ECC 2013 Report – Role of aggressive surgery for peritoneal metastases

by Peter Mas Mollinedo reporting on the presentation by Dominique Elias, Gustave-Roussy Institute, Paris, France.  – Aggressive complete cytoreductive surgery (CCRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment option for peritoneal metastases (PMs) of pseudomyxoma and mesothelioma origin, and should be considered in patients with PMs of colorectal origin. With optimal treatment, the prognosis for PM is the same as for liver metastases treated with hepatectomy. In a teaching lecture at this year’s ECCO 2013, Dr Dominique Elias, a liver surgeon from the Gustave-Roussy Institute in Paris, presented an overview of the outcomes that can be achieved with CCRS plus HIPEC in the treatment of PMs of different origins.

The peritoneal cavity is a common site for metastases, most commonly arriving via the bloodstream during surgical excision of the primary tumour [1]. Given the size of the peritoneal cavity surface area – equivalent to the entire body surface area – PMs are known to have a significantly poorer prognosis than other metastases. A pooled analysis comprising data from more than 2,000 patients with mCRC showed a median survival of 17.6 months in patients without PMs, compared with only 12.7 months in patients with PMs [2]. This difference has also been seen in clinical studies investigating targeted therapy [3], and recent cancer registry data shows it is even more pronounced in real life [4].

Until recently, the appearance of PMs was regarded as a terminal event and palliative treatment the only therapeutic option; however, Dr Elias’ own experience at the Gustave-Roussy Institute centre is that PMs treated with aggressive surgery using CCRS plus HIPEC will have a prognosis similar to that seen for liver metastases treated with hepatectomy.

CCRS plus HIPEC is regarded as the standard treatment option for PMs originating from peritoneal pseudomyxomas and mesotheliomas. A multicentre registry study involving 2,298 patients with PMs of pseudomyxoma origin who underwent CCRS plus HIPEC achieved a median survival of 16 years, with an overall survival rate at 10 years of 63% [5]. By comparison, patients receiving ‘classical’ treatment with CCRS alone had a 10-year survival rate of only 21% [6]. In PMs of mesothelioma origin, median survival following CCRS plus HIPEC was 53 months with a 5-year survival rate of 47% [7], whereas conventional treatment with systemic chemotherapy resulted in a median survival of less than 12 months [8].

More recent data indicate that aggressive surgical treatment with CCRS plus HIPEC may convey a survival benefit in the treatment of PMs of colorectal origin. With conventional treatment with systemic chemotherapy, median survival rates of 15 and 10 months with and without targeted therapy, respectively, have been reported [3]. In contrast, a review of 19 studies with nearly 2,500 patients treated with CCRS plus HIPEC  for colorectal PMs shows a median survival rate of 33 months, with a 5-year survival rate of 40% [9]. A direct comparison between CCRS plus HIPEC versus systemic chemotherapy alone showed median survival of 22.3 months of median survival in the former arm compared with 12.6 months in the latter (p=0.032) [10], and other studies further support the prospect of a cure for colorectal PMs using CCRS plus HIPEC [11-14]. The two major prognostic factors identified for the long-term outcome is the completeness of the cytoreductive surgery, and the extent of the peritoneal disease [11]. A randomised prospective, the PRODIGE 7 trial, is currently in progress to investigate the impact of the HIPEC element on the overall outcome.

CCRS plus HIPEC has also been evaluated for the treatment of PMs of other origins. The results in PMs originating from stomach cancer and sarcomas have been largely negative and CCRS plus HIPEC is not recommended in this indication. In PMs originating from ovarian and neuroendocrine tumours, results from published trials have been inconclusive and Dr Elias stressed that further studies are needed before recommendations can be made. However, the evidence in colorectal cancer definitely supports adopting CCRS plus HIPEC as the treatment of choice.

References

 

1.   Hansen, E., et al., Tumor cells in blood shed from the surgical field. Arch Surg, 1995. 130(4): p. 387-93.

2.   Franko, J., et al., Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol, 2012. 30(3): p. 263-7.

3.   Klaver, Y.L., et al., Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol, 2012. 38(7): p. 617-23.

4.   Thomassen, I., et al., Population-based incidence, treatment and survival of patients with peritoneal metastases of unknown origin. Eur J Cancer, 2013.

5.   Chua, T.C., 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(20): p. 2449-56.

6.   Miner, T.J., et al., Long-term survival following treatment of pseudomyxoma peritonei: an analysis of surgical therapy. Ann Surg, 2005. 241(2): p. 300-8.

7.   Yan, T.D., et al., Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol, 2009. 27(36): p. 6237-42.

8.   Markman, M., et al., Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer. J Clin Oncol, 1992. 10(9): p. 1479-84.

9.   Chua, T.C., et al., Summary of current therapeutic options for peritoneal metastases from colorectal cancer. J Surg Oncol, 2013. 107(6): p. 566-73.

10. Verwaal, V.J., 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(20): p. 3737-43.

11. Elias, D., et al., Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol, 2009. 27(5): p. 681-5.

12. Goere, D., et al., Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg, 2013. 257(6): p. 1065-71.

13. Tomlinson, J.S., et al., Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol, 2007. 25(29): p. 4575-80.

14. Adam, R., et al., Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol, 2009. 27(11): p. 1829-35.