BACKGROUND: The Stockholm I and II randomised trials demonstrated the value of preoperative radiotherapy in preventing local recurrence in rectal cancer. This, study investigated the potential for further improvement by introduction of the concept of total mesorectal excision (TME) to surgeons in Stockholm, Sweden. METHODS: Workshops started in 1994 and included 11 television-based demonstrations and two histopathology sessions. The study population consisted of all patients who underwent abdominal operations for rectal cancer in Stockholm County during 1995-96 (TME project; n=447). Outcomes at 2 years were compared with those from the Stockholm I (n=790) and II (n=542) trials as historical controls. FINDINGS: For patients with curative abdominal resections, there were no differences between the Stockholm I (n=686), Stockholm II (n=481), and TME project (n=381) groups in 30-day mortality (30 [4%], six [1%], and 12 [3%]), anastomotic leakage (27 [10%], 18 [9%], and 23 [9%]), or all complications (204 [30%], 169 [35%], and 134 [35%]). This similarity was achieved despite a decrease in the proportion of abdominoperineal procedures from 55-60% to 27%. Local recurrence occurred in significantly fewer of the TME group than of the Stockholm I and II groups (21 [6%] vs 103 [15%] and 66 [14%], p
Preoperative irradiation with 5 × 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer.
The aim of this study was to determine whether the same favorable effects could be observed in a population-based study.
This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry.
This study examined population-based data from Sweden.
All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry.
Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm).
Five-year cumulative local recurrence and survival rates.
The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors.
In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).
To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma.
Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and "elective" where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1--8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38--60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3--5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10--165 months).
Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery).
The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.
OBJECTIVE: To find out whether short-term high-dose preoperative radiotherapy can reduce local recurrence rate without increasing postoperative mortality in patients with resectable rectal cancer. DESIGN: Randomised trial. SETTING: Nationwide Swedish multicentre trial. SUBJECTS: From March 1987 to February 1990, 1168 patients were randomised. In each group, 454 patients had curative surgery. INTERVENTIONS: Patients were allocated to preoperative irradiation (25 Gy in five fractions in one week) followed by operation within a week, or to surgery alone. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality, and local recurrence rate. RESULTS: After a minimum follow-up of two years, 9% (51/553) of the patients in the irradiated group who had had the tumour resected had developed a local recurrence, compared with 24% (131/557) in the surgery alone group (p
A randomized, multicenter clinical trial was conducted in Western Norway to study the effectiveness of preoperative radiation therapy in operable rectal cancer, given at a dosage of 3150 cGy in 18 fractions, 2 to 3 weeks before radical surgery. Three hundred nine patients were entered into the trial between May 1976 and December 1985. After radiation no tumor was seen in 4.5% of the patients. There was no increased morbidity or mortality at surgery. The 5-year survival for evaluable patients was 57.5% in the control group and 56.7% in the radiotherapy group. For patients operated on for cure the 5-year survival was 60.9% and 64.2% in the control group and radiotherapy group, respectively. Radiation significantly delayed both local and distant recurrences in patients in the radiation group who had curative resection from 13.3 months in controls to 27.1 months. The local recurrence rate in the corresponding groups was 21.1% and 13.7%, respectively. We conclude that higher preoperative radiation doses should be used in new trials as a higher dosage may transform the observed positive effects into a survival benefit.
The search for improved disease control and survival for resectable but high-risk rectal cancers has led to studies that combine all 3 modalities. For surgically resected, high-risk rectal cancers, postoperative chemoradiation has been shown to improve both disease control (local and distant) and survival (disease free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health Colorectal Cancer Consensus Conference. Three randomized studies showed improved overall survival (OS) and local control for patients treated with postoperative irradiation and chemotherapy when compared with surgery alone or surgery plus irradiation control arms. These include 2 US trials, Gastrointestinal Tumor Study Group and Mayo/North Central Cancer Treatment Group (NCCTG) and a Norway trial. Although most preoperative external beam radiation trials show reductions in local relapse with the addition of preoperative EBRT to resection, only the large Swedish trial of approximately 1,100 patients showed a survival improvement when compared with a surgery alone control arm for resectable primary rectal cancers. In a recent pooled analysis of 3 postoperative adjuvant rectal cancer trials (NCCTG 794751, NCCTG 864751, and GI Intergroup 0114) survival and disease relapse were dependent on both TN and NT stage of disease (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more positive nodes), T substage influenced 5-year OS (T1-2, 69%; T3, 48%; and T4, 38%; P
To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management.
National, population-based, prospective registry data were used, including comprehensive 5-year follow up of 3783 patients operated on in the period 1998-2000. Local recurrence rates were compared using crude rate, Kaplan-Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed.
The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (= 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining = 1.0%) and some aspects of surgical strategy were also observed.
We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue.
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective studies and 17 other articles were used. A total of 131 scientific articles are included, involving 25 351 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized thus: The results after rectal cancer surgery have improved during the past decade. It is likely that local failure rates after 5 years of follow-up at hospitals adopting the TME-concept (TME = total mesorectal excision) have decreased from about 28% to 10-15%. Preoperative radiotherapy at biological effective doses above 30 Gy decreases the relative risk of a local failure by more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40% at doses that generally are higher than those used preoperatively. There is strong evidence that preoperative radiotherapy is more effective than postoperative. There is moderate evidence that preoperative radiotherapy significantly decreases the local failure rate (from 8% to 2% after 2 years) also with TME. There is strong evidence that preoperative radiotherapy improves survival (by about 10%). There is no evidence that postoperative radiotherapy improves survival. There is some indication that survival is prolonged when postoperative radiotherapy is combined with concomitant chemotherapy. Preoperative radiotherapy at adequate doses can be given with low acute toxicity. Higher, and unacceptable acute toxicity has been seen in some preoperative radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can also be given with acceptable acute toxicity. The long-term consequences of radiotherapy appear to be limited with adequate radiation techniques, although they have been less extensively studied. Longer follow-up periods are needed before firm conclusions can be drawn. Peroperative radiotherapy, preferably preoperative since it is more effective, is routinely recommended for most patients with rectal cancer since it can substantially decrease the risk of a local failure and increases survival. In a primarily non-resectable tumour, preoperative radiotherapy can cause tumour regression allowing subsequent radical surgery. This therapy is routinely indicated. Whether radiochemotherapy is more efficient than radiotherapy alone is not clear, since the results of four small randomized trials are partly conflicting. Preoperative radiotherapy, frequently combined with chemotherapy, has been used to increase the chances of sphincter-preserving surgery in low-lying tumours. The literature is inconclusive with respect to how frequently this occurs. Radiotherapy frequently produces symptom relief in patients with rectal cancer not amendable to surgery.
To determine if transanal local excision (TALE) of selected early low rectal cancer is an effective alternative to more radical resection and to determine the need for adjuvant radiotherapy in these patients.
A retrospective analysis of all 47 cases referred for consideration of radiotherapy after TALE for low rectal cancer.
Indications for TALE were elective, 32; concurrent medical problems, 11; and refusal of radical resection, 4. Median follow-up was 52 months. Local recurrence occurred in 7 of 27 T1 cases, 5 of 17 T2, and 2 of 3 T3. Three of 23 irradiated patients developed local recurrence, compared with 11 of 24 unirradiated (P = 0.023). Of 28 cases with favorable histological features, 1 of 13 irradiated patients developed local recurrence, compared with 4 of 16 unirradiated (P = 0.22). Seven patients had salvage resection, and 3 of these are alive with no evidence of disease at 21, 39, and 71 months postsalvage. Recurrence-free survival at 5 years was 81 % in the irradiated patients and 52% in the unirradiated (P = 0.025).
Transanal local excision of selected low rectal cancers, combined with adjuvant radiotherapy, results in a low recurrence rate and is, therefore, an effective alternative to more radical resection.