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Local excision followed by postoperative radiation therapy
Local Excision Followed by Postoperative Radiation Therapy Christopher G. Willett The management of distal rectal cancer is in evolution. Although abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with significant morbidity--loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction. To overcome these limitations, innovative efforts are underway studying the feasibility and efficacy of a variety of sphincter-preserving operations, usually in
combination with radiation therapy and chemotherapy. Local excision procedures with adjuvant therapy represent one such treatment strategy that attempts to optimize local control and survival with preservation of sphincter integrity. This article summarizes the current role of local excision and postoperative irradiation and chemotherapy for patients with carcinoma of the rectum. Copyright9 1998by W.B. Saunders Company
~
sexual dysfunction and less than perfect anorectal function, the avoidance of a permanent colostomy is perceived by the patient as an extremely fortunate situation. In contrast to tumors of the upper and middle rectum, management of distal rectal cancer continues to pose a major challenge to the surgeon and oncologist. Clearly an important consideration in treatment selection of patients with low rectal cancer is the local extent of the primary tumor. For small tumors in the distal rectum, there has been increasing interest in local excision procedures as an alternative to the abdominoperineal resection. These operations involve an excision of the primary tumor through the anus (peranal excision), by division of the anal sphincter (transanal, transsphincteric, or Park's resection), or using a parasacral approach (Kraske). The latter two procedures are somewhat more extensive than a simple peranal excision and have a greater degree of associated morbidity. Clearly, these techniques are limited to tumors that can be excised and the excision site closed without significant narrowing of the rectal lumen.
proximately 37,100 patients developed carcinoma of the rectum in the United States in 1997.1 Since the introduction of the abdominoperineal resection by Miles, a surgical approach to removal of this tumor and its adjacent tissues has offered a high probability of local control and survival. Despite its merits, the abdominoperineal resection has significant drawbacks: loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction. To overcome these limitations, an array of surgical procedures have been developed ranging from simple excision to complex resections with reconstruction. In appropriately staged patients, these operations appear to offer not only comparable rates of local control as the abdominoperineal resection, but also, importantly, they preserve sphincter integrity. With continued experience, selection criteria and the role of radiation therapy and chemotherapy have become more clearly defined. One obvious consideration in the selection of patients for sphincter preservation is tumor location within the rectum. Patients with tumors in the upper rectum have long been well managed by a sphincterpreserving resection with anastomosis. With the advent of the end-to-end anastomotic stapling instrument, tumors of the midrectum, even in a narrow pelvis, became amenable to low anterior resection and preservation of the anal sphincter. Although with the lower anastomoses there is a real incidence of
From the Deparlment of Radiation Oncology, Massachusetts General Hospital, Boston, MA. Address reprint requests to Christopher G. l/Villett, MD, Department of Radiation Oncology, Massachusetts General Ho~pilal, 100 Blossom St, Boston, MA, 02114. Copy@t 0 1998 by W.B. Saunders Company 1053-4296/98/0801-000458.00/0
24
Clinical and Radiological Evaluation The usual criteria for rectal cancers suitable for local excision are as follows: tumor size less than 4 cm, location 8 cm or less t?om the anal verge, welldifferentiated or moderately well-differentiated histology, mobile, not ulcerated, and no suspicion of perirectal or presacral nodes. 2 The goal is to select patients with tumors confined to the rectal wall, in which there is a low probability of lymph node metastases. Although impressive advances have been made in the radiological imaging of rectal cancer, digital examination by an experienced practitioner is one of
Seminars in Radiation Oncology, Vol 8, No 1 (January), 1998.'pp 24-29
Local Excision Followedby PostoperativeRadiation Therapy
the most reliable (and inexpensive) methods of determining the depth of penetration of the primary tumor. The accuracy rates of staging the primary tumor by digital examination have been reported to be approximately 80%. 3 Because lymph node metastases are seen only microscopically in a high percentage of cases, it is not surprising that digital examination is insensitive at identifying metastatic perirectal nodal involvement. In addition to digital examination, endoscopic ultrasonography (EUS) has been used as a staging tool in assessing local tumor extent as well as lymph node involvement. 5 Correlation of ultrasound T stage to pathological T stage ranges from 70% to greater than 90% in most series. 5 To achieve high accuracy rates (-->90%), this examination must be performed by experienced operators. In a study from the University of Minnesota, the accuracy rates rose from 59% during the early phase of the study to 88% in the latter phase of the study. 6 Because ultrasound and other imaging modalities can visualize only macroscopic changes, these techniques are inherently limited in their ability to discriminate lesser degrees of invasion between tumors. In one study, 30% of 24 patients believed to have T2 lesions based on EUS in fact had transmural invasion pathologically.7In assessing pararectal nodal involvement, EUS has been less helpful with reported accuracy rates ranging from 50% to 80%. 5 With these caveats, EUS is generally acknowleged to be complementary to digital examination in staging and more accurate than axial computed tomography (CT) and magnetic resonance imaging (MRI) scans. Although CT and MRI may be inferior to EUS in staging rectal cancer, there are potential advantages of these studies. These imaging modalities offer a larger field of view than EUS and may be less operator and technique dependent and allow study of stenotic tumors. 2,4 It is our policy to obtain a CT scan as well as EUS to aid in the selection of patients for local excision. Patients with convincing evidence of transmural penetration or perirectal lymph node involvement are probably best managed by radical surgical resection because of the risk of tumor cutthrough and inadequate lymph node removal by local excision procedures.
Surgery and Pathological Evaluation The selection of the local excision technique is important. Surgical procedures such as peranal and
25
transsphincteric (York-Mason) excision and excision via midline posterior proctotomy (Kraske) are advocated because these operations permit removal of the tumor and adjoining rectum in one piece without t~agmentation of the tumor and allow assessment of inked margins, histological differentiation, vessel involvement, and depth of penetration through bowel wall. The pathologist should carefully define the narrowest margin in fresh tissues and on slides using an ink margin. Fulguration or electrocoagulation are not recommended because these procedures are associated with a high likelihood of residual disease after the procedure and inadequate pathological analysis. A critical limitation of local excision procedures is the inability to sample or resect perirectal and mesenteric lymphatics. The incidence of perirectal lymph node metastases progressively rises as the tumor penetrates from submucosa through muscularis propria to fat. 2,8-1~ In a collective series, lymph node metastases were observed in 12%, 35%, and 44% of lesions involving the submucosa, muscularis propria, and perirectal fat. 2 In addition to T stage, histological grade and vascular involvement are independent predictors of lymph node metastasis. One analysis reported a 29% to 50% risk of perirectal nodal metastasis for patients with T1 and T2 tumors showing poorly differentiated histology or lymphatic and blood vessel involvement. 9 Table 1 summarizes the incidence of perirectal nodal metastases by T stage and histological features of the primary tumor. Because many patients with pathologically high-risk T1 and T2 tumors have perirectal lymph metastases, local excision procedures alone are inadequate treatment. Studies examining the outcome of patients undergoing local excision only show a clear association of local failure rate to the risk ofperirectal nodal
Table 1. Risk of Perirectal Lymph Nodes by Primary Tumor Histopathology Low risk: < 10% Well-differentiated histology Submucosa or inner muscularis propria invasion Intermediate risk: 10% to 20% Moderately well-differentiated histology Muscularis propria invasion High risk: >30% Poorly differentiated histology Muscularis propria or perirectal fat invasion Lymphatic or venous vessel invasion
26
Ch~'topher G. Willett
Table 2. Outcome After Local Excision and Postoperative Irradiation Local Control
(%)
Survival
Study Princess Margaret HospitaP 5 Fox Chase Cancer Center 16 Memorial Sloan-Kettering Cancer Center 17 CALGB Intergroup m
76 81
80 (6-y median) 75 (5-y DFS)
(%)
82
79 (overall)
98
96
(2-y)
Abbreviation: DFS, disease-free survival; CALGB, Cancer and Leukemia Group B.
metastases as assessed by primary tumor histopathology. In a study from Erlangen, patients with low-risk minors bad less than a "0% ioca! faiiur% whereas patients with high-risk tumors had greater than 30% local failure, m To improve the outcome of these
Figure 1. (A) Posteroanterior and (B) lateral simulation films of a patient after local excision with radiopaque clips placed to delineate tumor bed. With this three-field arrangement, this patient received 45 Gy in 25 fractions.
patients, treatment programs of postoperative pelvic irradiation with concurrent 5-fluorouracil (5-FU) after local excision of high-risk tumors are being investigated at many centers in the United States. I Ms The results of several studies are summarized in ] a b l e 2.
Treatment Recommendations and Results Treatment recommendations should be guided by the surgical and pathological finding of the local excision. For patients with small tumors invading the mucosa and submucosa, local excision alone probably suiticc~. 5tudic~ h o m ~cvcrai ~caLc;~ ha'~c oho;~:; that the results of local excision only for patients with T1 lesions with favorable histology is excellent with
Local Excision .Followedby PostoperativeRadiation Therapy
local control and recurrence-free survival rates of 90% or greater. Postoperative irradiation is usually not advised for patients with locally excised T1 tumors unless the margins are compromised or the primary tumor exhibits poorly differentiated histology or lymphatic or venous invasion. In tumors that are somewhat larger or in which there is deeper invasion of the tumor into the rectal wall, more aggressive techniques of combined local excision and radiation therapy and chemotherapy have been employed. Because of the risk ofperirectal nodal metastases and reported local failure rates of 20% or greater after local excision only, postoperative pelvic irradiation with 5-FU-based chemotherapy is advised for all patients with T2 lesions. Singleinstitution studies reporting on the results of postoperative irradiation for these patients indicate excellent local control and survival rates. In a report from the M.D. Anderson Hospital, the local control rate of 15 patients with T2 tumors treated by local excision with postoperative irradiation and 5-FU-based chemotherapy was 93%. 13 Similar results were reported by the Massachusetts General Hospital, where all 11 patients with T2 tumors treated by local excision and adjuvant irradiation and 5-FU have maintained local control. 12 The results from single-institution studies of local excision of T1 and T2 rectal cancer with appropriate selection of postoperative irradiation appear to be supported by preliminary results of the Cancer and Leukemia Group B (CALGB) Intergroup Phase II study) 8 In this study, 60 patients underwent local excision of T1 tumors without further therapy, whereas 53 patients with T2 tumors received postoperative irradiation with 5-FU after local excision. With a median follow-up of 24 months, 4 of 113 patients have died of their malignant disease with 2 of 4 patients having distant recurrence only. Only 2 of 113 patients experienced isolated local recurrences: Both underwent subsequent resection and remain alive. The investigators of this study conclude that sphincter preservation can be achieved with excellent cancer control without sacrifice of anal function in selected patients with superficial distal rectal cancer. For patients with tumors invading the perirectal fat (T3), radical surgical resection is recommended (if feasible) because of the risk of tumor cut-through and inadequate lymph node removal by local excision
97
procedures. The experience of local excision with postoperative irradiation and chemotherapy is limited, and the available data suggest higher local failure rates. Three of 15 patients (20%) with T3 tumors from M.D. Anderson have experienced local failure after local excision and postoperative irradiation with 5-FU. 13 In a study from Massachusetts General Hospital, three of four patients (75%) with T3 tumors suffered a local recurrence after local excision and postoperative irradiation) 2 Unless there is a medical contraindication or patient refusal, we do not advise a treatment program of local excision and postoperative irradiation and chemotherapy for patients with T3 tumors.
Figure 2. Lateral simulation film of a reduced field to high-risk region in pelvis as defined by radiopaque clips. An additional 5.4 Gy was given via these lateral fields.
28
Ch~topher G. Willett
Radiation Therapy Techniques and 5-FU Administration At the time of surgery, radiopaque markers are placed at the p e r i m e t e r of the excision identifying the high-risk region to aid in t r e a t m e n t planning (Figs 1 and 2). For patients with disease limited to the submucosa and muscularis propria, pelvic irradiation to 45 Gy in 25 fractions by a three- or four-field technique is given followed by the first field reduction with lateral fields to 50.4 Gy and a second field reduction (if appropriate) with lateral fields to 54.0 Gy. During the 5.5- to 6-week course of irradiation, our patients receive continuous infusion 5-FU (225 mg/mg/24 h) 5 days per week. C h e m o t h e r a p y alternatives could include bolus 5-FU with or without leucovorin during the first and last weeks of irradiation. Patients are treated in the prone position. For the initial fields (45 Gy), the superior border should be 1.5 cm above the level of the sacral promontory and the lower border of the field 4 to 5 cm below the defined tumor bed. Laterally the posteroanterioranteroposterior fields extend 1 to 1.5 cm beyond the true bony pelvis. To treat the entire presacral space with adequate margins and full dose, the lateral fields are designed so that the posterior border encompass the entire sacrum with a 1-cm margin posterior to the sacrum. Anteriorly the fields are designed to encompass the previous tumor bed, including the posterior wall of the vagina for women and a large portion of the prostate for men. The radiopaque markers placed at surgery are helpful in designing the field reductions. After 45 Gy, lateral fields with an approximately 3-cm margin around the m a r k e d tumor bed are typically used for three fi'actions to 50.4 Gy. This is followed by a further field reduction with a 2-cm margin around the m a r k e d tumor bed to 54 Gy. A small bowel series must be performed to ensure that no small bowel is within these lateral boost fields. For patients with positive or tight resection margins or poor prognostic features suggesting a higher risk of local recurrence, additional irradiation to 55 Gy to 65 Gy m a y be appropriate. Specialized techniques, such as interstitial implant, split beams with rectal dilation, or perineal proton-beam irradiation, allow homogeneous irradiation of high-risk regions in the rectum and adjacent perirectal fat with sparing of uninvolved rectum, perineum, and pelvic viscera. These techniques may allow a substantial number of patients to obtain local control with good preservation of anorectal function.
Conclusions Local excision and postoperative irradiation and chemotherapy appear to offer not only satisfactory local control and smwival, but also, importantly, sphincter preservation for selected patients with distal rectal cancer. For patients with favorable histology T1 rectal cancer, local excision alone suffices. Postoperative irradiation and chemotherapy should follow local excision procedures tbr patients with unthvorable histology T1 and all T2 tumors. The d a t a for T3 tumors with this approach are limited; however, results from single-institution studies suggest unacceptably high local failure rates. Radical resection is advised.
References 1. Parker SL, Tong T, Boldern S, et al: Cancer statistics, 1997. CancerJ Clin 47:5-27, 1997 2. Billingham RP: Conservative treatment of rectal cancer: Extending the indication.Cancer 70:1355-1363, 1992 3. Nichos RJ, York-MasonAM, Morson BC, et al: The clinical staging of rectal cancer. BrJ Surg 69:404-407, 1982 4. Ng A, Recht A, Busse PM: Sphincter preservation therapy for distal rectal cancer--a review.Cancer 79:671-683, 1997 5. Alexander AA: The effect of endorectal ultrasound scanning on the preoperative staging of rectal cancer. Surg Oncol Clin NorthAm 1:39-56, 1992 6. Orrom WJ, Wong WD, Rothenberger DA, et al: Endorectal ultrasound in the preoperative staging of rectal tumors: A learning experience. Dis Colon Rectum 33:654-659, 1990 7. Hulsmans FJH, Tio TL, FockensP, et ah Assessmentof tumor infiltration depth in rectal cancer with transrectal sonogxaphy: Caution is necessary.Radiology190:715-720, 1994 8. Minsky BD, Rich T, Recht A, et ah Selection criteria for local excisionwith or without adjuvant radiation therapy for rectal cancer. Cancer 63:1421-1429, 1989 9. BrodskyJT, Richard GK, Cohen AM, et al: Variables correlated with the risk of lymph node metastasis in early rectal cancer. Cancer 69:322-326, 1991 10. Gall FP, Hermanek P: Update of the German experience with local excision of rectal cancer. Surg Oncol Clin North Am 1:99-109, 1992 1i. Wiilett CG, Tepper JE, Donnelly S, et ah Patterns of failure following local excision and local excision and postoperativc radiation therapy for invasive rectal cancer. J Clin Oncol 7:1003-1008, 1989 12. WoodWC, Willett CG: Update of the Massachusetts General Hospital experience of combined local excision and radiotherapy for rectal cancer. Surg Oncol Clin North Am 1:131136, 1992 13. Ota DM, SkibberJ, Rich TA: MD Anderson Cancer Center experience with local excisionand multimodality therapy for rectal cancer. Surg Oncol Clin North Am 1:147-152, 1992
Local Excision Followed by Postoperative Radiation Therapy
14. JessupJM, Bothe A, Stone MD, et al: Preservation of sphincter function in rectal carcinoma by a multimodality treatment approach. Surg Oncol Clin North Am 1:137-145, 1992 15. Wong CS, Stern H, Cummings BJ: Local excision and postoperative radiation therapy for rectal carcinoma. Int J Radiat C l n o ~ l R ~ I PF, y~ 9 ~ , ~ Q _ ~ 7 ~
IQQR
16. Fortunato L, Ahmad NR, Yeung RS, et al: Long-term followup
29
of local excision and radiation therapy for invasive rectal cancer. Dis Colon Rectum 38:1193-1199, 1995 17. Minsky BD, Enker WE, Cohen AM, et al: Local excision and postoperative radiation therapy for rectal cancer. Am J Clin Onco117:411-416, 1994 18. Steele GD, HerndonJE, Burgess AM, et al: Sphincter sparing treatment for distal rectal adenocarcinoma: A phase ~ intergroup study. ASCO Proc 16:256a, 1997
combination with radiation therapy and chemotherapy. Local excision procedures with adjuvant therapy represent one such treatment strategy that attempts to optimize local control and survival with preservation of sphincter integrity. This article summarizes the current role of local excision and postoperative irradiation and chemotherapy for patients with carcinoma of the rectum. Copyright9 1998by W.B. Saunders Company
~
sexual dysfunction and less than perfect anorectal function, the avoidance of a permanent colostomy is perceived by the patient as an extremely fortunate situation. In contrast to tumors of the upper and middle rectum, management of distal rectal cancer continues to pose a major challenge to the surgeon and oncologist. Clearly an important consideration in treatment selection of patients with low rectal cancer is the local extent of the primary tumor. For small tumors in the distal rectum, there has been increasing interest in local excision procedures as an alternative to the abdominoperineal resection. These operations involve an excision of the primary tumor through the anus (peranal excision), by division of the anal sphincter (transanal, transsphincteric, or Park's resection), or using a parasacral approach (Kraske). The latter two procedures are somewhat more extensive than a simple peranal excision and have a greater degree of associated morbidity. Clearly, these techniques are limited to tumors that can be excised and the excision site closed without significant narrowing of the rectal lumen.
proximately 37,100 patients developed carcinoma of the rectum in the United States in 1997.1 Since the introduction of the abdominoperineal resection by Miles, a surgical approach to removal of this tumor and its adjacent tissues has offered a high probability of local control and survival. Despite its merits, the abdominoperineal resection has significant drawbacks: loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction. To overcome these limitations, an array of surgical procedures have been developed ranging from simple excision to complex resections with reconstruction. In appropriately staged patients, these operations appear to offer not only comparable rates of local control as the abdominoperineal resection, but also, importantly, they preserve sphincter integrity. With continued experience, selection criteria and the role of radiation therapy and chemotherapy have become more clearly defined. One obvious consideration in the selection of patients for sphincter preservation is tumor location within the rectum. Patients with tumors in the upper rectum have long been well managed by a sphincterpreserving resection with anastomosis. With the advent of the end-to-end anastomotic stapling instrument, tumors of the midrectum, even in a narrow pelvis, became amenable to low anterior resection and preservation of the anal sphincter. Although with the lower anastomoses there is a real incidence of
From the Deparlment of Radiation Oncology, Massachusetts General Hospital, Boston, MA. Address reprint requests to Christopher G. l/Villett, MD, Department of Radiation Oncology, Massachusetts General Ho~pilal, 100 Blossom St, Boston, MA, 02114. Copy@t 0 1998 by W.B. Saunders Company 1053-4296/98/0801-000458.00/0
24
Clinical and Radiological Evaluation The usual criteria for rectal cancers suitable for local excision are as follows: tumor size less than 4 cm, location 8 cm or less t?om the anal verge, welldifferentiated or moderately well-differentiated histology, mobile, not ulcerated, and no suspicion of perirectal or presacral nodes. 2 The goal is to select patients with tumors confined to the rectal wall, in which there is a low probability of lymph node metastases. Although impressive advances have been made in the radiological imaging of rectal cancer, digital examination by an experienced practitioner is one of
Seminars in Radiation Oncology, Vol 8, No 1 (January), 1998.'pp 24-29
Local Excision Followedby PostoperativeRadiation Therapy
the most reliable (and inexpensive) methods of determining the depth of penetration of the primary tumor. The accuracy rates of staging the primary tumor by digital examination have been reported to be approximately 80%. 3 Because lymph node metastases are seen only microscopically in a high percentage of cases, it is not surprising that digital examination is insensitive at identifying metastatic perirectal nodal involvement. In addition to digital examination, endoscopic ultrasonography (EUS) has been used as a staging tool in assessing local tumor extent as well as lymph node involvement. 5 Correlation of ultrasound T stage to pathological T stage ranges from 70% to greater than 90% in most series. 5 To achieve high accuracy rates (-->90%), this examination must be performed by experienced operators. In a study from the University of Minnesota, the accuracy rates rose from 59% during the early phase of the study to 88% in the latter phase of the study. 6 Because ultrasound and other imaging modalities can visualize only macroscopic changes, these techniques are inherently limited in their ability to discriminate lesser degrees of invasion between tumors. In one study, 30% of 24 patients believed to have T2 lesions based on EUS in fact had transmural invasion pathologically.7In assessing pararectal nodal involvement, EUS has been less helpful with reported accuracy rates ranging from 50% to 80%. 5 With these caveats, EUS is generally acknowleged to be complementary to digital examination in staging and more accurate than axial computed tomography (CT) and magnetic resonance imaging (MRI) scans. Although CT and MRI may be inferior to EUS in staging rectal cancer, there are potential advantages of these studies. These imaging modalities offer a larger field of view than EUS and may be less operator and technique dependent and allow study of stenotic tumors. 2,4 It is our policy to obtain a CT scan as well as EUS to aid in the selection of patients for local excision. Patients with convincing evidence of transmural penetration or perirectal lymph node involvement are probably best managed by radical surgical resection because of the risk of tumor cutthrough and inadequate lymph node removal by local excision procedures.
Surgery and Pathological Evaluation The selection of the local excision technique is important. Surgical procedures such as peranal and
25
transsphincteric (York-Mason) excision and excision via midline posterior proctotomy (Kraske) are advocated because these operations permit removal of the tumor and adjoining rectum in one piece without t~agmentation of the tumor and allow assessment of inked margins, histological differentiation, vessel involvement, and depth of penetration through bowel wall. The pathologist should carefully define the narrowest margin in fresh tissues and on slides using an ink margin. Fulguration or electrocoagulation are not recommended because these procedures are associated with a high likelihood of residual disease after the procedure and inadequate pathological analysis. A critical limitation of local excision procedures is the inability to sample or resect perirectal and mesenteric lymphatics. The incidence of perirectal lymph node metastases progressively rises as the tumor penetrates from submucosa through muscularis propria to fat. 2,8-1~ In a collective series, lymph node metastases were observed in 12%, 35%, and 44% of lesions involving the submucosa, muscularis propria, and perirectal fat. 2 In addition to T stage, histological grade and vascular involvement are independent predictors of lymph node metastasis. One analysis reported a 29% to 50% risk of perirectal nodal metastasis for patients with T1 and T2 tumors showing poorly differentiated histology or lymphatic and blood vessel involvement. 9 Table 1 summarizes the incidence of perirectal nodal metastases by T stage and histological features of the primary tumor. Because many patients with pathologically high-risk T1 and T2 tumors have perirectal lymph metastases, local excision procedures alone are inadequate treatment. Studies examining the outcome of patients undergoing local excision only show a clear association of local failure rate to the risk ofperirectal nodal
Table 1. Risk of Perirectal Lymph Nodes by Primary Tumor Histopathology Low risk: < 10% Well-differentiated histology Submucosa or inner muscularis propria invasion Intermediate risk: 10% to 20% Moderately well-differentiated histology Muscularis propria invasion High risk: >30% Poorly differentiated histology Muscularis propria or perirectal fat invasion Lymphatic or venous vessel invasion
26
Ch~'topher G. Willett
Table 2. Outcome After Local Excision and Postoperative Irradiation Local Control
(%)
Survival
Study Princess Margaret HospitaP 5 Fox Chase Cancer Center 16 Memorial Sloan-Kettering Cancer Center 17 CALGB Intergroup m
76 81
80 (6-y median) 75 (5-y DFS)
(%)
82
79 (overall)
98
96
(2-y)
Abbreviation: DFS, disease-free survival; CALGB, Cancer and Leukemia Group B.
metastases as assessed by primary tumor histopathology. In a study from Erlangen, patients with low-risk minors bad less than a "0% ioca! faiiur% whereas patients with high-risk tumors had greater than 30% local failure, m To improve the outcome of these
Figure 1. (A) Posteroanterior and (B) lateral simulation films of a patient after local excision with radiopaque clips placed to delineate tumor bed. With this three-field arrangement, this patient received 45 Gy in 25 fractions.
patients, treatment programs of postoperative pelvic irradiation with concurrent 5-fluorouracil (5-FU) after local excision of high-risk tumors are being investigated at many centers in the United States. I Ms The results of several studies are summarized in ] a b l e 2.
Treatment Recommendations and Results Treatment recommendations should be guided by the surgical and pathological finding of the local excision. For patients with small tumors invading the mucosa and submucosa, local excision alone probably suiticc~. 5tudic~ h o m ~cvcrai ~caLc;~ ha'~c oho;~:; that the results of local excision only for patients with T1 lesions with favorable histology is excellent with
Local Excision .Followedby PostoperativeRadiation Therapy
local control and recurrence-free survival rates of 90% or greater. Postoperative irradiation is usually not advised for patients with locally excised T1 tumors unless the margins are compromised or the primary tumor exhibits poorly differentiated histology or lymphatic or venous invasion. In tumors that are somewhat larger or in which there is deeper invasion of the tumor into the rectal wall, more aggressive techniques of combined local excision and radiation therapy and chemotherapy have been employed. Because of the risk ofperirectal nodal metastases and reported local failure rates of 20% or greater after local excision only, postoperative pelvic irradiation with 5-FU-based chemotherapy is advised for all patients with T2 lesions. Singleinstitution studies reporting on the results of postoperative irradiation for these patients indicate excellent local control and survival rates. In a report from the M.D. Anderson Hospital, the local control rate of 15 patients with T2 tumors treated by local excision with postoperative irradiation and 5-FU-based chemotherapy was 93%. 13 Similar results were reported by the Massachusetts General Hospital, where all 11 patients with T2 tumors treated by local excision and adjuvant irradiation and 5-FU have maintained local control. 12 The results from single-institution studies of local excision of T1 and T2 rectal cancer with appropriate selection of postoperative irradiation appear to be supported by preliminary results of the Cancer and Leukemia Group B (CALGB) Intergroup Phase II study) 8 In this study, 60 patients underwent local excision of T1 tumors without further therapy, whereas 53 patients with T2 tumors received postoperative irradiation with 5-FU after local excision. With a median follow-up of 24 months, 4 of 113 patients have died of their malignant disease with 2 of 4 patients having distant recurrence only. Only 2 of 113 patients experienced isolated local recurrences: Both underwent subsequent resection and remain alive. The investigators of this study conclude that sphincter preservation can be achieved with excellent cancer control without sacrifice of anal function in selected patients with superficial distal rectal cancer. For patients with tumors invading the perirectal fat (T3), radical surgical resection is recommended (if feasible) because of the risk of tumor cut-through and inadequate lymph node removal by local excision
97
procedures. The experience of local excision with postoperative irradiation and chemotherapy is limited, and the available data suggest higher local failure rates. Three of 15 patients (20%) with T3 tumors from M.D. Anderson have experienced local failure after local excision and postoperative irradiation with 5-FU. 13 In a study from Massachusetts General Hospital, three of four patients (75%) with T3 tumors suffered a local recurrence after local excision and postoperative irradiation) 2 Unless there is a medical contraindication or patient refusal, we do not advise a treatment program of local excision and postoperative irradiation and chemotherapy for patients with T3 tumors.
Figure 2. Lateral simulation film of a reduced field to high-risk region in pelvis as defined by radiopaque clips. An additional 5.4 Gy was given via these lateral fields.
28
Ch~topher G. Willett
Radiation Therapy Techniques and 5-FU Administration At the time of surgery, radiopaque markers are placed at the p e r i m e t e r of the excision identifying the high-risk region to aid in t r e a t m e n t planning (Figs 1 and 2). For patients with disease limited to the submucosa and muscularis propria, pelvic irradiation to 45 Gy in 25 fractions by a three- or four-field technique is given followed by the first field reduction with lateral fields to 50.4 Gy and a second field reduction (if appropriate) with lateral fields to 54.0 Gy. During the 5.5- to 6-week course of irradiation, our patients receive continuous infusion 5-FU (225 mg/mg/24 h) 5 days per week. C h e m o t h e r a p y alternatives could include bolus 5-FU with or without leucovorin during the first and last weeks of irradiation. Patients are treated in the prone position. For the initial fields (45 Gy), the superior border should be 1.5 cm above the level of the sacral promontory and the lower border of the field 4 to 5 cm below the defined tumor bed. Laterally the posteroanterioranteroposterior fields extend 1 to 1.5 cm beyond the true bony pelvis. To treat the entire presacral space with adequate margins and full dose, the lateral fields are designed so that the posterior border encompass the entire sacrum with a 1-cm margin posterior to the sacrum. Anteriorly the fields are designed to encompass the previous tumor bed, including the posterior wall of the vagina for women and a large portion of the prostate for men. The radiopaque markers placed at surgery are helpful in designing the field reductions. After 45 Gy, lateral fields with an approximately 3-cm margin around the m a r k e d tumor bed are typically used for three fi'actions to 50.4 Gy. This is followed by a further field reduction with a 2-cm margin around the m a r k e d tumor bed to 54 Gy. A small bowel series must be performed to ensure that no small bowel is within these lateral boost fields. For patients with positive or tight resection margins or poor prognostic features suggesting a higher risk of local recurrence, additional irradiation to 55 Gy to 65 Gy m a y be appropriate. Specialized techniques, such as interstitial implant, split beams with rectal dilation, or perineal proton-beam irradiation, allow homogeneous irradiation of high-risk regions in the rectum and adjacent perirectal fat with sparing of uninvolved rectum, perineum, and pelvic viscera. These techniques may allow a substantial number of patients to obtain local control with good preservation of anorectal function.
Conclusions Local excision and postoperative irradiation and chemotherapy appear to offer not only satisfactory local control and smwival, but also, importantly, sphincter preservation for selected patients with distal rectal cancer. For patients with favorable histology T1 rectal cancer, local excision alone suffices. Postoperative irradiation and chemotherapy should follow local excision procedures tbr patients with unthvorable histology T1 and all T2 tumors. The d a t a for T3 tumors with this approach are limited; however, results from single-institution studies suggest unacceptably high local failure rates. Radical resection is advised.
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