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Treatment results of colorectal cancer--10-years series of UMC Ljubljana (1991 - 2000)
Abstract
Unlabelled:
In Slovenia the incidence of colorectal cancer is growing rapidly. In 1998 1022 new cases were registered. Our study compares results of two groups of patients with colorectal cancer. Patients and methods. In the period from 1.1.1991 to 31.12.2000 1478 patients with a colorectal carcinoma underwent potentially curative resection. We divided them in two groups, one operated in the first 5-years and second in later 5-years period. 5-years survival was estimated with Kaplan-Meier statistical analysis. Patients who died within 30 days after the operation were censored. Differences in survival curves between both groups were assessed by the log rank test.
Results:
We resected 1478 /1599 (92,4%) patients. There was 913 (61,7%) patients resected with colon cancer and 528 (35,8%) with rectal cancer and 37 (2,5%) with sinhronius tumors. R0 resection was performed in 1174 (79,4%) patients, R1 in 29 (2,0%), and R2 in 273 (18,5%) patients. Postoperative mortality rate in resected patients was 5,48% (81/1478), in the group with paliative operations was 17,35% (21/121). Overall five-years survival rate was 54,9% (56,18% for colon cancer and 52,4% for rectal cancer Five-years survival rate for the patients with radical resection (R0) was 66,54% for colon cancer and 59,47% for rectal cancer.
Conclusion:
5-years survival for R0-resected patients with colon cancer was in the last period from 1996 to 2000 statistically significantly better compared with the period from 1991 to 1995 (76% vs 60%) in stage I (p = 0,04048) and in stage III (p = 0,01842). 5-years survival for R0-resected patients with rectal cancer was significantly better in the same period (63% vs 55%) (p = 0,03627) in stage III (p = 0,01663).
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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.
Rectal cancer surgery has been characterized by a high incidence of local recurrence, an occurrence which influences survival negatively. In Norway there was a growing recognition that local recurrence rates were related to surgeon performance and that surgeons applying a standardized surgical technique in the form of total mesorectal excision could achieve better results. This contrasts with the prevailing argument voiced by many opinion leaders that local recurrence rates and possibly survival rates can only be improved by adjuvant or neoadjuvant treatment strategies. The Norwegian Rectal Cancer Project-initiated in 1993-aimed at improving the outcome of patients with rectal cancer by implementing total mesorectal excision as the standard rectal resection technique.
This observational national cohort study covers all new patients (3,319) with rectal cancer from a population of 4.5 million treated between November 1993 and August 1997. The main outcome measures were local recurrence, survival, and postoperative mortality and morbidity rates. The technique of total mesorectal excision was compared with conventional surgery.
The proportion of patients undergoing total mesorectal excision was 78 percent in 1994, increasing to 92 percent in 1997. The observed local recurrence rate for patients undergoing a curative resection was 6 percent in the group treated by total mesorectal excision and 12 percent in the conventional surgery group. Four-year survival rate was 73 percent after total mesorectal excision and 60 percent after conventional surgery. Postoperative mortality rate was 3 percent and the anastomotic dehiscence rate was 10 percent. Radiotherapy was given to 5 percent and chemotherapy to 3 percent of the patients in the curative resection group.
A refinement of the surgical resection technique for rectal cancer can be achieved on a national level, the technique of total mesorectal excision can be widely distributed, and surgery alone can give good results.
Background Adjuvant radiotherapy for rectal cancer has been extensively studied, but no trial has unequivocally demonstrated improved overall survival with radiotherapy, despite a reduction in the rate of local recurrence. Methods Between March 1987 and February 1990, we randomly assigned 1168 patients younger than 80 years of age who had resectable rectal cancer to undergo preoperative irradiation (25 Gy delivered in five fractions in one week) followed by surgery within one week or to have surgery alone. Results The irradiation did not increase postoperative mortality. After five years of follow-up, the rate of local recurrence was 11 percent (63 of 553 patients) in the group that received radiotherapy before surgery and 27 percent (150 of 557) in the group treated with surgery alone (P<0.001). This difference was found in all subgroups defined according to Dukes' stage. The overall five-year survival rate was 58 percent in the radiotherapy-plus-surgery group and 48 percent in the surgery-alone group (P=0.004). The cancer-specific survival rates at nine years among patients treated with curative resection were 74 percent and 65 percent, respectively (P=0.002). Conclusions A short-term regimen of high-dose preoperative radiotherapy reduces rates of local recurrence and improves survival among patients with resectable rectal cancer. (C) 1997, Massachusetts Medical Society.
Background
Adjuvant radiotherapy for rectal cancer has been extensively studied, but no trial has unequivocally demonstrated improved overall survival with radiotherapy, despite a reduction in the rate of local recurrence.
Methods
Between March 1987 and February 1990, we randomly assigned 1168 patients younger than 80 years of age who had resectable rectal cancer to undergo preoperative irradiation (25 Gy delivered in five fractions in one week) followed by surgery within one week or to have surgery alone.
Results
The irradiation did not increase postoperative mortality. After five years of follow-up, the rate of local recurrence was 11 percent (63 of 553 patients) in the group that received radiotherapy before surgery and 27 percent (150 of 557) in the group treated with surgery alone (P<0.001). This difference was found in all subgroups defined according to Dukes' stage. The overall five-year survival rate was 58 percent in the radiotherapy-plus-surgery group and 48 percent in the surgery-alone group (P = 0.004). The cancer-specific survival rates at nine years among patients treated with curative resection were 74 percent and 65 percent, respectively (P = 0.002).
Conclusions
A short-term regimen of high-dose preoperative radiotherapy reduces rates of local recurrence and improves survival among patients with resectable rectal cancer.
BACKGROUND: The incidence of colorectal cancer has been rapidly increasing during the last decades. It represents the third
most common cancer in Slovenia. METHODS: In 1998, the incidence of colon cancer increased to 31.3 per 100,000 in men and to
25.8 per 100,000 in women, and the incidence of rectal cancer to 23.5 per 100,000 in men and to 13.1 per 100,000 in women.
By a national cancer registry, incidence and follow-up are assessed. RESULTS: An insight into the operative treatment of patients
with colorectal cancer in Slovenia was gained through surveys conducted in Slovenian hospitals between 1995 and 2000. CONCLUSIONS:
Nationwide outcomes of treatment remain lower than those in other countries. However, there are centers in Slovenia achieving
results in keeping with outcome reported from leading centers in Europe.
GRUNDLAGEN: Bei rasch zunehmender Inzidenz zählen die bösartigen Erkrankungen des Dick- und Enddarmes zu den dritthäufigsten
malignen Erkrankungen in Slowenien. METHODIK: Im Jahr 1998 stieg die Inzidenz von Dickdarmkrebs auf 31,3 je 100.000 bei Männern
und auf 25,8 je 100.000 bei Frauen, von Enddarmkrebs auf 23,5 je 100.000 bei Männern und auf 13,1 je 100.000 bei Frauen. Inzidenz
und Behandlungsergebnisse wurden in einem nationalen Krebsregister dokumentiert. ERGEBNISSE: Operative Behandlungsstrategien
von Patienten mit Dick- und Enddarmkrebs wurden durch eine Umfrage an slowenischen Krankenhäusern im Jahr 1995 und 2000 erhoben.
SCHLUSSFOLGERUNGEN: Im internationalen Vergleich sind die Behandlungsergebnisse beim kolorektalen Karzinom unbefriedigend.
Trotzdem erzielen einzelne Zentren Ergebnisse, die mit führenden europäischen Institutionen zu vergleichen sind.
The American Cancer Society, the National Cancer Institute (NCI), and the Centers for Disease Control and Prevention including the National Center for Health Statistics (NCHS) agreed to produce together an annual "Report Card" to the nation on progress related to cancer prevention and control in the U.S.
This report provides average annual percent changes in incidence and mortality during 1973-1990 and 1990-1995, plus age-adjusted cancer incidence and death rates for whites, blacks, Asians and Pacific Islanders, and Hispanics. Information on newly diagnosed cancer cases is based on data collected by NCI, and information on cancer deaths is based on underlying causes of death as reported to NCHS.
For all sites combined, cancer incidence rates decreased on average 0.7% per year during 1990-1995 (P > 0.05), in contrast to an increasing trend in earlier years. Among the ten leading cancer incidence sites, a similar reversal in trends was apparent for the cancers of the lung, prostate, colon/rectum, urinary bladder, and leukemia; female breast cancer incidence rates increased significantly during 1973-1990 but were level during 1990-1995. Cancer death rates for all sites combined decreased on average 0.5% per year during 1990-1995 (P < 0.05) after significantly increasing 0.4% per year during 1973-1990. Death rates for the four major cancers (lung, female breast, prostate, and colon/rectum) decreased significantly during 1990-1995.
These apparent successes are encouraging and signal the need to maximize cancer control efforts in the future so that even greater in-roads in reducing the cancer burden in the population are achieved.
In order to analyse the influence of low radiation doses on human rectal adenocarcinomas, gross and microscopical changes after preoperative radiation were compared to controls treated with immediate surgery in a randomised, prospective trial. The X-ray doses given were 31.5 Gy in 3.5 weeks, and the interval between radiation and operation was 2 to 3 weeks. A total of 138 patients having preoperative radiotherapy and 131 controls were analysed. The overall tumour size was reduced after radiation. Complete tumour regression was obtained in six (4.4%) patients. All of these tumours were exophytic and mobile at the initial examination and all were either well or moderately well differentiated. A significant downstaging was found after preoperative radiation. The incidence of positive lymph nodes was 27.5% in the resected specimens in controls and 18.4% after radiation (p less than 0.05). The total number of recurrences was reduced after radiation in stage C2 tumours, but not in the other stages. Preoperative radiation did not influence the histological grade of the tumours. There was no difference between the two randomised groups with respect to 5-year survival or disease-free survival in any histopathological stage.
A retrospective review of 325 patients was undertaken to analyse whether involvement of the radial resection margin (RRM) could predict locally recurrent disease or distant metastases in patients who had curative surgery for rectal or rectosigmoid cancer. Information on the RRM was available in 253 patients. The RRM was involved in 31 (12 per cent). Nine of these 31 patients developed local recurrence (29 per cent), while only 17 local recurrences were diagnosed in 217 patients (8 per cent) without involvement of the RRM (P < 0.01). At 2 years the overall local recurrence rate was 10 per cent. Distant metastases were diagnosed in 46 patients (18 per cent) and RRM involvement was identified as a prognostic factor depending on lymph node involvement (N stage) (P = 0.02). Local recurrence and some distant metastases result from microscopically incomplete resection. Assessment of the radial depth of tumour invasion by careful histological examination of x791p4ecimen may be used for selection of patients for adjuvant radiotherapy and/or chemotherapy.
Despite early scepticism, several studies of systemic adjuvant 5-fluorouracil (5-FU)-based chemotherapy demonstrated significant benefits in high-risk colon cancer. As many clinical investigations have since been conducted in this setting, a comprehensive literature review was undertaken to clarify the role of adjuvant therapy in the treatment of colorectal cancer.
Current and future adjuvant treatment approaches in colorectal cancer were reviewed, and differences in the present-day North American and European practices were highlighted.
5-FU plus leucovorin for six months is generally considered the 'standard' adjuvant treatment in Dukes' stage C (stage II) colon cancer. Large-scale international trials of other strategies are required to provide further advances in treatment outcome. Following the lead of the USA Intergroup trials, a recently initiated cooperative effort, the Pan-European Trials in Adjuvant Colon Cancer (PETACC), may serve as a European model for such investigations. In T3 and/or lymph-node positive rectal cancer, postoperative (chemo)radiotherapy in the USA is considered the adjuvant treatment of choice. However, most European investigators have advocated for preoperative intensive short-course irradiation instead. Randomized trials in this area are ongoing. In the near future, new drugs for the treatment of colorectal cancer may lead to tailored therapies.
Historically, rectal cancer with transmural spread and/or lymph node involvement has presented a major challenge to surgeons, with a variable and often high risk of local recurrence and poor survival outcomes. In recent years a large amount of literature has focused attention on the importance of surgical technique, tumor staging, and the optimal integration of CT and radiation therapy.
This article reviews the clinical trials that have defined the current approach to rectal cancer, the controversies regarding what should be considered the standard of care, and the ongoing clinical studies that will resolve some of these issues.
The preoperative staging of rectal cancer can be improved with the use of endorectal ultrasound and (where available) magnetic resonance imaging. Careful pathologic analysis, particularly of the radial margin, provides important prognostic information that enables better allocation of postoperative care. Although both radiation therapy and CT have a proven role in adjuvant therapy, the interpretation of many studies is confounded by unacceptably poor outcomes in the control arm, and in older studies the use of inferior chemotherapy and radiation therapy techniques. Ongoing studies will better define the optimal combination and timing of chemotherapy and radiation therapy, with respect to both toxicity and survival endpoints.
A combined modality approach to rectal cancer, integrating the colon and rectal surgeon, pathologist, medical oncologist, and radiation oncologist, is necessary to achieve optimal outcomes. The achievements to date and the ongoing vigorous debates regarding standard care continue to highlight the importance of quality ongoing research in a rapidly changing clinical environment.
The objective of this study was to examine the relationship between hospital surgical volume and long-term survival in patients with a new diagnosis of colorectal cancer who underwent surgical resection during fiscal years 1991-2000 in the Veterans Affairs (VA) health-care system.
This research was a cohort study of patients admitted to all VA hospitals with a new diagnosis of colorectal cancer who underwent surgical resection between October 1990 and September 2000 and followed through September 2001. Overall 5-yr cumulative survival was calculated from Kaplan-Meier estimates, while adjusted risk of death was estimated using a Cox proportional hazards model. Adjustment was made for differences in patient characteristics including comorbidity, receipt of therapy, and year of surgery.
We identified 34,888 individuals with a new diagnosis of colorectal cancer in VA hospitals during fiscal years 1991-2000, of whom 22,633 (65%) underwent surgical resection. The majority (98.5%) were men, the mean age was 68 yr, and the two largest race/ethnic groups were whites (75%) and blacks (17%). The 5-yr cumulative survival was greater among those who received surgery in high surgical volume hospitals as defined by 25 or more procedures per year (52.1%) than among those who received surgery in low volume hospitals (48.3%). After adjusting for differences in patient characteristics, comorbidity, receipt of adjuvant therapy, and year of surgery, we found 7% and 11% increases in 5-yr survival for patients with colon and rectal cancers, respectively, who underwent surgical resection in high volume hospitals compared with those who had surgery in low volume hospitals.
Greater hospital surgical volume is an independent predictor of prolonged long-term survival following surgery for both colon and rectal cancer in the VA health-care system. The volume-long-term mortality relationship is greater for rectal than for colon cancer patients, perhaps reflecting the fact that surgery for rectal cancer is more technically demanding. Future studies are needed to discover what aspects of clinical management explain these differences.
The purpose of this study was to examine the pattern of survival for colorectal adenocarcinoma (CRC), and to investigate the prognostic factors for the disease. In the analysis, 50993 cases of CRC aged 40-84 years, diagnosed between 1958 and 1997 in Norway, were included. Esteve's relative survival method was used, together with a time trend analysis, conducted by least-squares linear regression. Cox proportional hazards regression analysis was used to examine cause-specific mortality. Five-year relative CRC survival has increased by an estimated 3% per 5-year diagnostic period. In 1958-1962, relative survival was about 40% for both males and females, and increased to 56 and 60%, respectively, in 1993-1997. Rectal cancer had a higher cause-specific mortality (RR 1.26, 95% CI 1.22-1.30) than proximal colon (reference) and distal colon (RR 0.97, 95% CI 0.93-1.00 cancers), while females had a lower cause-specific mortality than males (RR 0.88, 95% CI 0.86-0.90). The increase in the relative survival rate in Norway is probably due to improved treatments and advanced diagnostics. Norway has a higher CRC survival rate than the EUROCARE average.
The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
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