The authors concluded that cytoreductive surgery plus perioperative intraperitoneal chemotherapy significantly improved survival compared with control in patients with colorectal peritoneal carcinomatosis. The limited search and evidence that was based on a small number of studies with different designs suggests that the authors’ conclusions should be interpreted with caution.

To evaluate the effects of cytoreductive surgery and perioperative intraperitoneal chemotherapy on survival in patients with colorectal peritoneal carcinomatosis.

MEDLINE via PubMed was searched from 1950 to February 2009 for studies reported in English. Search terms were not reported. Reference lists of selected studies were screened.

Studies that evaluated cytoreductive surgery, hyperthermic perioperative intraperitoneal chemotherapy, early postoperative intraperitoneal chemotherapy or combinations of these interventions in patients with histologically defined colorectal peritoneal carcinomatosis (CRCP) were eligible for inclusion. Studies in which more than 20% of patients had peritoneal carcinomatosis of appendiceal origin and studies that did not specify that tumours were of colorectal origin were excluded unless data regarding CRCP patients were presented separately. Case studies and studies with fewer than 10 patients were excluded.

The review assessed overall survival (defined as the time from surgical intervention to death or end of follow-up) yearly up to five years post intervention. The review also assessed median survival, morbidity rates and hospital stay.

Included studies evaluated different combinations of specified peritonectomy procedures and different chemotherapy regimens (details were reported). Studies used different criteria to select patients; some included patients with lymph node and/or liver metastases. Duration of follow-up ranged from 10 to 113 months.

The authors stated that two reviewers independently reviewed each study and resolved disagreements by discussion; it was unclear whether this referred to study selection.

The authors did not report a formal validity assessment. However, they discussed the quality of included randomised controlled trials (RCTs) in the text and classified studies using the hierarchy of evidence described by the Oxford Centre for Evidence-based Medicine Levels of Evidence.

The authors did not state how many reviewers classified studies.

Where possible, for each study the percentages of patient who survived one, two, three, four and five years were extracted together with the median survival, mortality and morbidity rates and duration of hospital stay. Hazard ratios (HR) with 95% confidence intervals (CIs) of survival were extracted or calculated.

The authors stated that two reviewers independently extracted survival rates from survival curves. In addition, two reviewers independently reviewed each study and resolved disagreements; it was unclear whether this referred to data extraction.

Studies were grouped by study design (comparative or observational). Pooled HRs with 95% CIs were calculated for overall survival using data from comparative studies. Heterogeneity was assessed using X² and I² statistics.
For observational studies, overall mean survival rates were calculated for one two, three, four and five years and the range of perioperative morbidity rates and duration of hospital stay were reported.

Forty-seven studies were included (n=3,941): two RCTs (n=140); two comparative studies (n=114); and 43 observational studies (n=3,687).

Comparative studies:

One RCT reported adequate concealed methods of stratified randomisation, baseline comparability of treatment groups and analysis on an intention-to-treat basis. The other RCT failed to recruit the intended number of patients and treatment groups appeared non-comparable at baseline.

Cytoreductive surgery in combination with perioperative intraperitoneal chemotherapy was associated with a statistically significant improvement in survival compared with control (HR 0.55, 95% CI 0.40 to 0.75; four studies, n=271).

Cytoreductive surgery in combination with hyperthermic perioperative intraperitoneal chemotherapy was associated with a statistically significant improvement in survival compared with palliative care (HR 0.47, 95% CI 0.32 to 0.69; two studies, n=201).

There was no statistically significant difference in survival between cytoreductive surgery plus early postoperative intraperitoneal chemotherapy plus systemic chemotherapy compared to surgery plus systemic chemotherapy (two studies, n=70). There was no significant heterogeneity for any analysis.

Observational studies:
Overall median survival ranged from 11.9 to 60.1 months. Median survival rates were 76% at one year, 55% at two years, 36% at three years, 28% at four years and 19% at five years. Perioperative morbidity rates ranged from 14.8% to 76% and perioperative mortality ranged from 0% to 12%. Average duration of hospital stay ranged from nine to 29 days.

Cytoreductive surgery in combination with perioperative intraperitoneal chemotherapy significantly improved survival compared with control in patients with colorectal peritoneal carcinomatosis.

The review question was clearly stated and inclusion criteria were defined for participants, intervention and outcomes. Criteria for study design were broad. Limiting the search to English-language studies identified in one database plus references raised the potential for publication and language biases and may have resulted in the omission of other relevant studies. Two reviewers were involved in some aspects of data extraction, which minimised reviewer error and bias; it was unclear whether similar methods were used for study selection and the entire data extraction process. Study validity was not formally assessed and so results from these studies and any synthesis may not be reliable. Data from RCTs and nonrandomised studies were pooled using meta-analysis; pooling studies with different design is questionable. The limited search and evidence that was based on a small number of studies with different designs suggests that the authors’ conclusions should be interpreted with caution.

Practice: The authors stated that patients with resectable liver metastases should not be excluded from treatment with cytoreductive surgery and perioperative intraperitoneal chemotherapy.

Research: The authors stated that large prospective studies were required to evaluate the effect of lymph node and liver involvement on the prognosis of patients with colorectal peritoneal carcinomatosis.

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.