According to the current opinion, local excision in rectal cancer should be limited to selected T1N0 tumours. The investigators addressed the question whether preoperative radio(chemo)therapy can expand the use of this procedure for more advanced cancers. The rationale of preoperative radiotherapy is eradication of mesorectal subclinical disease. Besides, there is a correlation between radiosensitivity of rectal cancers and low cancer aggressiveness. For this reason, conversion to abdominal surgery is needed in patients with radioresistant tumour. The investigators aim to compare the short-course radiotherapy schedule with the chemoradiation in order to determine an optimal scheme. The study hypothesis is that the chemoradiation assures 25% more patients who do not require conversion to an open surgery. In addition, the aim is to asses safety and efficiency of preoperative radiotherapy and local excision for radiosensitive rectal cancer.
Primary Outcome Measures:
- The rate of patients with downstaging after radiotherapy to pathological complete response or ypT1 disease with negative margins. [ Time Frame: Surrogate endpoint available immediatly after surgery. ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- The rate of local control, overall survival and disease-free survival and toxicity. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: |
102 |
| Study Start Date: |
November 2003 |
| Estimated Study Completion Date: |
November 2013 |
| Estimated Primary Completion Date: |
November 2010 (Final data collection date for primary outcome measure) |
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1: Experimental
Preoperative radiotherapy with five fractions of 5 Gy during one week and boost 4 Gy after 1 week interval, total dose 29 Gy; after 6 weeks full-thickness local excision
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Radiation: Short course of radiotherapy
5 x 5 Gy plus boost 4 Gy
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2: Active Comparator
Radiochemotherapy with 28 fractions of 1,8 Gy plus boost 5,4 Gy in 3 fractions
+ simultaneous bolus 5-Fluorouracil and leucovorin; after 6 weeks full-thickness local excision
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Radiation: Radiochemotherapy
28 x 1,8Gy plus boost 3 x 1,8 Gy with three 2-days cycles of chemotherapy during weeks 1, 3 and 5 of irradiation (the each cycle consisted of leukovorin 20 mg/m2 per day and 10-20 minutes later of 5-fluorouracil 400 mg/m2 per day, both administrated as rapid intravenous infusion)
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Local excision must involve all tissue invaded on pretreatment examination. For this reason, 4-5 tatoos of mucosa at the tumour border should be performed before the onset of treatment. Next, the long-course radiochemotherapy or short-course radiotherapy is randomly allocated. After 6 weeks interval, the full thickness local excision should be carried out with 1 cm margin. Patients with good pathological response (complete response or downstaging to ypT1 disease)are followed up. Conversion to open surgery is offered to patients with poor pathological response (ypT2-3 or positive margin). Close follow-up is carried out in order to detect an early local recurrence either in a bowel wall or in mesorectal lymph nodes. Rescue surgery is offered in patients with local recurrence.
Purpose
