Peritoneal carcinomatosis from CRC was considered in the past as a terminal neoplastic disease and, often, it was treated only with palliative approach or best supportive care. However, during the last decade, more effective cytotoxic chemotherapies and biological targeted therapies have been developed to improve the survival of patients with metastatic disease [14, 15].
CRS and HIPEC are becoming more and more a valid approach for isolated peritoneal metastases from CRC [16].
These procedures have been applied in selected patients with CRC and peritoneal diffusion, obtaining a median survival from 12 to 32 months, and the 1-year, 2-year, 3-year, and 5-year survival rates ranging from 65 to 90%, 25 to 60%, 18 to 47%, and 17 to 30%, respectively [17].
The results of our study demonstrate an overall median survival of 39 months for the entire cohort.
Completeness of cytoreduction and nonmucinous histology were the main factors found to be independently associated with improved overall survival.
Our results are largely in accordance with other published studies.
In the first randomized controlled trial published by Verwaal et al. [11], the authors demonstrated that CRS followed by HIPEC improves survival in patients with peritoneal metastases from CRC. However, patients with an extensive involvement of the abdominal cavity, or incomplete cytoreduction, had still a poor prognosis.
Ihemelandu et al. [18] further demonstrated that for patients with a limited extent of peritoneal metastases, a complete cytoreduction is the most important prognostic variable, presenting a median survival of 36.6 months.
Other large reported series [9, 10, 19,20,21,22] have shown similar results with a median overall survival ranging from 32 to 63 months.
Huang et al. [23], in a recent meta-analysis of 76 studies, reported a median overall survival of 29 months for selected patients with peritoneal metastases from CRC.
The recently published French PRODIGE 7 randomized controlled trial [24] demonstrated that CRS alone, performed at specialized peritonectomy centers, can offer a median survival of 41.2 months with a 36.7% 5-year survival in patients with peritoneal metastases from CRC, while the addition of HIPEC with oxaliplatin does not influence the OS.
The increasing role of CRS and HIPEC for low-volume peritoneal metastasis from CRC is supported by numerous international consensus guidelines, such as the American Society of Colon and Rectal Surgeons [25] and the European Society of Medical Oncology [26].
The British National Health Service Commissioning Board includes CRS and HIPEC as part of the treatment guidelines for patients with limited peritoneal metastases from CRC [27].
The Australian Cancer Council recommends referral to a specialized center in peritoneal surface malignancies for consideration of CRS and HIPEC in case of patients with low-volume peritoneal involvement [28].
Unfortunately, this multimodal procedure is burdened by higher or similar morbidity and mortality rates with respect to other major gastrointestinal interventions [29].
A mortality rate ranging from 0.9 to 11% [13, 28,29,30] and a major morbidity rate that ranges from 12 to 57% in high-volume centers were reported [28,29,30,31] in the literature, even if, in recent publications, overall grade III–IV morbidity rates is decreased between 7 and 41% [32,33,34,35,36,37,38]. These results are strictly related to the improvement of the experience of specialized centers in peritoneal surface malignancies [39, 40].
Kusamura et al. [33] demonstrated in their manuscript, on 209 peritoneal surface malignancies treated with closed HIPEC, a morbidity and mortality rate of 12% and 0.9%, respectively. On multivariate analysis, extent of cytoreduction and dose of intraperitoneal cisplatin were independent prognostic factors for major morbidity.
In the French study conducted by Glehen et al. [34] on 216 consecutive procedures, the authors found that morbidity was significantly related to the carcinomatosis stage (p = 0.016), the duration of surgery (p = 0.005), and the number of resections and peritonectomy procedures (p = 0.042).
High morbidity and mortality rates associated to CRS and HIPEC were also observed in the multivariate analysis conducted by Hansson et al. on 123 patients [35]. But, considering the potential benefit on long-term outcomes, the possible negative events are considered acceptable.
In the multivariate analysis conducted by Casado et al. [36] on 147 consecutive patients with peritoneal surface malignancy treated by CRS and HIPEC, only PCI was identified as a negative prognostic factor for gastrointestinal complications (p = 0.058). Moreover, the frequency of gastrointestinal complications was associated with a large extent of disease, according to a PCI > 30.
Finally, the Japanese study by Mizumoto et al. [37] showed a global morbidity rate of 49%, demonstrating that PCI greater than 20 was the only significant risk factor for postoperative complications (p < 0.01), whereas HIPEC significantly reduced postoperative complications (p < 0.05).
These results are worse than those achieved in our study. In fact, we recorded a postoperative morbidity rate of 35.8%, with a rate of grade 3–4 complications of 8.9%, while the mortality rate was 0%.
A number of prognostic factors have been found to be associated with overall survival. We found nonmucinous histology and completeness of cytoreduction to be independently associated with improved overall survival.
Other studies have found the completeness of cytoreduction, PCI, positive lymph nodes, histology, use of systemic perioperative chemotherapy, and the experience of the center to be prognostic factors influencing overall survival [9, 10, 41,42,43].