Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups.

BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

Multicentre study of the learning curve and surgical performance of cytoreductive surgery with intraperitoneal chemotherapy for pseudomyxoma peritonei.

BACKGROUND: The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. METHODS: Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. RESULTS: Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. CONCLUSION: The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Exercise intervention in breast cancer patients with aromatase inhibitor-associated arthralgia: a pilot study.

Aromatase inhibitors (AIs) block estrogen synthesis and are commonly used as adjuvant treatments for breast cancer patients. A common side effect is joint pain. This was a pilot study to examine implementation of an exercise program in reducing joint pain and improving quality of life (QoL) and functional performance in breast cancer patients treated with AIs. Twenty-six participants completed an 8-week, home-based program that combined upper and lower body resistance exercises with self-selected aerobic exercises. We measured: (1) anthropometry (2) functional performance (grip strength, biceps curl to exhaustion, and sit-to-stand and cardiovascular endurance (3-min step test). Joint pain and QoL were assessed using self-administered surveys. Participants reported a significantly lower number of painful joints, an improvement in QoL and a reduction in depressive symptoms. Significant improvements in grip strength, biceps curl, and sit-to-stand (by 14%, 51% and 15% respectively) were also observed. However, we found no significant changes in cardiovascular endurance or in anthropometric measures. An 8-week, home-based exercise program may provide potential benefit to the breast cancer patients undergoing AI treatment by reducing joint pain, improving functional performance and QoL, and reducing depressive symptoms. Further studies are needed to confirm these results.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer.

Peritoneal carcinomatosis (PC) arising from colorectal cancer (CRC) is generally considered a terminal condition with few treatment options. However, over the past few decades, new chemotherapeutic and biologic agents have improved the median overall survival of patients with unresectable metastatic disease up to 20 months. There has also been emergence of combining cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with PC. The literature supporting such an approach is significant, though not extensive, mainly consisting of small single-institution series, one international multicenter retrospective review, and one single-institution prospective randomized trial. Yet, there is remarkable homogeneity among the reported clinical outcomes, demonstrating 5-year OS rates of approximately 25-40% for patients undergoing a complete cytoreduction. These studies have fueled increasing interest in the use of CS and HIPEC for metastatic colorectal cancer over the past decade. However, despite the publication of a consensus statement on the role of CS and HIPEC for PC from CRC, there is still controversy regarding its appropriateness, effectiveness, safety, and application in this subset of patients. In this review we analyze the currently available scientific evidence supporting the clinical application of CS and HIPEC in the treatment of PC of colorectal origin.

Importance of gender in diffuse malignant peritoneal mesothelioma.

BACKGROUND: Combined therapy involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has been shown to improve survival outcomes for patients with diffuse malignant peritoneal mesothelioma (DMPM). The present study aims to investigate gender as a potential prognostic factor on overall survival. PATIENTS AND METHODS: Over a period of two decades, 294 patients who underwent CRS and perioperative intraperitoneal chemotherapy were selected from a large multi-institutional registry to assess the prognostic significance of gender on overall survival. RESULTS: Female patients were shown to have a significantly improved survival outcome than male patients (P < 0.001). Staging according to a recently proposed tumor-node-metastasis categorization system was significant in both genders. Older female patients had significantly worse survival than younger female patients (P = 0.019), a finding that was absent in male patients. Female patients with low-stage disease were found to have a very favorable long-term outcome after combined treatment. CONCLUSIONS: Gender has demonstrated a significant impact on overall survival for patients with DMPM after CRS and perioperative intraperitoneal chemotherapy. An improved understanding of the role of estrogen in the pathogenesis of DMPM may improve the prognostication of patients and determine the role of adjuvant hormonal treatment in the future.

Accuracy and clinical relevance of computed tomography scan interpretation of peritoneal cancer index in colorectal cancer peritoneal carcinomatosis: a multi-institutional study.

BACKGROUND: Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. METHODS: A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. RESULTS: Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P < 0.0005), RLQ (P = 0.003), distal jejunum (P = 0.004), and distal ileum (P < 0.0005). When CT-PCI was classified based on the extent of carcinomatosis, 17 cases (33%) were underestimations, of which, 11 cases (21%) were upstaged from low to moderate, 4 cases (8%) were upstaged from low to severe, and 2 cases (4%) were upstaged from moderate to severe. Relevant clinical discordance where an upstage occurred to severe carcinomatosis constituted a true inaccuracy and was observed in six cases (12%). CONCLUSIONS: The actual clinical impact of inaccuracies of CT-PCI was modest. CT-PCI will remain as a mandatory imaging tool and may be supplemented with other tools including positron emission tomography scan or diagnostic laparoscopy, in the patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).

BACKGROUND: The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. METHODS: Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). RESULTS: Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. CONCLUSION: In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.

Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

OBJECTIVE: Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. METHOD: A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). RESULTS: In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. CONCLUSION: Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.

Cost analysis of biomarker testing for mismatch repair deficiency in node-positive colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) in colorectal cancer is caused by defective DNA mismatch repair (MMR). It is present in 15 per cent of sporadic colorectal cancers owing to epigenetic mutL homologue 1 (MLH1) inactivation. The evidence suggests that patients with tumours caused by defective DNA MMR do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. METHODS: The proportion of cancers with defective DNA MMR identified by MSI analysis or immunohistochemistry was calculated from published data. The cost of analysis was compared with the potential savings if 5-FU-based chemotherapy was not administered to these patients. RESULTS: Some 16.3 per cent of sporadic colorectal cancers had defective DNA MMR. Immunostaining for MLH1 and mutS homologue 2 (MSH2) had a sensitivity of 92.4 per cent and a specificity of 99.6 per cent for identifying MSI-high tumours. The strongest predictive variable was right-sidedness, with positive and negative predictive values of 0.329 and 0.948 respectively. If 5-FU-based chemotherapy were not administered, potential savings of up to pound 1.2 million per 1000 patients tested could be made. Costs would be higher if alternative chemotherapeutic regimens were substituted as a result of testing. CONCLUSION: Knowledge of MMR status may enable participation in trials of non-5-FU-based chemotherapy. The cost of MMR testing may be offset by more efficient use of chemotherapy.

Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.

Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (P<0.002) in severe reactors compared to normal. Prediction of reaction severity of approximately 91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study.

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m(-2) to 60 mg m(-2) to 70 mg m(-2) to identify the maximum tolerated dose (60 mg m(-2)). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m(-2) per day) for 5 weeks. Irinotecan (60 mg m(-2)) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.

A prospective observational study of chemotherapy-related nausea and vomiting in routine practice in a UK cancer centre.

OBJECTIVE: The aim of the study was to assess levels of chemotherapy-induced nausea and vomiting (CINV) in routine practice. MATERIALS AND METHODS: The study was an observational prospective evaluation using patient self-reports. One hundred and two patients with cancer in a single cancer centre in UK receiving their first chemotherapy treatment participated in the study and were followed up over four cycles, providing a total of 272 assessments of nausea and vomiting. Data was collected with the use of the MASCC Antiemesis Tool (MAT), which is an eight-item short clinical scale assessing acute and delayed nausea and vomiting after chemotherapy. RESULTS: Results indicated that acute vomiting was experienced by 15.7% of the patients in cycle 1 and delayed vomiting by 14.7%, while acute nausea was present in 37.3% of the patients and delayed nausea in 47.1%, increasing over the subsequent cycles. Moderately emetogenic and highly emetogenic chemotherapy had the highest incidence of CINV, whereas patients receiving highly emetogenic chemotherapy showed significant levels of delayed nausea. Acute symptoms were more easily controlled than delayed symptoms. DISCUSSION: The data suggest that, while vomiting is well controlled, nausea remains a significant problem in practice, and optimal management of CINV is yet to be achieved. Understanding more clearly the biological basis of nausea will assist in managing this complex symptom more effectively in practice.

A phase I study of capecitabine and a modulatory dose of irinotecan in metastatic breast cancer.

PURPOSE: There is a need for chemotherapy regimens active against anthracycline- and taxane-refractory breast cancer. Data from preclinical and pilot studies performed at Roswell Park Cancer Institute (RPCI) suggested that when irinotecan (IRN) is given with 5-fluorouracil (5-FU) efficacy is affected by the sequence of drug administration. Pretreatment with IRN 24 h before 5-FU increased the number of tumor cells in S-phase and the antitumor activity in a preclinical system. These data provided the rationale for the evaluation of IRN and capecitabine, a 5-FU prodrug, sequentially administered in patients with metastatic breast cancer. The main objective of the study was to determine the MTD and identify dose-limiting toxicities (DLTs) of capecitabine and IRN. Additionally, the degree of accumulation of cells in S-phase in tumor biopsies obtained at 24 h after the first dose of IRN was measured in consenting patients. PATIENTS AND METHODS: Metastatic breast cancer patients who experienced disease progression after at least one (taxane or anthracycline based) chemotherapy regimen and an expected survival of at least 3 months and ECOG performance status 0-2 were eligible. Twelve patients were enrolled and treated. The starting doses were IRN 80 mg/m(2) given over 90 min on days 1, 8, 22, 29, and capecitabine 1,500 mg/m(2)/day given days 2-15 and 23-36. Evaluation for response was performed after the first cycle. Sequential tumor biopsies were performed on five patients. RESULTS: The first three patients treated exhibited modulation in cyclin A index on tumor biopsy as defined by the study, defining the modulatory dose of IRN as 80 mg/m(2). Overall, 4/5 biopsies showed modulation. Dose Limiting Toxicities (DLTs) were assessed during the first cycle of therapy. Two DLTs (Grade 3 nausea vomiting and dehydration; grade 3 pneumonia, hypoxia, hypotension) were seen at dose level 2 of capecitabine (2,000 mg/m(2)/day) and the first cohort was expanded. There were no DLTs for patients treated at DL 1. No grade 3-4 toxicities occurred at DL 1. Seven patients were evaluable for response following one cycle of treatment (partial response 1, stable disease 4, progressive disease 2) Of the five inevaluable patients, two experienced DLT, one received 50% of the planned capecitabine dose, one progressed prior to evaluation, and one withdrew consent. CONCLUSION: IRN 80 mg/m(2) days 1, 8, 22, 29 in combination with capecitabine 1,500 mg/m(2)/day in divided dose days 2-15 and 23-36 has an acceptable toxicity profile and resulted in modulation of S-phase in 4/5 specimens examined. Further studies of the activity of this combination and modulatory effect of IRN are warranted.

Combined modality treatment of early rectal cancer: the UK experience.

With the introduction of colorectal screening in the UK, more patients will probably be diagnosed with early rectal cancer. The UK has an increasingly elderly population and not all patients diagnosed with early rectal cancer will be suitable for radical surgery. Therefore, a national plan is needed to develop the provision of alternative local treatment with equity of access across the country. Here we review the Clatterbridge Centre for Oncology multimodality treatment policy, which has been in clinical practice since 1993 and we discuss its rationale. Clatterbridge is the only centre in the UK offering Papillon-style contact radiotherapy. In total, 220 patients have been treated over 14 years, most of whom were referred from other centres. One hundred and twenty-four patients received Papillon (contact radiotherapy) as part of their multimodality management. The guidelines of the Association of Coloproctology of Great Britain and Ireland recommend local treatment for T1 tumours<3 cm in diameter, but this refers to treatment by surgery alone. There are no published national guidelines for radiotherapy. We plan each treatment in stages and achieve excellent local control (93% at 3 years) with low morbidity. We conclude that radical local treatment for cure can be offered safely to carefully selected elderly patients. Close follow-up is necessary so that effective salvage treatment can be offered. Because of a lack of randomised trial evidence, at present local radiotherapy is not yet accepted as an alternative option to the gold standard surgical treatment. Even with international collaboration, a randomised trial will be difficult to complete as the number of cases requiring local radiotherapy is small due to the highly selective nature of the treatment involved. However, an observational phase II trial is planned. In addition, the Transanal Endoscopic Microsurgery Users Group is also planning a phase II trial using preoperative radiotherapy. These studies will provide evidence to help establish the true role of radiotherapy in early rectal cancer.

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study.

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m(-2)) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5(1/2) weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m(-2)) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35-79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control.

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.