Local and systemic treatments for metastatic colorectal cancer isolated in the peritoneum

National Guideline Alliance (UK)

Local and systemic treatments for metastatic colorectal cancer isolated in the peritoneum

Colorectal cancer (update)

Evidence review D4

NICE Guideline, No. 151

Authors

National Guideline Alliance (UK).

London: National Institute for Health and Care Excellence (NICE); 2020 Jan.

ISBN-13: 978-1-4731-3657-1

Optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum

This evidence review supports recommendation 1.5.9.

Review question

What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Introduction

Peritoneal carcinomatosis from colorectal cancer is the second-most common cause of death from colorectal cancer after liver metastases. Palliative systemic chemotherapy has commonly been used in an attempt to prolong survival for patients with peritoneal carcinomatosis. Efforts to achieve long-term survival have seen the combined use of cytoreductive surgery (CRS) to remove the metastases and heated intraperitoneal chemotherapy (HIPEC) to eradicate the residual disease. However, CRS with HIPEC is associated with high rates of morbidity and treatment-related mortality (Mehta 2016; Verwaal 2003). Therefore, the aim of this review was to determine the most effective combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the peritoneum that is potentially curable with local treatments such as CRS and HIPEC.

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

Two randomised controlled trials (RCTs) and 1 observational study (4 publications) were included in this review (PRODIGE 7 [Quenet 2016]; van Oudheusden 2015; Verwaal 2003 [Verwaal 2008]).

The included studies are summarised in Table 2.

One RCT compared CRS + HIPEC + oxaliplatin to CRS only (PRODIGE 7 [Quenet 2016]) and the other RCT compared CRS + HIPEC + SACT to surgery + SACT (Verwaal 2003; Verwaal 2008). The observational study compared chemotherapy (with or without Bevacizumab) to supportive care (van Oudheusden 2015).

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. No meta-analysis was conducted (and so there are no forest plots in appendix E).

Quality assessment of clinical outcomes 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: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT)

Critical outcomes

Progression-free survival

No evidence was identified to inform this outcome.

Overall survival

Low quality evidence from 1 RCT (N=265; median follow-up 64 months) showed no clinically important difference in 5-year overall survival between those receiving CRS + HIPEC + oxaliplatin compared to those receiving CRS alone.
Very low quality evidence from 1 RCT (N=105; median follow-up 22 months) showed a clinically important increase in 2 year overall survival between those receiving CRS + HIPEC + SACT compared to those receiving surgery + SACT.

Overall quality of life

No evidence was identified to inform this outcome.

Important outcomes

Treatment-related mortality

Low quality evidence from 1 RCT (N=265) showed no clinically important difference in 30-day treatment-related mortality between those receiving CRS + HIPEC + oxaliplatin compared to those receiving CRS alone.
Very low quality evidence from 1 RCT (N=105) showed no clinically important difference in 30-day treatment-related mortality between those receiving CRS + HIPEC + SACT compared to those receiving surgery + SACT.

Any grade 3 or 4 complications

Low quality evidence from 1 RCT (N=265) showed a clinically important increase in grade 3 or 4 complications between those receiving CRS + HIPEC + oxaliplatin compared to those receiving CRS alone.

Length of hospital stay

No evidence was identified to inform this outcome.

Comparison 2: Systemic anti-cancer therapy (SACT) versus supportive care

Critical outcomes

Progression free survival

No evidence was identified to inform this outcome.

Overall survival

Very low quality evidence from 1 retrospective cohort study (N=186) showed a clinically important increase in 50-month overall survival between those receiving SACT (chemotherapy alone) compared to those receiving supportive care.
Very low quality evidence from 1 retrospective cohort study (N=186) showed a clinically important increase in 50-month overall survival between those receiving SACT (chemotherapy + bevacizumab) compared to those receiving supportive care.

Overall quality of life

No evidence was identified to inform this outcome.

Important outcomes

Treatment-related mortality

No evidence was identified to inform this outcome.

Any grade 3 or 4 complications

No evidence was identified to inform this outcome.

Length of hospital stay

No evidence was identified to inform this outcome.

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

Progression-free survival, overall survival, and overall quality of life were considered critical outcomes for decision making because progression of the metastases suggests ineffective treatment, potentially requiring further treatment and affecting overall survival. Quality of life was a critical outcome because of the impact that different treatment options can have on patients’ functioning and the potential long term adverse effects.

Treatment-related mortality, grade 3 or 4 complications, and length of hospital stay were identified as important outcomes because they are indicative of the short-term side effects of treatment.

The quality of the evidence

Evidence was available from 1 RCT comparing CRS + HIPEC + SACT to surgery + SACT, 1 RCT comparing CRS + HIPEC + oxaliplatin to CRS only and 1 observational study which compared chemotherapy (with or without bevacizumab) to supportive care without any systemic therapy.

Evidence was available for overall survival, any grade 3 or 4 complications and treatment-related mortality. The evidence was assessed using GRADE and varied from very low to low quality. The quality of evidence was downgraded because of methodological limitations affecting the risk of bias and imprecision in the risk estimate.

Methodological limitations affecting the risk of bias were due to a lack of information regarding certain details such as randomisation, allocation methods, and outcomes measured. One study failed to report the number of patients randomised; another reported high levels of attrition; and another reported differences between the two groups at baseline.

Indirectness was also an issue as three studies included patients with appendiceal disease; and in two of these studies, protocol violations also occurred.

Uncertainty around the risk estimate was generally attributable to low event rates and small sample sizes.

Benefits and harms

Despite the low quality of the evidence, it showed SACT to be beneficial in terms of overall survival. Offering SACT is also current practice. Based on the clinical evidence and their clinical expertise, the committee decided that SACT should be offered to patients with colorectal cancer with isolated peritoneal metastases.

Evidence for CRS and HIPEC were more mixed. In the PRODIGE 7 trial (Quenet 2018), overall survival rates for all patients were higher than expected (both arms received CRS), which the committee interpreted as evidence that high quality surgery is beneficial for survival outcomes. Additionally, the evidence indicated that there could be some benefit in overall survival for those whose treatment included CRS, HIPEC and SACT. Receiving active treatment, as opposed to supportive care increases the chance for survival. However, there are also risks of mortality and morbidity that are associated with surgical interventions.

The committee noted that the doses of oxaliplatin used in the PRODIGE 7 trial are much higher than those used in the UK and could explain the high level of toxicity in the treatment arm (CRS + HIPEC + oxaliplatin vs CRS alone). While lower doses of oxaliplatin are used in the UK, this drug still has a risk of severe toxicity. The committee were aware of non-randomised evidence (Prada-Villeverde 2014) that compared CRS + HIPEC (mitomycin C) versus CRS + HIPEC (oxaliplatin) that found that there was no statistically significant difference between groups in terms of median overall survival and that effectiveness of regimens with oxaliplatin was linked to the patient’s Peritoneal Surface Disease Severity Score (PSDSS).

Based on the evidence and their clinical expertise, the committee decided that a referral to a nationally commissioned specialist centre where CRS with HIPEC could be considered should be discussed within a multidisciplinary team. The committee made the recommendation in line with the NICE interventional procedure guidance (IPG331) on cytoreductive surgery followed by HIPEC for peritoneal carcinomatosis,

The committee decided that offering chemotherapy and MDT discussion of referral to a nationally commissioned specialist centre should be in the same recommendation because these interventions should happen at the same time. That is, making a referral should not wait until chemotherapy has been given, and chemotherapy could be started before the person is reviewed in the specilialist centre.

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 to offer SACT is not anticipated to have a significant resource impact as it is already standard practice to offer SACT to patients who are considered fit enough. The recommendation to offer referral to specialist centres has the potential to increase the number of referrals to specialist centres but this does not necessarily mean that more procedures will take place because a significant proportion of patients with colorectal peritoneal metastases are not suitable for CRS with HIPEC. Therefore it was considered unlikely that the recommendation would have a significant resource impact. Currently in the UK there are only 3 nationally commissioned specialist CRS and HIPEC centres. If the demand exceeds the capacity of these centres, there may be a need to expand the current centres or develop new centres in the future.

In cost-effectiveness terms, the use of CRS and HIPEC would increase treatment costs but this may be offset, at least partially, by downstream cost savings associated with better disease control. Also if potential benefits in survival were realised then the interventions could be cost-effective in cost per QALY terms.

Other factors the committee took into account

The committee acknowledged the ongoing CAIRO 6 trial, which is assessing perioperative systemic therapy and cytoreductive surgery with HIPEC compared to upfront cytoreductive surgery with HIPEC alone for resectable colorectal peritoneal metastases. The results from this trial may provide evidence regarding optimal treatment strategies.

The committee recognised that there may be barriers to accessing specialist centres for some people who live far away from these centres due to the distance and difficulty or cost of transport. The option of receiving treatment in a centre far away from home and family could impact the decision that a patient makes about their care. There are currently 3 nationally commissioned specialist centres offering CRS with HIPEC in the country, one in Basingstoke, one in Birmingham and one in Manchester. Even if a referral to a nationally commissioned specialist centre is done, the patient would only need to travel to the specialist centre once the team in the specialist centre has reviewed the patient’s records and deemed CRS with HIPEC is appropriate for them. Barriers to care in the specialist centres for those living far away from these centres could be alleviated by ensuring transport is available to those who require assistance and suitable hostel type accommodation for relatives and carers is made available at major referral sites when daily visiting is not realistic because of the distance.

References

Mehta 2016
Mehta S, Gelli M and Agarwal D (2016) Complications of cytoreductive surgery and HIPEC in the treatment of peritoneal metastases. Indian Journal of Surgical Oncology 7(2): 225–229 [PMC free article: PMC4818615] [PubMed: 27065713]
Prada-Villaverde 2014
Prada-Villaverde A, Esquivel J, Lowy A, et al. (2014) The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. Journal of Surgical Oncology 110(7): 779–785 [PubMed: 25088304]
PRODIGE 7 [Quenet 2018]
Quenet F, Dominique E, Lise R, et al. (2018) A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. Journal of Clinical Oncology 36: LBA3503
van Oudheusden 2015
van Oudheusden T, Razenberg L, van Gestel Y, et al. (2015) Systemic treatment of patients with metachronous peritoneal carcinomatosis of colorectal origin. Scientific Reports 21(5): 18632 [PMC free article: PMC4685443] [PubMed: 26686250]
Verwaal 2003
Verwaal V, Van Ruth S and De Bree E (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. Journal of Clinical Oncology 21(20): 3737–3743 [PubMed: 14551293]
Verwaal V, Bruin S, Boot H, et al. (2008) 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Annals of Surgical Oncology 15(9): 2426–32 [PubMed: 18521686]

Appendices

Appendix A. Review protocol

Review protocol for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Table 3. Review protocol for the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum

Appendix B. Literature search strategies

Literature search strategies for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Databases: Embase/Medline

Last searched on: 21/05/2018

Table

Database: Cochrane Library

Last searched on: 21/05/2018

Table

Appendix C. Clinical evidence study selection

Clinical study selection for: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Figure 1. Study selection flow chart

Appendix D. Clinical evidence tables

Clinical evidence tables for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Table 4. Clinical evidence tables (PDF, 304K)

Appendix E. Forest plots

Forest plots for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Figure 2. Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – overall survival

Figure 3. Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – treatment-related mortality

Figure 4. Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – treatment-related mortality

Figure 5. Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – grade 3 or 4 complications

Figure 6. Comparison 2 – systemic anti-cancer therapy (SACT) versus supportive care – overall survival

Appendix F. GRADE tables

GRADE tables for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Table 5. Clinical evidence profile for profile for comparison 1: cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) + SACT versus CRS +/- systemic anti-cancer therapy (SACT)

Table 6. Clinical evidence profile for comparison 2: Systemic anti-cancer therapy (SACT) versus supportive care

Appendix G. Economic evidence study selection

Economic evidence study selection for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

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 optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

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 optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

No economic evidence was identified which was applicable to this review question.

Appendix J. Economic analysis

Economic evidence analysis for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

No economic analysis was conducted for this review question.

Appendix K. Excluded studies

Excluded clinical studies for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

Table 7. Excluded studies and reasons for their exclusion

Appendix L. Research recommendations

Research recommendations for review question: What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?

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.

Bookshelf ID: NBK559929PMID: 32730006

Table 1Summary of the protocol (PICO table)

Population	Adults with colorectal cancer with metastases isolated in the peritoneum. Subgroups: Symptomatic or asymptomatic primary colorectal tumour Synchronous or metachronous metastases
Intervention	Cytoreductive surgery (CRS) CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) Systemic anti-cancer therapy (SACT) alone
Comparison	Individual interventions or combinations of interventions compared to each other Best supportive care
Outcomes	Critical Progression-free survival Overall survival Overall quality of life Important Treatment-related mortality Any grade 3 or 4 complications Length of hospital stay

Table 2Summary of included studies

Study	Population	Intervention/Comparison	Outcomes
Comparison 1: CRS with HIPEC versus CRS +/- SACT
PRODIGE 7 (Quenet 2016) Multi-centre RCT France	N=264 patients aged 18-70 with histopathologically confirmed colorectal cancer; peritoneal carcinoma extension ≤ 25 (Sugarbaker Index, determined intra operatively).	CRS + HIPEC + oxaliplatin versus CRS alone	Overall survival Treatment-related mortality Grade 3 or 4 complications
Verwaal 2003; Verwaal 2008 Single-centre RCT Netherlands	N=105 patients with histologically proven peritoneal metastases of colorectal adenocarcinoma or positive cytology of ascites.	CRS + HIPEC + SACT versus standard surgery and chemotherapy.	Overall survival Treatment-related mortality
Comparison 2: SACT versus supportive care
van Oudheusden 2015 Retrospective cohort study Netherlands	N=186 patients with metachronous peritoneal carcinomatosis of colorectal origin.	Systemic treatment versus no systemic treatment.	Overall survival

: CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; N: number; RCT: randomised controlled trial; SACT: systemic anti-cancer therapy

Table 3Review protocol for the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum

Field (based on PRISMA-P)	Content
Review question in guideline	What is the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum?
Type of review question	Intervention
Objective of the review	To determine the optimal combination and sequence of local and systemic treatments in patients presenting with metastatic colorectal cancer isolated in the peritoneum.
Eligibility criteria – population/disease/condition/is sue/domain	Adults with colorectal cancer with metastases isolated in the peritoneum Subgroups (analysed separately): Symptomatic or asymptomatic primary colorectal tumour Synchronous or metachronous metastases
Eligibility criteria – intervention(s)/exposure(s)/pro gnostic factor(s)	Cytoreductive surgery (CRS) CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) Systemic anti-cancer therapy (SACT) alone
Eligibility criteria – comparator(s)/control or reference (gold) standard	Individual interventions or combinations of interventions compared to each other Best supportive care
Outcomes and prioritisation	Critical: Progression-free survival (MID: statistical significance) Overall survival (MID: statistical significance) Overall quality of life measured using validated scales (MID: published MIDs from literature, see below) Important: Treatment-related mortality (MID: statistical significance) Any grade 3 or 4 complications (MID: statistical significance) Length of hospital stay (MID: statistical significance) Quality of life MIDs from the literature: EORTC QLQ-C30: 5 points EORTC QLQ-CR29: 5 points EORTC QLQ-CR38: 5 points EQ-5D: 0.09 using FACT-G quintiles FACT-C: 5 points FACT-G: 5 points SF-12: > 3.77 for the mental component summary and > 3.29 for the physical component summary SF-36: > 7.1 for the physical functioning scale, > 4.9 for the bodily pain scale, and > 7.2 for the physical component summary
Eligibility criteria – study design	Systematic reviews of RCTs RCTs Comparative observational studies will only be considered if eligible RCTs are not available
Other inclusion exclusion criteria	Inclusion: English-language All settings will be considered that consider medications and treatments available in the UK Studies published post 1995 Studies conducted post 1995 will be considered for this review question because the guideline committee considered that some of the treatments were not commercially available before then.
Proposed sensitivity/sub-group analysis, or meta-regression	Observational studies should include multivariate analysis controlling for the following confounding factors: Age Synchronous or metachronous Peritoneal cancer index
Selection process – duplicate screening/selection/analysis	Sifting, data extraction, appraisal of methodological quality and GRADE assessment will be performed by the systematic reviewer. Resolution of any disputes will be with the senior systematic reviewer and the Topic Advisor. Quality control will be performed by the senior systematic reviewer. Dual sifting will be undertaken for this question for a random 10% sample of the titles and abstracts identified by the search.
Data management (software)	Pairwise meta-analyses will be performed using Cochrane Review Manager (RevMan5). ‘GRADEpro’ will be used to assess the quality of evidence for each outcome. NGA STAR software will be used for study sifting, data extraction, recording quality assessment using checklists and generating bibliographies/citations.
Information sources – databases and dates	Potential sources to be searched: Medline, Medline In-Process, CCTR, CDSR, DARE, HTA, Embase Limits (e.g. date, study design): Apply standard animal/non-English language exclusion Limit to RCTs and systematic reviews in first instance, but download all results Dates: from 1995
Identify if an update	Not an update
Author contacts	https://www.nice.org.uk/guidance/indevelopment/gid-ng10060 Developer: NGA
Highlight if amendment to previous protocol	For details please see section 4.5 of Developing NICE guidelines: the manual
Search strategy – for one database	For details please see appendix B.
Data collection process – forms/duplicate	A standardised evidence table format will be used, and published as appendix D (clinical evidence tables) or H (economic evidence tables).
Data items – define all variables to be collected	For details please see evidence tables in appendix D (clinical evidence tables) or H (economic evidence tables).
Methods for assessing bias at outcome/study level	Standard study checklists were used to critically appraise individual studies. For details please see section 6.2 of Developing NICE guidelines: the manual Appraisal of methodological quality: The methodological quality of each study will be assessed using an appropriate checklist: ROBIS for systematic reviews Cochrane risk of bias tool for RCTs ROBINS-I for non-randomised studies The quality of the evidence for an outcome (i.e. across studies) will be assessed using GRADE. The risk of bias across all available evidence was evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group http://www.gradeworkinggroup.org/
Criteria for quantitative synthesis (where suitable)	For details please see section 6.4 of Developing NICE guidelines: the manual
Methods for analysis – combining studies and exploring (in)consistency	Synthesis of data: Pairwise meta-analysis of randomised trials will be conducted where appropriate. When meta-analysing continuous data, final and change scores will be pooled if baselines are comparable. If any studies report both, the method used in the majority of studies will be analysed. Minimally important differences: The guideline committee identified statistically significant differences as appropriate indicators for clinical significance for all outcomes except quality of life for which published MIDs from literature will be used (see outcomes section for more information).
Meta-bias assessment – publication bias, selective reporting bias	For details please see section 6.2 of Developing NICE guidelines: the manual. If sufficient relevant RCT evidence is available, publication bias will be explored using RevMan 5 software to examine funnel plots.
Assessment of confidence in cumulative evidence	For details please see sections 6.4 and 9.1 of Developing NICE guidelines: the manual
Rationale/context – Current management	For details please see the introduction to the evidence review.
Describe contributions of authors and guarantor	A multidisciplinary committee developed the guideline. The committee was convened by The National Guideline Alliance and chaired by Peter Hoskin in line with section 3 of Developing NICE guidelines: the manual Staff from The National Guideline Alliance undertook systematic literature searches, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the guideline in collaboration with the committee. For details please see Supplement 1.
Sources of funding/support	The NGA is funded by NICE and hosted by the Royal College of Obstetricians and Gynaecologists.
Name of sponsor	The NGA is funded by NICE and hosted by the Royal College of Obstetricians and Gynaecologists
Roles of sponsor	NICE funds the NGA to develop guidelines for those working in the NHS, public health, and social care in England
PROSPERO registration number	Not registered

: CCTR: Cochrane Central Register of Controlled Trials; CDSR: Cochrane Database of Systematic Reviews; DARE: Database of Abstracts of Reviews of Effects; EQ-5D: EuroQol five dimensions questionnaire; EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items; EORTC QLQ-CR29: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire colorectal cancer module (29 items); EORTC QLQ-CR38: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire colorectal cancer module (38 items); FACT-C: Functional Assessment of Cancer Therapy questionnaire (colorectal cancer); FACT-G: Functional Assessment of Cancer Therapy questionnaire (general); GRADE: Grading of Recommendations Assessment, Development and Evaluation; HTA: Health Technology Assessment; MID: minimal important difference; NGA: National Guideline Alliance; NHS: National Health Service; NICE: National Institute for Health and Care Excellence; PRISMA-P: Preferred Reporting Items for Systematic reviews and Meta-Analysis Protocols; PROSPERO: International prospective register of systematic reviews; RCT: randomised controlled trial; ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions; ROBIS: a tool for assessing risk of bias in systematic reviews; SF-12: 12-Item Short Form Survey; SF-36: 36-Item Short Form Survey

#	Search
1	(exp colorectal cancer/ or exp colon tumour/ or exp rectum tumour/) use emez
2	exp colorectal neoplasms/ use ppez
3	((colorect* or colo rect* or colon or colonic or rectal or rectum) adj3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)).tw.
4	or/1-3
5	Peritoneum metastasis/ use emez
6	peritoneal neoplasms/ use ppez
7	((peritoneum or peritoneal) adj3 (disseminat* or metasta* or migrat*)).tw.
8	((colorect* or colo rect* or colon or colonic or rectal or rectum) adj3 (peritoneum metasta* or peritoneal metasta* or peritoneal carcinom*)).tw.
9	or/5-7
10	4 and 9
11	10 or 8
12	cytoreductive surgery/ use emez or cytoreduction Surgical Procedures/ use ppez
13	surgery/ use emez or surgical procedures, operative/ use ppez or laparotomy/
14	(cytoreduc* or cyto-reduc* or CRS or debulk* or excis* or peritonectom* or operat* or resect* or surg*).tw.
15	or/12-14
16	exp antineoplastic agent/ use emez
17	exp antineoplastic agents/ use ppez
18	exp Antineoplastic Protocols/ use ppez
19	multimodality cancer therapy/ use emez
20	cancer therapy/ use emez
21	exp chemotherapy/ use emez
22	cancer combination chemotherapy/ use emez
23	Cancer Vaccines/ use ppez
24	cancer vaccine/ use emez
25	cancer immunotherapy/ use emez
26	exp antibodies, monoclonal/ use ppez or monoclonal antibody/ use emez
27	((anti canc* or anticanc* or anticancerogen* or anticarcinogen* or anti neoplas* or antineoplas* or anti tumo?r* or antitumo?r* or cytotoxic) adj3 (agent or drug* or protocol* or regimen* or treatment* or therap*)).tw.
28	(SACT or chemosaturat* or chemotherap* or immunotherap* or biological agent* or biological therap*).tw.
29	or/16-28
30	15 or 29
31	11 and 30
32	Letter/ use ppez
33	letter.pt. or letter/ use emez
34	note.pt.
35	editorial.pt.
36	Editorial/ use ppez
37	News/ use ppez
38	exp Historical Article/ use ppez
39	Anecdotes as Topic/ use ppez
40	Comment/ use ppez
41	Case Report/ use ppez
42	case report/ or case study/ use emez
43	(letter or comment*).ti.
44	or/32-43
45	randomized controlled trial/ use ppez
46	randomized controlled trial/ use emez
47	random*.ti,ab.
48	or/45-47
49	44 not 48
50	animals/ not humans/ use ppez
51	animal/ not human/ use emez
52	nonhuman/ use emez
53	exp Animals, Laboratory/ use ppez
54	exp Animal Experimentation/ use ppez
55	exp Animal Experiment/ use emez
56	exp Experimental Animal/ use emez
57	exp Models, Animal/ use ppez
58	animal model/ use emez
59	exp Rodentia/ use ppez
60	exp Rodent/ use emez
61	(rat or rats or mouse or mice).ti.
62	or/49-61
63	31 not 62
64	limit 63 to (yr=“1995 - current” and english language)
65	remove duplicates from 64

#	Search
1	MeSH descriptor: [Colorectal Neoplasms] explode all trees
2	((colorect* or colo rect* or colon or colonic or rectal or rectum) near/3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)):ti,ab,kw (Word variations have been searched)
3	#1 or #2
4	MeSH descriptor: [Peritoneal Neoplasms] explode all trees
5	MeSH descriptor: [Peritoneum] explode all trees
6	MeSH descriptor: [Neoplasm Metastasis] explode all trees
7	#5 and #6
8	((peritoneum or peritoneal) near/3 (disseminat* or metasta* or migrat*)):ti,ab,kw
9	((colorect* or colo rect* or colon or colonic or rectal or rectum) near/3 (peritoneum metasta* or peritoneal metasta* or peritoneal carcinom*)):ti,ab,kw
10	#4 or #7 or #8
11	#3 and #10
12	#11 or #9
13	MeSH descriptor: [Cytoreduction Surgical Procedures] this term only
14	MeSH descriptor: [Surgical Procedures, Operative] explode all trees
15	MeSH descriptor: [Laparotomy] explode all trees
16	(cytoreduc* or cyto-reduc* or CRS or debulk* or excis* or peritonectom* or operat* or resect* or surg*):ti,ab,kw
17	MeSH descriptor: [Antineoplastic Agents] explode all trees
18	MeSH descriptor: [Antineoplastic Protocols] explode all trees
19	MeSH descriptor: [Cancer Vaccines] this term only
20	MeSH descriptor: [Antibodies, Monoclonal] explode all trees
21	((anti canc* or anticanc* or anticarcinogen* or anti neoplas* or antineoplas* or cytotoxic) near/3 (agent or drug* or protocol* or regimen* or treatment* or therap*)):ti,ab,kw (Word variations have been searched)
22	(SACT or chemotherap* or immunotherap* or biological agent* or biological therap*):ti,ab,kw (Word variations have been searched)
23	{or #13-#22}
24	#12 and #23 Publication Year from 1995 to 2018

Figure 1Study selection flow chart

Figure 2Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – overall survival

CI: confidence interval; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; IV: inverse variance; SACT: systemic anti-cancer therapy; SE: standard error

Figure 3Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – treatment-related mortality

CI: confidence interval; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; M-H: Mantel–Haenszel; SACT: systemic anti-cancer therapy

Figure 4Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – treatment-related mortality

CI: confidence interval; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; SACT: systemic anti-cancer therapy

Figure 5Comparison 1 – cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) versus CRS +/- systemic anti-cancer therapy (SACT) – grade 3 or 4 complications

CI: confidence interval; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; M-H: Mantel–Haenszel; SACT: systemic anti-cancer therapy

Figure 6Comparison 2 – systemic anti-cancer therapy (SACT) versus supportive care – overall survival

CI: confidence interval; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; IV: inverse variance; SACT: systemic anti-cancer therapy; SE: standard error

Table 5Clinical evidence profile for profile for comparison 1: cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) + SACT versus CRS +/- systemic anti-cancer therapy (SACT)

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	CRS + HIPEC + SACT	CRS +/- SACT	Relative (95% CI)	Absolute	Quality	Importance
Progression-free survival
0	no evidence available	-	-	-	-	-	-	-	-	-	-	CRITICAL
Overall survival (median follow up of 21.6 months), event is death from any cause - CRS + HIPEC + SACT versus surgery + SACT
1	randomised trials	serious risk of bias¹	no serious inconsistency	serious²	serious³	none	24/54 (44.4%)	31/51 (60.7%)	HR 0.55 (0.32 to 0.95)	At 2 years surgery + SACT 60.7%^a, CRS + HIPEC + SACT 76.0% (62.2% to 85.2%)	VERY LOW	CRITICAL
Overall survival (median follow up 63.8 months), event is death from any cause – CRS + HIPEC + oxaliplatin vs CRS alone
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious³	none	133	132	HR 1.00 (0.73 to 1.37)	Not calculable⁵	LOW	CRITICAL
Overall quality of life
0	no evidence available	-	-	-	-	-	-	-	-	-	-	CRITICAL
30-day treatment-related mortality - CRS + HIPEC + oxaliplatin versus CRS alone
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious³	none	2/133 (1.5%)	2/132 (1.5%)	RR 0.99 (0.14 to 6.94)	990 fewer per 1000 (from 2410 fewer to 4390 more)	LOW	IMPORTANT
30-day treatment-related mortality - CRS + HIPEC + SACT versus surgery + SACT
1	randomised trials	serious risk of bias¹	no serious inconsistency	serious²	serious³	none	4/48 (8.3%)	0/51 (0%)	Peto OR 8.39 (1.15 to 61.51)	-	VERY LOW	IMPORTANT
Grade 3 or 4 complications - CRS + HIPEC + oxaliplatin versus CRS alone
1	randomised trials	serious⁴	no serious inconsistency	no serious indirectness	serious³	none	32/133 (24.1%)	18/132 (13.6%)	RR 1.76 (1.04 to 2.98)	136 fewer per 1000 (from 136 fewer to 136 more)	LOW	IMPORTANT

: CI: confidence interval; CRS: cytoreductive surgery; HIPEC: hyperthermic intraperitoneal chemotherapy; HR: hazard ratio; OR: odds ratio; RR: relative risk; SACT: systemic anti-cancer therapy

1: 7/51 patients (14%) in standard arm never started SCT; 12/38 in standard arm did not complete SCT; 5/54 in treatment arm complete CRS + HIPEC; 14/54 never started adjuvant CT after CRS + HIPEC (Verwaal 2003)

2: Quality of evidence was downgraded by 1 due to 18/105 (17%) patients having appendiceal disease (Verwaal 2003)

3: Quality of evidence downgraded by 1 because of imprecision of the effect estimate (< 300 events for dichotomous outcomes or < 400 participants for continuous outcomes).

4: Quality of evidence was downgraded by 1 because the study did not report the event rates (PRODIGE 7)

5: The absolute effect was not calculable because the study did not report the event rates (PRODIGE 7)

a: The absolute risk at 2 years in the control group taken from Verwaal 2003

Table 6Clinical evidence profile for comparison 2: Systemic anti-cancer therapy (SACT) versus supportive care

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	SACT	Supportive care	Relative (95% CI)	Absolute	Quality	Importance
Progression free survival
0	no evidence available	-	-	-	-	-	-	-	-	-	-	CRITICAL
50-month overall survival, event is death from any cause, controlled for sex, age, comorbidity, primary tumour location and systemic therapy - Chemotherapy only versus no systemic therapy
1	observational studies	serious¹	no serious inconsistency	serious²	serious³	none	49/56 (87.5%)	90/94 (95.7%)	HR 0.51 (0.35 to 0.74)	At 50 months no systemic treatment 4.3%^a, CT only 20.1% (9.7% to 33.2%)	VERY LOW	CRITICAL
50-month overall survival, event is death from any cause, controlled for sex, age, comorbidity, primary tumour location and systemic therapy - Chemotherapy + bevacizumab versus no systemic therapy
1	observational studies	serious¹	no serious inconsistency	serious²	serious³	none	31/36 (86.1%)	90/94 (95.7%)	HR 0.35 (0.22 to 0.56)	At 50 months no systemic treatment 4.3%^a, CT + Bevacizu mab 33.2% (17.2% to 50%)	VERY LOW	CRITICAL
Overall quality of life
0	no evidence available	-	-	-	-	-	-	-	-	-	-	CRITICAL
Treatment-related mortality
0	no evidence available	-	-	-	-	-	-	-	-	-	-	IMPORTANT
Any grade 3/4 complications
0	no evidence available	-	-	-	-	-	-	-	-	-	-	IMPORTANT
Length of hospital stay
0	no evidence available	-	-	-	-	-	-	-	-	-	-	IMPORTANT

: CI: confidence interval; CT: chemotherapy; HR: hazard ratio; SACT: systemic anti-cancer therapy

1: Quality of evidence was downgraded by 1 as differences in characteristics between groups at baseline, deviations from intended protocol (van Oudheusden 2015)

2: Quality of evidence downgraded by 1 due to proportion of patients having other distant metastases (van Oudheusden 2015)

3: Quality of evidence downgraded by 1 because of imprecision of the effect estimate (< 300 events for dichotomous outcomes or < 400 participants for continuous outcomes)

a: The absolute risk at 50 months in the control group taken from van Oudheusden (2015)

Table 7Excluded studies and reasons for their exclusion

Study	Reason for exclusion
Akbarov, E. T., Navruzov, S. N., Abdujapparov, S. B., Hakimov, A. M., Khudayarov, S. S., Islamov, K. J., Babakulob, H. B., Turaev, G. Kh, Use targeted therapy with endolymphatic chemotherapy in peritoneal carcinomatosis of colorectal cancer, Annals of Oncology, Conference, 2009	Full text is an abstract
Baratti, D., Kusamura, S., Iusco, D., Bonomi, S., Grassi, A., Virzi, S., Leo, E., Deraco, M., Postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal metastases from colorectal cancer: A two-center study of 101 patients, Diseases of the Colon and Rectum, 57, 858–868, 2014 [PubMed: 24901687]	Cohort study design not relevant; RCT evidence available
Baratti, D., Kusamura, S., Pietrantonio, F., Guaglio, M., Niger, M., Deraco, M., Progress in treatments for colorectal cancer peritoneal metastases during the years 2010-2015. A systematic review, Critical Reviews in Oncology/Hematology, 100, 209–222, 2016 [PubMed: 26867984]	Systematic review - studies assessed individually
Bloemendaal, A. L. A., Verwaal, V. J., van Ruth, S., Boot, H., Zoetmulder, F. A. N., Conventional surgery and systemic chemotherapy for peritoneal carcinomatosis of colorectal origin: A prospective study, European Journal of Surgical Oncology, 31, 1145–1151, 2005 [PubMed: 16084051]	Not comparative - analyses the control arm from Verwaal 2003
Braam, H. J., Boerma, D., Wiezer, M. J., van Ramshorst, B., Hyperthermic intraperitoneal chemotherapy during primary tumour resection limits extent of bowel resection compared to two-stage treatment, European Journal of Surgical Oncology, 39, 988–93, 2013 [PubMed: 23810334]	Comparison not relevant - one-stage primary tumour resection HIPEC versus two-stage procedure
Cao, C., Yan, T. D., Black, D., Morris, D. L., A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin, Annals of Surgical Oncology, 16, 2152–65, 2009 [PubMed: 19434455]	Systematic review - studies assessed individually
Cashin, P. H., Mahteme, H., Spang, N., Syk, I., Frodin, J. E., Torkzad, M., Glimelius, B., Graf, W., Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial, European Journal of Cancer, 53, 155–162, 2016 [PubMed: 26751236]	Intervention not relevant, did not include HIPEC
Cashin, P. H., Mahteme, H., Syk, I., Frodin, J. E., Glimelius, B., Graf, W., Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases, European Journal of Surgical Oncology., 2018 [PubMed: 29530346]	Intervention not relevant, did not include HIPEC
Cashin, P. H., Graf, W., Nygren, P., Mahteme, H., Patient selection for cytoreductive surgery in colorectal peritoneal carcinomatosis using serum tumour markers: An observational cohort study, Annals of Surgery, 256, 1078–1083, 2012 [PubMed: 22580940]	Cohort study design not relevant; RCT evidence available
Cashin, P. H., Graf, W., Nygren, P., Mahteme, H., Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: Prognosis and treatment of recurrences in a cohort study, European Journal of Surgical Oncology, 38, 509–515, 2012 [PubMed: 22475555]	Comparison not relevant - CRS HIPEC versus CRS sequential postoperative intraperitoneal CT
Cashin, P. H., Graf, W., Nygren, P., Mahteme, H., Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: A case-control study, Annals of Oncology, 23, 647–652, 2012 [PubMed: 21685413]	Comparison not relevant - HIPEC versus normothermic sequential postoperative intraperitoneal chemotherapy (SPIC)
Cavaliere, F., Perri, P., Di Filippo, F., Giannarelli, D., Botti, C., Cosimelli, M., Tedesco, M., Principi, F., Laurenzi, L., Cavaliere, R., Treatment of peritoneal carcinomatosis with intent to cure, Journal of Surgical Oncology, 74, 41–4, 2000 [PubMed: 10861608]	Not comparative
Ceelen, W., Van Nieuwenhove, Y., Putte, D. V., Pattyn, P., Neoadjuvant chemotherapy with bevacizumab may improve outcome after cytoreduction and hyperthermic intraperitoneal chemoperfusion (HIPEC) for colorectal carcinomatosis, Annals of Surgical Oncology, 21, 3023–3028, 2014 [PubMed: 24756812]	Not comparative
Chia, C. S., Seshadri, R. A., Kepenekian, V., Vaudoyer, D., Passot, G., Glehen, O., Survival outcomes after Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from gastric cancer: A systematic review, Pleura and Peritoneum, 1, 67–77, 2016 [PMC free article: PMC6386497] [PubMed: 30911610]	Population not relevant - patients had gastric cancer
Chua, T. C., Morris, D. L., Saxena, A., Esquivel, J., Liauw, W., Doerfer, J., Germer, C. T., Kerscher, A. G., Pelz, J. O. W., Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: A multicenter study, Annals of Surgical Oncology, 18, 1560–1567, 2011 [PubMed: 21203904]	Cohort study design not relevant; RCT evidence available
Chua, T. C., Quinn, L. E., Zhao, J., Morris, D. L., Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases, Journal of Surgical Oncology, 108, 81–88, 2013 [PubMed: 23737041]	Comparison not relevant - primary CRS versus iterative CRS
Devilee, R, Simkens, G, Oudheusden, T, Rutten, H, Creemers, G, Tije, B, Nieuwenhuijzen, G, Hingh, I, Timing of systemic treatment in patients undergoing cytoreductive surgery and HIPEC for peritoneal metastases of colorectal origin, Annals of surgical oncology., 23, S80–s81, 2016	Full text is an abstract
Devilee, R. A., Simkens, G. A., van Oudheusden, T. R., Rutten, H. J., Creemers, G. J., ten Tije, A. J., de Hingh, I. H., Increased Survival of Patients with Synchronous Colorectal Peritoneal Metastases Receiving Preoperative Chemotherapy Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Annals of Surgical Oncology, 23, 2841–2848, 2016 [PubMed: 27044447]	Cohort study design not relevant; RCT evidence available
Elias, D., Delperro, J. R., Sideris, L., Benhamou, E., Pocard, M., Baton, O., Giovannini, M., Lasser, P., Treatment of peritoneal carcinomatosis from colorectal cancer: Impact of complete cytoreductive surgery and difficulties in conducting randomized trials, Annals of Surgical Oncology, 11, 518–521, 2004 [PubMed: 15123461]	Intervention not relevant, did not include HIPEC
Elias, D., Blot, F., Elotmany, A., Antoun, S., Lasser, P., Boige, V., Rougier, P., Ducreux, M., Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy, Cancer, 92, 71–76, 2001 [PubMed: 11443611]	Cohort study design not relevant; RCT evidence available
Elias, D., Gilly, F., Boutitie, F., Quenet, F., Bereder, J. M., Mansvelt, B., Lorimier, G., Dube, P., Glehen, O., Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: Retrospective analysis of 523 patients from a multicentric french study, Journal of Clinical Oncology, 28, 63–68, 2010 [PubMed: 19917863]	Cohort study design not relevant; RCT evidence available
Elias, D., Lefevre, J. H., Chevalier, J., Brouquet, A., Marchal, F., Classe, J. M., Ferron, G., Guilloit, J. M., Meeus, P., Goere, D., Bonastre, J., Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin, Journal of Clinical Oncology, 27, 681–685, 2009 [PubMed: 19103728]	Cohort study design not relevant; RCT evidence available
Elias, D., Pocard, M., Goere, D., HIPEC with oxaliplatin in the treatment of peritoneal carcinomatosis of colorectal origin, Cancer treatment and research, 134, 303–318, 2007 [PubMed: 17633062]	Summaries of previously completed cohort studies and trials
Esquivel, J., Lowy, A. M., Markman, M., Chua, T., Pelz, J., Baratti, D., Baumgartner, J. M., Berri, R., Bretcha-Boix, P., Deraco, M., Flores-Ayala, G., Glehen, O., Gomez-Portilla, A., Gonzalez-Moreno, S., Goodman, M., Halkia, E., Kusamura, S., Moller, M., Passot, G., Pocard, M., Salti, G., Sardi, A., Senthil, M., Spilioitis, J., Torres-Melero, J., Turaga, K., Trout, R., The American Society of Peritoneal Surface Malignancies (ASPSM) Multiinstitution Evaluation of the Peritoneal Surface Disease Severity Score (PSDSS) in 1,013 Patients with Colorectal Cancer with Peritoneal Carcinomatosis, Annals of Surgical Oncology, 21, 4195–4201, 2014 [PubMed: 24854493]	Cohort study design not relevant; RCT evidence available
Eveno, C., Passot, G., Goere, D., Soyer, P., Gayat, E., Glehen, O., Elias, D., Pocard, M., Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin, Annals of Surgical Oncology, 21, 1792–1800, 2014 [PubMed: 24337648]	Cohort study design not relevant; RCT evidence available
Eveno, C., Pocard, M., Randomized controlled trials evaluating Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in prevention and therapy of peritoneal metastasis: A Systematic review, Pleura and Peritoneum, 1, 169–182, 2016 [PMC free article: PMC6386515] [PubMed: 30911621]	Systematic review - studies assessed individually
Franko, J., Ibrahim, Z., Gusani, N. J., Holtzman, M. P., Bartlett, D. L., Zeh, Iii H. J., Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis, Cancer, 116, 3756–3762, 2010 [PubMed: 20564081]	Cohort study design not relevant; RCT evidence available
Franko, J., Shi, Q., Goldman, C. D., Pockaj, B. A., Nelson, G. D., Goldberg, R. M., Pitot, H. C., Grothey, A., Alberts, S. R., Sargent, D. J., Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: A pooled analysis of North Central Cancer Treatment Group phase III trials N9741 and N9841, Journal of Clinical Oncology, 30, 263–267, 2012 [PMC free article: PMC3269953] [PubMed: 22162570]	Comparison not relevant - patients with peritoneal carcinomatosis CRC (pcCRC) versus non-pcCRC
Franko, J., Shi, Q., Meyers, J. P., Maughan, T. S., Adams, R. A., Seymour, M. T., Saltz, L., Punt, C. J. A., Koopman, M., Tournigand, C., Tebbutt, N. C., Diaz-Rubio, E., Souglakos, J., Falcone, A., Chibaudel, B., Heinemann, V., Moen, J., De Gramont, A., Sargent, D. J., Grothey, A., Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database, The Lancet Oncology, 17, 1709–1719, 2016 [PubMed: 27743922]	< 25% of patients in each included trial had peritoneal metastases
Gervais, M. K., Dube, P., McConnell, Y., Drolet, P., Mitchell, A., Sideris, L., Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from colorectal cancer, Journal of Surgical Oncology, 108, 438–443, 2013 [PubMed: 24018983]	Cohort study design not relevant; RCT evidence available
Glehen, O., Cotte, E., Schreiber, V., Sayag-Beaujard, A. C., Vignal, J., Gilly, F. N., Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin, British Journal of Surgery, 91, 747–754, 2004 [PubMed: 15164446]	Cohort study design not relevant; RCT evidence available
Glehen, O., Kwiatkowski, F., Sugarbaker, P. H., Elias, D., Levine, E. A., De Simone, M., Barone, R., Yonemura, Y., Cavaliere, F., Quenet, F., Gutman, M., Tentes, A. A. K., Lorimier, G., Bernard, J. L., Bereder, J. M., Porcheron, J., Gomez-Portilla, A., Shen, P., Deraco, M., Rat, P., Gilly, F. N., Cytoreductive Surgery Combined with Perioperative Intraperitoneal Chemotherapy for the Management of Peritoneal Carcinomatosis from Colorectal Cancer: A Multi-Institutional Study, Journal of Clinical Oncology, 22, 3284–3292, 2004 [PubMed: 15310771]	Cohort study design not relevant; RCT evidence available
Glockzin, G., Gerken, M., Lang, S. A., Klinkhammer-Schalke, M., Piso, P., Schlitt, H. J., Oxaliplatin-based versus irinotecan-based hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis from appendiceal and colorectal cancer: A retrospective analysis, BMC Cancer, 14 (1) (no pagination), 2014 [PMC free article: PMC4228082] [PubMed: 25369730]	Cohort study design not relevant; RCT evidence available
Glockzin, G., von Breitenbuch, P., Schlitt, H. J., Piso, P., Treatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicin-based HIPEC protocol in patients with peritoneal carcinomatosis: a matched-pair analysis, Journal of Surgical Oncology, 107, 574–8, 2013 [PubMed: 22833286]	Cohort study design not relevant; RCT evidence available
Goere, D., Souadka, A., Faron, M., Cloutier, A. S., Viana, B., Honore, C., Dumont, F., Elias, D., Extent of Colorectal Peritoneal Carcinomatosis: Attempt to Define a Threshold Above Which HIPEC Does Not Offer Survival Benefit: A Comparative Study, Annals of Surgical Oncology, 22, 2958–2964, 2015 [PubMed: 25631064]	Cohort study design not relevant; RCT evidence available
Grass, F., Vuagniaux, A., Teixeira-Farinha, H., Lehmann, K., Demartines, N., Hubner, M., Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis, British Journal of Surgery, 104, 669–678, 2017 [PubMed: 28407227]	Intervention not relevant - pressurized intraperitoneal aerosol chemotherapy
He, T., Chen, Z., Xing, C., Cytoreductive surgery combined with intraperitoneal chemotherapy in the treatment of colorectal peritoneal metastasis: A meta-analysis, International Journal of Clinical and Experimental Medicine, 9, 20562–20570, 2016	Systematic review - studies assessed individually
Hompes, D., D’Hoore, A., Wolthuis, A., Fieuws, S., Mirck, B., Bruin, S., Verwaal, V., The of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: A comparative study, Journal of Surgical Oncology, 109, 527–532, 2014 [PubMed: 24375059]	Cohort study design not relevant; RCT evidence available
Huang, C. Q., Feng, J. P., Yang, X. J., Li, Y., Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: A case-control study from a Chinese center, Journal of Surgical Oncology, 109, 730–739, 2014 [PMC free article: PMC4283734] [PubMed: 24374987]	Cohort study design not relevant; RCT evidence available
Huang, C. Q., Min, Y., Wang, S. Y., Yang, X. J., Liu, Y., Xiong, B., Yonemura, Y., Li, Y., Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for peritoneal carcinomatosis from colorectal cancer: A systematic review and meta-analysis of current evidence, Oncotarget, 8, 55657–55683, 2017 [PMC free article: PMC5589691] [PubMed: 28903452]	Systematic review - studies assessed individually
Huang, C. Q., Yang, X. J., Yu, Y., Wu, H. T., Liu, Y., Yonemura, Y., Li, Y., Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for patients with peritoneal carcinomatosis from colorectal cancer: A phase II study from a Chinese Center, PLoS ONE, 9 (9) (no pagination), 2014 [PMC free article: PMC4178169] [PubMed: 25259574]	Not comparative
Klaver, C. E. L., Groenen, H., Morton, D. G., Laurberg, S., Bemelman, W. A., Tanis, P. J., Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines, Colorectal Disease, 19, 224–236, 2017 [PubMed: 28008728]	Study design not relevant - systematic review of guidelines
Klaver, Y. L. B., Leenders, B. J. M., Creemers, G. J., Rutten, H. J. T., Verwaal, V. J., Lemmens, V. E. P. P., De Hingh, I. H. J. T., Addition of biological therapies to palliative chemotherapy prolongs survival in patients with peritoneal carcinomatosis of colorectal origin, American Journal of Clinical Oncology: Cancer Clinical Trials, 36, 157–161, 2013 [PubMed: 22314003]	Comparison not relevant - compares different systemic treatments
Kobayashi, H., Kotake, K., Sugihara, K., Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: Data from a multi-center registry, International Journal of Clinical Oncology, 19, 98–105, 2014 [PubMed: 23239055]	Cohort study design not relevant; RCT evidence available
Kobayashi, H., Kotake, K., Sugihara, K., Impact of surgical resection of synchronous peritoneal metastasis from colorectal cancer: A propensity scorematched analysis, Diseases of the Colon and Rectum, 61 (5), e226, 2018	Full text is an abstract
Kok, N. F., de Hingh, I. H., Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases of colorectal origin, The British journal of surgery, 104, 313–315, 2017 [PubMed: 28112791]	Cohort study design not relevant; RCT evidence available
Kuijpers, A. M., Mehta, A. M., Boot, H., Van leerdam, M. E., Hauptmann, M., Aalbers, A. G., Verwaal, V. J., Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node positive colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, Annals of Oncology, 25, 864–869, 2014 [PubMed: 24667719]	Cohort study design not relevant; RCT evidence available
Lam, J. Y., McConnell, Y. J., Rivard, J. D., Temple, W. J., Mack, L. A., Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis, American Journal of Surgery, 210, 424–30, 2015 [PubMed: 26051744]	Comparison not relevant - HIPEC EPIC versus HIPEC alone
Lee, L., Alie-Cusson, F., Dube, P., Sideris, L., Postoperative complications affect long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis, Journal of Surgical Oncology, 116, 236–243, 2017 [PubMed: 28409831]	Cohort study design not relevant; RCT evidence available
Maciver, A. H., Lee, N., Skitzki, J. J., Boland, P. M., Francescutti, V., Cytoreduction and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) in colorectal cancer: Evidence-based review of patient selection and treatment algorithms, European Journal of Surgical Oncology, 43, 1028–1039, 2017 [PubMed: 28029523]	Narrative review
Maggiori, L., Goere, D., Viana, B., Tzanis, D., Dumont, F., Honore, C., Eveno, C., Elias, D., Should patients with peritoneal carcinomatosis of colorectal origin with synchronous liver metastases be treated with a curative intent?: A case-control study, Annals of Surgery, 258, 116–121, 2013 [PubMed: 23207243]	Cohort study design not relevant; RCT evidence available
Mahteme, H., Hansson, J., Berglund,, Pahlman, L., Glimelius, B., Nygren, P., Graf, W., Improved survival in patients with peritoneal metastases from colorectal cancer: A preliminary study, British Journal of Cancer, 90, 403–407, 2004 [PMC free article: PMC2409568] [PubMed: 14735184]	Population not relevant, only 8/18 patients had peritoneal metastases
Maillet, M., Glehen, O., Lambert, J., Goere, D., Pocard, M., Msika, S., Passot, G., Elias, D., Eveno, C., Sabate, J. M., Lourenco, N., Andre, T., Gornet, J. M., Early Postoperative Chemotherapy After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Isolated Peritoneal Carcinomatosis of Colon Cancer: A Multicenter Study, Annals of Surgical Oncology, 23, 863–869, 2016 [PubMed: 26480848]	Cohort study design not relevant; RCT evidence available
McConnell, Y. J., Mack, L. A., Francis, W. P., Ho, T., Temple, W. J., HIPEC+EPIC versus HIPEC-alone: differences in major complications following cytoreduction surgery for peritoneal malignancy, Journal of Surgical Oncology, 107, 591–6, 2013 [PubMed: 23129533]	Comparison not relevant - HIPEC EPIC versus HIPEC alone
Mirnezami, R., Mehta, A. M., Chandrakumaran, K., Cecil, T., Moran, B. J., Carr, N., Verwaal, V. J., Mohamed, F., Mirnezami, A. H., Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone, British Journal of Cancer, 111, 1500–1508, 2014 [PMC free article: PMC4200082] [PubMed: 25225906]	Systematic review; studies assessed individually
Mirnezami, R., Moran, B. J., Harvey, K., Cecil, T., Chandrakumaran, K., Carr, N., Mohamed, F., Mirnezami, A. H., Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases, World Journal of Gastroenterology, 20, 14018–32, 2014 [PMC free article: PMC4194588] [PubMed: 25320542]	Systematic review - studies assessed individually
Nadler, A., McCart, J. A., Govindarajan, A., Peritoneal Carcinomatosis from Colon Cancer: A Systematic Review of the Data for Cytoreduction and Intraperitoneal Chemotherapy, Clinics in Colon & Rectal Surgery, 28, 234–46, 2015 [PMC free article: PMC4655111] [PubMed: 26648794]	Systematic review - studies assessed individually
Park, S. Y., Choi, G. S., Park, J. S., Kim, H. J., Yang, C. S., Kim, J. G., Kang, B. W., Efficacy of Early Postoperative Intraperitoneal Chemotherapy After Complete Surgical Resection of Peritoneal Metastasis from Colorectal Cancer: A Case-Control Study from a Single Center, Annals of Surgical Oncology, 23, 2266–2273, 2016 [PubMed: 26951148]	Cohort study design not relevant; RCT evidence available
Passot, G., Vaudoyer, D., Cotte, E., You, B., Isaac, S., Noel Gilly, F., Mohamed, F., Glehen, O., Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis, Annals of Surgery, 256, 125–129, 2012 [PubMed: 22580942]	Cohort study design not relevant; RCT evidence available
Passot, G., You, B., Boschetti, G., Fontaine, J., Isaac, S., Decullier, E., Maurice, C., Vaudoyer, D., Gilly, F. N., Cotte, E., Glehen, O., Pathological response to neoadjuvant chemotherapy: A new prognosis tool for the curative management of peritoneal colorectal carcinomatosis, Annals of Surgical Oncology, 21, 2608–2614, 2014 [PubMed: 24668148]	Cohort study design not relevant; RCT evidence available
Pelz, J. O. W., Chua, T. C., Esquivel, J., Stojadinovic, A., Doerfer, J., Morris, D. L., Maeder, U., Germer, C., Kerscher, A. G., Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified according to the retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin, BMC Cancer, 10, 689, 2010 [PMC free article: PMC3014907] [PubMed: 21176206]	No case mix adjustments
Pestieau, S. R., Sugarbaker, P. H., Ota, D. M., Treatment of primary colon cancer with peritoneal carcinomatosis: Comparison of concomitant versus. delayed management, Diseases of the Colon and Rectum, 43, 1341–1348, 2000 [PubMed: 11052509]	Cohort study design not relevant; RCT evidence available
Piso, P., Koller, M., Arnold, D., Schlitt H. J., Glockzin, G., Multimodality treatment of colorectal peritoneal metastasis with perioperative systemic chemotherapy, cytoreductive surgery (CRS), and HIPEC: First safety results of the COMBATAC trial, Journal of Clinical Oncology. Conference, 32, 2014	Full text is an abstract; not comparative
Prada-Villaverde, A., Esquivel, J., Lowy, A. M., Markman, M., Chua, T., Pelz, J., Baratti, D., Baumgartner, J. M., Berri, R., Bretcha-Boix, P., Deraco, M., Flores-Ayala, G., Glehen, O., Gomez-Portilla, A., Gonzalez-Moreno, S., Goodman, M., Halkia, E., Kusamura, S., Moller, M., Passot, G., Pocard, M., Salti, G., Sardi, A., Senthil, M., Spiliotis, J., Torres-Melero, J., Turaga, K., Trout, R., The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery, Journal of Surgical Oncology, 110, 779–785, 2014 [PubMed: 25088304]	Cohort study design not relevant; RCT evidence available
Rivard, J. D., McConnell, Y. J., Temple, W. J., Mack, L. A., Cytoreduction and heated intraperitoneal chemotherapy for colorectal cancer: Are we excluding patients who may benefit?, Journal of Surgical Oncology, 109, 104–109, 2014 [PubMed: 24449172]	Not comparative
Rovers, K. P., Simkens, G. A., Punt, C. J., van Dieren, S., Tanis, P. J., de Hingh, I. H., Perioperative systemic therapy for resectable colorectal peritoneal metastases: Sufficient evidence for its widespread use? A critical systematic review, Critical Reviews in Oncology/Hematology, 114, 53–62, 2017 [PubMed: 28477747]	Systematic review - studies assessed individually
Sammartino, P., Sibio, S., Biacchi, D., Cardi, M., Accarpio, F., Mingazzini, P., Rosati, M. S., Cornali, T., Di Giorgio, A., Prevention of peritoneal metastases from colon cancer in high-risk patients: Preliminary results of surgery plus prophylactic HIPEC, Gastroenterology Research and Practice, (no pagination), 2012 [PMC free article: PMC3356888] [PubMed: 22645605]	Cohort study design not relevant; RCT evidence available
Sammartino, P., Sibio, S., Biacchi, D., Cardi, M., Mingazzini, P., Rosati, M. S., Cornali, T., Sollazzo, B., Atta, J. M., Di Giorgio, A., Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases, International Journal of Colorectal Disease, 29, 1081–1089, 2014 [PubMed: 24980687]	Cohort study design not relevant; RCT evidence available
Scaringi, S., Leo, F., Canonico, G., Batignani, G., Ficari, F., Tonelli, F., The role of cytoreductive surgery alone for the treatment of peritoneal carcinomatosis of colorectal origin. A retrospective analysis with regard to multimodal treatments, Hepato-Gastroenterology, 56, 650–655, 2009 [PubMed: 19621673]	Not comparative
Shen, P., Stewart, Iv J. H., Levine, E. A., Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Overview and Rationale, Current Problems in Cancer, 33, 125–141, 2009 [PubMed: 19647612]	Narrative review
Shen, P., Stewart, J. H, Levine, E. A., The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer with peritoneal surface disease, Current Problems in Cancer, 33, 154–67, 2009 [PubMed: 19647614]	Not comparative
Ung, L., Chua T. C., Morris D. L., Peritoneal metastases of lower gastrointestinal tract origin: A comparative study of patient outcomes following cytoreduction and intraperitoneal chemotherapy, Journal of Cancer Research and Clinical Oncology, 139, 1899–1908, 2013 [PMC free article: PMC4079609] [PubMed: 24052322]	Cohort study design not relevant; RCT evidence available
Ung, L., Chua, T. C., Morris, D. L., Cure for peritoneal metastases? An evidence-based review, ANZ Journal of Surgery, 83, 821–826, 2013 [PubMed: 23809063]	Narrative review
Vaira, M., Cioppa, T., D’Amico, S., De Marco, G., D’Alessandro, M., Fiorentini, G., De Simone, M., Treatment of Peritoneal carcinomatosis from colonic cancer by cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Experience of ten years, In Vivo, 24, 79–84, 2010 [PubMed: 20133981]	Cohort study design not relevant; RCT evidence available
Vallicelli, C., Cavaliere, D., Catena, F., Coccolini, F., Ansaloni, L., Poiasina, E., Abongwa, H. K., De Simone, B., Alberici, L., Framarini, M., Verdecchia, G. M., Management of peritoneal carcinomatosis from colorectal cancer: review of the literature, International Journal of Colorectal Disease, 29, 895–8, 2014 [PubMed: 24915844]	Narrative review
van Oudheusden, T. R., Braam, H. J., Nienhuijs, S. W., Wiezer, M. J., van Ramshorst, B., Luyer, M. D., Lemmens, V. E., de Hingh, I. H., Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and effective option for colorectal cancer patients after emergency surgery in the presence of peritoneal carcinomatosis, Annals of Surgical Oncology, 21, 2621–6, 2014 [PubMed: 24671638]	Cohort study design not relevant; RCT evidence available
Van Oudheusden, T. R., Nienhuijs, S. W., Luyer, M. D., Nieuwenhuijzen, G. A., Lemmens, V. E., Rutten, H. J., De Hingh, I. H., Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: A systematic review, European Journal of Surgical Oncology, 41, 1269–1277, 2015 [PubMed: 26175345]	Systematic review - studies assessed individually
Verwaal, V. J., Cytoreduction and HIPEC for peritoneal carcinomatosis from colorectal origin: The Amsterdam experience, Acta Chirurgica Belgica, 106, 283–284, 2006 [PubMed: 16909999]	Editorial
Verwaal, V. J., Results of cytoreduction followed by HIPEC in carcinomatosis of colorectal origin, Cancer Treatment & Research, 134, 291–301, 2007 [PubMed: 17633061]	Narrative review
Verzijden, Jcm, Klaver, Ylb, de, Hingh Ignace Hjt, Bleichrodt, Rp, Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis in patients with colorectal cancer, Cochrane Database of Systematic Reviews, 2010	Protocol
Waite, K., Youssef, H., The Role of Neoadjuvant and Adjuvant Systemic Chemotherapy with Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Systematic Review, Annals of Surgical Oncology, 24, 705–720, 2017 [PubMed: 28058545]	Systematic review - studies assessed individually
Wu, W., Yan, S., Liao, X., Xiao, H., Fu, Z., Chen, L., Mou, J., Yu, H., Zhao, L., Liu, X., Curative versus palliative treatments for colorectal cancer with peritoneal carcinomatosis: A systematic review and metaanalysis, Oncotarget, 8, 113202–113212, 2017 [PMC free article: PMC5762584] [PubMed: 29348899]	Systematic review - studies assessed individually
Yan, T. D., Black, D., Savady, R., Sugarbaker, P. H., Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma, Journal of Clinical Oncology, 24, 4011–4019, 2006 [PubMed: 16921055]	Systematic review - studies assessed individually
Yuan, H., Zheng, B., Tu, S., Clinical research of intraperitoneal implantation of sustained-release 5-fluorouracil in advanced colorectal cancer, World Journal of Surgical Oncology, 13, 320, 2015 [PMC free article: PMC4657249] [PubMed: 26596801]	Population not relevant - mixed population with peritoneal, liver and other liver metastases. Intervention not relevant - not HIPEC
Zani, S., Papalezova, K., Stinnett, S., Tyler, D., Hsu, D., Blazer, Iii D. G., Modest advances in survival for patients with colorectal-associated peritoneal carcinomatosis in the era of modern chemotherapy, Journal of Surgical Oncology, 107, 307–311, 2013 [PubMed: 22811275]	Comparison not relevant - received CT pre or post 2003
Zhu, Y., Hanna, N., Boutros, C., Alexander Jr, H. R., Assessment of clinical benefit and quality of life in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for management of peritoneal metastases, Journal of Gastrointestinal Oncology, 4, 62–71, 2013 [PMC free article: PMC3562622] [PubMed: 23450068]	Narrative review