| II. | CURRENT INDICATIONS FOR CYTOREDUCTIVE SURGERY AND INTRAPERITONEALCHEMOTHERAPY |
Table 4presents the current indications for the use ofintraperitoneal chemotherapy to treat peritoneal carcinomatosisor sarcomatosis or to prevent the progression of microscopicresidual disease in high-risk groups. Adenocarcinoma or sarcomaof low malignant potential may arise from many differentintraabdominal sites and seed the abdominal or pelvic cavityextensively. Most of these non-invasive malignancies can beeradicated from the abdomen. Cytoreductive surgery followed byintraperitoneal chemotherapy should be considered the standardtherapy for patients with pseudomyxoma peritonei syndrome. Alsothese treatments have demonstrated benefits for patients withlarge volume peritoneal surface disease from grade I sarcoma andperitoneal mesothelioma.
TABLE 4 |
Current indications for cytoreductive surgery and intraperitoneal chemotherapy |
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Patients withperitoneal seeding from invasiveadenocarcinomas or sarcomas are selectively treated at this pointin time according to the Peritoneal Cancer Index. This is aclinical summary of both lesion size and distribution ofperitoneal surface malignancy(Figure 4).It should beused in the decision making process as the abdomen is explored.To arrive at a score, the size of intraperitoneal nodules must beassessed. The lesion size or LS score should be used. An LS-0score means that no malignant deposits are visualized. An LS-1score signifies that tumor nodules less than 0.5 cm in greatestdimension are present. The number of nodules is not scored, onlythe size of the largest nodules. An LS-2 score signifies tumornodules between 0.5 and 5.0 cm present. LS-3 signifies tumornodules greater than 5.0 cm in any dimension present. If there isa confluence of tumor, the lesion size is scored as 3.
In order to assess the distribution of peritoneal surfacedisease, the abdominopelvic regions are utilized. For each ofthese 13 regions, a lesion size score is determined. Thesummation of the lesion size score in each of the 13abdomino-pelvic regions is the Peritoneal Cancer Index for thatpatient. 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 andperitoneal mesothelioma are sometimes non-invasive. In thesesituations, the status of the abdomen and pelvis aftercytoreduction may have no relationship to the status at the timeof abdominal exploration. In other words, even though the surgeonmay find an abdomen with a Peritoneal Cancer Index of 39, it canbe converted to an index of 0 by cytoreduction. In thesediseases, the prognosis will only be related to the completenessof cytoreduction and not to the Peritoneal Cancer Index.
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Peritoneal Cancer Index is used to estimate the likelihood ofcomplete cytoreduction in patients with peritoneal surfacemalignancy. The score is a summation of cancer implant lesionsize (scored 0 to 3) present in the 13 abdominopelvic regions.From Esquivel J. Sugarbaker PH: Elective surgery in recurrentcolon cancer with peritoneal seeding: When to and when not toproceed.Cancer Therapeutics, Nov, l998.
A second caveat for the Peritoneal Cancer Index is invasivecancer at CRUCIAL ANATOMIC SITES. For example, unresectablecancer on the common bile duct will cause a poor prognosisdespite a low Peritoneal Cancer Index. Cancer implants atnumerous sites on the small bowel surface will confer a poorprognosis. Lymph nodes resected because there was nodalmetastases within groups unrelated to the primary cancerrepresent dissemination from peritoneal surface cancer(metastases from metastases). Cancer at crucial anatomic sitesbecomes a systemic disease equivalent in assessing prognosis andwill override a favorable score with the Peritoneal Cancer Index(6).
The use of the Peritoneal Cancer Index will vary with the type ofperitoneal surface malignancy treated. Berthet, et al in a studyof sarcomatosis found an index of < 13 associated with a 74%five-year survival; an index of> 13 was associatedwith an 11% five-year survival (7). For colon cancer withcarcinomatosis, Sugarbaker reported a Peritoneal Cancer Index of
< 10 associated with a 50% five-year survival; an indexof 11-20 was associated with a 20% five-year survival; and anindex of > 20 was associated with a 0% five-year survival (8).
Completeness of cytoreduction score
The final assessment to be used to assess prognosis withperitoneal surface malignancy is the completeness ofcytoreduction (CC) score. This information is of less value tothe surgeon in planning treatments than the Peritoneal CancerIndex because the CC score is not available until after thecytoreduction is complete, rather than as the abdomen is beingexplored. If during exploration it becomes obvious thatcytoreduction will not be complete, the surgeon may decide that apalliative debulking that will provide symptomatic relief isappropriate and discontinue plans for a potentially curativecytoreduction with intraperitoneal chemotherapy. In bothnoninvasive and invasive peritoneal surface malignancy, thecompleteness of cytoreduction score is thought to be theprinciple prognostic indicator.
For gastrointestinal cancer, the completeness of cytoreductionscore has been defined as follows: A CC-0 score indicates that novisible peritoneal carcinomatosis remains after cytoreduction. ACC-1 score indicates that tumor nodules persisting aftercytoreduction are less than2.5mm. This is a nodule sizethought to be penetrable by intracavitary chemotherapy. A CC-2score indicates tumor nodules between2.5mm and 2.5 cm. ACC-3 score indicates tumor nodules greater than 2.5 cm or aconfluence of unresected tumor nodules at any site within theabdomen or pelvis (Figure 5). In high-grade malignancy,complete cytoreduction may require a CC-0 score. In less invasivemalignancy such as pseudomyxoma peritonei, a completecytoreduction may include CC-0 and CC-1 cytoreduction.
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Completeness of cytoreduction score CC-0 to CC-3. A completecytoreduction for a noninvasive malignancy such as pseudomyxomaperitonei includes CC-0 and CC-1 resection for invasive cancersuch as gastric cancer, only CC-O resection is consideredcomplete cytoreduction.
In the current approach to peritoneal carcinomatosis andsarcomatosis,implant size and extent oftumordistribution are the fundamental criteria for the selectionof patients for treatment with intraperitoneal chemotherapy. Anattempt at cytoreduction of peritoneal surface disease fromextensive invasive cancer is always to be avoided. Only patientswith MICROSCOPIC RESIDUAL DISEASE of high-grade peritonealsurface cancer should be treated with curative intent usingcytoreductive surgery and intraperitoneal chemotherapy. Patientswith small lesion size peritoneal seeding with limiteddistribution on peritoneal surfaces should be expected to benefitand are candidates for an aggressive management strategy.Figure6 shows the predictive effect of the Peritoneal Cancer Indexon the long-term survival of patients with sarcomatosis.
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Survival by the Peritoneal Cancer Index of patients withsarcomatosis treated by cytoreductive surgery and intraperitonealchemotherapy. Patients with a score of < 13 showed astatistically significant improvement in survival as compared toa score of> 13 (p=0.0107).
A major role for intraperitoneal chemotherapy is the preventionof subsequent peritoneal carcinomatosis or sarcomatosis. Itshould be used in all patients who are at high risk for diseaseprogression on peritoneal surfaces. Virtually every patient whohas a free intraabdominal perforation of gastrointestinal cancerthrough the malignancy itself subsequently develops peritonealcarcinomatosis. Patients with primary cancer adherent to theadjacent organs or structures (T4 lesions) are at great risk forperitoneal carcinomatosis. The same is true for patients withpositive peritoneal cytology. Not infrequently, patients who areundergoing the resection of a large intraabdominal tumor willhave a tumor spill. This maybe extremely common with advancedprimary or recurrent rectal malignancy and recurrent coloniccancer. It may occur almost routinely in resections of advancedgastric cancer. If there is a tumor spill, then in order toprevent subsequent development of peritoneal carcinomatosis orsarcomatosis, we recommend the use of intraperitonealchemotherapy. Intraperitoneal chemotherapy is an importanttreatment option for recurrent ovarian malignancy. In patientswith recurrent ovarian cancer who have failed systemicchemotherapy, cytoreduction is followed by intraperitonealchemotherapy with mitomycin C and 5-fluorouracil.
A final indication for intraperitoneal chemotherapy isdebilitating malignant ascites. This is one of the few instanceswhen intraperitoneal chemotherapy is not always combined withcytoreductive surgery.
