Therapeutic efficacy of systemic therapy for colorectal peritoneal carcinomatosis: Surgeon's perspective

Abstract

Treatment choices for colorectal peritoneal carcinomatosis/metastases include systemic therapy and increasingly cytoreductive surgery with intraperitoneal chemotherapy delivery. These options are best considered as complementary and not exclusive alternatives. Two prospective randomized trials support use of peritonectomy procedures and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. This overview examines efficacy, limitations and landscape of systemic therapy focusing on colorectal peritoneal carcinomatosis. Observations from literature support notions that (1) systemic therapy provides survival benefit for all prototypical patients with mCRC irrespective of metastatic disease site; (2) the magnitude of this benefit is considerably reduced among patients with peritoneal metastases who consequently experience significantly shorter overall survival; (3) efficacy of systemic therapy improved over time but at a slower pace for those with carcinomatosis; (4) this therapeutic difference has not diminished with introduction of targeted therapy, but perhaps widened; (5) further research of cytoreductive surgery and/or intraperitoneal regional therapies is thus a multidisciplinary responsibility of the entire oncology community; (6) peritonectomy procedures with intraperitoneal regional therapy are not scientifically supported in absence of systemic therapies.

Keywords: cytoreduction; hyperthermia; intraperitoneal chemotherapy; intraperitoneal therapy; peritoneal surface; peritonectomy.

Figure 1:

Overall survival in patients with metastatic colorectal cancer with metastases in a single organ. Adapted with permission from [10].

Figure 2:

Overall survival of mCRC treated by first-line systemic therapy in 14 prospective randomized trials. Individual groups are selected by peritoneal involvement (solid lines - mCRC with peritoneal involvement; dashed lines – mCRC without peritoneal involvement) and number of metastatic disease sites (1 or ≥2). Adapted with permission from [10].

Figure 3:

Median overall survival in selected studies of systemic chemotherapy published after adoption of oxaliplatinum and irinotecan. All presented studies are secondary/retrospective analysis of individual patient data collected prospectively on randomized trials of systemic therapy for mCRC. Larger size of circle corresponds to larger dataset. Blue circles=mCRC patients without peritoneal involvement, red circles=patients with colorectal peritoneal carcinomatosis (pmCRC+).

Figure 4:

Response rates depending on site of metastases in mCRC patients treated with historical 5-FU combinations. Data from Royal Marsden Hospital studies [7].

Figure 5:

Hazard ratios for overall survival by site of metastases in cytotoxic-only therapy (left panel) and combined therapy including at least one targeted agent (right panel). * denotes statistical significance at least p<0.05. Data from [10].