59_04
Lymph Node Metastases
Lymph node metastases can be eradicated by the same radiation and chemotherapy doses effective against the primary tumor. Data from patients managed by surgery show that, when patients are first diagnosed, pelvic nodes are present in about 30% and inguinal node metastases are detectable clinically in 15% to 20% (10,51,113). It is of interest that the reported incidence of clinically abnormal inguinal nodes in patients managed by radiation tends to be somewhat lower, in the range of 10% to 15% (46). Late failure in the inguinal nodes after surgery for the primary tumor, consistent with the presence of subclinical metastases at the time of original presentation, has been described in 15% to 25% (10,51,113). However, in one recent series in which the primary tumor was treated by radiation, without elective treatment of clinically normal inguinal nodes, late inguinal failure occurred in only 8% (46). Approaches to the management of inguinal node metastases vary from radical dissection to excision or needle biopsy of enlarged nodes followed by radiation therapy or radiation and chemotherapy (22,46,94). Local control of the involved inguinal nodal areas is very good, usually ≥80% (22,46,94). However, 5-year survival rates are usually 10% to 20% lower than in those who do not have demonstrable node metastases (22,46,120).
Prophylactic or therapeutic radical dissection of the inguinofemoral nodes is not necessary and carries a high risk of late morbidity (113). High-dose irradiation to the pelvis or groin areas after extensive nodal resections increases the risk of morbidity. Elective irradiation of clinically normal inguinal node areas, with or without chemotherapy, reduces the risk of late node failure in that area to <5% (22,94,120).
Control of subclinical pelvic node metastases by irradiation and chemotherapy can be inferred from the low failure rates reported in pelvic node sites. Although large pelvic node masses may respond completely to radiation and chemotherapy, control and cure rates in these patients are low, particularly if the metastatic nodes are attached to the pelvic walls.
Extrapelvic Metastases
Deaths from extrapelvic metastases alone are relatively infrequent. Extrapelvic metastases are identified in 10% to 20% of patients. In the UKCCCR trial group treated by radiation, 5-FU, and mitomycin, although 27% (21/77) of those dying from cancer had metastases only, this represented only 7% of that trial group (121). By comparison, 38 deaths (49% of cancer deaths) in that study arm were due to pelvic cancer only. The overall crude rate of metastasis in those who received radiation and chemotherapy was 10%, compared to 17% in those treated by radiation alone. In the EORTC trial, 17% of those treated by radiation and chemotherapy developed metastases, as did 21% of those treated by radiation only (6). These rates are similar
P.1389
P.1390
to those reported following management of the primary cancer and regional nodes by surgery or radiation therapy only. The median survival time after diagnosis of extrapelvic metastases ranges from 8 to 12 months (55,115). Anal cancer metastases have been relatively resistant so far to all chemotherapy, radiation treatment, or combined modality protocols. The most active combination is 5-FU and cisplatin, although complete or durable responses are uncommon. Many recently developed drugs and molecular targeted agents have not yet been evaluated.
The role of adjuvant systemic chemotherapy has not been established. Treatment with 5-FU and mitomycin for up to 1 year in patients found to have residual cancer at surgery after preoperative combined modality therapy did not reduce recurrence rates and produced considerable morbidity (82). The one or two courses of chemotherapy given concurrently with radiation improve locoregional control rates but are not sufficient to reduce the rates of systemic metastases significantly. Both induction (neoadjuvant) and adjuvant chemotherapy, principally with 5-FU and cisplatin, are currently being evaluated (3,12,64,81,100,114). The initial report of the first randomized trial of two courses of neoadjuvant 5-FU and cisplatin showed no benefit in disease-free or overall survival (3). The intent of the additional chemotherapy in these studies is principally to further improve locoregional control, but reduction of the rate of metastases is also sought.
Radiation Therapy
The use of radiation therapy alone, either brachytherapy or external beam, has been greatly reduced since the confirmation of improved outcome of combined modality therapy. Radiation alone is now recommended mainly to patients who are unable to undergo radiation plus chemotherapy, especially elderly patients (14), or for the treatment of smaller cancers up to about 3 to 4 cm in size. Selected results are shown in Table 59.6.
Surgery
Surgery is the principal treatment for anal intraepithelial neoplasia (110) but retains only a limited place in the initial management of primary invasive anal cancer. A few patients (<5% in most series) present with extensive tumors that have destroyed the competence of the anal sphincters or fistulized into the vagina. Eradication of cancer by irradiation with or without chemotherapy does not restore continence in such patients because the cancer is replaced by fibrous tissue rather than the specialized muscle of the anal sphincters. These patients may be managed by abdominoperineal resection with postoperative irradiation and chemotherapy, using drug schedules similar to those for primary treatment and radiation doses of about 45 Gy in 5 weeks. An alternative approach is to perform colostomy before irradiation and chemotherapy, followed by immediate or delayed resection. Severe stricturing of the canal may follow irradiation and chemotherapy in patients who have had a prior colostomy, making assessment of tumor control difficult. It is frequently not possible to close the colostomy later because of the stricture. However, patients with extensive or circumferential cancers who have not lost continence and in whom a colostomy can be avoided often respond well to irradiation and chemotherapy with long-term preservation of anorectal function. Surgery should be considered for any patient unable to tolerate radiation, with or without chemotherapy. Serious postradiation morbidity may require surgical management, but the frequency of such morbidity appears to be decreasing as radiation techniques improve.
Local excision, preserving anorectal function, is possible in some patients, although this approach is now usually restricted to small well-differentiated squamous cell cancers that have
P.1391
not invaded the sphincter muscles and are located distal to the dentate line (56,57). This approach is based on the finding in surgical series that pararectal or superior hemorrhoidal system lymph node metastases were associated with <5% of well-differentiated squamous cell cancers <2 cm in size (10,44). Excision of small cancers, especially of the distal canal and anal verge, is more expedient and generally associated with less morbidity than radiation-based treatments.
Lymph node metastases can be eradicated by the same radiation and chemotherapy doses effective against the primary tumor. Data from patients managed by surgery show that, when patients are first diagnosed, pelvic nodes are present in about 30% and inguinal node metastases are detectable clinically in 15% to 20% (10,51,113). It is of interest that the reported incidence of clinically abnormal inguinal nodes in patients managed by radiation tends to be somewhat lower, in the range of 10% to 15% (46). Late failure in the inguinal nodes after surgery for the primary tumor, consistent with the presence of subclinical metastases at the time of original presentation, has been described in 15% to 25% (10,51,113). However, in one recent series in which the primary tumor was treated by radiation, without elective treatment of clinically normal inguinal nodes, late inguinal failure occurred in only 8% (46). Approaches to the management of inguinal node metastases vary from radical dissection to excision or needle biopsy of enlarged nodes followed by radiation therapy or radiation and chemotherapy (22,46,94). Local control of the involved inguinal nodal areas is very good, usually ≥80% (22,46,94). However, 5-year survival rates are usually 10% to 20% lower than in those who do not have demonstrable node metastases (22,46,120).
Prophylactic or therapeutic radical dissection of the inguinofemoral nodes is not necessary and carries a high risk of late morbidity (113). High-dose irradiation to the pelvis or groin areas after extensive nodal resections increases the risk of morbidity. Elective irradiation of clinically normal inguinal node areas, with or without chemotherapy, reduces the risk of late node failure in that area to <5% (22,94,120).
Control of subclinical pelvic node metastases by irradiation and chemotherapy can be inferred from the low failure rates reported in pelvic node sites. Although large pelvic node masses may respond completely to radiation and chemotherapy, control and cure rates in these patients are low, particularly if the metastatic nodes are attached to the pelvic walls.
Extrapelvic Metastases
Deaths from extrapelvic metastases alone are relatively infrequent. Extrapelvic metastases are identified in 10% to 20% of patients. In the UKCCCR trial group treated by radiation, 5-FU, and mitomycin, although 27% (21/77) of those dying from cancer had metastases only, this represented only 7% of that trial group (121). By comparison, 38 deaths (49% of cancer deaths) in that study arm were due to pelvic cancer only. The overall crude rate of metastasis in those who received radiation and chemotherapy was 10%, compared to 17% in those treated by radiation alone. In the EORTC trial, 17% of those treated by radiation and chemotherapy developed metastases, as did 21% of those treated by radiation only (6). These rates are similar
P.1389
P.1390
to those reported following management of the primary cancer and regional nodes by surgery or radiation therapy only. The median survival time after diagnosis of extrapelvic metastases ranges from 8 to 12 months (55,115). Anal cancer metastases have been relatively resistant so far to all chemotherapy, radiation treatment, or combined modality protocols. The most active combination is 5-FU and cisplatin, although complete or durable responses are uncommon. Many recently developed drugs and molecular targeted agents have not yet been evaluated.
The role of adjuvant systemic chemotherapy has not been established. Treatment with 5-FU and mitomycin for up to 1 year in patients found to have residual cancer at surgery after preoperative combined modality therapy did not reduce recurrence rates and produced considerable morbidity (82). The one or two courses of chemotherapy given concurrently with radiation improve locoregional control rates but are not sufficient to reduce the rates of systemic metastases significantly. Both induction (neoadjuvant) and adjuvant chemotherapy, principally with 5-FU and cisplatin, are currently being evaluated (3,12,64,81,100,114). The initial report of the first randomized trial of two courses of neoadjuvant 5-FU and cisplatin showed no benefit in disease-free or overall survival (3). The intent of the additional chemotherapy in these studies is principally to further improve locoregional control, but reduction of the rate of metastases is also sought.
Radiation Therapy
The use of radiation therapy alone, either brachytherapy or external beam, has been greatly reduced since the confirmation of improved outcome of combined modality therapy. Radiation alone is now recommended mainly to patients who are unable to undergo radiation plus chemotherapy, especially elderly patients (14), or for the treatment of smaller cancers up to about 3 to 4 cm in size. Selected results are shown in Table 59.6.
Surgery
Surgery is the principal treatment for anal intraepithelial neoplasia (110) but retains only a limited place in the initial management of primary invasive anal cancer. A few patients (<5% in most series) present with extensive tumors that have destroyed the competence of the anal sphincters or fistulized into the vagina. Eradication of cancer by irradiation with or without chemotherapy does not restore continence in such patients because the cancer is replaced by fibrous tissue rather than the specialized muscle of the anal sphincters. These patients may be managed by abdominoperineal resection with postoperative irradiation and chemotherapy, using drug schedules similar to those for primary treatment and radiation doses of about 45 Gy in 5 weeks. An alternative approach is to perform colostomy before irradiation and chemotherapy, followed by immediate or delayed resection. Severe stricturing of the canal may follow irradiation and chemotherapy in patients who have had a prior colostomy, making assessment of tumor control difficult. It is frequently not possible to close the colostomy later because of the stricture. However, patients with extensive or circumferential cancers who have not lost continence and in whom a colostomy can be avoided often respond well to irradiation and chemotherapy with long-term preservation of anorectal function. Surgery should be considered for any patient unable to tolerate radiation, with or without chemotherapy. Serious postradiation morbidity may require surgical management, but the frequency of such morbidity appears to be decreasing as radiation techniques improve.
Local excision, preserving anorectal function, is possible in some patients, although this approach is now usually restricted to small well-differentiated squamous cell cancers that have
P.1391
not invaded the sphincter muscles and are located distal to the dentate line (56,57). This approach is based on the finding in surgical series that pararectal or superior hemorrhoidal system lymph node metastases were associated with <5% of well-differentiated squamous cell cancers <2 cm in size (10,44). Excision of small cancers, especially of the distal canal and anal verge, is more expedient and generally associated with less morbidity than radiation-based treatments.
posted by stefanoxx at 5:41 AM
0 Comments:
Post a Comment
<< Home