Quantitative prognostic indicators have been successfully used in several surgical disciplines and served as guidelines in the selection of treatments to maximize benefits. Often, the major value of the quantitative prognostic indicators is to exclude patients who have no chance to benefit from high risk and costly management protocols. Major requirements of a quantitative prognostic indicator are reproducibility within a defined patient population and simplicity.#

Concerning peritoneal carcinomatosis, five different staging systems are available: the Lyon staging system, the Peritoneal Cancer Index (PCI), the Japanese Research Society for Gastric Cancer carcinomatosis staging (JRSGS), the Dutch simplified peritoneal carcinomatosis index (SPCI) and the Completeness of Cytoreduction Score (CCR).#

This staging was first described in 1994 by Gilly and coworkers and takes into account the size of malignant implants (<5mm, 5mm to 2cm, >2cm) and their distribution (localized or diffuse).¹ The details of this staging system are summarized in Table 1.#

This staging system can be used as the abdominal exploration is performed as well as after cytoreduction is complete, allowing a downstaging index. For example, a stage 4 peritoneal carcinomatosis which has underwent a complete macroscopic surgical cytoreduction can be described as a stage 4 downstaged to 0 (4-DS0). DS is used to designate the downstaging that may result from cytoreduction.#

The two principal advantages of the Lyon staging system are simplicity and reproducibility. Its utility was demonstrated in the multicentric prospective study EVOCAPE 1, which gathered data from 370 patients with peritoneal carcinomatosis from non gynecologic malignancies who underwent surgery at nine different treatment centers by more than 30 surgeons.² This staging system has also demonstrated itself as an important prognostic indicator in several clinical trials.^3–5 In the EVOCAPE 1 study, the natural history of peritoneal carcinomatosis was determined. A significant difference in survival rates was observed between peritoneal carcinomatosis stage 1 and 2 (carcinomatosis with peritoneal implants less than 5mm in diameter) and stage 3 and 4 (carcinomatosis with malignant implants more than 5mm in diameter): the median survival rates were 6 and 3months, respectively, in stage 1 and 3 compared with stage 3 and 4.#

Rey et al., in a prospective study of 35 patients with carcinomatosis treated by cytoreductive surgery and intraperitoneal chemohyperthermia (IPCH), reported 1-year and 2-year actuarial survival rates that were 63% and 31% for stage 1 and 2 carcinomatosis, and 31% and 12% for stage 3 and 4, respectively.³ Similar results have been reported for patients with residual peritoneal malignant implants less than 5mm in diameter treated with IPCH and mitomycin C.⁴#

In all the phase II prospective studies reported from Lyon on carcinomatosis treated by IPCH, there were significant differences between the prognosis of stage 1 and 2, and stage 3 and 4. For resectable gastric cancers with stage 1 and 2, 1-year survival rate was 80%, whereas it was only 10% for stage 3 and 4.⁵ Beaujard et al. reported a series of 83 patients with peritoneal carcinomatosis from digestive origin with a 16months median survival time for stage 1 and 2 and a 6months median survival time for stage 3 and 4.⁶ Routinely used by several surgical teams, this staging system is also used by medical oncologists and radiologists who appreciate its simplicity and consider it as a valuable guide to assist them in patient selection.#

The Peritoneal Cancer Index (PCI) was reported by Jacquet and Sugarbaker: it is a quantitative assessment of both cancer distribution and cancer implant size throughout the abdomen and the pelvis.⁷ This scoring system has been used to quantitate carcinomatosis, sarcomatosis and peritoneal mesothelioma. Two components are involved in its calculation. One component is the distribution of tumor in the abdominopelvic regions and the other component is the lesion size score. Distribution of the implants on abdominal and pelvic surfaces greatly influences the likelihood of a complete cytoreduction by visceral resections and peritonectomy procedures. The current description of PCI uses 13 abdominal and pelvic regions, as described in Fig. 1.#

To determine the lesion size score included in the PCI, accurate measurement of lesion size in each abdominopelvic region by direct visual inspection intraoperatively is an essential part of the PCI. Lesion size refers to the greatest diameter of the implants that are distributed to the peritoneal surfaces. If there are many implants within an abdominopelvic region, the diameter of the largest implant is measured and recorded. Primary tumors or localized recurrences at the primary site that can be removed definitively en bloc are excluded from lesion size assessment. Implants are scored as lesion size 0 through 3 (LS-0 to LS-3). LS-0 means no implants are seen throughout the region; this measurement is determined after a complete lysis of all adhesions and the complete inspection of all parietal and visceral peritoneal surfaces. LS-1 refers to implants that are visible up to 0.5cm in greatest diameter. LS-2 identifies nodules greater than 0.5cm and up to 5cm. LS-3 refers to implants 5cm or greater in diameter. Furthermore, if there is a confluence of disease matting abdominal or pelvic structures together, this automatically is scored as LS-3. Even a thin confluence of cancerous implants is designated as LS-3.#

PCI is determined before and after cytoreductive surgery, allowing an assessment of the downstaging achieved by cytoreductive surgery. PCI has been tested all over the world by surgical teams dealing with peritoneal carcinomatosis. For carcinomatosis from colon cancer treated by cytoreductive surgery and IPCH or early postoperative intraperitoneal chemotherapy, Elias et al. reported that the survival results were significantly better when the PCI was lower than 16.⁸ Sugarbaker reported on 100 patients with carcinomatosis from colon cancer and recorded a 5-year survival rate of 50% when the PCI was less than 10, a 5-year survival rate of 20% with a PCI of 11–20, and a 5-year survival rate of 0% with a PCI >20.⁹ Gomez Portilla et al. also showed that the PCI could be used to predict long-term survival in patients with carcinomatosis from colon cancer having a second cytoreduction.¹⁰ Berthet et al. showed that the PCI predicted benefits of treatment of sarcomatosis from recurrent visceral or parietal sarcoma.¹¹ Routinely used by surgeons involved in peritoneal carcinomatosis treatment, the PCI is rarely used by medical oncologists or radiologists. Its accuracy when CT is used to assess lesion size has not been determined.#

In Japan, carcinomatosis from gastric cancer is classified by the JRSGC as follows: P0 means no implants to the peritoneum. P1 means cancerous implants directly adjacent to the stomach peritoneum, including the greater omentum. P2 means several scattered metastases to the distant peritoneum or ovarian metastasis alone. P3 means numerous metastases to the distant peritoneum. This classification has been used in Japanese studies as an accurate quantitative prognostic indicator for gastric cancer. Fujimoto et al. reported significant lower survival rates in patients with P3 carcinomatosis than in patients with P2 or P1 after cytoreductive surgery combined with IPCH, but no difference was found between P1 and P2.¹² This JRSGC carcinomatosis staging has also been used for quality of life study after palliative gastric resections. Ouchi et al. reported that palliative total gastrectomy performed in P2 or P3 patients revealed a poorer outcome than palliative total gastrectomy performed in P0 or P1 patients.¹³ For gastric cancer, JRSGC carcinomatosis staging continues to be a useful quantitative prognostic indicator.#

At the Netherlands Institute, the extent of tumor is recorded on standardized forms indicating large (>5cm), moderate (1–5cm), small (<1cm) or no involvement. The tumor distribution was recorded according to the presence of tumor deposits in seven abdominal areas: left and right subdiaphragmatic, subhepatic, omentum/transverse colon, small intestine/mesenterium, ileocecal and pelvic. This assessment has been referred to as the “simplified PCI” or SPCI. The system is routinely used for colorectal and appendiceal cancer while it has prognostic implications for outcome following cytoreductive surgery and IPCH.¹⁴#

Using UICC score for surgical resections in carcinomatosis is possible. However, in patients with peritoneal carcinomatosis, it is difficult or impossible to confirm a real R0 resection and the UICC score is “R0–R1” for complete cytoreduction and R2 for incomplete cytoreduction. This UICC score has been used in evaluation of cytoreductive surgery combined with IPCH. In a series of 56 patients with carcinomatosis from colon and ovarian cancer treated by cytoreductive surgery and IPCH, Glehen et al. reported a 2-year survival rate of 79% after R0–R1 resection while it was 44.7% after R2 resection.¹⁵ In gastric cancer, Yonemura et al. reported survival rates at 3years of 40% in patients with R0–R1 cytoreduction combined with IPCH, while it was 10% in patients with R2 cytoreduction.¹⁶#

In order to describe more precisely the type of cytoreduction performed, Sugarbaker reported the CCR Score (Completeness of Cytoreduction Score).^91017–19 For gastrointestinal cancers, the CCR Score has been defined as summarized in Fig. 2 and as follows. A CCR-0 indicates that no peritoneal seeding was exposed during the complete exploration. A CCR-1 indicates that tumor nodules persisting after cytoreduction are less than 2.5mm in diameter (this is a nodule size though to be penetrable by intracavitary chemotherapy). A CCR-2 indicates residual tumor nodules 2.5mm to 2.5cm in diameter. A CCR-3 indicates residual tumor nodules greater than 2.5cm in diameter or a confluence of unresectable tumor nodules at any site within the abdomen and the pelvis.#

This CCR Score has been evaluated through numerous prospective series. This scoring system has demonstrated its accuracy in the international registry reporting survival rates from 506 patients with colorectal cancer and peritoneal carcinomatosis treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy.²⁰#

One may be surprised by the number of peritoneal carcinomatosis staging system available all over the world. In fact, at least three of them are complementary ones: the Lyon staging system, the PCI and the SPCI.#

The Lyon staging system and the PCI contribute to the precise intraoperative description of carcinomatosis implants within the abdominopelvic cavity. Using both of them allows an accurate “map” of the lesions. For some diagnosis of peritoneal carcinomatosis, Lyon staging system is the more objective one. An example is ovarian cancer with peritoneal carcinomatosis confined to the pelvic region and realizing a large confluence of implants: it will be scored as a stage 4 with a poor prognosis, while the PCI will only scored 3 indicating a favorable prognosis. For other patients with peritoneal carcinomatosis, PCI is the more objective assessment. An example is colorectal cancer with 5mm implants under right diaphragmatic cupula and large bulky malignant nodules in the right flank: it will be scored as a Lyon staging system 3 indicating a poor prognosis while PCI will be scored 3 indicating a favorable prognosis.#

In Lyon, we systematically used both the Lyon staging system and PCI. A specific form is available in the operating room to allow a complete intraoperative description of lesions. At the end of surgical procedure, the surgeon underline on the same form either he performed a CCR-0, CCR-1, CCR-2 or CCR-3 resection. Combining these three scores appears like a complete, useful and exhaustive method within the medical-surgical teams involved in peritoneal carcinomatosis treatments. On the other hand, the Lyon staging system used alone facilitates the presentation of an individual patient the whole therapeutic strategy in a multidisciplinary approach, with other physicians. Another reason for using both the Lyon staging system and PCI comes from differences in prognosis according to which primary site from which the carcinomatosis arose. A Lyon staging system 4 from gastric cancer is probably not a correct indication for cytoreductive surgery with IPCH, even if PCI is only 15; in the same way, an ovarian cancer with massive bilateral invasive cancer at the uretero-vesicle junction can be scored as PCI 3 and Lyon staging system 4 and is not a candidate for extensive surgery.²¹²² In contrast, a peritoneal carcinomatosis arising from pseudomyxoma peritonei can undergo a complete cytoreduction even with a PCI scored at 39.²²#

The real challenge for these scoring systems is obviously the accurate selection of patients for complete cytoreduction. Cytoreductive surgery allowing a macroscopic complete resection combined with IPCH has been reported to allow long-term survival in a prospective randomized study,²³ in numerous prospective phase II studies^24–26 and in a multicentric international registration;²⁰ however, cytoreductive surgery combined with IPCH exposed patients to postoperative morbidity of 30%.²⁷ Careful patient selection must be performed before any therapeutic decision: it should be carefully assessed by physical examination at the initial encounter and at the interpretation of CT scan, MRI and PET scan (preferably in consultation with an experienced radiologist). Moreover, the final therapeutic decision is made at the time of complete abdominal exploration. If at any time the assessment becomes “no possibility for complete cytoreduction,” the management plan for that patient changes immensely and the therapeutic strategy will move from extensive surgery with a curative intent to palliative debulking surgery to relieve symptoms or even to low morbidity and mortality palliative treatments.#

Moreover, because of the profound implications complete cytoreduction has on long-term survival, a new assessment has been proposed at the peritoneal surface malignancy workshop held in December 2002, Basingstoke, UK. The score may be referred to as the “Probability of complete cytoreduction.” The scores are possible, indeterminant, or not possible. This assessment should be made at the initial encounter, from the interpretation of pathologic studies and radiologic imaging, and at the time of abdominal exploration. It would of course profoundly change the management plan from elective comprehensive treatment with cytoreductive surgery and perioperative intraperitoneal chemotherapy (curative intent) to palliative treatments (debulking surgery with symptom management).#

A major problem for the management of peritoneal surface malignancy remains the preoperative assessments. Many patients are still subjected to explorative laparotomy without the possibility of curative treatment because cytoreductive surgery is determined impossible. Most often tumor implants on small bowel or on the pelvis sidewall have been underestimated by the preoperative exams. Occasionally small sized but diffuse liver metastases will make complete cytoreduction impossible.#

For mucinous carcinomatosis, CT scan with two distinctive radiologic criteria (segmental obstruction of the small bowel and presence of tumor nodules greater than 5cm in diameter on small bowel surfaces or directly adjacent to small bowel mesentery) may distinguish patients with resectable disease from those with non-resectable malignancy. But sensitivity of CT scan for malignant nodules less than 5mm, especially on small bowel surfaces, remains low. Carcinomatosis with implants less than 5mm would not be imaged or underestimated in their distribution, especially in patients with postoperative changes. Results of magnetic resonance imaging (MRI) that were recently evaluated in Lyon were not encouraging and did not demonstrate superiority to the CT scan in the preoperative assessment of carcinomatosis. Laparoscopy with cytological examination and biopsies could be an effective way to diagnose carcinomatosis in the absence of exploratory laparotomy. Unfortunately, even with great skill, there is great difficulty in exploration of the abdomen and especially the pelvis. Other exams are currently under evaluation for the clinical diagnosis or quantitative assessment of carcinomatosis: immunoscintigraphy, PET scan and especially fused PET/CT imaging, which may be considered as the future best tool for preoperative assessment of carcinomatosis and is currently under evaluation in Lyon. It seems to significantly improve sensitivity, specificity and accuracy in the detection and localization of malignant nodules.#

In conclusion, the more precise is the description of peritoneal lesions (location, number, size), the better is the patient selection. A combination of scores is probably the key for optimal selection. The better the selection is, the better the results of treatment.#