Current Indications

Table 4 presents the current indications for the use of intraperitoneal chemotherapy to treat peritoneal carcinomatosis or sarcomatosis or to prevent the progression of microscopic residual disease in high-risk groups. Adenocarcinoma or sarcoma of low malignant potential may arise from many different intraabdominal sites and seed the abdominal or pelvic cavity extensively. Most of these non-invasive malignancies can be eradicated from the abdomen. Cytoreductive surgery followed by intraperitoneal chemotherapy should be considered the standard therapy for patients with pseudomyxoma peritonei syndrome. Also these treatments have demonstrated benefits for patients with large volume peritoneal surface disease from grade I sarcoma and peritoneal mesothelioma.

TABLE 4

Current indications for cytoreductive surgery and intraperitoneal chemotherapy

Large volume of noninvasive peritoneal carcinomatosis or sarcomatosis.
Peritoneal mesothelioma.
Low volume peritoneal seeding from invasive cancer.
Perforated gastrointestinal cancers.
Cancer adherent to adjacent organs or structures.
Gastrointestinal cancer with positive peritoneal cytology.
Gastrointestinal cancer with ovarian involvement.
Tumor spill intraoperatively.
Systemic chemotherapy for recurrent ovarian cancer after a long disease-free interval.
Palliation of patients with malignant ascites.

Patients with peritoneal seeding from invasive adenocarcinomas or sarcomas are selectively treated at this point in time according to the Peritoneal Cancer Index. This is a clinical summary of both lesion size and distribution of peritoneal surface malignancy (Figure 4). It should be used in the decision making process as the abdomen is explored. To arrive at a score, the size of intraperitoneal nodules must be assessed. The lesion size or LS score should be used. An LS-0 score means that no malignant deposits are visualized. An LS-1 score signifies that tumor nodules less than 0.5 cm in greatest dimension are present. The number of nodules is not scored, only the size of the largest nodules. An LS-2 score signifies tumor nodules between 0.5 and 5.0 cm present. LS-3 signifies tumor nodules greater than 5.0 cm in any dimension present. If there is a confluence of tumor, the lesion size is scored as 3.

In order to assess the distribution of peritoneal surface disease, the abdominopelvic regions are utilized. For each of these 13 regions, a lesion size score is determined. The summation of the lesion size score in each of the 13 abdomino-pelvic regions is the Peritoneal Cancer Index for that patient. A maximal score is 39 (13x3).

There are some caveats in the use of the Peritoneal Cancer Index. Diseases such as pseudomyxoma peritonei, grade I sarcoma and peritoneal mesothelioma are sometimes non-invasive. In these situations, the status of the abdomen and pelvis after cytoreduction may have no relationship to the status at the time of abdominal exploration. In other words, even though the surgeon may find an abdomen with a Peritoneal Cancer Index of 39, it can be converted to an index of 0 by cytoreduction. In these diseases, the prognosis will only be related to the completeness of cytoreduction and not to the Peritoneal Cancer Index.

Peritoneal Cancer Index is used to estimate the likelihood of complete cytoreduction in patients with peritoneal surface malignancy. The score is a summation of cancer implant lesion size (scored 0 to 3) present in the 13 abdominopelvic regions. From Esquivel J. Sugarbaker PH: Elective surgery in recurrent colon cancer with peritoneal seeding: When to and when not to proceed. Cancer Therapeutics, Nov, l998.

A second caveat for the Peritoneal Cancer Index is invasive cancer at CRUCIAL ANATOMIC SITES. For example, unresectable cancer on the common bile duct will cause a poor prognosis despite a low Peritoneal Cancer Index. Cancer implants at numerous sites on the small bowel surface will confer a poor prognosis. Lymph nodes resected because there was nodal metastases within groups unrelated to the primary cancer represent dissemination from peritoneal surface cancer (metastases from metastases). Cancer at crucial anatomic sites becomes a systemic disease equivalent in assessing prognosis and will override a favorable score with the Peritoneal Cancer Index (6).

The use of the Peritoneal Cancer Index will vary with the type of peritoneal surface malignancy treated. Berthet, et al in a study of sarcomatosis found an index of < 13 associated with a 74% five-year survival; an index of > 13 was associated with an 11% five-year survival (7). For colon cancer with carcinomatosis, Sugarbaker reported a Peritoneal Cancer Index of
< 10 associated with a 50% five-year survival; an index of 11-20 was associated with a 20% five-year survival; and an index of > 20 was associated with a 0% five-year survival (8).

Completeness of cytoreduction score

The final assessment to be used to assess prognosis with peritoneal surface malignancy is the completeness of cytoreduction (CC) score. This information is of less value to the surgeon in planning treatments than the Peritoneal Cancer Index because the CC score is not available until after the cytoreduction is complete, rather than as the abdomen is being explored. If during exploration it becomes obvious that cytoreduction will not be complete, the surgeon may decide that a palliative debulking that will provide symptomatic relief is appropriate and discontinue plans for a potentially curative cytoreduction with intraperitoneal chemotherapy. In both noninvasive and invasive peritoneal surface malignancy, the completeness of cytoreduction score is thought to be the principle prognostic indicator.

For gastrointestinal cancer, the completeness of cytoreduction score has been defined as follows: A CC-0 score indicates that no visible peritoneal carcinomatosis remains after cytoreduction. A CC-1 score indicates that tumor nodules persisting after cytoreduction are less than 2.5 mm. This is a nodule size thought to be penetrable by intracavitary chemotherapy. A CC-2 score indicates tumor nodules between 2.5 mm and 2.5 cm. A CC-3 score indicates tumor nodules greater than 2.5 cm or a confluence of unresected tumor nodules at any site within the abdomen or pelvis (Figure 5). In high-grade malignancy, complete cytoreduction may require a CC-0 score. In less invasive malignancy such as pseudomyxoma peritonei, a complete cytoreduction may include CC-0 and CC-1 cytoreduction.

Completeness of cytoreduction score CC-0 to CC-3. A complete cytoreduction for a noninvasive malignancy such as pseudomyxoma peritonei includes CC-0 and CC-1 resection for invasive cancer such as gastric cancer, only CC-O resection is considered complete cytoreduction.

In the current approach to peritoneal carcinomatosis and sarcomatosis, implant size and extent of tumor distribution are the fundamental criteria for the selection of patients for treatment with intraperitoneal chemotherapy. An attempt at cytoreduction of peritoneal surface disease from extensive invasive cancer is always to be avoided. Only patients with MICROSCOPIC RESIDUAL DISEASE of high-grade peritoneal surface cancer should be treated with curative intent using cytoreductive surgery and intraperitoneal chemotherapy. Patients with small lesion size peritoneal seeding with limited distribution on peritoneal surfaces should be expected to benefit and are candidates for an aggressive management strategy. Figure 6 shows the predictive effect of the Peritoneal Cancer Index on the long-term survival of patients with sarcomatosis.

Survival by the Peritoneal Cancer Index of patients with sarcomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Patients with a score of < 13 showed a statistically significant improvement in survival as compared to a score of > 13 (p=0.0107).

A major role for intraperitoneal chemotherapy is the prevention of subsequent peritoneal carcinomatosis or sarcomatosis. It should be used in all patients who are at high risk for disease progression on peritoneal surfaces. Virtually every patient who has a free intraabdominal perforation of gastrointestinal cancer through the malignancy itself subsequently develops peritoneal carcinomatosis. Patients with primary cancer adherent to the adjacent organs or structures (T4 lesions) are at great risk for peritoneal carcinomatosis. The same is true for patients with positive peritoneal cytology. Not infrequently, patients who are undergoing the resection of a large intraabdominal tumor will have a tumor spill. This maybe extremely common with advanced primary or recurrent rectal malignancy and recurrent colonic cancer. It may occur almost routinely in resections of advanced gastric cancer. If there is a tumor spill, then in order to prevent subsequent development of peritoneal carcinomatosis or sarcomatosis, we recommend the use of intraperitoneal chemotherapy. Intraperitoneal chemotherapy is an important treatment option for recurrent ovarian malignancy. In patients with recurrent ovarian cancer who have failed systemic chemotherapy, cytoreduction is followed by intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil.

A final indication for intraperitoneal chemotherapy is debilitating malignant ascites. This is one of the few instances when intraperitoneal chemotherapy is not always combined with cytoreductive surgery.