58_03_01
Therapy of Rectal Cancer
Management of cancer of the rectum has undergone a dramatic change in the past decade. Until recently surgery had remained the primary treatment modality, but in spite of “curative” resections, a significant proportion of patients develop local recurrence of disease (20% to 50%) (136,142). Local tumor recurrence is highly correlated with both the depth of penetration of the tumor and the number of regional nodes involved by metastatic disease (41). Recent results of national cooperative group studies and several European randomized trials indicate that a multimodality treatment approach results in a significantly better outcome than surgery alone.
Defining the True Rectum and Impact of Tumor Location
Rectal cancer represents a spectrum of disease stages that needs careful definition to optimize multimodality treatment strategies, and defining the true rectum is of critical importance. Traditionally the rectum extends for 12 to 15 cm from the anal verge. The true surgical rectum begins at the anorectal ring, just proximal to the dentate line (47,102). This represents the internal anal sphincteric muscle and is necessary for anal continence. It also represents the inferior limit for functional sphincter preservation surgery and defines the lymphatic watershed for rectal cancer spread. Tumors arising above the anorectal ring tend to metastasize along the distribution of the middle rectal vessels to the internal iliac lymph nodes as compared to tumors that may extend into the anal canal, which spread via nodes along the inferior rectal and external iliac pathways (5) (Fig. 58.4). Cancers that arise in the anal canal generally metastasize to the lungs rather than the liver, as is common with most true rectal cancers. The prognosis of patients worsens with more distal location of cancer, and these differences persist even with the addition of adjunctive therapy (96,160). The proximal and distal rectum have historically been defined by the level at which the peritoneum is reflected along the anterior surface of the rectum (usually at the level of S3) (91). This is a surgical observation and difficult to define in an intact patient. The middle valve of Hoston is a useful landmark that can often be identified endoscopically (usually about 6 cm from the anorectal ring), and can be used to differentiate proximal tumors from more distal lesions. All tumors that can be digitally palpated are generally considered distal cancers.
Prognostic Factors
Several prognostic factors, in addition to tumor location, have been shown to have a significant impact on tumor behavior (4). Tumor extent as defined by the American Joint Committee on Cancer (AJCC) staging clearly remains the dominant determinant of survival (155). Other patient factors such as
P.1373
age, gender, and ethnicity have little association with outcome but may affect choice of therapy (15,35,141). Histopathological grade is of borderline significance, however, and signet cell cancers have a particularly poor outcome (148). In some reports lymph-vascular invasion has been shown on univariate analysis to have a negative impact on survival (34,36). Circumferential tumors or those with total or near total obstruction (lumen <1 cm) respond very poorly, and tumors with deep central ulceration are associated with a high incidence of lymph node involvement (32,182). Tumor mobility remains a key factor in both choice and outcome of treatment (67,120). Mobile cancers have a much more favorable outcome as compared to tethered or fixed cancers. Some studies report that even among mobile cancers only 75% to 80% are completely resected with negative surgical margins (86). Surgery for fixed cancers has proven ineffective, and these tumors are often classified as unresectable. Tumor fixation, while harder to assess in the proximal rectum, is less often encountered without other adverse factors such as circumferential disease with obstruction or perforation (28). Tumor fixation is much more problematic in the distal rectum as the confines of the bony pelvis inhibits the surgeons ability to achieve adequate lateral/circumferential margins. Distal rectal cancers therefore require a more vigorous approach to adjuvant therapy than proximal cancers.
View Figure
FIGURE 58.4. Lymphatics of the rectum.
Imaging
Efforts to improve the clinical assessment of rectal cancers have been helped considerably with the evolution of new imaging modalities. Pelvic CT has been utilized extensively and is part of the routine work-up of patients. CT appears to be much more useful in identifying enlarged pelvic lymph nodes and metastasis outside the pelvis than the extent or stage of the primary tumor (48). Standard CT does not permit the visualization of the layers of the rectal wall, and, therefore, its utility in the assessment of small primary cancers is limited (82). The sensitivity of CT scan is reported as 50% to 80% accurate, with a 30% to 80% specificity (65% to 75% accurate for tumor staging and 55% to 65% accurate in mesorectal lymph node staging) (1). The ability of CT scans for detecting distant metastasis, including pelvic and para-aortic lymph nodes, is higher than for detecting perirectal nodal involvement (75% to 87% vs. 45%) (13,106). Any lymphadenopathy near the rectum seen on a CT scan should be considered abnormal.
Transrectal endoscopic ultrasound (EUS) techniques have been more helpful in efforts to clinically stage rectal cancers. EUS can be 80% to 95% accurate in tumor staging and 70% to 75% accurate in mesorectal lymph node staging (18,154). The transrectal ultrasound is very good at demonstrating layers of the rectal wall especially the mucosa, muscularis mucosa, submucosa, and muscularis propria (79,132). Its use is limited to lesions <14 cm from the anus and not applicable for the upper rectum or for stenosing tumors. EUS can also identify enlarged perirectal lymph nodes but is not effective outside of the perirectum (76). One area where EUS can be very useful is in determining extension of disease into the anal canal, which is an area that is poorly visualized on CT but of critical importance for planning sphincter preserving surgical procedures (61).
More recently, MRI techniques have been found to be of greater accuracy in defining the extent of rectal cancer extension and also determining the location and stage of tumor (21,25). Different approaches to MRI have been explored including the use of body coils, endorectal MRI and phased array techniques. Although MRI appears to have greater accuracy, it requires a significant learning curve but is becoming a greater part of the standard presurgical work-up for rectal cancer.
Body coil MRI, which first became available in the mid-1980s, has had an accuracy of 54% to 66% for T staging, but this has improved with the use of endorectal coil MRI with reported accuracy rates of 80% to 95% (16,90). A significant advantage of both endorectal coil and surface coil MRI is that it is less operator dependent and permits a larger field of view than EUS. It also allows assessment for proximal tumors and stenotic lesions where EUS is not an option. Another advantage of MRI is that it can detect involved lymph nodes on the basis of characteristics other than size. MRI can also be very helpful in determining the extent of lateral extension of disease, which is critical in predicting the adequacy of circumferential margins for surgical excision (17). Several studies using phased array MRI have reported accuracy rates of 80% to 97% in predicting lateral disease extent and have correlated the likelihood of tumor-free resection margin by visualizing tumor involvement of the mesorectal fascia (110).
All of these imaging techniques have advantages and limitations and should be considered complementary to a good physical examination. They are all less accurate in predicting response after neoadjuvant therapy with high rates of false positivity (51,161) and should be interpreted with caution in this setting.
Management of cancer of the rectum has undergone a dramatic change in the past decade. Until recently surgery had remained the primary treatment modality, but in spite of “curative” resections, a significant proportion of patients develop local recurrence of disease (20% to 50%) (136,142). Local tumor recurrence is highly correlated with both the depth of penetration of the tumor and the number of regional nodes involved by metastatic disease (41). Recent results of national cooperative group studies and several European randomized trials indicate that a multimodality treatment approach results in a significantly better outcome than surgery alone.
Defining the True Rectum and Impact of Tumor Location
Rectal cancer represents a spectrum of disease stages that needs careful definition to optimize multimodality treatment strategies, and defining the true rectum is of critical importance. Traditionally the rectum extends for 12 to 15 cm from the anal verge. The true surgical rectum begins at the anorectal ring, just proximal to the dentate line (47,102). This represents the internal anal sphincteric muscle and is necessary for anal continence. It also represents the inferior limit for functional sphincter preservation surgery and defines the lymphatic watershed for rectal cancer spread. Tumors arising above the anorectal ring tend to metastasize along the distribution of the middle rectal vessels to the internal iliac lymph nodes as compared to tumors that may extend into the anal canal, which spread via nodes along the inferior rectal and external iliac pathways (5) (Fig. 58.4). Cancers that arise in the anal canal generally metastasize to the lungs rather than the liver, as is common with most true rectal cancers. The prognosis of patients worsens with more distal location of cancer, and these differences persist even with the addition of adjunctive therapy (96,160). The proximal and distal rectum have historically been defined by the level at which the peritoneum is reflected along the anterior surface of the rectum (usually at the level of S3) (91). This is a surgical observation and difficult to define in an intact patient. The middle valve of Hoston is a useful landmark that can often be identified endoscopically (usually about 6 cm from the anorectal ring), and can be used to differentiate proximal tumors from more distal lesions. All tumors that can be digitally palpated are generally considered distal cancers.
Prognostic Factors
Several prognostic factors, in addition to tumor location, have been shown to have a significant impact on tumor behavior (4). Tumor extent as defined by the American Joint Committee on Cancer (AJCC) staging clearly remains the dominant determinant of survival (155). Other patient factors such as
P.1373
age, gender, and ethnicity have little association with outcome but may affect choice of therapy (15,35,141). Histopathological grade is of borderline significance, however, and signet cell cancers have a particularly poor outcome (148). In some reports lymph-vascular invasion has been shown on univariate analysis to have a negative impact on survival (34,36). Circumferential tumors or those with total or near total obstruction (lumen <1 cm) respond very poorly, and tumors with deep central ulceration are associated with a high incidence of lymph node involvement (32,182). Tumor mobility remains a key factor in both choice and outcome of treatment (67,120). Mobile cancers have a much more favorable outcome as compared to tethered or fixed cancers. Some studies report that even among mobile cancers only 75% to 80% are completely resected with negative surgical margins (86). Surgery for fixed cancers has proven ineffective, and these tumors are often classified as unresectable. Tumor fixation, while harder to assess in the proximal rectum, is less often encountered without other adverse factors such as circumferential disease with obstruction or perforation (28). Tumor fixation is much more problematic in the distal rectum as the confines of the bony pelvis inhibits the surgeons ability to achieve adequate lateral/circumferential margins. Distal rectal cancers therefore require a more vigorous approach to adjuvant therapy than proximal cancers.
View Figure
FIGURE 58.4. Lymphatics of the rectum.
Imaging
Efforts to improve the clinical assessment of rectal cancers have been helped considerably with the evolution of new imaging modalities. Pelvic CT has been utilized extensively and is part of the routine work-up of patients. CT appears to be much more useful in identifying enlarged pelvic lymph nodes and metastasis outside the pelvis than the extent or stage of the primary tumor (48). Standard CT does not permit the visualization of the layers of the rectal wall, and, therefore, its utility in the assessment of small primary cancers is limited (82). The sensitivity of CT scan is reported as 50% to 80% accurate, with a 30% to 80% specificity (65% to 75% accurate for tumor staging and 55% to 65% accurate in mesorectal lymph node staging) (1). The ability of CT scans for detecting distant metastasis, including pelvic and para-aortic lymph nodes, is higher than for detecting perirectal nodal involvement (75% to 87% vs. 45%) (13,106). Any lymphadenopathy near the rectum seen on a CT scan should be considered abnormal.
Transrectal endoscopic ultrasound (EUS) techniques have been more helpful in efforts to clinically stage rectal cancers. EUS can be 80% to 95% accurate in tumor staging and 70% to 75% accurate in mesorectal lymph node staging (18,154). The transrectal ultrasound is very good at demonstrating layers of the rectal wall especially the mucosa, muscularis mucosa, submucosa, and muscularis propria (79,132). Its use is limited to lesions <14 cm from the anus and not applicable for the upper rectum or for stenosing tumors. EUS can also identify enlarged perirectal lymph nodes but is not effective outside of the perirectum (76). One area where EUS can be very useful is in determining extension of disease into the anal canal, which is an area that is poorly visualized on CT but of critical importance for planning sphincter preserving surgical procedures (61).
More recently, MRI techniques have been found to be of greater accuracy in defining the extent of rectal cancer extension and also determining the location and stage of tumor (21,25). Different approaches to MRI have been explored including the use of body coils, endorectal MRI and phased array techniques. Although MRI appears to have greater accuracy, it requires a significant learning curve but is becoming a greater part of the standard presurgical work-up for rectal cancer.
Body coil MRI, which first became available in the mid-1980s, has had an accuracy of 54% to 66% for T staging, but this has improved with the use of endorectal coil MRI with reported accuracy rates of 80% to 95% (16,90). A significant advantage of both endorectal coil and surface coil MRI is that it is less operator dependent and permits a larger field of view than EUS. It also allows assessment for proximal tumors and stenotic lesions where EUS is not an option. Another advantage of MRI is that it can detect involved lymph nodes on the basis of characteristics other than size. MRI can also be very helpful in determining the extent of lateral extension of disease, which is critical in predicting the adequacy of circumferential margins for surgical excision (17). Several studies using phased array MRI have reported accuracy rates of 80% to 97% in predicting lateral disease extent and have correlated the likelihood of tumor-free resection margin by visualizing tumor involvement of the mesorectal fascia (110).
All of these imaging techniques have advantages and limitations and should be considered complementary to a good physical examination. They are all less accurate in predicting response after neoadjuvant therapy with high rates of false positivity (51,161) and should be interpreted with caution in this setting.
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