Patients who develop peritoneal carcinomatosis (PC) from colorectal cancer (CRC) are generally considered to have a grim prognosis, with a median survival of six months.1-2 Treatment approaches have included aggressive surgical techniques combined with intraperitoneal chemotherapy, with the addition of hyperthermia. Since PC occurs in approximately 30-40% of patients with CRC who develop progressive disease, improvements in management are needed.

Authors Elias and colleagues3 recently reported on a retrospective analysis of 523 patients in the Journal of Clinical Oncology. Study facts include:
 
  • Consecutive patients with PC from CRC were analyzed in a retrospective-cohort, multicentric study from French-speaking countries
  • All patients who were treated with cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) were included in the analyses
  • Patients were included between 1990 and 2007, with a median follow-up of 45 months
  • Mortality and grade 3-4 morbidity at 30 days was 3% and 31%, respectively
  • Overall median survival was 30.1 months, with a five year overall survival (OS) of 27%; the five year disease free survival (DFS) was 10%

After the best surgical effort was performed, patients received intraperitoneal chemotherapy, either hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC). The advantage of using intraperitoneal chemotherapy allows for a higher concentration of the agents used with a decrease in systemic toxicity; hyperthermia may help to potentiate the cytostatic effects and lead to direct cytotoxicity.1 Chemotherapy variations in the study included temperature of the perfusate, type of perfusate, and flow rates. Mitomycin in conjunction with cisplatin and oxaliplatin and leucovorin-based regimens were used. An additional 232 (47%) of the patients in the study had received postoperative adjuvant systemic chemotherapy when they achieved an objective response to preoperative chemotherapy (if given) or if they demonstrated poor prognostic factors. In the study analysis, the following was noted:

  • Neoadjuvant chemotherapy and the use of HIPEC or IPIC did not have a significant prognostic effect
  • However, completeness of surgery had a significant impact (P < .001); additionally where the procedure was performed (ie. surgery center) made a difference in patient outcome (P< .001)
  • The use of adjuvant chemotherapy had a significant impact on the risk of death
  • Because of the wide variation in the administration of PIC treatments, the impact on patient outcome could not be measured

The authors of the study note that because mortality and morbidity was low, the study results demonstrate that combined treatment is acceptable for this patient population. They also note that the expertise of the treatment center does have an impact on patient prognosis and that aggressive cytoreduction therapy is challenging and requires a significant number of resources to deliver patient care. The procedures require an experienced clinician for optimal delivery of the therapy and the centers that treated higher numbers of patients (providing clinicians with more experience) had the best outcomes.

The study also demonstrated that a strong correlation exists between the extent of peritoneal disease, optimal CRS, and morbidity and mortality. Because HIPEC and EPIC did not show a difference in survival and because many variations of chemotherapy delivery were used in the study, the authors of the paper note that more standardized and unified techniques should be used in future studies. However, they also concluded that these multicentric study results show the improvement in survival rates make this combined treatment the gold standard for therapy for PC and continued improvement in patient selection and clinical delivery will continue to increase efficacy of therapy.

References

  1. Glockzin G, Schlitt HJ, Piso P. Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol. 2009;7:1-8. doi:10.1186/1477-7819-7-5. Free full text available at: http://www.wjso.com/content/7/1/5  
  2. Jayne DG, Fook S, Loi C, et al. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89:1545-1550. doi:10.1046/j.1365-2168.2002.02274.x. Link to abstract  http://www3.interscience.wiley.com/journal/101521063/abstract
  3. Elias D, Gilly F, Boutitie F, 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. doi:10.1200/JCO.2009.23.9285 Link to abstract http://jco.ascopubs.org/cgi/content/abstract/28/1/63