HIPEC in Colorectal Cancer With Peritoneal Carcinomatosis

Colorectal cancer (CRC) is the third most common cancer diagnosed in the United States.¹ Unfortunately, up to 20% of new CRC cases have metastases at time of diagnosis. The most common sites of metastatic disease in CRC are the liver, lung, and peritoneum. Close to 5% of patients with CRC will present with peritoneal carcinomatosis (PC), and have an average 6-month survival if not treated.² Even when these patients are treated with systemic chemotherapy, survival outcomes are worse in contrast with those patients with distant metastases (12.7 months vs 17.6 months). Overall, stage IV patients with CRC and PC have limited treatment options and worse survival.

One treatment modality that is accumulating data for patients with CRC and PC is hyperthermia intraperitoneal chemotherapy (HIPEC) combined with cytoreduction surgery (CRS). One of the many challenges of treating PC in stage IV CRC patients is drug delivery. It is often difficult to attain adequate drug levels within the peritoneum. If chemotherapy doses are subsequently increased in attempts to raise drug concentrations, the patient is exposed to more systemic side effects. HIPEC aims to deliver chemotherapy directly to the peritoneum, which can increase local drug concentrations, as well as reduce the total systemic exposure from the chemotherapy.

HIPEC is typically preceded by CRS. CRS assists in removing as much peritoneal disease as possible, so that HIPEC can have the best local exposure possible. The patient must be thoroughly evaluated for CRS, as many patients may not be candidates for surgery. Potential contraindications to CRS include extensive intra-abdominal lymph node metastases and extensive small bowel involvement. In addition to PC, many patients with prior intra-abdominal surgical history may have adhesions that can be cleared to help increase chemotherapy exposure. HIPEC can be administered directly into the peritoneal cavity after CRS.

There are at least 3 prognostic scales to consider using when evaluating a patient for CRS and HIPEC, which include the COREP (colorectal peritoneal) score, prognostic score (PS), and peritoneal surface disease severity score (PSDS).³ Although there is no consensus on which prognostic score is the best to use, much of the recent data support the COREP score.

As CRS and HIPEC are still accumulating data, there are a limited number of clinical trials off which to base regimens. One study showed a median overall survival of 19.2 months in patients treated with CRS and HIPEC.⁴ The overall survival was increased to approximately 32 months when there was complete CRS. Another study demonstrated an overall median survival advantage when comparing CRS and HIPEC (22.3 months) to palliative surgery combined with systemic chemotherapy (12.6 months).⁵ A systematic review reported improved medial survival—33 vs 12.5 months—and 5-year survival—40% vs 13%—when comparing CRS and HIPEC to palliative surgery and systemic chemotherapy.⁶

The same chemotherapy that is used in the intravenous form is not always used for HIPEC. The ideal agents for HIPEC have advantageous pharmacokinetic profiles that will have limited systemic absorption and an increased effect with heat. Mitomycin C and 5-fluorouracil have both been used for HIPEC.

CRS and HIPEC do appear to have promising data when used in the optimal patient population. It is important, when considering CRS and HIPEC, that a patient reviews an institution’s experience with this collaborative treatment approach.

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30. doi: 10.3322/caac.21332
2. Spiliotis J, Halkia E, de Bree E. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives. Curr Oncol. 2016;23(3):e266-75.
3. Cashin PH, Graf W, Nygren P, Mahteme H. Comparison of prognostic scores for patients with colorectal cancer peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20(13):4183-9.
4. Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284-92.
5. Chua TC, Esquivel J, Pelz JO, Morris DL. Summary of current therapeutic options for peritoneal metastases from colorectal cancer. J Surg Oncol. 2013;107:566-73.
6. Verwaal VJ, van Ruth S, de Bree E, 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;21:3737-43.