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Age alone is not a barrier to efficacy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: analysis of 1138 patients from the UK and Ireland Colorectal Peritoneal Metastases Registry
Abstract
Background:
The management of colorectal peritoneal metastases continues to be a challenge but recent evidence suggests cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival. Uncertainty about the relationship between age and tumour biology makes patient selection challenging particularly when reported procedure related morbidity is high and impact on survival outcomes unknown. The UK and Ireland Colorectal Peritoneal Metastases Registry was reviewed to assess the influence of age on efficacy of CRS and HIPEC.
Methods:
A review of outcomes from the UK and Ireland Colorectal Peritoneal Metastases Registry was performed. Data from 2000 to 2021 were included from five centres in the UK and Ireland, and the cohort were sub-divided into three age groups; <45 years, 45-65 years and >65 years old. Primarily, we examined post-operative morbidity and survival outcomes across the three age groups. In addition, we examined the impact that the completeness of cytoreduction, nodal status, or adverse pathological features had on long-term survival.
Results:
During the study period, 1138 CPM patients underwent CRS HIPEC. 202 patients(17.8%) were <45 years, 549 patients(48.2%) aged 45-65 years and 387 patients(34%) >65 years. Overall, median length of surgery (CRS and HIPEC), median PCI score and rate of HIPEC administration was similar in all three groups, as was overall rates of major morbidity and/or mortality. Complete cytoreduction rates (CC0) were similar across the three cohorts; 77%, 80.6% and 81%, respectively. Median overall survival for all patients was 38 months following complete cytoreduction.
Conclusion:
Age did not appear to influence morbidity or long-term survival following CRS and HIPEC. When complete cytoreduction is achieved survival outcomes are good. The addition of HIPEC can be performed safely and may reduce local recurrence within the peritoneum.
Background:
The incidence of colorectal cancer (CRC) in patients under 50 years of age, i.e., early-onset CRC, has increased in the past two decades. Colorectal peritoneal metastases (CPM) will develop in 10-30% of CRC patients. CPM traditionally had a dismal prognosis, but surgery and novel systemic treatments appear to increase survival. Determining potential age-associated risk and prognostic factors is optimized when analyses use standardized age groupings.
Methods:
We performed a review of early-onset CPM studies and compared variables used, e.g., age stratification and definitions of synchronous and metachronous CPM. We included studies published in PubMed up to November 2022 if results were stratified by age.
Results:
Of 114 screened publications in English, only 10 retrospective studies met inclusion criteria. Incidence of CPM was higher in younger CRC patients (e.g. 23% vs. 2% for <25 vs. ≥25 years, P < 0.0001; and 57% vs. 39% vs. 4% for <20 vs. 20-25 vs. >25 years, P < 0.001); two studies reported higher proportion of younger African American CPM patients (e.g. 16% vs. 6% for <50 vs. ≥50 years). Studies used seven different age-stratification methods, presenting comparison challenges.
Conclusion:
Studies showed a higher proportion of CPM in younger patients, but directly comparing results was not possible due to inconsistent reporting. To better address this issue, CRC and CPM studies stratified by standard age groups (e.g. <50 vs. ≥50) are needed.
Background
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases (PM) from colorectal carcinoma (CRC). Because of considerable morbidity, optimal patient selection is essential. This study was designed to determine the impact of the onset of PM (synchronous vs. metachronous) on survival outcomes after CRS-HIPEC.
Methods
Patients undergoing CRS-HIPEC for colorectal PM in two academic centers in the Netherlands between 2010 and 2020 were eligible for inclusion. Patients were classified as synchronous (s-PM, i.e., diagnosis at time of presentation, staging, or primary surgery) or metachronous onset (m-PM, i.e., diagnosis during follow-up) of colorectal PM. Survival outcomes were compared between groups by Kaplan–Meier survival and Cox regression analyses.
Results
Of 390 included patients, 179 (45.9%) had synchronous onset of colorectal PM. These patients more often presented with higher TN-stage and poor differentiation/signet cell histology. Treatment with perioperative chemotherapy was more common in s-PM patients. m-PM patients experienced more serious postoperative complications (Clavien-Dindo ≥ III). There was no significant difference in disease-free survival (DFS) between s-PM (median 9 months, interquartile range [IQR] 5–15) and m-PM patients (median 8 months, IQR 5–17). Overall survival (OS) was significantly shorter for s-PM (median 28 months, IQR 11–48) versus m-PM patients (median 33 months, IQR 18–66, p = 0.049). Synchronous onset of PM was not independently associated with OS in a multivariable analysis.
Conclusions
Synchronous onset of colorectal PM was associated with poor tumor characteristics and more advanced disease, but was not an independent predictor of survival outcomes after CRS-HIPEC.
Objective:
Peritoneal cancer is an uncommon form of terminal malignancy with substantial morbidity and mortality. While both young and elderly population groups with peritoneal cancer are treated by joint cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, studies suggest that they might have a differential prognostic outcome in terms of postoperative morbidity and mortality. To date, only one review has attempted to evaluate the comparative impact of postoperative complications and overall mortality in these age groups. However, a recent publication of several high-quality cohort trials needs an update of the existing consensus. To compare the impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on postoperative complications and overall mortality in younger and elderly population groups.
Materials and methods:
A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases: Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to evaluate the comparative outcomes between the impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on postoperative complications and overall mortality in younger and elderly population groups.
Results:
From 963 studies, 16 eligible studies that evaluated the comparative outcomes of morbidity and mortality between 3067 young and 878 elderly patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included. A meta-analysis revealed higher risks of postoperative complications (Odds ratio: 1.18, 95% C.I: 0.90 to 1.55) and overall mortality (3.28, 1.93 to 5.5) for elderly patients as compared to the younger patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There were no differences in risks of the onset of anastomotic leakage (1.0, 0.47 to 2.14) and duration of hospital stay (Hedge's g: 0.02, -0.08 to 0.14) between elderly and younger patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Conclusions:
The study provides updated evidence regarding poor postoperative morbidity and mortality outcomes in elderly patients as compared to younger patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and may help clinicians to better stratify the risks associated with the conventional management of peritoneal carcinomatosis in elderly population groups.
Neoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the “tumor core” (TC) and the “tumor border” (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based “clinical-radiomic” machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10 –5 ). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.
Background:
Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited.
Aim:
To evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors.
Methods:
One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient's demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival.
Results:
The two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis.
Conclusion:
In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.
The analysis of tumor cells or tumor cell products obtained from blood or other body fluids (“liquid biopsy” [LB]) provides a broad range of opportunities in the field of oncology. Clinical application areas include early detection of cancer or tumor recurrence, individual risk assessment and therapy monitoring. LB allows to portray the entire disease as tumor cells or tumor cell products are released from all metastatic or primary tumor sites, providing comprehensive and real‐time information on tumor cell evolution, therapeutic targets and mechanisms of resistance to therapy. Here, we focus on the most prominent LB markers, circulating tumor cells (CTCs) and circulating tumor‐derived DNA (ctDNA), in the blood of patients with breast, prostate, lung and colorectal cancer, as the four most frequent tumor types in Europe. After a brief introduction of key technologies used to detect CTCs and ctDNA, we discuss recent clinical studies on these biomarkers for early detection and prognostication of cancer as well as prediction and monitoring of cancer therapies. We also point out current methodological and biological limitations that still hamper the implementation of LB into clinical practice.
Background:
Previous studies have shown that, overall, quality of life (QoL) decreases within the first 3-6 months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), returning to baseline levels by 6-12 months. This systematic review aims to evaluate the factors affecting QoL after CRS + HIPEC within 12 months of surgery.
Methods:
Electronic databases were investigated searching for articles reporting QoL with validated questionnaires up to September 2019. Risk of bias was assessed with the methodological index for non-randomized studies tool. The primary outcomes were short-term (< 6 months after surgery) and medium-term (6-12 months after surgery) determinants of QoL after CRS + HIPEC. Secondary outcomes were QoL and reported symptoms over time.
Results:
We included 14 studies that used 12 different questionnaires. The reported data were collected prospectively or retrospectively for 1556 patients (dropout < 50% in four studies). Overall, studies showed diminished QoL within 3 months after surgery and a recovery to baseline or greater by 12 months. QoL was negatively influenced by higher age, female sex, prolonged operation time, extensive disease, residual disease, adjuvant chemotherapy, complications, stoma placement, and recurrent disease. QoL results were comparable between studies, with dropout rates above and below 50%.
Conclusions:
QoL returns to baseline levels within 12 months after CRS + HIPEC provided the disease does not recur, and this recovery process is influenced by several factors.
Background:
Up to 15 per cent of colorectal cancers present with peritoneal metastases (CPM). Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) aims to achieve macroscopic tumour resection combined with HIPEC to destroy microscopic disease. CRS + HIPEC is a major operation with significant morbidity and effects on quality of life (QoL). Improving patient selection is crucial to maximize patient outcomes while minimizing morbidity and mortality. The aim of this study was to identify prognostic factors for patients with CPM undergoing CRS + HIPEC.
Methods:
A systematic search of MEDLINE, Embase and Cochrane Library electronic databases was performed using terms for colorectal cancer, peritoneal metastasis and CRS + HIPEC. Included studies focused on the impact of prognostic factors on overall survival following CRS + HIPEC in patients with CPM.
Results:
Twenty-four studies described 3128 patients. Obstruction or perforation of the primary tumour (hazard ratio (HR) 2·91, 95 per cent c.i. 1·5 to 5·65), extent of peritoneal metastasis as described by the Peritoneal Carcinomatosis Index (PCI) (per increase of 1 PCI point: HR 1·07, 1·02 to 1·12) and the completeness of cytoreduction (CC score above zero: HR 1·75, 1·18 to 2·59) were associated with reduced overall survival after CRS + HIPEC.
Conclusion:
Primary tumour obstruction or perforation, PCI score and CC score are valuable prognostic factors in the selection of patients with CPM for CRS + HIPEC.
Treatment of young adults with colorectal cancer (CRC) represents an unmet clinical need, especially as diagnosis in this population might lead to the greatest loss of years of life. Since 1994, CRC incidence in individuals younger than 50 years has been increasing by 2% per year. The surge of CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Early‐onset CRCs are characterized by more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left‐colon sided location of the primary tumor. Among EO‐CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have CRC familiarity. Most notably, the remaining 50% of EO‐CRC have neither hereditary syndromes nor family history of CRC, thus representing a formidable challenge for research. In this review article we summarize epidemiology, clinical and molecular features, hereditariness and outcome to treatments of EO‐CRC, finally providing considerations for future perspectives.
Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important component of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are currently underway, clinical translation of ctDNA detection in various types of cancers has been attracting much attention, due to the great potential of ctDNA as blood-based biomarkers for early diagnosis and treatment of cancers. ctDNAs are detected and tracked primarily based on tumor-related genetic and epigenetic alterations. In this article, we reviewed the available studies on ctDNA detection and described the representative methods. We also discussed the current understanding of ctDNAs in cancer patients and their availability as potential biomarkers for clinical purposes. Considering the progress made and challenges involved in accurate detection of specific cell-free nucleic acids, ctDNAs hold promise to serve as biomarkers for cancer patients, and further validation is needed prior to their broad clinical use.
The prognosis of early-onset sporadic colorectal cancer (CRC) patients remains controversial. The objective of this study was to assess the long-term outcome and prognostic factors of sporadic CRC in young patients.
From 2006 to 2011, 8207 patients underwent curative or palliative surgery for CRCs in our institution. A total of 693 patients who were ≤45 years old with sporadic CRC were enrolled as the young group. A total of 1823 patients aged between 56 and 65 years were identified as middle-aged control group for this study. Survival outcome and prognostic factors were compared between the two groups.
Young patients had higher recurrence rate than older patients in stages I and II (8.8% vs 2.7%, P <0.001). There was no significant difference of recurrence rate in stage III and IV cancers (27.5% vs 27.9%, P = 0.325). Metachronous cancers were developed more frequently in young patients (1.4% vs 0.6%, P = 0.038). Advanced stage CRC was diagnosed significantly more common in the young group (55.6% vs 47.9%, P = 0.001). High microsatellite instability (MSI) tumors are less likely to have advanced stage cancers (odds ratio (OR) 0.23, 95% confidence interval (CI) = 0.07–0.70) or cancer recurrence (OR 0.11, 95% CI = 0.01–0.85) in young patients. Cancer-specific survival was worse in young patients than that in older patients (81.2% vs 87.8%, P <0.001). However, there was no significant difference in cancer-specific survival for each stage between the two groups. Independent prognostic factors for survival in young patients were undifferentiated cancer (hazard ratio (HR) 2.30, 95% CI = 1.23–4.31) and 3 months or longer duration of symptom (HR 2.57, 95% CI = 1.34–4.94). Young women had better survival compared with young men (HR 0.55, 95% CI = 0.33–0.90).
Prognosis of sporadic CRC in young patients is poorer than older patients, because of poorer histologic differentiation and delay in diagnosis. Early detection of CRC confers survival benefit to young patients. Because of higher recurrence rate and metachronous cancer risk, post-operative surveillance is also important in young patients.
The main prognostic factors after complete cytoreductive surgery (CCRS) of colorectal peritoneal carcinomatosis (PC) followed by intraperitoneal chemotherapy (IPC) are completeness of the resection and extent of the disease. This study aimed to determine a threshold value above which CCRS plus IPC may not offer survival benefit compared with systemic chemotherapy.
Between March 2000 and May 2010, 180 patients underwent surgery for PC from colorectal cancer with intended performance of CCRS plus IPC.
Among the 180 patients, CCRS plus IPC could be performed for 139 patients (curative group, 77 %), whereas it could not be performed for 41 patients (palliative group, 23 %). The two groups were comparable in terms of age, gender, primary tumor characteristics, and pre- and postoperative systemic chemotherapy. The mean peritoneal cancer index (PCI) was lower in the curative group (11 ± 7) than in the palliative group (23 ± 7) (p < 0.0001). After a median follow-up period of 60 months (range 47-74 months), the 3-year overall survival (OS) rate was 52 % [95 % confidence interval (CI) 43-61 %] in the curative group compared with 7 % (95 % CI 2-25 %) in the palliative group. Comparison of the survivals for each PCI (ranging from 5 to 36) shows that OS did not differ significantly between the two groups of patients when the PCI was higher than 17 (hazard ratio 0.64; range 0.38-1.09).
This study confirmed the major prognostic impact of PC extent. When the PCI exceeds 17 in PC of colorectal origin, CCRS plus IPC does not seem to offer any survival benefit.
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery.Methods
The American Society of Peritoneal Surface Malignancies (ASPSM) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C (MMC), stratifying them by the Peritoneal Surface Disease Severity Score (PSDSS).ResultsMedian overall survival (OS) of 539 patients with complete cytoreduction was 32.6 months, 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group (P = 0.925). However, when stratified by PSDSS, median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin (P = 0.012), whereas in PSDSS III/IV patients, median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin (P = 0.427).Conclusion
These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC, favorable histologies and low burden of disease (PSDSS I/II) undergoing complete cytoreduction. Propsective studies are warranted, which stratify patients by their PSDSS and randomize them to HIPEC with MMC vs. Oxaliplatin. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
Background
Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy.
Patients and methods
A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included.
Results
The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups.
Conclusion
For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.
Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study.
A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International.
Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival.
The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.
Peritoneal carcinomatosis (PC) from gastric cancer has long been regarded a terminal disease with a short median survival. New locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival.
A retrospective multicentric study was performed in French-speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC: hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC).
The study included 159 patients from 15 institutions between February 1989 and August 2007. The median follow-up was 20.4 months. HIPEC was the PIC used for 150 procedures. Postoperative mortality and grade 3-4 morbidity rates were 6.5 and 27.8%, respectively. By multivariate analysis, the institution had a significant influence on toxicity. The overall median survival was 9.2 months and 1-, 3-, and 5-year survival rates were 43, 18, and 13%, respectively. The only independent prognostic indicator by multivariate analysis was the completeness of cytoreductive surgery. For patients treated by complete cytoreductive surgery, the median survival was 15 months with a 1-, 3-, and 5-year survival rate of 61, 30, and 23%, respectively.
The therapeutic approach combining cytoreductive surgery with PIC for patients with gastric carcinomatosis may achieve long-term survival in a selected group of patients (limited and resectable PC). The high mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions involved in the management of PC and gastric surgery.
To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC).
All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time.
Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test).
Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.
Background:
Cytoreductive surgery (CRS) is at the forefront of treatment for colorectal cancer with peritoneal metastasis or "carcinomatosis" (CRC-PC). We report outcomes of the operative management of CRC-PC at a single center.
Study design:
We retrospectively reviewed our database from 1992 through 2021. The Kaplan-Meier method was used to estimate survival. Proportional hazards regression and multivariable models were used for assessments.
Results:
This study included 345 patients with mean age 53.5 years. Multivariate analysis revealed performance and resection status were associated with overall survival (OS; p < 0.001). Within the R0/R1 group, adverse impact on OS was found with increasing Peritoneal Cancer Index (PCI) score starting at 9 (hazard ratio [HR] = 1.98, CI 1.39-2.82, p = 0.0001) with the most significant hazard noted at PCI >14 (HR = 2.35, CI 1.52-3.63, p = 0.0001). Incomplete resection (R2) had significantly worse OS compared with complete CRS 33.4 (n = 206) vs R2: 12.7 months (n = 139; p < 0.0001. When stratified by PCI for the R0/R1 group, median OS for PCI less than 10, 10 to 15, and greater than 15 was 38.2, 19.7, and 22.2 m, respectively (p = 0.0007 comparing PCI less than 10 and greater than 15). Ten-year increments-1991 through 2000, 2001 through 2010, 2011 through 2020-revealed improvement in median OS (13.4 [n = 66], 19.3 [n = 139], and 29.1 months [n = 140]). However, by resection status, median OS remained stable for R0/R1 (32.3 [n = 23], 31.1 [n = 76], and 34.1 months [n = 107]) and improved for R2 (5.2 [n = 43], 14.4 [n = 63], and 14.6 months [n = 33]). Clavien-Dindo complication rate (greater than or equal to grade III) was 29.4%.
Conclusion:
CRS improves outcomes for CRC-PC compared with historic outcomes with nonoperative management. This benefit is greatest with complete resection and lower disease burden. Results of CRS (with or without heated intraperitoneal chemotherapy) are improving, and surgery for CRC-PC should be routinely considered.
Background
Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization.MethodsA critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed.ResultsThe preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging.Conclusions
Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.
Introduction
The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.
Materials and methods
CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.
Results
The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.
Conclusion
The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.
The aim is to evaluate the feasibility and the prognosis of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for resectable peritoneal metastases (RPM) in elderly patients. Patients who underwent CRS with HIPEC for RPM between 2012 and 2018 in one tertiary reference center were retrospectively included and divided according to the age: Group A (< 65 years) and Group B (≥ 65 years). Postoperative outcomes and survivals were compared. Ninety-five patients were included in Groups A (n = 65) and B (n = 30). The incidence of comorbidities was significantly higher in elderly patients (65 vs 90%, p = 0.01), but RPM characteristics were similar between groups. There was no difference between groups in terms of postoperative results: 30-day major morbidity (33 vs 23%, p = 0.4), 30-day mortality (0 vs 3%, p = 0.3), mean length of stay (26.7 ± 19.4 vs 22.4 ± 10.3 days, p = 0.3) and readmission's rate (15 vs 33%, p = 0.06). The only one significant difference was the 90-day mortality which never occurred before 65 years but in 10% of elderly patients (p = 0.03). There was no difference regarding recurrence's rate (56 vs 37%, p = 0.1), neither 1-, 3- and 5-year overall survival rates (86, 64 and 52% vs 85, 74% and not reached, p = 0.8) and disease-free survival rates (61, 28 and 28% vs 56, 45% and not reached, p = 0.6). CRS with HIPEC is feasible in elderly patients. Since the 90-day mortality appeared to be higher in elderly patients, additional criteria are necessary to improve the selection of elderly patients for this major surgery.
Background
The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone.
Methods
We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18–70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m ²) or open (460 mg/m ²) abdomen techniques, and systemic chemotherapy (400 mg/m ² fluorouracil and 20 mg/m ² folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed.
Findings
Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0–77·1), median overall survival was 41·7 months (95% CI 36·2–53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1–49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63–1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).
Interpretation
Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.
Funding
Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.
Background
Women 65 years of age or older with epithelial ovarian cancer (EOC) are thought to have a worse prognosis than younger patients. However, no consensus exists concerning the best treatment for ovarian cancer in this age group. This report presents outcomes for patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA prospective database of EOC patients treated with CRS/HIPEC (1998–2019) was analyzed. Perioperative variables were compared by treatment including upfront CRS/HIPEC, neoadjuvant chemotherapy plus CRS/HIPEC (NACT + CRS/HIPEC), and salvage CRS/HIPEC, and by age at surgery (< 65 and ≥ 65 years). Survival analysis was performed, and outcomes were compared.ResultsOf the 148 patients identified, 42 received upfront CRS/HIPEC, 48 received NACT + CRS/HIPEC, and 58 received salvage CRS/HIPEC. Each group was subdivided by age groups (< 65 and ≥ 65 years). The median overall survival (OS) after the upfront CRS/HIPEC was 69.2 months for the patients < 65 years of age versus 69.3 months for those ≥ 65 years of age. The OS after NACT + CRS/HIPEC was 26.9 months for the patients < 65 years of age versus 32.9 months for those ≥ 65 years of age, and the OS after salvage CRS/HIPEC was 45.6 months for the patients < 65 years of age versus 23.9 months for those ≥ 65 years of age. The median progression-free survival (PFS) after upfront CRS/HIPEC was 41.3 months for the patients < 65 years of age versus 45.4 months for those ≥ 65 years of age. The PFS after NACT + CRS/HIPEC was 16.2 months for the patients < 65 years of age versus 11.2 months for those ≥ 65 years of age, and the PFS after salvage CRS/HIPEC was 18.7 months for the patients < 65 years of age versus 10 months for those ≥ 65 years of age. The median follow-up period for the entire cohort was 44.6 months [95% confidence interval (CI) 34.7–60.6 months].Conclusion
Age and feasibility of complete cytoreduction should be considered when treatment methods are selected for elderly patients. A carefully selected elderly population can benefit significantly from aggressive treatment methods.
Background:
Whether cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is safe and worthwhile for elderly patients remains unclear. This meta-analysis of outcomes after CRS plus HIPEC for the elderly aimed to generate a higher level of evidence and precise indications for these patients.
Methods:
A systematic literature search for studies reporting postoperative outcomes after CRS plus HIPEC for elderly patients was performed in the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Knowledge Conference Proceedings Citation Index-Science, and Google Scholar databases. The included studies evaluated the overall 30-day postoperative morbidity, 90-day postoperative mortality, grade 3 or higher postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay.
Results:
The inclusion criteria were met by 13 retrospective studies involving 2544 patients. Considering only comparative studies, the 90-day postoperative mortality was significantly increased for elderly patients [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.88; I 2 = 79%]. The 30-day grade 3 or higher postoperative morbidity was increased in the patients 70 years of age or older (14.5%; 95% CI 8.1-24.4 vs. 32.3%; 95% CI 22.4-44.0%; p = 0.004; I 2 = 85%). The overall 30-day postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay were not affected by age.
Conclusions:
Treatment of the elderly with CRS plus HIPEC was associated with increased severe postoperative morbidity and mortality. However, these conclusions should be weighted given the existence of major biases in the included studies. Age alone probably would not be a formal contraindication, but frailty should be taken into account. Further prospective studies are needed.
Improved oncological outcomes after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in highly selected patients have been well documented. The extensive nature of the procedure adversely affects quality of life (QoL). The aim of this study is to longitudinally evaluate QoL following CRS/HIPEC. This is a retrospective review of a prospectively maintained database of patients with peritoneal malignancies undergoing CRS/HIPEC. Clinicopathological data, oncologic outcomes, and QoL were analyzed preoperatively and postoperatively at 2 weeks, and 1, 3, 6, and 12 months. The Functional Assessment of Cancer Therapy-Colorectal instrument was used to determine changes in QoL after CRS/HIPEC and the impact of early recurrence (<12 months) on QoL. Thirty-six patients underwent CRS/HIPEC over 36 months. The median peritoneal cancer index score was 18 and the completeness of cytoreduction-0/1 rate was 97.2 per cent. Postoperative major morbidity was 16.7 per cent with one perioperative death. Disease-free survival was 12.6 months in patients with high-grade tumors versus 31.0 months in those with low-grade tumors (P = 0.03). QoL decreased postoperatively and improved to baseline in six months. Patients with early recurrence had a decrease in global QoL compared with preoperative QoL at 6 (P < 0.03) and 12 months (P < 0.05). This correlation was not found in patients who had not recurred. Patients who undergo CRS/HIPEC have a decrease in QoL that plateaus in 3 to 6 months. Early recurrence adversely impacts QoL at 6 and 12 months. This study emphasizes the importance of patient selection for CRS/HIPEC. The expected QoL trajectory in patients at risk for early recurrence must be carefully weighed against the potential oncological benefit of CRS/HIPEC.
Background:
Patients with peritoneal metastatic colorectal cancer have reduced overall survival compared with patients with metastatic colorectal cancer without peritoneal involvement. Here we further investigated the effect of the number and location of metastases in patients receiving first-line systemic chemotherapy.
Methods:
We analysed individual patient data for previously untreated patients enrolled in 14 phase 3 randomised trials done between 1997 and 2008. Trials were included if protocols explicitly pre-specified and solicited for patients with peritoneal involvement in the trial data collection process or had done a formal peritoneum-focused review of individual pre-treatment scans. We used stratified multivariable Cox models to assess the prognostic associations of peritoneal metastatic colorectal cancer with overall survival and progression-free survival, adjusting for other key clinical-pathological factors (age, sex, Eastern Cooperative Oncology Group (ECOG) performance score, primary tumour location [colon vs rectum], previous treatment, and baseline BMI). The primary endpoint was difference in overall survival between populations with and without peritoneal metastases.
Findings:
Individual patient data were available for 10 553 patients. 9178 (87%) of 10 553 patients had non-peritoneal metastatic colorectal cancer (4385 with one site of metastasis, 4793 with two or more sites of metastasis), 194 (2%) patients had isolated peritoneal metastatic colorectal cancer, and 1181 (11%) had peritoneal metastatic colorectal cancer and other organ involvement. These groups were similar in age, ethnic origin, and use of targeted treatment. Patients with peritoneal metastatic colorectal cancer were more likely than those with non-peritoneal metastatic colorectal cancer to be women (565 [41%] of 1371 vs 3312 [36%] of 9169 patients; p=0·0003), have colon primary tumours (1116 [84%] of 1334 patients vs 5603 [66%]; p<0·0001), and have performance status of 2 (136 [10%] vs 521 [6%]; p<0·0001). We recorded a higher proportion of patients with mutated BRAF in patients with peritoneal-only (eight [18%] of 44 patients with available data) and peritoneal metastatic colorectal cancer with other sites of metastasis (34 [12%] of 289), compared with patients with non-peritoneal metastatic colorectal cancer (194 [9%] of 2230; p=0·028 comparing the three groups). Overall survival (adjusted HR 0·75, 95% CI 0·63-0·91; p=0·003) was better in patients with isolated non-peritoneal sites than in those with isolated peritoneal metastatic colorectal cancer. Overall survival of patients with two of more non-peritoneal sites of metastasis (adjusted HR 1·04, 95% CI 0·86-1·25, p=0.69) and those with peritoneal metastatic colorectal cancer plus one other site of metastasis (adjusted HR 1·10, 95% CI 0·89-1·37, p=0·37) was similar to those with isolated peritoneal metastases. Compared with patients with isolated peritoneal metastases, those with peritoneal metastases and two or more additional sites of metastasis had the shortest survival (adjusted HR 1·40; CI 1·14-1·71; p=0·0011).
Interpretation:
Patients with peritoneal metastatic colorectal cancer have significantly shorter overall survival than those with other isolated sites of metastases. In patients with several sites of metastasis, poor survival is a function of both increased number of metastatic sites and peritoneal involvement. The pattern of metastasis and in particular, peritoneal involvement, results in prognostic heterogeneity of metastatic colorectal cancer.
Funding:
None.
The optimal treatment for peritoneal carcinomatosis (PC) of colorectal origin is a combination of cytoreductive surgery and intraperitoneal chemotherapy (CRS + IPC). Although 5-year survival rates of up to 40% have been reported, recurrent disease remains common and is estimated to be a strong negative prognostic factor for survival. This systematic review elaborates on the incidence of recurrent disease and the possibilities to prevent and treat recurrence.
Two searches were performed. To identify the magnitude of recurrent the disease, a search was performed in Pubmed and EMBASE until September 2014. A second search was performed in Pubmed to identify treatment of recurrent disease with secondary CRS + IPC.
The first search resulted in 139 and 94 articles in Pubmed and EMBASE respectively. Among those, 28 were included. Overall recurrence rates ranged from 22.5 to 82%. Local, systemic and combined local-systemic recurrence ranged from 6 to 42.5%, 10.4-43% and 5.8-21.5%. Median time to recurrence varied from 9 to 23 months, three-year disease free survival ranged from 14 to 41.5%. The second search resulted in 140 articles among which 17 met the inclusion criteria. A total of 190 patients underwent secondary CRS. Median survival after the second procedure ranged from 18 to 55.7 months. One, two and three-year survival ranged between 66 and 94, 44-50 and 0-66%.
Recurrence is very common after cytoreductive surgery and intraperitoneal chemotherapy for PC of colorectal origin. Repeat cytoreductive surgery suggests a potential survival benefit for a highly selected group. Therefore, strategies to prevent recurrence are of the utmost importance.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Inferior outcomes in younger patients with colorectal cancer may be associated with multiple factors, including tumor biology, delayed diagnosis, disparities such as access to care, and/or treatment differences.
This study aims to examine age-based colorectal cancer outcomes in an equal-access health care system.
This study is a retrospective large multi-institutional database analysis.
Patients with colorectal cancer included in the Department of Defense Automated Central Tumor Registry (January 1993 to December 2008) were stratified by age <40, 40 to 49, 50 to 79, and ≥80 years to determine the effect of age on incidence, treatment, and outcomes.
The primary outcomes measured were the stage at presentation, adjuvant therapy use, 3- and 5-year disease-free survival, and overall survival.
Some 7948 patients were identified; most (77%) patients were in the 50- to 79-year age group. Overall, 25% presented with stage III disease. Compared with patients aged 50 to 79 and ≥80 years, patients aged <40 and 40 to 49 years presented more frequently with advanced disease (stage III (35% and 35% vs 28% and 26%) and stage IV (24% and 21% vs 18% and 15%); all p < 0.001). Adjuvant chemotherapy use in stage III patients was 62%; those patients ≥80 and 50 to 79 years had decreased use (p < 0.001). Overall recurrence was 8.1% at 3 years and 9.7% at 5 years, with the highest rates in patients <40 years (11.8%; p = 0.007). Overall survival was worse in patients ≥80 years, whereas the remaining cohorts were similar. For stage III disease, patients 40 to 49 years had the highest survival among all cohorts (p < 0.001).
This study was limited by the lack of specific comorbid information and the limitations inherent to large database reviews.
In an equal-access system, young age at presentation (<50 years) was associated with advanced stage and higher recurrence of colorectal cancer, but similar survival in comparison with older patients. Although increased adjuvant therapy use in younger patients may partially account for stage-specific increases in survival, the relative decreased chemotherapy use overall requires further evaluation.
A new therapeutic approach to treat colorectal peritoneal carcinomatosis (PC) is becoming increasingly popular. Its main principle is to treat the macroscopic (visible) malignant peritoneal disease with complete cytoreductive surgery and, immediately after, to treat the remaining microscopic (non visible) malignant peritoneal disease with hyperthermic intraperitoneal chemotherapy (HIPEC). This combined treatment has become the gold standard approach when feasible. It is associated with good oncologic results, considering a 5-year survival rate close to 40% when complete cytoreductive surgery is achieved, and acceptable surgical results, considering a postoperative mortality rate ranging from 3 to 5% and a postoperative morbidity rate ranging from 30 to 50%. The exact effects of each steps of this combined treatment are currently unknown; therefore a randomized controlled trial is on going evaluating the real impact of HIPEC by itself (randomization with or without HIPEC after a complete cytoreductive surgery). One of the future indications of this combined approach might be its use in the very early development of PC. Indeed, early PC is currently only detectable and treatable during a second-look surgery, as recently demonstrated in high-risk patients. A trial is currently comparing the oncologic benefits of this second-look approach with HIPEC to the usual simple survey in patients with a high risk to develop PC.
Although cancer surgery has been of great benefit to patients with large bowel cancer, a flaw that has caused the death of countless patients has gone unrecognized. Although surgeons have dealt successfully with the primary tumor, they have neglected to treat microscopic residual disease. Persistent cancer cells within the abdomen and pelvis are responsible for the death of 30-50% of the patients who die with this disease and for quality of life consequences that result from intestinal obstruction caused by cancer recurrence at the resected site and on peritoneal surfaces. New surgical techniques for large bowel cancer resection minimize the surgery-induced microscopic residual disease that may result from surgical trauma. New developments in exposure, hemostasis, adequate lymphadenectomy, and qualitatively superior margins of excision have occurred. Clinical data show that a 40% improvement in survival with an optimization of surgical technique is possible. Not only should the surgical event for primary colon and rectal cancer be optimized, but also the successful treatment of peritoneal carcinomatosis should be pursued. Resected site disease and peritoneal carcinomatosis can be prevented through the use of perioperative intraperitoneal chemotherapy in patients at high risk of persistent microscopic residual disease. These are patients with perforated cancer, positive peritoneal cytology, ovarian involvement, tumor spill during surgery, and adjacent organ involvement. Patients with established peritoneal carcinomatosis can be salvaged with an approximate 50% long-term survival rate if the timely use of peritonectomy procedures, intraperitoneal chemotherapy, and knowledgeable patient selection are utilized. Peritonectomy procedures allow the removal of all visible peritoneal carcinomatosis with acceptable surgical morbidity (25%) and mortality (1.5%) rates. Heated intraoperative intraperitoneal chemotherapy using mitomycin C, in addition to early postoperative intraperitoneal 5-fluorouracil, can eradicate microscopic residual disease in the majority of patients. The peritoneal cancer index, which quantitates colon cancer peritoneal carcinomatosis by distribution and by lesion size, must be used in the selection of patients who may benefit from these advanced oncologic surgical treatment strategies. The completeness of the cytoreduction score is the most powerful prognostic indicator in this group of patients. The surgeon must be aware that there are no long-term survivors unless complete cytoreduction occurs. With a combination of proper techniques for the resection of primary disease, peritonectomy procedures for the removal of all visible peritoneal implants, intraoperative and early postoperative chemotherapy for the eradication of microscopic residual disease, and quantitative tools for proper patient selection, one can optimize the surgical treatment of patients with large bowel cancer.
After treatment of peritoneal carcinomatosis of colorectal cancer origin by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC), recurrences develop in approximately 80% of patients. This study evaluates the outcome of such recurrences after initial treatment by cytoreduction and HIPEC.
Between November 1995 and May 2003, 106 patients underwent cytoreduction and HIPEC. The progression-free interval, the location of the recurrence, and its treatment were recorded. Factors potentially related to survival after recurrences were studied.
Sixty-nine patients had a recurrence within the study period. For patients who had undergone a gross incomplete initial cytoreduction, the median duration of survival after recurrence was 3.7 months (standard error of the mean [SE], .3). If a complete cytoreduction had been accomplished initially, the median duration of survival after the recurrence was 11.1 months (SE, .9). A shorter interval between HIPEC and recurrence was associated with shorter survival after treatment of recurrence (hazard ratio, .94; SE, .02). After effective initial treatment, a second surgical debulking for recurrent disease resulted in a median survival duration of 10.3 months (SE, 1.9), and after treatment with chemotherapy it was 8.5 months (SE, 1.6). The survival was 11.2 months (SE, .5) for patients who received radiotherapy for recurrent disease. Patients who did not receive further treatment survived 1.9 months (SE, .3).
Treatment of recurrence after cytoreduction and HIPEC is often feasible and seems worthwhile in selected patients. Selection should be based mainly on the completeness of initial cytoreduction and the interval between HIPEC and recurrence.
The aim of this study was to analyze the anatomic distribution, timing, and outcomes of recurrent disease after complete cytoreduction and perioperative intraperitoneal chemotherapy (PIC) for peritoneal carcinomatosis of colorectal origin.
Data regarding all patients who underwent complete cytoreduction and PIC for carcinomatosis from colorectal cancer were extracted from a prospectively collected database. The information regarding recurrent disease found on diagnostic evaluation and/or abdominal exploration was analyzed.
Seventy patients underwent complete cytoreduction and perioperative intraperitoneal chemotherapy, and 49 of them had documented recurrent disease. The median time to progression for these 49 patients was 9 months while their median survival was 30 months. Eighteen patients had a localized intra-abdominal recurrence, 10 had diffuse intraperitoneal recurrence, 10 had isolated distant metastases, and 11 had a combination of distant metastases and intra-abdominal recurrence. There was a statistically significant difference in survival for patients with different patterns of recurrence (P = .012). Twenty-six patients underwent a second operation. The median survival of these patients was significantly longer than that of patients who did not have a second operation (39 vs 20 months, P = .0003). Four of the 49 patients with recurrences were still alive at the time of last follow-up, and three of them have no evidence of disease 73, 96, and 206 months after the diagnosis of recurrence.
Recurrence is a frequent event after optimal cytoreduction and PIC for carcinomatosis from colorectal cancer. Surgical treatment for a selected group of patients with recurrent disease may result in long-term survival.