Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Management of Peritoneal Carcinomatosis

Rahul Rajeev, MBBS; Kiran K. Turaga, MD


Cancer Control. 2016;23(1):36-46. 

In This Article

Preemptive Approaches

Repeat Combination Treatment for Peritoneal Recurrences

Recurrences are not uncommon after initial intervention in peritoneal cancers, so iterative rounds of HIPEC have been reported.[84–89] Iterative cytoreductive surgery/HIPEC offers reasonable rates of survival when compared with conservative treatment using palliative chemotherapy, particularly in appendiceal neoplasms and malignant peritoneal mesotheliomas.[84–86] However, effectiveness of a second round of HIPEC in the setting of CRC-PC is questionable. Careful patient selection using factors such as performance status, tumor volume, and symptom severity may improve outcomes.[87] Some authors advocate using rates of progression- free survival to determine outcomes, but it is rational to select those patients for whom a second complete resection is feasible as survival after a second procedure is based on the completeness of the resection.[85,87] Certain presentations, such as peritoneal mucinous carcinoma of the appendix with positive lymph nodes, incur poor survival rates even after additional procedures.[88] Morbidity and mortality rates do not differ between initial and subsequent procedures; however, attempts to ensure complete cytoreduction using intensive surgery may result in undesirable complications.[89] We recommend a second round of HIPEC in patients with recurrent disease for whom complete cytoreduction is feasible and histology is favorable.

Prophylactic Combination Treatment vs Routine Second-look Surgery

Patients with known risk factors for peritoneal recurrence present a clinical quandary, as current diagnostic techniques for peritoneal carcinomatosis can be inaccurate. The choice between watchful waiting vs early intervention can be difficult to resolve on current evidence. Two approaches being tested are second-look surgery and prophylactic HIPEC, both of which involve selecting patients without detectable peritoneal metastases or those with low-volume peritoneal disease but who harbor risk factors.[90,91] In the former, patients without clinically or radiologically detectable disease undergo a second-look surgery at the end of a fixed period of follow-up. HIPEC is systemically performed in all patients, with cytoreductive surgery performed in those with macroscopic peritoneal disease alone. In a prospective trial of 41 patients with CRC, more than one-half of study patients had detectable peritoneal disease and the reported 5-year OS rate was 90%.[90] In a similar study looking at routine second-look surgery in patients with CRC-PC who underwent complete initial resection, rates of peritoneal recurrence and 2-year OS were 71% and 91%, respectively, after the second intervention was reported.[91] The morbidity and mortality rates were 7% to 9.7% and 0% to 2.4%, respectively.[91]

Prophylactic HIPEC is offered to patients with advanced disease who are at high risk for peritoneal spread at the time of diagnosis. Risk is determined on the basis of histology and pathological stage. A prospective study of 25 patients with nonmetastatic CRC reported morbidity rates comparable to standard surgery.[92] After 4 years of follow-up, the aggressive group exhibited significantly lower rates of peritoneal metastasis and higher rates of OS and disease-free survival.[92] A similar study of gastric cancer in patients with either locally advanced disease or with positive peritoneal washings identified a potential role for prophylactic HIPEC.[93] However, the sample sizes were small, so future research is warranted before definitive conclusions can be reached.[93] Sloothaak et al[94] reported the feasibility of delayed laparoscopic HIPEC in patients with CRC who had a high risk for peritoneal carcinomatosis.

Selection criteria vary across studies, so the advantage of one approach over another cannot be compared and quantified. In addition, adjuvant chemotherapy was administered in some of the studies, confounding the interpretation of the results. Despite the successes of both techniques, the dilemma lies in identifying patients at high risk for peritoneal recurrence.