By Robert Smeenk (MD), Vic Verwaal (MD, PHD), Ninja Antonini (MSc) and Frans A.N Zoetmulder, (MD, PHD)
Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam.

Annals of Surgical Oncology Vol 14, No 2, (2007)

Link to abstract

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal Chemotherapy (HIPEC) is the standard treatment strategy for PMP at the Netherlands Cancer Institute. This treatment carries the potential to cure the cancer. Cytoreductive surgery involves peritonectomy procedures (at least 6 procedures to strip the lining of the abdominal cavity where it is affected by cancer), the removal of the mucus that the cancer cells produce, and the removal of affected organs. CRS is usually followed by hyperthermic intraperitoneal Chemotherapy (HIPEC). HIPEC is the administration of heated liquid chemotherapy directly into the abdominal cavity. This form of chemotherapy is given at a higher temperature and concentration, and is usually more effective than chemotherapy given through the vein. HIPEC is most effective when given during or following CRS because it kills tumor cells not visible to the human eye.

A common problem with PMP is the recurrence of the disease even after CRS and HIPEC. The factors that influence recurrence include but are not limited to the subtype of PMP, and the completeness of cytoreductive surgery. The progression of PMP varies in different patients; the more malignant the disease the faster the progression. Unfortunately even with the combination of aggressive surgery and chemotherapy treatments, recurrence is frequent and repeat surgeries carry the risk of more complications and more scar tissue.

This study aims at discerning what causes the combined treatment to fail. This analysis can help clinicians decide what forms of treatment may be more effective and beneficial to the patient. The study analyzed the recurrence rates of 96 PMP patients treated at the Netherlands Cancer Institute in Amsterdam from1996-2004. 66 patients had DPAM at the time of primary treatment while 30 patients had PMCA-I. PMCA-I is an intermediate subtype of PMP that has properties of both the malignant and benign forms of PMP. Ct scans and/or tumor marker tests, which are indicative of the level of cancer progression, were used to measure the progression rate in both groups.

The study determined that the progression was closely related to the success of the initial cytoreductive surgery. Patients who had incomplete CRS showed higher progression rates. An incomplete CRS can result from the inability to reach certain areas during surgery. An example of this situation is encountered in the spread of the cancer in areas surrounding the liver. These areas are very difficult to remove during surgery, thus in this instance, where progression is seen in one or two regions, it can be blamed on the incomplete CRS. However, 36% of patients (many with PMCA-I or dedifferentiated DPAM) had a diffused recurrence (in different areas in the abdomen that were cleared of all visible tumor). This can be attributed to failure of HIPEC treatment to clear all microscopic tumor possible because of the malignant nature of the tumor itself. In a number of patients of patients progressive disease was found in suture lines and scars, this is most likely caused by underexposure of these sites to HIPEC. Still in others, disease was found outside the abdominal cavity which is most likely the result of inadvertently cutting through the abdominal cavity into other parts of the body during surgery.

In conclusion, the longer the period of time a patient has without progression since the primary CRS and HIPEC the better will be their survival after treatment of this progression. Patients with PMCA-I in this series tend to have earlier progressive disease and don't seem to benefit from any available treatment including systemic chemotherapy. Patients with early progression but who have limited cancer can be treated surgically, but again patients with DPAM will benefit more than patients with PMCA-I. cancer infections in certain localized area can be treated by resection. However PMCA-i subtypes have less chances of survival than DPAM. Conversely, patients who have progression and are in good health can be treated with a second CRS and HIPEC with the possibility of a cure. As for patients who have limited disease of no progression over a long period it is better to keep a watchful eye on them than expose them to another surgery. In conclusion, the management of patients with progressive disease after the primary CRS and HIPEC can result in long-term survival in a considerable number of patients. Systemic chemotherapy is the only treatment modality that showed no improvement. A second CRS and HIPEC is indicated only in patients who had no progression for 12 months after initial surgery and have benign disease.