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Preoperative radiotherapy and chemoradiotherapy for rectal cancer
Evidence review C2
NICE Guideline, No. 151
National Guideline Alliance (UK).
The effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer
This evidence review supports recommendation 1.3.3.
Review question
What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
Introduction
The treatment of rectal cancer has become increasingly complex. The aim of this review was to assess how effective the use of preoperative therapy is in the treatment of rectal cancer, and to see whether there are any particular clinical situations where this treatment is beneficial, or alternatively, where it may be potentially omitted.
Summary of the protocol
Please see Table 1 for a summary of the population, intervention, comparison and outcomes (PICO) characteristics of this review.
Table 1
Summary of the protocol (PICO table).
For further details see the review protocol in appendix A.
Methods and process
This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual 2014. Methods specific to this review question are described in the review protocol in appendix A.
Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy until 31 March 2018. From 1 April 2018, declarations of interest were recorded according to NICE’s 2018 conflicts of interest policy. Those interests declared until April 2018 were reclassified according to NICE’s 2018 conflicts of interest policy (see Register of Interests).
Clinical evidence
Included studies
Thirty-two publications from 22 RCTs (number of participants, N=9,210) were included in this evidence review (Appelt 2014; Atif 2012; CAO/ARO/AIO-94 trial [Sauer 2003; Sauer 2012]; Eitta 2010; Dutch TME trial [Marijnen 2005; Peeters 2005, 2007; van Gijn 2011; Wiltink 2014]; GCR-03 trial [Fernandos-Martos 2015]; Kacar 2009; Lithuanian trial [Kairevice 2017; Latkauskas 2016]; Lyon R96-02 trial [Gerard 2004]; Marechal 2012; MRC CR07 trial [Sebag-Montefiore 2009; Stephens 2010]; NSABP R03 trial [Roh 2009]; Park 2011; Polish trial 1 [Bujko 2006; Pietrzak 2007]; Polish trial 2 [Bujko 2016]; Stockholm III trial [Erlandsson 2017]; Swedish Rectal Cancer Trial [Cedermark 1997; Folkesson 2005]; Taher 2006; TROG 01.04 trial [McLachlan 2016; Ngan 2012]; Wang 2018; Zhang 2008).
The included studies are summarised in Table 2.
Twelve RCTs (19 publications) compared any preoperative therapy to no preoperative therapy (comparison 1) (Atif 2012; CAO/ARO/AIO-94 trial [Sauer 2003; Sauer 2012]; Fan 2015; Dutch TME trial [Marijnen 2005; Peeters 2005, 2007; van Gijn 2011; Wiltink 2014]; Kacar 2009; MRC CR07 trial [Sebag-Montefiore 2009; Stephens 2010]; NSABP R03 trial [Roh 2009]; Park 2011; Swedish Rectal Cancer Trial [Cedermark 1997; Folkesson 2005]; Taher 2006; Wang 2018; Zhang 2008). Six RCTs (9 publications) compared short-course radiotherapy to long-course radiotherapy with or without chemotherapy (comparison 2) (Eitta 2010; Lithuanian trial [Kairevice 2017; Latkauskas 2016]; Polish trial 1 [Bujko 2006; Pietrzak 2007]; Polish trial 2 [Bujko 2016]; Stockholm III trial [Erlandsson 2017]; TROG 01.04 trial [McLachlan 2016; Ngan 2012]). Two RCTs compared chemoradiotherapy with prior chemotherapy to chemoradiotherapy without prior chemotherapy (comparison 3) (GCR-03 trial [Fernandos-Martos 2015]; Marechal 2012). Finally, 2 RCTs compared internal radiotherapy with or without external radiotherapy to external radiotherapy without internal radiotherapy (comparison 4) (Appelt 2014; Lyon R96-02 trial [Gerard 2004]).
See the literature search strategy in appendix B and study selection flow chart in appendix C.
Excluded studies
Studies not included in this review with reasons for their exclusions are provided in appendix K.
Summary of clinical studies included in the evidence review
Summaries of the studies that were included in this review are presented in Table 2.
Table 2
Summary of included studies.
See the full evidence tables in appendix D and the forest plots in appendix E.
Quality assessment of clinical studies included in the evidence review
See the clinical evidence profiles in appendix F.
Economic evidence
Included studies
A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.
Excluded studies
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.
Economic model
No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.
Evidence statements
Clinical evidence statements
Comparison 1: Any preoperative therapy versus no preoperative therapy
Critical outcomes
Overall survival
- One study (Zhang 2008) reported overall survival as observed events (n/N [%]) with no HR (95% CI), this study was not included in the pooled analysis.
- Moderate quality evidence from 8 RCTs (N=5,620; median follow-up 1.5 to 11.6 years) showed that receiving preoperative (chemo) radiotherapy produces a clinically important increase in overall survival compared to not receiving preoperative (chemo) radiotherapy in people with non-metastatic rectal cancer.
Complete (R0) resection rate
- Moderate quality evidence from 5 RCTs (N=4,356) showed no clinically important difference in complete (R0) resection rate between receiving and not receiving preoperative (chemo) radiotherapy in people with non-metastatic rectal cancer.
Overall quality of life
- Low quality evidence from 1 RCT (N not reported) showed no difference in overall health-related quality of life at 3, 6, 12 and 24 months after surgery (measured using a visual analogue scale) between receiving preoperative radiotherapy and undergoing surgery alone in people with non-metastatic rectal cancer. This result was reported narratively. Low quality evidence from the same RCT (N=478) showed no difference in global health status at median 14 years of follow-up (measured using EORTC QLQ-C30) between receiving preoperative radiotherapy and undergoing surgery alone.
- Low quality evidence from 1 RCT (N=519) showed no clinically important difference in health-related quality of life general health subscale score or physical function subscale score at 2 year follow-up (measured using SF-36) between receiving preoperative short-course radiotherapy and undergoing surgery alone (with selective postoperative chemoradiotherapy) in people with non-metastatic rectal cancer.
Important outcomes
Local recurrence
- Moderate quality evidence from 9 RCTs (N=5,807; median 1.5 to 11.6 years of follow-up) showed that receiving preoperative (chemo)radiotherapy produces a clinically important increase in local recurrence-free survival compared to not receiving preoperative (chemo)radiotherapy in people with non-metastatic rectal cancer.
- Low quality evidence from 2 RCTs (N=240) showed that receiving preoperative (chemo)radiotherapy produces a clinically important decrease in local recurrence rate at median 5.2 year follow-up compared to receiving postoperative (chemo)radiotherapy in people with non-metastatic rectal cancer.
- Low quality evidence from 1 RCT (N=162) showed that receiving preoperative (chemo)radiotherapy produces a clinically important decrease in local recurrence rate (follow-up time not reported) compared to undergoing surgery alone in people with non-metastatic rectal cancer.
Disease-free survival
- Moderate quality evidence from 6 RCTs (N=2,937; median 1.5 to 11.2 years of follow-up) showed that receiving preoperative (chemo)radiotherapy produces a clinically important increase in disease-free survival compared to not receiving preoperative (chemo)radiotherapy in people with non-metastatic rectal cancer.
Sphincter preservation/permanent stoma
- Low quality evidence from 1 RCT (N=597) showed no clinically important difference in permanent stoma rate at median 5 year follow-up between receiving preoperative radiotherapy and undergoing surgery alone in people with non-metastatic rectal cancer.
- Moderately quality evidence from 2 RCTs (N=419) showed no clinically important difference in sphincter preservation at 5 year follow-up between receiving and not receiving preoperative chemoradiotherapy in people with non-metastatic rectal cancer.
Treatment-related mortality
- Low quality evidence from 4 RCTs (N=3,935) showed no clinically important difference in treatment-related mortality (preoperative or postoperative) between receiving and not receiving preoperative (chemo) radiotherapy in people with non-metastatic rectal cancer.
- Low quality evidence from 1 RCT (N=1,350) showed no clinically important different in 30-day and 60-day operative mortality between receiving preoperative short-course radiotherapy and undergoing surgery alone (with selective postoperative chemoradiotherapy) in people with non-metastatic rectal cancer.
Comparison 2: Short-course radiotherapy versus long-course radiotherapy with or without chemotherapy
Critical outcomes
Overall survival
- Meta-analysis of overall survival showed considerable heterogeneity, therefore, subgroup analysis according to treatment subtype was done.
- Moderate quality evidence from 2 RCTs (N=635; median 4 to 5.9 years of follow up) showed no clinically important difference in overall survival between receiving preoperative short-course radiotherapy with immediate surgery and receiving preoperative long-course (chemo) radiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 1 RCT (N=150; median 5 years of follow-up) showed that receiving preoperative short-course radiotherapy with delayed surgery showed a clinically important decrease in overall survival compared to receiving preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 1 RCT (N=515; median 2.9 years of follow-up) showed no clinically important difference in overall survival between receiving preoperative short-course radiotherapy with consolidation chemotherapy and receiving preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 1 RCT (N=357; median 5.2 years of follow-up) showed that receiving preoperative short-course radiotherapy showed no clinically important difference in overall survival compared with long-course radiotherapy in people with non-metastatic rectal cancer.
Complete (R0) resection rate
- Meta-analysis of complete (R0) resection rate showed considerable heterogeneity, therefore, the results are presented separately for each study.
- Moderate quality evidence from 1 RCT (N=140) showed no clinically important difference in complete (R0) resection rate between receiving preoperative short course with delayed surgery or preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
- High quality evidence from 1 RCT (N=515) showed that receiving preoperative short-course radiotherapy with consolidation chemotherapy may produce a clinically important increase in complete (R0) resection rate compared to receiving preoperative long-course chemoradiotherapy and selective postoperative chemotherapy in people with non-metastatic rectal cancer, but there is uncertainty around the estimate.
- High quality evidence from 1 RCT (N=315) showed no clinically important difference in complete (R0) resection rate between receiving preoperative short course or long-course radiotherapy in people with non-metastatic rectal cancer.
Overall quality of life
- Low quality evidence from 1 RCT (N=296) showed no clinically important difference in health-related quality of life global health status score change from baseline to 12 months (measured using QLQ-C30) between receiving preoperative short-course or long-course radiotherapy in people with non metastatic rectal cancer.
- Low quality evidence from 1 RCT (N=221) showed no clinically important difference in health-related quality of life global health status score at 12 month follow-up (measured using EORTC QLQ-C30) between receiving preoperative short-course radiotherapy and receiving preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
Important outcomes
Local recurrence
- Moderate quality evidence from 2 RCTs (N=618; median 4 to 5.9 years of follow up) showed no clinically important difference in local recurrence-free survival between receiving preoperative short-course or long-course radiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 2 RCTs (N=286) showed no clinically important difference in local recurrence rate at median 1.5 to 5.2 years of follow-up between receiving preoperative short-course (with immediate surgery) or long-course radiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence frm 2 RCTs (N=396) showed no clinically important difference in local recurrence rate at median 5 to 5.2 years of follow-up between receiving preoperative short-course (chemo)radiotherapy with delayed surgery or long-course (chemo)radiotherapy in people with non-metastatic rectal cancer.
Disease-free survival
- Meta-analysis for disease-free survival showed considerable heterogeneity, therefore, subgroup analysis according to treatment subtype was done.
- Moderate quality evidence from 3 RCTs (N=892; median 4 to 5.9 years of follow up) showed no clinically important difference in disease-free survival between receiving preoperative short-course or long-course (chemo) radiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 1 RCT (N=140; median 5 years of follow-up) showed that receiving preoperative short-course radiotherapy with delayed surgery produces a clinically important decrease in disease-free survival compared to receiving preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 1 RCT (N=515; median 2.9 years of follow-up) showed no clinically important difference in disease-free survival between receiving preoperative short-course radiotherapy with consolidation chemotherapy and preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
Sphincter preservation/permanent stoma
- Moderate quality evidence from 2 RCTs (N=252) showed no clinically important difference in permanent stoma rate at median 3.3 to 4 year follow-up between receiving preoperative short-course radiotherapy or receiving preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
Treatment-related mortality
- Moderate quality evidence from 2 RCTs (N=569) showed no clinically important difference in treatment-related mortality between receiving preoperative short-course radiotherapy with immediate surgery and receiving preoperative long-course (chemo)radiotherapy in people with non-metastatic rectal cancer.
- Low quality evidence from 1 RCT (N=256) showed no clinically important difference in treatment-related mortality between receiving preoperative short-course radiotherapy with delayed surgery and receiving preoperative long-course radiotherapy in people with non-metastatic rectal cancer.
- Moderate quality evidence from 1 RCT (N=515) showed no clinically important difference in treatment-related mortality between receiving preoperative short-course radiotherapy with consolidation chemotherapy and receiving preoperative long-course chemoradiotherapy in people with non-metastatic rectal cancer.
Comparison 3: Chemoradiotherapy with prior chemotherapy versus chemoradiotherapy without prior chemotherapy
Critical outcomes
Overall survival
- Moderate quality evidence from 1 RCT (N=108; median 5.8 years of follow-up) showed no clinically important difference in overall survival between receiving induction chemotherapy and not receiving induction chemotherapy before preoperative chemoradiotherapy in people with non-metastatic rectal cancer.
Complete (R0) resection rate
- Moderate quality evidence from 2 RCTs (N=165) showed no clinically important difference in complete (R0) resection rate between receiving induction chemotherapy and not receiving induction chemotherapy before preoperative chemoradiotherapy in people with non-metastatic rectal cancer.
Overall quality of life
No evidence was identified to inform this outcome.
Important outcomes
Local recurrence
- Low quality evidence from 1 RCT (N=108; median 5.8 years of follow-up) showed no clinically important difference in local recurrence-free survival between receiving induction chemotherapy and not receiving induction chemotherapy before preoperative chemoradiotherapy in people with non-metastatic rectal cancer.
Disease-free survival
- Low quality evidence from 1 RCT (N=108; median 5.8 years of follow-up) showed no clinically important difference in disease-free survival between receiving induction chemotherapy and not receiving induction chemotherapy before preoperative chemoradiotherapy in people with non-metastatic rectal cancer.
Sphincter preservation/permanent stoma
No evidence was identified to inform this outcome.
Treatment-related mortality
- Moderate quality evidence from 2 RCTs (N=165) showed no clinically important difference in treatment-related mortality between receiving induction chemotherapy and not receiving induction chemotherapy before preoperative chemoradiotherapy in people with non-metastatic rectal cancer.
Comparison 4: Internal radiotherapy with or without external radiotherapy versus any external radiotherapy
Critical outcomes
Overall survival
- Moderate quality evidence from 1 RCT (N=221; median 5.4 years of follow-up) showed no clinically important difference in overall survival between receiving external chemoradiotherapy with brachytherapy boost and external chemoradiotherapy alone in people with non-metastatic rectal cancer.
Complete (R0) resection rate
- Moderate quality evidence from 1 RCT (N=194) showed no clinically important difference in complete (R0) resection rate between receiving external chemoradiotherapy with brachytherapy boost and external chemoradiotherapy alone in people with non-metastatic rectal cancer who underwent resection.
Overall quality of life
No evidence was identified to inform this outcome.
Important outcomes
Local recurrence
- Moderate quality evidence from 1 RCT (N=194; median 5.4 years of follow-up) showed that receiving external chemoradiotherapy with brachytherapy boost may have a clinically important decrease in locoregional recurrence-free survival compared to receiving external chemoradiotherapy alone in people with non-metastatic rectal cancer who underwent resection, but there is uncertainty around the estimate.
- Moderate quality evidence from 1 RCT (N=88; median 2.9 years of follow-up) showed no clinically important difference in pelvic local recurrence rate between receiving external radiotherapy with endocavity contact x-ray boost and external radiotherapy alone in people with non-metastatic rectal cancer.
Disease-free survival
- Moderate quality evidence from 1 RCT (N=221; median 5.4 years of follow-up) showed no clinically important difference in disease-free survival between receiving external chemoradiotherapy with brachytherapy boost and external chemoradiotherapy alone in people with non-metastatic rectal cancer.
Sphincter preservation/permanent stoma
No evidence was identified to inform this outcome.
Treatment-related mortality
Moderate quality evidence from 1 RCT (N=88) showed no clinically important difference in 60-day operative mortality between receiving external radiotherapy with endocavity contact x-ray boost and external radiotherapy alone in people with non-metastatic rectal cancer.
Economic evidence statements
No economic evidence was identified which was applicable to this review question.
The committee’s discussion of the evidence
Interpreting the evidence
The outcomes that matter most
The aim of this review was to evaluate the effectiveness of preoperative radiotherapy or chemoradiotherapy on treating rectal cancer. Overall survival, complete (R0) resection rate and quality of life were considered critical outcomes for decision making. Overall survival was considered a critical outcome because ultimately the aim of cancer treatment is to improve survival. From the patient’s perspective it is also critical to consider the treatment’s effect on quality of life. Complete (R0) resection rate was considered a critical outcome because preoperative radiotherapy or chemoradiotherapy can downstage disease and facilitate complete surgical removal of the primary tumour. Local recurrence, disease-free survival, sphincter preservation/permanent stoma and treatment-related mortality were considered important outcomes.
The quality of the evidence
Evidence was available for the comparison of any preoperative therapy versus no preoperative therapy, short course radiotherapy versus long course radiotherapy with or without chemotherapy, chemoradiotherapy with prior chemotherapy versus chemotherapy without prior chemotherapy, and internal radiotherapy with or without external radiotherapy versus any external radiotherapy (without radiotherapy).
For comparison 1 and 2, evidence was available for all of the outcomes except quality of life. The quality of the evidence was assessed using GRADE and was mostly of moderate quality, varying from low to high quality. For comparisons 3 and 4, evidence was available for all outcomes except for overall quality of life and sphincter preservation/permanent stoma. The quality of the evidence, assessed using GRADE, was mostly of moderate quality varying from low to moderate quality.
The main reasons for downgrading the quality of evidence were population indirectness. Some of the trials included up to one third of participants who had early rectal cancer (T1-T2, N0).
Although the evidence was of moderate quality there was consistent benefit in terms of overall survival and local recurrence free survival which enabled the guideline committee to make a strong recommendation in favour of preoperative radiotherapy or chemotherapy.
Benefits and harms
Evidence showed that preoperative radiotherapy or chemoradiotherapy lowers the rate of local recurrence in people with T3-T4 or node positive, non-metastatic rectal cancer. The evidence also showed that preoperative therapy gives a small improvement in overall survival and disease-free survival.
The benefits of preoperative therapy on local recurrence and survival should be balanced against the potential adverse effects of preoperative radiotherapy or chemoradiotherapy. However, no difference was found in short-term or long-term quality of life, sphincter preservation or permanent stoma rate, or treatment-related mortality between people who received and did not receive preoperative therapy.
The risk of recurrence varies according to the stage and the height of the tumour (height meaning which part of the rectum (upper, middle or lower), the tumour is located in). The largest trials included in this review included a mix of participants with different clinical or pathological tumour stages and different tumour heights. This evidence review did not stratify outcomes according to tumour stage or height, and it is rare for papers to report results in such a way without losing statistical power. However, data from 2 large randomised trials, the Dutch TME trial and the MRC CR07 trial have shown that while the local recurrence rate for upper rectal tumours is lower, the beneficial effect of preoperative radiotherapy (compared to surgery alone or selective postoperative chemoradiotherapy) on local recurrence was stronger for upper rectal tumour compared to low or mid rectal tumours (van Gijn 2011; Sebag Montefiore 2009). No difference in overall survival was detected according to tumour height in the Dutch TME trial (van Gijn 2011).
In order to avoid the potential harmful effects of radiotherapy or chemoradiotherapy on people with lower risk rectal cancers, not all people with upper rectal tumours or T1-T2 N1-N2 tumours receive preoperative radiotherapy in current practice. Therefore, the committee recognised that with the new recommendation it is likely that there will be an increase in preoperative treatment for rectal cancer and there is a risk of overtreatment.
The committee was not able to make a recommendation on the duration and type of radiotherapy or chemoradiotherapy based on the available evidence. The evidence comparing short-course and long-course radiotherapy did generally not show a difference between the two treatment arms, apart from one small RCT favouring long-course chemoradiotherapy over short-course radiotherapy with delayed surgery on survival. The evidence on chemoradiotherapy with or without induction chemotherapy showed no difference between the two arms. Finally, the evidence on internal radiotherapy (either or brachy or contact) combined with external radiotherapy versus external radiotherapy alone did not show any difference between the two treatment arms.
Cost effectiveness and resource use
A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question.
The recommendation largely reflects current practice and so no substantial resource impact is anticipated. However, the recommendation might increase preoperative radiotherapy or chemoradiotherapy for people with lower risk tumours and therefore there is a possibility of some increased costs and need for more clinical oncologists and radiotherapy equipment and staff.
References
Appelt 2014
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McLachlan S, Fisher R, Zalcberg J, et al. (2016) The impact on health-related quality of life in the first 12 months: A randomised comparison of preoperative short-course radiation versus long-course chemoradiation for T3 rectal cancer (Trans-Tasman Radiation Oncology Group Trial 01.04). European Journal of Cancer 55: 15–26 [PubMed: 26771873]
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Appendices
Appendix A. Review protocol
Review protocol for review question: What is the effectiveness of preoperative radiotherapy or chemoradiotherapy for rectal cancer?
Appendix B. Literature search strategies
Literature search strategies for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
A combined search was conducted for the following three review questions:
- What is the most effective treatment for early rectal cancer?
- What is the effectiveness of preoperative radiotherapy or chemoradiotherapy for rectal cancer?
- What is the optimal surgical technique for rectal cancer?
Databases: Embase/Medline
Last searched on: 12/02/2019
| # | Search |
|---|---|
| 1 | exp Rectal Neoplasms/ use prmz |
| 2 | *rectum cancer/ or *rectum tumor/ |
| 3 | 2 use oemezd |
| 4 | exp Adenocarcinoma/ |
| 5 | (T1 or T2 or N0 or M0).ti,ab. |
| 6 | 1 or 3 |
| 7 | 4 or 5 |
| 8 | 6 and 7 |
| 9 | ((rectal or rectum) adj3 (cancer* or neoplas* or malignan* or tumo?r* or carcinom* or adeno*)).ti,ab. |
| 10 | early rect* cancer.ti,ab. |
| 11 | 6 or 8 or 9 or 10 |
| 12 | exp radiotherapy/ or exp radiation oncology/ or exp external beam radiotherapy/ or exp Brachytherapy/ or exp preoperative care/ or exp neoadjuvant therapy/ or exp multimodality cancer therapy/ or exp chemotherapy/ or exp antineoplastic agent/ or exp drug therapy/ or exp chemoradiotherapy/ or exp fluorouracil/ or exp folinic acid/ or exp capecitabine/ or exp oxaliplatin/ or exp bevacizumab/ or exp methotrexate/ or exp radiation dose fractionation/ or exp tumor recurrence/ |
| 13 | 12 use oemezd |
| 14 | exp Radiotherapy/ or exp Radiation Oncology/ or exp Radiotherapy, Computer-Assisted/ or exp Brachytherapy/ or exp Preoperative Care/ or exp Neoadjuvant Therapy/ or exp Combined Modality Therapy/ or exp Chemoradiotherapy/ or exp Antineoplastic Combined Chemotherapy Protocols/ or exp Drug Therapy/ or exp Antineoplastic Agents/ or exp Fluorouracil/ or exp Leucovorin/ or exp Capecitabine/ or exp Bevacizumab/ or exp Methotrexate/ or exp Dose Fractionation/ |
| 15 | 14 use prmz |
| 16 | ((radiotherap* or chemoradio* or radiation or brachytherapy* or chemotherapy*) adj (pre?op* or preop* or periop* or neoadjuvant)).ti,ab. |
| 17 | (5-fluorouracil or 5-FU or leucovorin or folinic acid or capecitabine or oxaliplatin or bevacizumab or methotrexate or dose* or fraction* or recurren*).ti,ab. |
| 18 | 13 or 15 or 16 or 17 |
| 19 | exp Laparoscopy/ or exp Transanal Endoscopic Microsurgery/ or exp Minimally Invasive Surgical Procedures/ or exp Endoscopy/ or exp Endoscopic Mucosal Resection/ or exp Surgical Procedures, Operative/ or exp Robotic Surgical Procedures/ or exp Surgery, Computer-Assisted/ or exp Dissection/ |
| 20 | 19 use prmz |
| 21 | exp laparoscopy/ or exp endoscopic surgery/ or exp transanal endoscopic microsurgery/ or exp endoscopy/ or exp minimally invasive surgery/ or exp endoscopic mucosal resection/ or exp surgery/ or exp robotic surgical procedure/ or exp computer assisted surgery/ or exp dissection/ or exp total mesorectal excision/ or exp excision/ or exp rectum resection/ or exp endoscopic polypectomy/ or exp polypectomy/ or exp endoscopic submucosal dissection/ |
| 22 | 21 use oemezd |
| 23 | (laparoscop* or endoscop* or transanal excision* or TAE or transanal endoscopic microsurger* or TEM or TEMS or transanal resection or TART or transanal minimally invasive surger* or TAMIS or total mesorectal excision* or TaTME or transanal total mesorectal excision* or TME or anterior resection* or abdominoperineal resection* or endoscopic resection* or polypectomy or endoscopic submucosal dissection* or ESD or endoscopic mucosal resection* or EMR or surger* or surgic* or operat*).ti,ab. |
| 24 | 20 or 22 or 23 |
| 25 | 11 and 18 |
| 26 | 11 and 18 and 24 |
| 27 | 25 or 26 |
| 28 | limit 27 to english language |
| 29 | limit 28 to yr=“1997 -Current” |
| 30 | (conference abstract or letter).pt. or letter/ or editorial.pt. or note.pt. or case report/ or case study/ use oemezd |
| 31 | Letter/ or editorial/ or news/ or historical article/ or anecdotes as topic/ or comment/ or case report/ use prmz |
| 32 | (letter or comment* or abstracts).ti. |
| 33 | or/30–32 |
| 34 | randomized controlled trial/ use prmz |
| 35 | randomized controlled trial/ use oemezd |
| 36 | random*.ti,ab. |
| 37 | or/34–36 |
| 38 | 33 not 37 |
| 39 | (animals/ not humans/) or exp animals, laboratory/ or exp animal experimentation/ or exp models, animal/ or exp rodentia/ use prmz |
| 40 | (animal/ not human/) or nonhuman/ or exp animal experiment/ or exp experimental animal/ or animal model/ or exp rodent/ use oemezd |
| 41 | (rat or rats or mouse or mice).ti. |
| 42 | 38 or 39 or 40 or 41 |
| 43 | 29 not 42 |
| 44 | clinical Trials as topic.sh. or (controlled clinical trial or pragmatic clinical trial or randomized controlled trial).pt. or (placebo or randomi#ed or randomly).ab. or trial.ti. |
| 45 | 44 use prmz |
| 46 | crossover procedure/ or double blind procedure/ or randomized controlled trial/ or single blind procedure/ or (assign* or allocat* or crossover* or cross over* or ((doubl* or singl*) adj blind*) or factorial* or placebo* or random* or volunteer*).ti,ab. |
| 47 | 46 use oemezd |
| 48 | or/45,47 |
| 49 | 43 and 48 |
| 50 | epidemiologic studies/ or observational study/ or case control studies/ or retrospective studies/ or cohort studies/ or longitudinal studies/ or follow-up studies/ or prospective studies/ or cross-sectional studies/ |
| 51 | 50 use prmz |
| 52 | exp observational study/ or exp case control study/ or exp retrospective study/ or exp cohort analysis/ or exp longitudinal study/ or exp follow up/ or exp prospective study/ or exp cross-sectional study/ |
| 53 | 52 use oemezd |
| 54 | ((retrospective* or cohort* or longitudinal or follow?up or prospective or cross section*) adj3 (stud* or research or analys*)).ti. |
| 55 | 51 or 53 or 54 |
| 56 | 43 and 55 |
| 57 | 49 or 56 |
| 58 | 57 not 56 |
| 59 | 56 or 58 |
Database: Cochrane Library
Last searched on: 12/02/2019
| # | Search |
|---|---|
| 1 | MeSH descriptor: [Rectal Neoplasms] explode all trees |
| 2 | MeSH descriptor: [Adenocarcinoma] explode all trees |
| 3 | T1 or T2 or N0 or M0 |
| 4 | #2 or #3 |
| 5 | #1 and #4 |
| 6 | (rectal or rectum) near (cancer* or neoplas* or malignan* or tumo?r* or carcinom* or adeno*) |
| 7 | early rect* cancer |
| 8 | #1 or #5 or #6 or #7 |
| 9 | MeSH descriptor: [Radiotherapy] explode all trees |
| 10 | MeSH descriptor: [Radiation Oncology] explode all trees |
| 11 | MeSH descriptor: [Radiotherapy, Computer-Assisted] explode all trees |
| 12 | MeSH descriptor: [Brachytherapy] explode all trees |
| 13 | MeSH descriptor: [Preoperative Care] explode all trees |
| 14 | MeSH descriptor: [Neoadjuvant Therapy] explode all trees |
| 15 | MeSH descriptor: [Combined Modality Therapy] explode all trees |
| 16 | MeSH descriptor: [Chemoradiotherapy] explode all trees |
| 17 | MeSH descriptor: [Antineoplastic Combined Chemotherapy Protocols] explode all trees |
| 18 | MeSH descriptor: [Drug Therapy] explode all trees |
| 19 | MeSH descriptor: [Antineoplastic Agents] explode all trees |
| 20 | MeSH descriptor: [Fluorouracil] explode all trees |
| 21 | MeSH descriptor: [Capecitabine] explode all trees |
| 22 | MeSH descriptor: [Bevacizumab] explode all trees |
| 23 | MeSH descriptor: [Methotrexate] explode all trees |
| 24 | MeSH descriptor: [Dose Fractionation] explode all trees |
| 25 | (radiotherap* or chemoradio* or radiation or brachytherapy* or chemotherapy*) near (pre?op* or preop* or periop* or neoadjuvant) |
| 26 | 5-fluorouracil or 5-FU or leucovorin or folinic acid or capecitabine or oxaliplatin or bevacizumab or methotrexate or dose* or fraction* or recurren* |
| 27 | #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 |
| 28 | MeSH descriptor: [Laparoscopy] explode all trees |
| 29 | MeSH descriptor: [Transanal Endoscopic Microsurgery] explode all trees |
| 30 | MeSH descriptor: [Minimally Invasive Surgical Procedures] explode all trees |
| 31 | MeSH descriptor: [Endoscopy] explode all trees |
| 32 | MeSH descriptor: [Endoscopic Mucosal Resection] explode all trees |
| 33 | MeSH descriptor: [Surgical Procedures, Operative] explode all trees |
| 34 | MeSH descriptor: [Robotic Surgical Procedures] explode all trees |
| 35 | MeSH descriptor: [Surgery, Computer-Assisted] explode all trees |
| 36 | MeSH descriptor: [Dissection] explode all trees |
| 37 | laparoscop* or endoscop* or transanal excision* or TAE or transanal endoscopic microsurger* or TEM or TEMS or transanal resection or TART or transanal minimally invasive surger* or TAMIS or total mesorectal excision* or TME or anterior resection* or abdominoperineal resection* or endoscopic resection* or polypectomy or endoscopic submucosal dissection* or ESD or endoscopic mucosal resection* or EMR or surger* or surgic* or operat* |
| 38 | #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 |
| 39 | #8 and #27 |
| 40 | #8 and #27 and #38 |
| 41 | #39 or #40 Publication Year from 1997 to 2017 |
Appendix C. Clinical evidence study selection
Clinical study selection for review question: What is the effectiveness of preoperative radiotherapy or chemoradiotherapy for rectal cancer
Appendix D. Clinical evidence tables
Clinical evidence tables for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
Table 4. Clinical evidence tables (PDF, 1.2M)
Appendix E. Forest plots
Forest plots for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
Appendix F. GRADE tables
GRADE tables for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
Appendix G. Economic evidence study selection
Economic evidence study selection for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.
Appendix H. Economic evidence tables
Economic evidence tables for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
No economic evidence was identified which was applicable to this review question.
Appendix I. Economic evidence profiles
Economic evidence profiles for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
No economic evidence was identified which was applicable to this review question.
Appendix J. Economic analysis
Economic analysis: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
No economic analysis was conducted for this review question.
Appendix K. Excluded studies
Excluded clinical studies for review question: What is the effectiveness of preoperative radiotherapy or chemoradiotherapy for rectal cancer?
Appendix L. Research recommendations
Research recommendations for review question: What is the effectiveness of preoperative radiotherapy and chemoradiotherapy for rectal cancer?
No research recommendations were made for this review question.
Final
Evidence reviews
Developed by the National Guideline Alliance part of the Royal College of Obstetricians and Gynaecologists
Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.
- Evolving role of neoadjuvant therapy in rectal cancer.[Curr Treat Options Oncol. 2013]Evolving role of neoadjuvant therapy in rectal cancer.Schrag D. Curr Treat Options Oncol. 2013 Sep; 14(3):350-64.
- Alternative clinical end points in rectal cancer--are we getting closer?[Ann Oncol. 2006]Alternative clinical end points in rectal cancer--are we getting closer?Glynne-Jones R, Mawdsley S, Pearce T, Buyse M. Ann Oncol. 2006 Aug; 17(8):1239-48.
- Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer.[Eur J Cancer. 2016]Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer.Lutz MP, Zalcberg JR, Glynne-Jones R, Ruers T, Ducreux M, Arnold D, Aust D, Brown G, Bujko K, Cunningham C, et al. Eur J Cancer. 2016 Aug; 63:11-24. Epub 2016 May 30.
- Omission of or Poor Response to Preoperative Chemoradiotherapy Impacts Radial Margin Positivity Rates in Locally Advanced Rectal Cancer.[Dis Colon Rectum. 2021]Omission of or Poor Response to Preoperative Chemoradiotherapy Impacts Radial Margin Positivity Rates in Locally Advanced Rectal Cancer.Ore AS, Dombek GE, Cordova-Cassia CA, Quinn JF, Cataldo TE, Schlechter BL, Abrams MJ, Messaris E. Dis Colon Rectum. 2021 Jun 1; 64(6):669-676.
- Review Neoadjuvant treatment in rectal cancer: do we always need radiotherapy-or can we risk assess locally advanced rectal cancer better?[Recent Results Cancer Res. 2012]Review Neoadjuvant treatment in rectal cancer: do we always need radiotherapy-or can we risk assess locally advanced rectal cancer better?Glynne-Jones R. Recent Results Cancer Res. 2012; 196:21-36.
- Preoperative radiotherapy and chemoradiotherapy for rectal cancerPreoperative radiotherapy and chemoradiotherapy for rectal cancer
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