53_03_02
Treatment
Surgery
Surgery remains the mainstay of curative treatment for carcinoma of the rectum. Surgical management depends on the stage
P.1374
and location of a tumor within the rectum. Early cancers can be managed with limited surgery; however, the majority of tumors tend to present as more advanced disease and require either a low anterior resection (LAR) or abdominoperineal resection (APR). The general principles of a surgical approach remain the removal of all gross and microscopic disease with negative proximal, distal, and circumferential margins. In the case of radical resection, this means removal of the adjacent mesorectal tissue containing the regional lymphatics and the superior hemorrhoidal artery pedicle. Several studies have now shown that the surgeon's experience with resection of colorectal cancer is an independent variable in the outcome of treatment (107). The Intergroup 0114 trial found that for stage II and III rectal cancers, APR rates were not only higher in hospitals performing low volume procedures (46% vs. 32%), but also more patients had positive resection margins (111).
Historically the distal and proximal resection margins were considered important determinants in outcome. A 5-cm distal margin of normal rectum was considered necessary for adequate surgical resection (20,58,139). However, several retrospective studies have shown that distal intramural spread of tumor is rare beyond 1.5 cm, and, therefore, a 2-cm distal margin is currently considered acceptable, except in lesions that are poorly differentiated or widely metastatic (137,163,175,180). The reduced requirement of 2-cm distal margin for adequate resection has lead to a significant increase in the likelihood of sphincter preservation procedures in this disease.
Radial Margin
The National Institute of Health Consensus Conference on Rectal Cancer indicated that the principal reason for local recurrence in resected rectal cancer appears to be related to the anatomic constraints in obtaining wide radial margins, even though the proximal and distal margins appear adequate (127). Quirke et al. (140), using whole mount specimens, found that 27% (14/52) of patients had spread to the lateral radial margin, even though the margins appeared negative with standard pathological assessment. Eighty-six percent of those with positive margins developed local regional recurrence of disease as compared to only 3% without lateral resection margin involvement. The mean surgical margin of resection has been shown to decrease with increasing stage of disease ranging from 14 mm for T1 cancers to 3 mm for T4 cancers, with a corresponding increase in local recurrence from 0% to 75% (128). A positive radial margin is an independent prognostic factor for local recurrence with a hazard ratio of 12:2, and for survival with a hazard ratio of 3:2 compared to patients with clear circumferential margins (2,70).
Total Mesorectal Excision
The high local recurrence of disease following standard APR or LAR (15% to 30%) has been thought by some to be due to blunt dissection that violates the planes of the mesorectal circumference (46). Lateral spread of disease has been shown to occur not only at the level of the tumor but distally within the mesorectum as well (31). Heald et al. (74) have recommended that en bloc removal of the tumor within the envelope of the endopelvic fascia is necessary to obtain adequate lateral clearance of disease and reduce the likelihood of local recurrence. Total mesorectal excision (TME), as they described, has now become the established standard for all radical rectal cancer resections and requires sharp dissection along the plane that separates the visceral from the parietal pelvic fascia with complete en bloc removal of the rectum so that all of the rectal mesentery remains within the envelope of the specimen (98). On gross pathology, a correct TME specimen will have a bilobed encapsulated appearance with the surface looking smooth and unbroken like a lipoma. On pathological review, an adequate dissection should include 12 to 15 perirectal and pelvic lymph nodes (14,73). Careful nerve sparring dissection with TME reduces the incidence of retrograde ejaculation and postoperative impotence as compared to conventional surgery (10% to 29% instead of 25% to 75%) (71,104,158). TME, while more difficult with APR than LAR, may be associated with a somewhat higher anastomotic leak rate especially for low rectal lesions (15% to 17%) (86,87). Several series using TME surgery have reported low rates of local recurrence (4% to 7%) and an improvement in survival approaching 80% to 85% for stage II and 65% to 70% for stage III disease (9,22,45,72).
Abdominoperineal Resection
APR has been considered the gold standard for surgical resection of distal rectal cancer and requires removal of the primary tumor along with a complete proctectomy, leading to a permanent colostomy (85). Recent data suggest a decline in the rate of abdominoperineal resections being performed. APR is associated with a slightly higher morbidity and mortality than LAR and a worse quality of life related to changes in body image and depression due to the presence of a colostomy (59,177). There is also a higher risk of positive margins with APR as the mesorectum is very thin in the distal segment of the rectum and lateral margins are restricted by the close presence of the prostate in the male and vagina in females (105). The bony confines of the lower pelvis also restrict surgical access especially in males.
Low Anterior Resection
The availability of circular stapling devices has expanded the role of sphincter preservation surgical options in rectal cancers, and LARs are now being performed not just for cancers of the upper third of the rectum but also for middle and lower third cancers (95). Preserving adequate anorectal function becomes a bigger problem the more distal the level of anorectal anastomosis (183). Patients should have good anal sphincter continence prior to considering sphincter-preserving options. Patient age, pelvic anatomy, gender, and body habitus can affect suitability for sphincter preservation. A 2-cm distal margin of preserved normal rectum is considered optimal for preservation of good bowel function. In carefully selected patients a functional coloanal anastomosis can be achieved with significantly reduced margins for more distal cancers especially after neoadjuvant therapy. If LAR is planned following neoadjuvant radiation therapy, it is necessary to mobilize the splenic flexure to allow an unirradiated segment of the bowel to be used for an anastomosis. The latter can be performed with several techniques, either an end-to-end, side-to-end, or with a colonic J-pouch technique to maximize preservation of sphincter function (99,135). Several studies comparing results of LAR to APR have generally reported similar outcomes for local and distant recurrence rates and survival as long as all surgical margins are negative (88,124,176). The absence of a colostomy, while offering a better quality of life with LAR, can be compromised with bowel urgency and frequency or poor sphincter control (10).
Local Excision
Early rectal cancer may also be treated by local excision techniques, avoiding major surgery and a colostomy, but patients need to be carefully selected for these procedures. A transanal approach is usually associated with the least morbidity, but to be amenable for local excision, tumors generally need to be located <8 cm from the anal verge. An anal sphincter splitting
P.1375
approach can be used for tumors close to the anorectal junction, and occasionally a presacral Kraske approach can be used to access more proximal tumors. The adequacy of the resection needs to be full thickness into the fat, and it is important that the tumor be removed in one piece with at least a 1-cm margin without fragmentation so that careful assessment of margins can be performed. A primary closure of the defect of the rectum is then performed. The inability to sample perirectal and mesenteric lymph nodes can result in underestimation of the cancer stage. Lymph node metastases have been observed in 5% to 10% of T1 lesions and 20% to 35% of patients with T2 lesions (24). It is therefore necessary to restrict local excision to patients with low-risk tumors where the risk of recurrence is <10% (i.e., T1 or favorable T2 cancers). T1 lesions have excellent results with local excision alone, with 5-year control rates ranging from 82% to 97% and survival rates of 90% or better (53,126). The risk of perirectal nodal metastasis and high incidence of reported local failure rates for T2 cancers following local excision alone indicate the need for further adjuvant therapy (108).
Radiation Therapy Oncology Group (RTOG) Protocol 89-02 (145) examined the efficacy of local excision in a study of 65 patients with distal rectal cancers. Tumors had to have margins ≥3 mm, no LVI, no regional LN ≥2 cm by CT scan, and be grade 1 or 2 to be eligible for observation. T2 tumors with margins ≤3 mm received 59.4 to 65 Gy. Fourteen patients with T1 tumors were observed after surgery, whereas 13 patients with T1 tumors, 25 patients with T2 tumors, and 13 patients with T3 tumors received local excision with postoperative radiation of 50 to 65 Gy with 5-FU (1,000 mg for meter squared on days 1 to 3 and 29 to 31). None of the T1 tumors that had postoperative treatment had any relapse as compared to one distant metastasis and one local failure in the T1 observation arm. Five patients in the T2 group had relapses (two local, one distant, three both), and four patients in the T3 group suffered relapse (one distant, three both). Therefore, 20% of T2 and 23% of T3 tumors experienced local failure after local excision plus radiation chemotherapy. Therefore, while it is possible that highly selected T2 and limited T3 tumors may be treated with local excision and postoperative adjuvant therapy, the high locoregional failures makes this a nonstandard approach.
The Cancer and Leukemia Group B (CALGB) 8984 study provides some support for postoperative combined radiation and chemotherapy after local excision for T1 and T2 rectal cancers (157). Fifty-nine patients with T1 disease were treated with local excision alone, while 51 patients with T2 disease received adjuvant therapy consisting of T2 postoperative 54 Gy and 5-Fu (500 mg per meter squared on days of 1 to 3 and 29 to 31). T1 tumors had a 95% 4-year local control and 85% overall survival at 6 years as compared to T2 patients, who had a 85% local control and 70% overall survival. One out of two T1 local failures and four out five T2 local failures were salvaged by APR. Five T2 patients died with distant failure. Of note, 25% of the clinical T1 and T2 tumors were actually pathological T3. The 20% recurrence rate for T2 cancers in this trial and a 6-year disease-free survival rate of 71% is considerably inferior to the results of radical surgery with TME alone or neoadjuvant therapy followed by surgery. Therefore, although this study supports the use of adjuvant radiation and chemotherapy for adverse T1 and favorable T2 tumors, one should proceed with caution given the high local failure rate.
Based on the available data, local excision should be limited to tumors that are small (<4 cm), are clinically T1 or T2, well to moderately differentiated, and involve <40% of the circumference of the rectum. These tumors are usually mobile, polypoid, not ulcerated, and have favorable pathology including no lymphovascular or blood-vascular invasion (116).
Surgery
Surgery remains the mainstay of curative treatment for carcinoma of the rectum. Surgical management depends on the stage
P.1374
and location of a tumor within the rectum. Early cancers can be managed with limited surgery; however, the majority of tumors tend to present as more advanced disease and require either a low anterior resection (LAR) or abdominoperineal resection (APR). The general principles of a surgical approach remain the removal of all gross and microscopic disease with negative proximal, distal, and circumferential margins. In the case of radical resection, this means removal of the adjacent mesorectal tissue containing the regional lymphatics and the superior hemorrhoidal artery pedicle. Several studies have now shown that the surgeon's experience with resection of colorectal cancer is an independent variable in the outcome of treatment (107). The Intergroup 0114 trial found that for stage II and III rectal cancers, APR rates were not only higher in hospitals performing low volume procedures (46% vs. 32%), but also more patients had positive resection margins (111).
Historically the distal and proximal resection margins were considered important determinants in outcome. A 5-cm distal margin of normal rectum was considered necessary for adequate surgical resection (20,58,139). However, several retrospective studies have shown that distal intramural spread of tumor is rare beyond 1.5 cm, and, therefore, a 2-cm distal margin is currently considered acceptable, except in lesions that are poorly differentiated or widely metastatic (137,163,175,180). The reduced requirement of 2-cm distal margin for adequate resection has lead to a significant increase in the likelihood of sphincter preservation procedures in this disease.
Radial Margin
The National Institute of Health Consensus Conference on Rectal Cancer indicated that the principal reason for local recurrence in resected rectal cancer appears to be related to the anatomic constraints in obtaining wide radial margins, even though the proximal and distal margins appear adequate (127). Quirke et al. (140), using whole mount specimens, found that 27% (14/52) of patients had spread to the lateral radial margin, even though the margins appeared negative with standard pathological assessment. Eighty-six percent of those with positive margins developed local regional recurrence of disease as compared to only 3% without lateral resection margin involvement. The mean surgical margin of resection has been shown to decrease with increasing stage of disease ranging from 14 mm for T1 cancers to 3 mm for T4 cancers, with a corresponding increase in local recurrence from 0% to 75% (128). A positive radial margin is an independent prognostic factor for local recurrence with a hazard ratio of 12:2, and for survival with a hazard ratio of 3:2 compared to patients with clear circumferential margins (2,70).
Total Mesorectal Excision
The high local recurrence of disease following standard APR or LAR (15% to 30%) has been thought by some to be due to blunt dissection that violates the planes of the mesorectal circumference (46). Lateral spread of disease has been shown to occur not only at the level of the tumor but distally within the mesorectum as well (31). Heald et al. (74) have recommended that en bloc removal of the tumor within the envelope of the endopelvic fascia is necessary to obtain adequate lateral clearance of disease and reduce the likelihood of local recurrence. Total mesorectal excision (TME), as they described, has now become the established standard for all radical rectal cancer resections and requires sharp dissection along the plane that separates the visceral from the parietal pelvic fascia with complete en bloc removal of the rectum so that all of the rectal mesentery remains within the envelope of the specimen (98). On gross pathology, a correct TME specimen will have a bilobed encapsulated appearance with the surface looking smooth and unbroken like a lipoma. On pathological review, an adequate dissection should include 12 to 15 perirectal and pelvic lymph nodes (14,73). Careful nerve sparring dissection with TME reduces the incidence of retrograde ejaculation and postoperative impotence as compared to conventional surgery (10% to 29% instead of 25% to 75%) (71,104,158). TME, while more difficult with APR than LAR, may be associated with a somewhat higher anastomotic leak rate especially for low rectal lesions (15% to 17%) (86,87). Several series using TME surgery have reported low rates of local recurrence (4% to 7%) and an improvement in survival approaching 80% to 85% for stage II and 65% to 70% for stage III disease (9,22,45,72).
Abdominoperineal Resection
APR has been considered the gold standard for surgical resection of distal rectal cancer and requires removal of the primary tumor along with a complete proctectomy, leading to a permanent colostomy (85). Recent data suggest a decline in the rate of abdominoperineal resections being performed. APR is associated with a slightly higher morbidity and mortality than LAR and a worse quality of life related to changes in body image and depression due to the presence of a colostomy (59,177). There is also a higher risk of positive margins with APR as the mesorectum is very thin in the distal segment of the rectum and lateral margins are restricted by the close presence of the prostate in the male and vagina in females (105). The bony confines of the lower pelvis also restrict surgical access especially in males.
Low Anterior Resection
The availability of circular stapling devices has expanded the role of sphincter preservation surgical options in rectal cancers, and LARs are now being performed not just for cancers of the upper third of the rectum but also for middle and lower third cancers (95). Preserving adequate anorectal function becomes a bigger problem the more distal the level of anorectal anastomosis (183). Patients should have good anal sphincter continence prior to considering sphincter-preserving options. Patient age, pelvic anatomy, gender, and body habitus can affect suitability for sphincter preservation. A 2-cm distal margin of preserved normal rectum is considered optimal for preservation of good bowel function. In carefully selected patients a functional coloanal anastomosis can be achieved with significantly reduced margins for more distal cancers especially after neoadjuvant therapy. If LAR is planned following neoadjuvant radiation therapy, it is necessary to mobilize the splenic flexure to allow an unirradiated segment of the bowel to be used for an anastomosis. The latter can be performed with several techniques, either an end-to-end, side-to-end, or with a colonic J-pouch technique to maximize preservation of sphincter function (99,135). Several studies comparing results of LAR to APR have generally reported similar outcomes for local and distant recurrence rates and survival as long as all surgical margins are negative (88,124,176). The absence of a colostomy, while offering a better quality of life with LAR, can be compromised with bowel urgency and frequency or poor sphincter control (10).
Local Excision
Early rectal cancer may also be treated by local excision techniques, avoiding major surgery and a colostomy, but patients need to be carefully selected for these procedures. A transanal approach is usually associated with the least morbidity, but to be amenable for local excision, tumors generally need to be located <8 cm from the anal verge. An anal sphincter splitting
P.1375
approach can be used for tumors close to the anorectal junction, and occasionally a presacral Kraske approach can be used to access more proximal tumors. The adequacy of the resection needs to be full thickness into the fat, and it is important that the tumor be removed in one piece with at least a 1-cm margin without fragmentation so that careful assessment of margins can be performed. A primary closure of the defect of the rectum is then performed. The inability to sample perirectal and mesenteric lymph nodes can result in underestimation of the cancer stage. Lymph node metastases have been observed in 5% to 10% of T1 lesions and 20% to 35% of patients with T2 lesions (24). It is therefore necessary to restrict local excision to patients with low-risk tumors where the risk of recurrence is <10% (i.e., T1 or favorable T2 cancers). T1 lesions have excellent results with local excision alone, with 5-year control rates ranging from 82% to 97% and survival rates of 90% or better (53,126). The risk of perirectal nodal metastasis and high incidence of reported local failure rates for T2 cancers following local excision alone indicate the need for further adjuvant therapy (108).
Radiation Therapy Oncology Group (RTOG) Protocol 89-02 (145) examined the efficacy of local excision in a study of 65 patients with distal rectal cancers. Tumors had to have margins ≥3 mm, no LVI, no regional LN ≥2 cm by CT scan, and be grade 1 or 2 to be eligible for observation. T2 tumors with margins ≤3 mm received 59.4 to 65 Gy. Fourteen patients with T1 tumors were observed after surgery, whereas 13 patients with T1 tumors, 25 patients with T2 tumors, and 13 patients with T3 tumors received local excision with postoperative radiation of 50 to 65 Gy with 5-FU (1,000 mg for meter squared on days 1 to 3 and 29 to 31). None of the T1 tumors that had postoperative treatment had any relapse as compared to one distant metastasis and one local failure in the T1 observation arm. Five patients in the T2 group had relapses (two local, one distant, three both), and four patients in the T3 group suffered relapse (one distant, three both). Therefore, 20% of T2 and 23% of T3 tumors experienced local failure after local excision plus radiation chemotherapy. Therefore, while it is possible that highly selected T2 and limited T3 tumors may be treated with local excision and postoperative adjuvant therapy, the high locoregional failures makes this a nonstandard approach.
The Cancer and Leukemia Group B (CALGB) 8984 study provides some support for postoperative combined radiation and chemotherapy after local excision for T1 and T2 rectal cancers (157). Fifty-nine patients with T1 disease were treated with local excision alone, while 51 patients with T2 disease received adjuvant therapy consisting of T2 postoperative 54 Gy and 5-Fu (500 mg per meter squared on days of 1 to 3 and 29 to 31). T1 tumors had a 95% 4-year local control and 85% overall survival at 6 years as compared to T2 patients, who had a 85% local control and 70% overall survival. One out of two T1 local failures and four out five T2 local failures were salvaged by APR. Five T2 patients died with distant failure. Of note, 25% of the clinical T1 and T2 tumors were actually pathological T3. The 20% recurrence rate for T2 cancers in this trial and a 6-year disease-free survival rate of 71% is considerably inferior to the results of radical surgery with TME alone or neoadjuvant therapy followed by surgery. Therefore, although this study supports the use of adjuvant radiation and chemotherapy for adverse T1 and favorable T2 tumors, one should proceed with caution given the high local failure rate.
Based on the available data, local excision should be limited to tumors that are small (<4 cm), are clinically T1 or T2, well to moderately differentiated, and involve <40% of the circumference of the rectum. These tumors are usually mobile, polypoid, not ulcerated, and have favorable pathology including no lymphovascular or blood-vascular invasion (116).
posted by stefanoxx at 1:25 PM
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