: not stated
11. Late tox post S: Y


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Latkauskas 2011

Methods1. Randomization method: not stated

2. Abdominal imaging: abdominal US, EUS, CT scan and MRI pelvis

3. Chest imaging: CXR

4. Study arm: CRT 46
5. Control arm: RT 37


Participants1. Rectal cancer stage II and III

2. less than 15 cm from anal verge

3. <80 years old, no other cancer during last 5 years


Interventions1. CRT: 50 Gy in 25 fractions, 1.8-2 Gy/fraction over 5 weeks with 5-FU/LV during week 1 and 5

2. RT: 25 Gy in 5 fractions

3. Surgery: after 6 weeks in both groups


Outcomes1. Duration of FU: not stated
2. Perioperative mortality: not stated
3. Mets @ lap: not stated
4. Curative resection: 91.3% (CRT), 86.5% (RT)
5. Overall resection: 37/37 (RT), 46/46 (CRT)
6. Compliance to radiotherapy: not stated
7. OAS: not stated
8. CSS: not stated
9. Tox (gr 3-4) post RT: not stated
10: Acute tox post S: not stated
11. Late tox post S: not stated


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low risk

 
Characteristics of ongoing studies [ordered by study ID]
Siegel 2009

Trial name or titlePreoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society

MethodsProspective Randomized trial

ParticipantsPrimary rectal cancer within 12 cm from anal verge, cT3N+, cT3N0, or cT2N+

InterventionsShort course RT consists of single doses of 5.0 Gy in five fractions within one week up to a total dose of 25 Gy. For CRT, standard fractions of 1.8 Gy/d are given 5 times a week up to a total dose of 50.4 Gy; concomitant chemotherapy consists of continuous 5-FU-infusion 225 mg per square meter per day.

OutcomesLocal recurrence after five years follow up has been chosen as primary endpoint.

Starting date2008

Contact informationPeter M Schlag email: pmschlag@charite.de

Department of Surgery and Surgical Oncology, Charité – Universitätsmedizin Berlin, Berlin, Germany

Notes

 
Comparison 1. radiotherapy vs radiochemotherapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Overall Survival at 5y32000Odds Ratio (M-H, Fixed, 95% CI)1.05 [0.88, 1.27]

 2 HR_OS40Hazard Ratio (95% CI)1.02 [0.89, 1.17]

 3 Disease free survival at 5 y21753Odds Ratio (M-H, Fixed, 95% CI)0.90 [0.74, 1.09]

 4 Mortality 30 d52322Odds Ratio (M-H, Random, 95% CI)1.48 [0.83, 2.63]

 5 Postop morbidity42077Odds Ratio (M-H, Random, 95% CI)0.82 [0.67, 1.00]

 6 Grade III - IV toxicity32032Odds Ratio (M-H, Random, 95% CI)4.10 [1.68, 10.00]

 7 Sphincter preservation52302Odds Ratio (M-H, Random, 95% CI)1.09 [0.92, 1.30]

 8 pCR52284Odds Ratio (M-H, Random, 95% CI)3.52 [2.12, 5.84]

 9 Anastomotic leak41151Odds Ratio (M-H, Random, 95% CI)1.07 [0.62, 1.84]

 10 Local Recurrence at 5y31494Odds Ratio (M-H, Fixed, 95% CI)0.53 [0.39, 0.72]

 11 HR_DFS40Hazard Ratio (95% CI)0.99 [0.84, 1.17]

 12 HR_LR30Hazard Ratio (95% CI)0.71 [0.52, 0.95]

 
Table 1. excluded studies

TypeN

Non randomized trials144

Adjuvant therapy trials28

Trials not including at least one chemotherapy arm combined with radiotherapy71

Trials not including radiotherapy27

Trials using local or no resection18

Trials including other tumour types25

Trials not including stage II/III cancer7

Total320