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      Colorectal cancer survival in the USA and Europe: a CONCORD high-resolution study

      1 , 1 , 2 , 2 , 3 , 3 , 4 , 5 , 6 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 1

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      Epidemiology, Public Health, Statistics & Research Methods

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          To assess the extent to which stage at diagnosis and adherence to treatment guidelines may explain the persistent differences in colorectal cancer survival between the USA and Europe.


          A high-resolution study using detailed clinical data on Dukes’ stage, diagnostic procedures, treatment and follow-up, collected directly from medical records by trained abstractors under a single protocol, with standardised quality control and central statistical analysis.

          Setting and participants

          21 population-based registries in seven US states and nine European countries provided data for random samples comprising 12 523 adults (15–99 years) diagnosed with colorectal cancer during 1996–1998.

          Outcome measures

          Logistic regression models were used to compare adherence to ‘standard care’ in the USA and Europe. Net survival and excess risk of death were estimated with flexible parametric models.


          The proportion of Dukes’ A and B tumours was similar in the USA and Europe, while that of Dukes’ C was more frequent in the USA (38% vs 21%) and of Dukes’ D more frequent in Europe (22% vs 10%). Resection with curative intent was more frequent in the USA (85% vs 75%). Elderly patients (75–99 years) were 70–90% less likely to receive radiotherapy and chemotherapy. Age-standardised 5-year net survival was similar in the USA (58%) and Northern and Western Europe (54–56%) and lowest in Eastern Europe (42%). The mean excess hazard up to 5 years after diagnosis was highest in Eastern Europe, especially among elderly patients and those with Dukes’ D tumours.


          The wide differences in colorectal cancer survival between Europe and the USA in the late 1990s are probably attributable to earlier stage and more extensive use of surgery and adjuvant treatment in the USA.

          Elderly patients with colorectal cancer received surgery, chemotherapy or radiotherapy less often than younger patients, despite evidence that they could also have benefited.

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          Most cited references 27

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          Preoperative versus postoperative chemoradiotherapy for rectal cancer.

          Postoperative chemoradiotherapy is the recommended standard therapy for patients with locally advanced rectal cancer. In recent years, encouraging results with preoperative radiotherapy have been reported. We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer. We randomly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day, five days per week, and fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy. Surgery was performed six weeks after the completion of chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil (500 mg per square meter per day) were given. Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy. The primary end point was overall survival. Four hundred twenty-one patients were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy. The overall five-year survival rates were 76 percent and 74 percent, respectively (P=0.80). The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group, as compared with 40 percent of the patients in the postoperative-treatment group (P=0.001); the corresponding rates of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01). Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, improved local control and was associated with reduced toxicity but did not improve overall survival. Copyright 2004 Massachusetts Medical Society.
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            Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.

            Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision. We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and quality-control measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques. Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001). Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.
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              Chemotherapy with preoperative radiotherapy in rectal cancer.

              Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer. We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival. We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%. In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. ( number, NCT00002523 [].). Copyright 2006 Massachusetts Medical Society.

                Author and article information

                BMJ Open
                BMJ Open
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                10 September 2013
                : 3
                : 9
                [1 ]Cancer Research UK Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine , London, UK
                [2 ]Division of Cancer Prevention and Control, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                [3 ]Côte-d'Or Digestive Cancer Registry, Faculté de Médecine , Dijon Cédex, France
                [4 ]Evaluative Epidemiology Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy
                [5 ]National Center of Epidemiology, Surveillance and Promotion of Health, National Institute of Health , Rome, Italy
                [6 ]Descriptive Studies and Health Planning Unit, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy
                [7 ]Alleanza Contro il Cancro , Rome, Italy
                [8 ]Department of Epidemiology and Biostatistics, National Institute for Health Development , Tallinn, Estonia
                [9 ]Navarra Cancer Registry, Navarra Public Health Institute , Navarra, Spain
                [10 ]CIBER Epidemiology and Public Health CIBERESP , Madrid, Spain
                [11 ]National Institute of Public Health, National Institute of Hygiene , Warszawa, Poland
                [12 ]SC Department of Health and Environmental Control, South Carolina Central Cancer Registry, Office of Public Health Statistics and Information Systems , Columbia, South Carolina, USA
                [13 ]Public Health Institute, Cancer Registry of Greater California , Sacramento, California, USA
                [14 ]Comprehensive Cancer Centre the Netherlands , Utrecht, The Netherlands
                [15 ]Rhode Island Department of Health, Rhode Island Cancer Registry , Providence, Rhode Island, USA
                [16 ]Tarragona Cancer Registry, Foundation Society for Cancer Research and Prevention, Pere Virgili Health Research Institute , Tarragona, Spain
                [17 ]Świeętokrzyskie Centrum Onkologii (Holycross Cancer Centre) , Kielce, Poland
                [18 ]Faculty of Health Sciences, Jan Kochanowski University of Humanities and Sciences in Kielce , Kielce, Poland
                [19 ]Finnish Cancer Registry, Helsinki, Finland
                [20 ]Epidemiology and Cancer Registry, Institute of Oncology Ljubljana , Ljubljana, Slovenia
                [21 ]Cracow Cancer Registry, Centre of Oncology, M Skłodowska-Curie Memorial Cancer Institute , Krakow, Poland
                [22 ]National Cancer Registry of Slovakia, National Health Information Center , Bratislava, Slovakia
                [23 ]Andalusian School of Public Health , Granada, Spain
                [24 ]CIBER Epidemiología y Salud Pública (CIBERESP) , Madrid, Spain
                [25 ]New York State Department of Health, New York State Cancer Registry , Albany, New York, USA
                [26 ]Illinois Department of Public Health, Illinois State Cancer Registry , Springfield, Illinois, USA
                [27 ]Cancer Registry and Environmental Epidemiology Division, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy
                [28 ]Cancer Registry and Histopathology Unit, Civile-MP Arezzo Hospital, ASP Ragusa , Ragusa, Italy
                [29 ]UOS Epidemiologia Descrittiva, USM-IST (IRCCS Azienda Ospedaliera Universitaria San Martino—IST Istituto Nazionale per la Ricerca sul Cancro), Largo R Benzi , Genova, Italy
                [30 ]Sez. Epidemiologia Descrittiva, Dipartimento di Scienze della Salute, Università di Genova , Genova, Italy
                [31 ]Cancer Prevention and Control Division, University of Colorado Cancer Center, Colorado School of Public Health , Aurora, Colorado, USA
                [32 ]Louisiana Tumor Registry, LSU Health Sciences Center School of Public Health , New Orleans, Louisiana, USA
                Author notes
                [Correspondence to ] Dr Claudia Allemani; claudia.allemani@
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