Leading article
Treatment of surgically resectable colorectal peritoneal metastases B. J. Moran and T. D. Cecil Peritoneal Malignancy Institute Basingstoke, Hampshire Hospitals Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK (e-mail: [email protected])
Published online 20 November 2013 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9281
Surgical resection cures selected patients with colorectal liver or lung metastases, or local recurrence. In contrast, peritoneal spread has been considered inevitably fatal. Emerging evidence suggests, however, that certain patients can now be cured by a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)1 . The concept of operable ‘colorectal peritoneal metastases (CPM)’, as opposed to ‘peritoneal carcinomatosis’, demands clear definition in order to identify this subset of patients with treatable and curable disease. CRS and HIPEC were popularized by Sugarbaker and others, predominantly for the treatment of pseudomyxoma peritonei (PMP), generally originating from a perforated lowgrade mucinous appendiceal tumour2 . In PMP the relatively non-invasive tumour biology, combined with the pathophysiology of intraperitoneal fluid dynamics, culminates in a ‘redistribution phenomenon’. Pooling of tumour cells by gravity occurs in the pelvis and paracolic gutters, and at normal sites of peritoneal fluid absorption (omentum and diaphragmatic peritoneum), with relative ‘visceral sparing’ of the motile, peristaltic, gastrointestinal tract, particularly the small bowel3 . The surgical treatment involves procedure times in excess of 9 h, extensive peritonectomy and excision of involved viscera4 . Although outcomes of treatment for PMP are excellent, 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
peritoneal carcinomatosis secondary to colorectal cancer generally has aggressive tumour biology with tissue invasion and often extensive gastrointestinal involvement. However, a subset of patients with either limited disease or visceral sparing may be amenable to CRS and HIPEC for resectable CPM. Such patients have disease spread analogous to that in PMP, with ‘redistribution’ to the omentum, pelvis and often right subdiaphragm, with either no, or at least limited, involvement of the small bowel or other vital abdominal viscera; complete macroscopic tumour removal is therefore feasible, with preservation of adequate gastrointestinal tract function. How common is the problem, what is the evidence and how are appropriate patients selected? The incidence of resectable CPM, without extra-abdominal spread, has been estimated at 3 per cent of patients with colorectal cancer, which extrapolates to approximately 1000 per year in England alone5 , although many will be unfit, or unwilling, to undergo the complex strategy of CRS and HIPEC. Emerging evidence for CRS and HIPEC in selected patients with CPM is substantial, and accumulating, with animal experiments6 , a randomized clinical trial (RCT)7 and numerous case series8 . The landmark Dutch RCT7 demonstrated that CRS and HIPEC significantly improved patient survival compared with systemic chemotherapy. Published case series have recently been
reviewed comprehensively by the English National Institute for Health and Clinical Excellence8 , with an overall 5-year survival rate of 19 per cent, and a recommendation that CRS and HIPEC is an appropriate strategy ‘in selected patients’. Much has been learnt from these trials, with the development of preoperative and intraoperative scoring, and staging systems to aid selection in order to improve outcomes. Complete macroscopic tumour removal is pivotal, with extent of CPM the most important prognostic factor determining this, and also survival, even with complete cytoreduction1 . Scoring systems such as the Peritoneal Carcinomatosis Index (PCI, range 0–39) , the Simplified Peritoneal Cancer Index (range 0–21) and the seven-region count from the Netherlands Cancer Institute all describe the volume and spread of peritoneal disease within the abdomen, and unsurprisingly ‘less is better’8 . Complete cytoreduction is crucial, although often this cannot be determined until laparotomy. In this context, median survival was 35·4 months after complete cytoreduction compared with 8·4 months if macroscopic tumour removal could not be achieved1 . In the Dutch RCT7 , 41 per cent of patients had R1 resection (complete macroscopic tumour removal) with a median survival of 48 months and a 5-year survival rate of 45 per cent. The ongoing challenge is establishing an accurate preoperative PCI BJS 2014; 101: 5–7
6
score (and likelihood of complete cytoreduction) by preoperative imaging (and increasingly laparoscopy) to aid selection and reduce ineffectual laparotomy9 . The best results are in limited disease, usually confined to one or two quadrants of the abdomen and with a minimum of 200 cm of uninvolved small bowel1 . The combination of major surgery and HIPEC in patients with cancer carries significant risks in terms of morbidity and mortality. In the largest multicentre review1 of 523 patients undergoing CRS and HIPEC, the postoperative mortality rate was 3·3 per cent, serious complications occurred in 31 per cent and 57 patients (10·9 per cent) required reoperation. The increasing use of laparoscopic colorectal surgery will detect patients with low-volume CPM, not identified during preoperative staging. Although symptomatic primary tumours need to be dealt with appropriately, surgery can be deferred in those with minimal symptoms and performed in conjunction with CRS and HIPEC. Patients with major symptoms, particularly if obstructive, are not amenable to this strategy, and either bypass or resection may be required. Thereafter, systemic chemotherapy, a ‘trial of time’, clinical reassessment, further imaging and liaison with a peritoneal malignancy unit may clarify a way forward. Even though it is virtually impossible to perform CRS and HIPEC safely within 6 months or so after a major resectional procedure, the patient who has had laparoscopy only may proceed as soon as logistically possible in a specialized unit. A further emerging concept is ‘second look’ at 6–12 months for patients at high risk of CPM based on a perforated tumour, Krukenberg ovarian metastases or localized resected peritoneal disease at the 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
B. J. Moran and T. D. Cecil
primary operation10 . In one series10 , 41 patients had systemic chemotherapy and normal imaging at 12 months after primary surgery, and subsequently underwent laparotomy. Low-volume resectable peritoneal metastases were present in 60 per cent who had initially resected localized peritoneal metastases, 62 per cent of those with Krukenberg tumours and 37 per cent of those with primary tumour perforation. Guidance8,11 that supports the use of CRS and HIPEC in selected patients with peritoneal colorectal carcinomatosis presents both resource and training implications for these complex patients. Initiatives in a number of European countries to develop training programmes focused on rectal cancer or laparoscopic colorectal surgery are now required to establish and train peritoneal malignancy teams to provide optimal care for appropriate patients.
3
4
5
6
Acknowledgements
The authors acknowledge the input in design and writing by F. Mohamed, Consultant Surgeon, Peritoneal Malignancy Institute Basingstoke. Disclosure: The authors declare no conflict of interest.
7
References 1 Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 2010; 28: 63–68. 2 Youssef H, Newman C, Chandrakumaran K, Mohamed F, Cecil TD, Moran BJ. Operative findings, early complications, and long-term survival in 456 patients with pseudomyxoma peritonei syndrome of appendiceal origin.
www.bjs.co.uk
8
9
Dis Colon Rectum 2011; 54: 293–299. Sugarbaker PH. Pseudomyxoma peritonei. A cancer whose biology is characterized by a redistribution phenomenon. Ann Surg 1994; 219: 109–111. Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol 2012; 30: 2449–2456. Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg 2002; 89: 1545–1550. Klaver YL, Hendriks T, Lomme RM, Rutten HJ, Bleichrodt RP, de Hingh IH. Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model. Br J Surg 2010; 97: 1874–1880. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003; 21: 3737–3743. National Institute for Health and Clinical Excellence (NICE). Cytoreduction Surgery followed by Hyperthermic Intraoperative Peritoneal Chemotherapy for Peritoneal Carcinomatosis. IPG 331. http://www.nice.org.uk/guidance/ IPG331 [accessed 12 August 2013]. Iversen LH, Rasmussen PC, Laurberg S. Value of laparoscopy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis. Br J Surg 2013; 100: 285–29.
BJS 2014; 101: 5–7
Surgically resectable colorectal peritoneal metastases
10 Elias D, Honor´e C, Dumont F, Ducreux M, Boige V, Malka D et al. Results of systematic second look surgery plus HIPEC in asymptomatic patients presenting a high risk of
7
developing colorectal peritoneal carcinomatosis. Ann Surg 2011; 254: 289–293. 11 NHS Commissioning Board. Clinical Commissioning Policy: Cytoreductive
Surgery for Peritoneal Carcinomatosis. 2012. Reference: NHSCB/A8f. www.england.nhs.uk/wpcontent/uploads/2013/04/a08-p-a.pdf [accessed 12 August 2013].
Snapshot quiz
Snapshot quiz 14/1 Question: What is this condition and how is it treated?
The answer to the above question is found on p. 99 of this issue of BJS. Saurabh S1 and Singh N2 : 1 Department of Surgery, Drexel University College of Medicine, and 2 Temple University Hospital, Philadelphia, Pennsylvania, USA (e-mail: [email protected])
Snapshots in Surgery: to view submission guidelines, submit your snapshot and view the archive, please visit www.bjs.co.uk
2013 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2014; 101: 5–7
Treatment of surgically resectable colorectal peritoneal metastases B. J. Moran and T. D. Cecil Peritoneal Malignancy Institute Basingstoke, Hampshire Hospitals Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK (e-mail: [email protected])
Published online 20 November 2013 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9281
Surgical resection cures selected patients with colorectal liver or lung metastases, or local recurrence. In contrast, peritoneal spread has been considered inevitably fatal. Emerging evidence suggests, however, that certain patients can now be cured by a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)1 . The concept of operable ‘colorectal peritoneal metastases (CPM)’, as opposed to ‘peritoneal carcinomatosis’, demands clear definition in order to identify this subset of patients with treatable and curable disease. CRS and HIPEC were popularized by Sugarbaker and others, predominantly for the treatment of pseudomyxoma peritonei (PMP), generally originating from a perforated lowgrade mucinous appendiceal tumour2 . In PMP the relatively non-invasive tumour biology, combined with the pathophysiology of intraperitoneal fluid dynamics, culminates in a ‘redistribution phenomenon’. Pooling of tumour cells by gravity occurs in the pelvis and paracolic gutters, and at normal sites of peritoneal fluid absorption (omentum and diaphragmatic peritoneum), with relative ‘visceral sparing’ of the motile, peristaltic, gastrointestinal tract, particularly the small bowel3 . The surgical treatment involves procedure times in excess of 9 h, extensive peritonectomy and excision of involved viscera4 . Although outcomes of treatment for PMP are excellent, 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
peritoneal carcinomatosis secondary to colorectal cancer generally has aggressive tumour biology with tissue invasion and often extensive gastrointestinal involvement. However, a subset of patients with either limited disease or visceral sparing may be amenable to CRS and HIPEC for resectable CPM. Such patients have disease spread analogous to that in PMP, with ‘redistribution’ to the omentum, pelvis and often right subdiaphragm, with either no, or at least limited, involvement of the small bowel or other vital abdominal viscera; complete macroscopic tumour removal is therefore feasible, with preservation of adequate gastrointestinal tract function. How common is the problem, what is the evidence and how are appropriate patients selected? The incidence of resectable CPM, without extra-abdominal spread, has been estimated at 3 per cent of patients with colorectal cancer, which extrapolates to approximately 1000 per year in England alone5 , although many will be unfit, or unwilling, to undergo the complex strategy of CRS and HIPEC. Emerging evidence for CRS and HIPEC in selected patients with CPM is substantial, and accumulating, with animal experiments6 , a randomized clinical trial (RCT)7 and numerous case series8 . The landmark Dutch RCT7 demonstrated that CRS and HIPEC significantly improved patient survival compared with systemic chemotherapy. Published case series have recently been
reviewed comprehensively by the English National Institute for Health and Clinical Excellence8 , with an overall 5-year survival rate of 19 per cent, and a recommendation that CRS and HIPEC is an appropriate strategy ‘in selected patients’. Much has been learnt from these trials, with the development of preoperative and intraoperative scoring, and staging systems to aid selection in order to improve outcomes. Complete macroscopic tumour removal is pivotal, with extent of CPM the most important prognostic factor determining this, and also survival, even with complete cytoreduction1 . Scoring systems such as the Peritoneal Carcinomatosis Index (PCI, range 0–39) , the Simplified Peritoneal Cancer Index (range 0–21) and the seven-region count from the Netherlands Cancer Institute all describe the volume and spread of peritoneal disease within the abdomen, and unsurprisingly ‘less is better’8 . Complete cytoreduction is crucial, although often this cannot be determined until laparotomy. In this context, median survival was 35·4 months after complete cytoreduction compared with 8·4 months if macroscopic tumour removal could not be achieved1 . In the Dutch RCT7 , 41 per cent of patients had R1 resection (complete macroscopic tumour removal) with a median survival of 48 months and a 5-year survival rate of 45 per cent. The ongoing challenge is establishing an accurate preoperative PCI BJS 2014; 101: 5–7
6
score (and likelihood of complete cytoreduction) by preoperative imaging (and increasingly laparoscopy) to aid selection and reduce ineffectual laparotomy9 . The best results are in limited disease, usually confined to one or two quadrants of the abdomen and with a minimum of 200 cm of uninvolved small bowel1 . The combination of major surgery and HIPEC in patients with cancer carries significant risks in terms of morbidity and mortality. In the largest multicentre review1 of 523 patients undergoing CRS and HIPEC, the postoperative mortality rate was 3·3 per cent, serious complications occurred in 31 per cent and 57 patients (10·9 per cent) required reoperation. The increasing use of laparoscopic colorectal surgery will detect patients with low-volume CPM, not identified during preoperative staging. Although symptomatic primary tumours need to be dealt with appropriately, surgery can be deferred in those with minimal symptoms and performed in conjunction with CRS and HIPEC. Patients with major symptoms, particularly if obstructive, are not amenable to this strategy, and either bypass or resection may be required. Thereafter, systemic chemotherapy, a ‘trial of time’, clinical reassessment, further imaging and liaison with a peritoneal malignancy unit may clarify a way forward. Even though it is virtually impossible to perform CRS and HIPEC safely within 6 months or so after a major resectional procedure, the patient who has had laparoscopy only may proceed as soon as logistically possible in a specialized unit. A further emerging concept is ‘second look’ at 6–12 months for patients at high risk of CPM based on a perforated tumour, Krukenberg ovarian metastases or localized resected peritoneal disease at the 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
B. J. Moran and T. D. Cecil
primary operation10 . In one series10 , 41 patients had systemic chemotherapy and normal imaging at 12 months after primary surgery, and subsequently underwent laparotomy. Low-volume resectable peritoneal metastases were present in 60 per cent who had initially resected localized peritoneal metastases, 62 per cent of those with Krukenberg tumours and 37 per cent of those with primary tumour perforation. Guidance8,11 that supports the use of CRS and HIPEC in selected patients with peritoneal colorectal carcinomatosis presents both resource and training implications for these complex patients. Initiatives in a number of European countries to develop training programmes focused on rectal cancer or laparoscopic colorectal surgery are now required to establish and train peritoneal malignancy teams to provide optimal care for appropriate patients.
3
4
5
6
Acknowledgements
The authors acknowledge the input in design and writing by F. Mohamed, Consultant Surgeon, Peritoneal Malignancy Institute Basingstoke. Disclosure: The authors declare no conflict of interest.
7
References 1 Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 2010; 28: 63–68. 2 Youssef H, Newman C, Chandrakumaran K, Mohamed F, Cecil TD, Moran BJ. Operative findings, early complications, and long-term survival in 456 patients with pseudomyxoma peritonei syndrome of appendiceal origin.
www.bjs.co.uk
8
9
Dis Colon Rectum 2011; 54: 293–299. Sugarbaker PH. Pseudomyxoma peritonei. A cancer whose biology is characterized by a redistribution phenomenon. Ann Surg 1994; 219: 109–111. Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol 2012; 30: 2449–2456. Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg 2002; 89: 1545–1550. Klaver YL, Hendriks T, Lomme RM, Rutten HJ, Bleichrodt RP, de Hingh IH. Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model. Br J Surg 2010; 97: 1874–1880. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003; 21: 3737–3743. National Institute for Health and Clinical Excellence (NICE). Cytoreduction Surgery followed by Hyperthermic Intraoperative Peritoneal Chemotherapy for Peritoneal Carcinomatosis. IPG 331. http://www.nice.org.uk/guidance/ IPG331 [accessed 12 August 2013]. Iversen LH, Rasmussen PC, Laurberg S. Value of laparoscopy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis. Br J Surg 2013; 100: 285–29.
BJS 2014; 101: 5–7
Surgically resectable colorectal peritoneal metastases
10 Elias D, Honor´e C, Dumont F, Ducreux M, Boige V, Malka D et al. Results of systematic second look surgery plus HIPEC in asymptomatic patients presenting a high risk of
7
developing colorectal peritoneal carcinomatosis. Ann Surg 2011; 254: 289–293. 11 NHS Commissioning Board. Clinical Commissioning Policy: Cytoreductive
Surgery for Peritoneal Carcinomatosis. 2012. Reference: NHSCB/A8f. www.england.nhs.uk/wpcontent/uploads/2013/04/a08-p-a.pdf [accessed 12 August 2013].
Snapshot quiz
Snapshot quiz 14/1 Question: What is this condition and how is it treated?
The answer to the above question is found on p. 99 of this issue of BJS. Saurabh S1 and Singh N2 : 1 Department of Surgery, Drexel University College of Medicine, and 2 Temple University Hospital, Philadelphia, Pennsylvania, USA (e-mail: [email protected])
Snapshots in Surgery: to view submission guidelines, submit your snapshot and view the archive, please visit www.bjs.co.uk
2013 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2014; 101: 5–7
