Cytoreduction surgery followed by hyperthermic intraoperative peritoneal chemotherapy for peritoneal carcinomatosis (interventional procedures consultation)
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Interventional procedure consultation document
Cytoreduction surgery followed by hyperthermic intraoperative peritoneal chemotherapy for peritoneal carcinomatosis
Peritoneal carcinomatosis is an advanced form of cancer found in the peritoneal cavity (the space between the two membranes that separate the organs in the abdomen from the abdominal wall). This type of cancer happens when cancers from the appendix, bowel, rectum or ovaries spread. It is associated with short survival and poor quality of life, and may lead to bowel obstruction, accumulation of fluid in the peritoneal cavity and pain.
Cytoreduction surgery involves removing all of the visible (macroscopic) tumour. During the same operation, the peritoneal cavity is flushed with heated chemotherapy fluid with the aim of eliminating any microscopic traces of disease left behind.
The National Institute for Health and Clinical Excellence (NICE) is examining cytoreduction surgery followed by hyperthermic intraoperative peritoneal chemotherapy for peritoneal carcinomatosis and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about cytoreduction surgery followed by hyperthermic intraoperative peritoneal chemotherapy for peritoneal carcinomatosis.
This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:
- comments on the provisional recommendations
- the identification of factual inaccuracies
- additional relevant evidence, with bibliographic references where possible.
Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.
The process that NICE will follow after the consultation period ends is as follows.
- The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
- The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.
For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).
NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.
Closing date for comments: 18 November 2009
Target date for publication of guidance: February 2010
1 Provisional recommendations
1.1 Current evidence on the efficacy of cytoreduction surgery (CRS) followed by hyperthermic intraoperative peritoneal chemotherapy (HIPEC) for peritoneal carcinomatosis shows some improvement in survival for selected patients with colorectal metastases, but evidence is inadequate for other types of cancer. The evidence on safety shows significant risks of morbidity and mortality which need to be balanced against the perceived benefit for each individual patient. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.
1.2 Clinicians wishing to undertake CRS followed by HIPEC for peritoneal carcinomatosis should take the following actions.
- Inform the clinical governance leads in their Trusts.
- Ensure that patients and their carers understand the uncertainty about the procedure’s safety and efficacy in relation to the potential morbidity and mortality and the prolonged recovery period, and provide them with clear written information. In addition, the use of NICE’s information for patients (‘Understanding NICE guidance’) is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). [[details to be completed at publication]]
- Audit and review clinical outcomes of all patients having CRS followed by HIPEC for peritoneal carcinomatosis (see section 3.1).
1.3 Patient selection and treatment should be carried out in the context of a multidisciplinary team, including clinical oncologists and surgeons with experience in this operation.
1.4 NICE encourages further research into this procedure, which should take the form of randomised controlled trials (RCTs) with clear descriptions of patient selection criteria and the types of cancer being treated. The chemotherapy regimes used should be well defined. Outcome measures should include survival and quality of life.
2 The procedure
2.1 Indications and current treatments
2.1.1 Peritoneal carcinomatosis is advanced cancer associated with short survival and poor quality of life.
2.1.2 Current treatments include systemic chemotherapy with the aim of prolonging survival, and/or surgery for short-term palliation of complications such as bowel obstruction.
2.2 Outline of the procedure
2.2.1 The aim of CRS is to remove all macroscopic tumour, including non-essential involved organs and peritoneum. Intraoperative intraperitoneal administration of chemotherapy allows the drug to be distributed uniformly to all surfaces of the abdomen and pelvis.
2.2.2 With the patient under general anaesthesia, appropriate CRS is carried out, followed by perfusion of the abdomen with heated chemotherapy solution (heating increases penetration and cytotoxic effects). The abdomen is drained prior to closure. A further course of systemic or early postoperative intraperitoneal chemotherapy (EPIC) may be administered postoperatively.
| Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/IP256aoverview. |
2.3 Efficacy
2.3.1 An RCT of 105 patients with peritoneal carcinomatosis of colorectal origin reported that disease-specific survival was significantly higher for patients treated by CRS, HIPEC and systemic chemotherapy (22.2 months; 54 patients) compared with patients treated by systemic chemotherapy (12.6 months; 51 patients) (p = 0.028).
2.3.2 A non-randomised comparative study of 506 patients with peritoneal carcinomatosis of colorectal origin comparing CRS and HIPEC (271 patients) with CRS and EPIC (123 patients) and CRS and HIPEC plus EPIC (112 patients), reported no significant difference in median survival between the groups (19.2 months, 19.2 months and 21.6 months respectively) (p = 0.61).
2.3.3 A case series of 96 patients with peritoneal carcinomatosis of varying primary tumour origin treated by CRS and HIPEC reported a significant improvement in quality of life (using the Short Form-36 questionnaire), with an increase in mean score from 69.5 to 80 at 6-month follow-up (significance not stated).
2.3.4 The Specialist Advisers listed key efficacy outcomes as survival, quality of life, symptom palliation, recurrence rate, treatment-related morbidity and return to work and recreational activities.
2.4 Safety
2.4.1 A postoperative mortality rate of 4% (20/506) was reported in the non-randomised comparative study of 506 patients. Deaths were attributed to the following causes: septic shock (9), respiratory complications (5), pulmonary embolus (1), stroke (1), peritonitis (1), acute renal failure (1), aplasia (not otherwise described) (1) and unknown causes (1) (timing of events not stated). In the RCT of 105 patients (CRS, HIPEC and systemic chemotherapy group) 3 patients died from abdominal sepsis; 2 within 40-days and 1 more than 3 months after the procedure and 1 patient died of pulmonary embolism more than 3 months after the procedure.
2.4.2 Arrhythmia was reported in 2 patients each in case series of 241 and 59 patients respectively (varying tumour origins; timing of events not stated). Myocardial necrosis and myocardial infarction were reported in 1 patient each in case series of 207 and 122 patients (varying tumour origin; timing of events not stated).
2.4.3 Acute renal failure was reported in 3% (2/59) (successfully treated by medical therapy) and 1% (1/140) (requiring dialysis in intensive care) of patients in the case series of 59 and 140 patients (varying tumour origin). Haemolytic–uraemic syndrome occurred in 1 patient in the case series of 122 patients.
2.4.4 Acute respiratory distress syndrome was reported in 1 patient in the case series of 241 patients (timing of event not stated). Pneumothorax was reported in 3% (5/200), 2% (3/174), 7% (10/140) and 2% (1/64) of patients in case series of 200, 174, 140 and 64 patients respectively (variety of cancers).
2.4.5 Haematological toxicity related to chemotherapy was reported in 2% (12/506) of patients in the non-randomised comparative study of 506 patients (timing of event not stated).
2.4.6 Pancreatitis was reported in 1 patient each in the RCT of 105 patients (CRS, HIPEC and systemic chemotherapy group) and the case series of 241 patients. Gastrointestinal fistulae were reported in 15% (7/48) of patients in the RCT of 105.
2.4.7 Pulmonary embolism was reported in 0.4% (2/506) to 6% (4/174) of patients across the studies.
2.4.8 Deep vein thrombosis was reported in 1% (2/200) to 5% (5/100) of patients across the studies.
2.4.9 The Specialist Advisers listed possible adverse events as anastomotic leakage, bowel obstruction, bleeding, abdominal pain, eating disturbances, vascular, ureteric and bile duct injury, liver dysfunction and failure, neuropathy and anaphylaxis.
3 Further information
3.1 This guidance requires that clinicians undertaking the procedure make special arrangements for audit. NICE has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.
3.2 This document is a review of the NICE interventional procedures guidance 116 published in 2005. For related NICE guidance see www.nice.org.uk.
Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
October 2009
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It is the responsibility of consultees to accurately cite academic work in order that they can be validated.