Cytoreductive surgery and intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis from colorectal origin

Abstract

Peritoneal carcinomatosis (PC) is a common form of tumour metastasis stemming from gastrointestinal and colorectal cancers. For a long time, PC has been considered a terminal clinical condition treated only with palliative systemic chemotherapy and associated with very limited results. During the last decade, the treatment of advanced colorectal disease has greatly improved with the emergence of new chemotherapy drugs and biological agents. However, the median survival rates still do not surpass 24 months, even though most of these studies correspond to groups of patients with metastatic disease to the liver and/or lung. The approach and development of cytoreductive radical surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) are based on performing radical surgery of the entire visible tumour within the abdomen/peritoneum, followed immediately by HIPEC, which acts upon microscopic tumour that remains present after surgery and which is responsible for the persistence or relapse of peritoneal disease. Peritonectomy procedures are demanding surgical techniques that permit elimination of the tumour present in the peritoneal lining and any other organs and/or structures that are infiltrated. The synergistic effect of hyperthermia and chemotherapy has been well documented. Hyperthermia increases the cytotoxicity of some cytostatic agents and increases the penetration of certain drugs into the neoplastic cells. The prognosis for patients with PC who undergo combined treatment correlates with the volume of PC (tumour burden) measured as the Peritoneal Cancer Index (PCI) and the ability to perform a CRS, to completely eliminate the gross tumour. At least one phase III study and an important number of phase II studies have shown that CRS + HIPEC provides important survival benefits for patients with PC of colorectal origin. The combination of CRS + HIPEC is indicated for patients with good general health, a low PCI, absence of extra-abdominal metastasis and who can, technically, undergo CRS. The early identification of this group of patients, rapid referral to centres specialised in CRS + HIPEC, together with the correct application of this treatment, are key in achieving the best results.

Cytoreductive Strategies in the Treatment of Carcinomatosis of Colorectal Origin: Results of a Transdisciplinary National Survey

“…Ideally surgery should achieve a completeness of cytoreduction score (CC) 1 to achieve optimal outcome, meaning that residual tumour nodules are 2.5 mm in diameter. Various studies have shown that intraperitoneal chemotherapeutic agents can effectively penetrate to a maximum depth of 2-3mm [13]. Fig.…”

“…Good candidates for surgery are those who are aged 65 years or younger, not morbidly obese (BMI >40) with good nutritional status [12], and an Eastern Cooperative Oncology Group (ECOG) score of 2 or less. One study considered patients aged up to 70 for the procedure [13]; older patients with localized peritoneal carcinomatosis and good general health (absence of severe cardiopulmonary or renal failure) should be assessed on a case by case basis.…”

Multidisciplinary Treatment for Colorectal Peritoneal Metastases: Review of the Literature

“…However, it is still controversial whether HIPEC is the indispensable cornerstone of the best modality of multidisciplinary treatment for CPM [71]. It is not yet possible to evaluate the morbidity and mortality rates related to HIPEC alone independently of CRS, as both procedures are performed jointly during the same surgery.…”

“…Only those patients who undergo CRS can receive HIPEC. The published mortality rates in CRS + HIPEC range from 0 to 11% (mean 4–6%) [71]. Survival rates are reported better in patients who undergo CRS + HIPEC versus those who receive systemic chemotherapy [72].…”

Prevention and Management of Peritoneal Metastases from Gastrointestinal Cancer: A Short History of a Paradigm for Peritoneal Surface Malignancies

“…Table 7.1 lists national guidelines of several nations around the world that now include CRS plus HIPEC as a standard of care for patients with AMN with peritoneal dissemination, epithelioid MPM, and CRC with limited peritoneal surface metastases. As shown in Table 7.1, these national guidelines occurred first in France [3], then in Holland [4], Germany [5], Spain [6], and the United Kingdom [7]. In the United States, the National Comprehensive Cancer Network guidelines have not as yet been changed to include CRS plus HIPEC for treating these three diseases.…”