- Email: [email protected]
Rectal cancer
review M. McCourt1 J. Armitage1 J. R.T. Monson2 1
Academic Surgical Unit, Castle Hill Hospital, Cottingham, East Yorkshire, UK 2 Division of Colorectal Surgery, University of Rochester Medical Center, Rochester, New York, USA Correspondence to: J.R.T. Monson, Department of Surgery, Division of Colorectal Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box SURG, Rochester, New York 14642, USA Tel: +15852733678 Fax: +1 5852762655 Email: john_monson@ urmc.rochester.edu
RECTAL CANCER Surgery is the cornerstone of rectal cancer treatment. Oncological cure and overall survival continue to be the main goals, but sparing of the anal sphincter mechanism and functional results are also important. The modern management of rectal cancer is a multidisciplinary approach, and pre-operative staging is of crucial importance when planning treatment in these patients. Pre-operative staging is used to determine the indication for neoadjuvant therapy prior to surgical resection or to determine whether local excision is an option in carefully selected patients with early rectal cancer. Surgery in the form of total mesorectal excision (TME) has become the standard of care for mid and distal rectal cancers. Early rectal cancers do not require neoadjuvant therapy. For locally advanced cancers of the lower two-thirds of the rectum, the combination of surgical resection with chemoradiotherapy decreases local recurrence rates and probably improves overall survival. Whereas in the past local excision was only contemplated in patients who were unt for radical surgery or for local palliation in cases of metastatic disease, over the last number of years there has been increasing interest in local treatment with curative intent in early rectal cancer. keywords: rectal cancer, pre-operative staging, adjuvant therapy, local excision Surgeon, 1 June 2009, pp. 162-9
Introduction In 2004 there were 28,837 new cases of colorectal cancer in the UK, around 63% in the colon and 37% in the rectum.1 Five thousand eight hundred and thirty patients died from rectal cancer in 2004. Rectal cancer is a very different tumour from colon cancer, because of the anatomical narrow confines of the pelvis and the proximity of the genitourinary organs and nerves and the anal sphincter mechanism. It is important, therefore, to have a clear anatomical definition of the rectum. Any tumour whose distal margin is seen at 15cm or less from the anal verge using a rigid sigmoidoscope should be classified as rectal.2 Oncological cure remains the primary aim of treatment for rectal cancer, but sparing of the anal sphincters with adequate bowel, genitourinary and sexual function must also be considered. The aim of this review is to outline some of the important surgical issues in the current management of rectal cancer, namely pre-operative staging, the role of neoadjuvant and adjuvant therapy and the role of local excision.
Pre-operative staging The T stage, N stage, circumferential resection margin and identification of any distant metastatic disease are all of crucial importance when planning curative rectal cancer resections. Traditionally the challenge for pre-operative imaging is to identify those patients most likely to benefit from neoadjuvant therapy. Current practice is to stratify patients 162
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into one of three groups: those with superficial tumours requiring surgery alone, those with operable tumours but at an increased risk of local recurrence, who can be treated with short course radiotherapy and then optimal surgery, and those with more locally advanced rectal cancers with close or involved circumferential resection margins, who require long course chemoradiotherapy followed by surgery. More recently, local excision has gained popularity as a valid alternative to radical surgery in selected patients with early rectal cancer; however, this can only be considered in the presence of reliable pre-operative staging. There are a number of modalities used in the pre-operative staging of rectal cancer as outlined below.
Digital rectal examination Digital rectal examination is vital in the assessment of a rectal tumour and a mass can be palpated in 40-80% of cases.3 Evidence suggests that this does not require specialist colorectal experience with studies showing that up to 80% of palpable rectal cancers can be detected by a general practitioner.4 Rectal tumours within reach of the index finger can be palpated for distance from the anal verge, location, size and fixity. Higher lesions in the rectum obviously require rigid sigmoidoscopy, which can be carried out easily in the outpatient setting. This may be facilitated if the patient has taken a self-administered glycerine suppository.5 © 2009 Surgeon 7; 3: 162-9
Fig. 1. Axial T2 weighted MRI of pelvis with a T3N1 mid rectal cancer.
Fig. 2. Sagital T2 weighted MRI of pelvis with a T3N1 mid rectal cancer
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If a suspected rectal cancer is seen then it can be biopsied and brushed in that same outpatient sitting. The addition of brush cytology to forceps biopsy increases the diagnostic yield in a single examination and can be a complementary method of establishing the diagnosis.6 If a rectal cancer is detected by sigmoidoscopy then complete visualisation of the colon is achieved by total colonoscopy or a double contrast barium enema as the incidence of synchronous lesions is 4-5%.
Endorectal ultrasound Endorectal ultrasound (ERUS) is an established modality for the evaluation of the T stage, with accuracies varying from 62% to 92%.7 In a meta-analysis of 11 studies it has been shown that the sensitivity can be affected by the T stage, with more accurate staging for more superficial tumours and less accurate for more advanced lesions.8 There are large variations in the accuracy for nodal detection ranging from 67% to 88%.9 ERUS is limited by its operator-dependent nature, steep learning curve and limitations in staging of bulky T3 cancers, those which are stenotic and down-staged tumours after neoadjuvant therapy.10,11
CT scan The role of pre-operative CT scanning in the local staging of rectal cancer is at best limited. In a meta-analysis of 78 studies published over a period of 18 years covering 4897 patients with rectal cancer, CT showed an accuracy of 73% for T staging with wide variations in accuracy for nodal detection ranging from 22% to 73%.12,13 The low spacial and contrast resolution of CT does not give a detailed evaluation of the rectal wall and hence is poor at evaluating superficial tumours, but it can easily identify intra-abdominal metastatic disease. Initially optimistic results were achieved with CT for staging of locally advanced rectal cancer, and this imaging modality has long been used in patients with fixed rectal cancers.14 CT has now been replaced by MR imaging for loco-regional rectal cancer staging.
MRI Initial MRI studies were performed using a body coil with overall accuracy for T stage and N stage not being any better than CT scan, and certainly less accurate than ERUS. However, newer techniques with the introduction of endoluminal coils and phased-array MRI can improve T stage accuracy to a range of 71-91%.15 Endorectal MRI can be as accurate as ERUS for staging of superficial tumours, but it does have its drawbacks. It has limited availability, is costly, has a limited field of view and can be uncomfortable for patients. Also similar to ERUS, the mesorectal fascia and relationship to other pelvic structures is difficult to visualise. It has been shown that circumferential resection margin (CRM) involvement after TME is the strongest predictor of local recurrence.16,17 Phased-array MRI is now considered the best imaging tool for the pre-operative assessment of the CRM with accuracy up to 100%.18 Unfortunately MRI is not very accurate in restaging tumours after neoadjuvant chemoradiotherapy and tends to overstage tumours. This may be due to difficulty in being able to differentiate fibrosis from viable residual tumour.19 Figure 1 shows an axial T2 weighted MRI of pelvis with a T3N1 mid rectal cancer. Figure 2 shows the same tumour in saggital section. For superficial rectal cancer, ERUS and endorectal MRI are the most accurate staging methods. Although both provide clear details of the rectal wall, they are not as accurate in assessing the mesorectal fascia and the CRM. For the more advanced cancers, phased-array MRI is at present the best technique for evaluating the CRM. 164 |
Adjuncts to surgery Neoadjuvant therapy In the past when curative resection of the rectum was performed in a non-standardised fashion, local recurrence rates varied from 15% to 45%.20 Complete excision of the mesorectum or total mesorectal excision (TME) is associated with a low rate of local recurrence of 7% or less.21 TME involves precise dissection in the ‘holy’ plane of areolar tissue between the visceral fascia that envelops the mesorectum and the parietal fascia overlying the other pelvic wall structures. TME emphasises the attainment of negative distal margins and CRM, and should be considered the gold-standard surgical technique for tumours in the lower two-thirds of the rectum. Local recurrence is associated with significant morbidity and directly affects patients’ overall survival. The combination of TME with adjuvant or neoadjuvant chemotherapy and radiotherapy has resulted in greater sphincter sparing rates, with decreased local recurrence and possibly improved overall survival. At the same time as TME was being introduced, there have been a number of large European randomized trials looking at neoadjuvant radiotherapy and chemoradiotherapy in patients with rectal cancer. There are a number of theoretical advantages to giving pre-operative therapy. There is a well defined target, the rectum with good blood supply and oxygenation. Pre-operative irradiation is more ‘dose-effective’ than post-operative treatment; that is to say that a lower dose is needed pre-operatively to reduce rates of local recurrence.22 Lack of post-operative changes and adhesions reduces small bowel toxicity.23 Tumour regression and downstaging following neoadjuvant therapy is associated with increased tumour resectability and a higher rate of sphincter preservation.24 The Swedish Rectal Cancer Trial in 1997 showed that a short course of high-dose pre-operative radiation therapy (25 Gy delivered in five fractions in one week) followed by surgery within one week reduced local recurrence rates at five years from 27% to 11% and overall five year survival rate improved from 48% in the surgery-alone group to 58% in the radiotherapy-plus-surgery group.25 However, the local recurrence rate in the surgery alone arm was unacceptably high as the surgery was non-standardised. The Dutch randomised trial addressed this issue by comparing pre-operative short course radiotherapy and TME to TME alone without radiotherapy in patients with mobile rectal cancers.26 The results showed that short course pre-operative radiotherapy reduced local recurrence rate from 8.2% to 2.4% at two years. No survival benefit was apparent. These results indicate the value of pre-operative radiotherapy when used in addition to standardised TME. There was no significant difference in morbidity and mortality between the two groups except in the patients who underwent abdominoperineal excision of the rectum ( n=485). There were increased perineal infection rates of 26% versus 18% and increased sexual difficulties (impotence and dyspareunia) in the irradiated group. The results of the Medical Research Council CR07 study have recently been published in abstract form.27 This multicentre trial involving 1350 patients compared routine short course pre-operative radiotherapy with selective post-operative chemoradiation. The results showed a benefit in local recurrence rate in the short course group irrespective of quality of TME. However, median follow-up was only three years and data concerning tumour height, tumour grade and patient morbidity are yet to be published.
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The German Rectal Cancer Study Group recently published a large (823 patients) prospective randomized trial comparing pre-operative versus post-operative chemoradiation in the treatment of T3/T4 or node-positive disease.28 All patients underwent TME. They demonstrated that, although no survival benefit was achieved between the two groups, there was a superior compliance rate, a significant reduction both in local recurrence rate (6% vs 13%) and treatment toxicity in the pre-operative group and an increased rate of sphincter preservation in this group. Two other randomized trials, the Uppsala trial and the NSABP R03 trial, have also demonstrated the superiority of pre-operative radiotherapy regimen, compared with post-operative in terms of better compliance, better local control and lower toxicity.29,30 At present preoperative chemoradiotherapy followed by TME provides the treatment standard for rectal cancer patients with T3, T4, N0 or any T stage with nodal disease.31 The use of pre-operative short course radiotherapy in T1 and T2 is becoming more widespread. This generally applies to patients with cancers in the lower two-thirds of the rectum. Cancers higher up in the rectum (i.e. above 12cm) behave more like colon cancers and are usually treated with surgical resection and then adjuvant therapy if required. The role of pre-operative chemoradiation therapy continues to evolve. Several new chemotherapeutic agents like capecitabine, irinotecan and oxaloplatin have been used successfully in patients with metastatic colorectal cancer. The combinations of these new drugs together with new radiotherapy regimens are being investigated in an attempt to optimize neoadjuvant treatment in rectal cancer.32,33
Adjuvant therapy Whereas pre-operative chemoradiotherapy is the standard treatment for T3/T4 or N1 rectal cancer in Europe, post-operative chemoradiotherapy has been the standard treatment in the USA. A number of trials have shown that for locally advanced rectal cancer, post-operative chemoradiotherapy significantly improves local control as compared with surgery alone. In 1985, the Gastrointestinal Tumor Study Group (GITSG) trial randomised 227 patients into four groups following curative resection for rectal cancer: patients who had surgery alone, patients who received post-operative irradiation, patients who received post-operative chemotherapy (5-FU and semustine) and patients who received both radio- and chemotherapy.34 The combination of chemotherapy and radiation therapy reduced disease recurrence from 55% to 33%. There was no difference in overall survival. In 1988, the National Surgical Adjuvant Breast and Bowel Project (NASBP) R-01 trial randomized 555 patients into three groups following surgery: surgery alone, post-operative chemotherapy and postoperative radiotherapy.35 Radiation therapy reduced local recurrence from 25% to 16%, without any effect on overall survival. In the North Central Cancer Treatment Group (NCCTG) trial 204 patients received post-operative irradiation alone or in combination with chemotherapy.36 After a median follow-up of more than seven years, the combined therapy reduced the rate of recurrence by 34%. The combined therapy also reduced the rate of cancerrelated deaths by 36% and reduced the overall death rate by 29%. The information from these trials prompted a National Institutes of Health consensus conference, in 1990, to recommend post-operative chemoradiotherapy as standard treatment for stage II (T3 or T4, N0) or stage III (any T stage, N1, N2) rectal cancer.37 © 2009 Surgeon 7; 3: 162-9
The NSABP R-02 trial showed that the addition of post-operative radiotherapy to chemotherapy reduced local recurrence (13% to 8% at five years) but had no effect on overall survival.38 There was an improvement in survival in the 5-FU and leucorvorin chemotherapy arm. Overall, adjuvant chemoradiation reduces locoregional recurrence by 50% and improves survival by 10-15%. However, in the above studies, surgery was not standardised in the form of TME and the toxicity from post-operative radiotherapy is significant. Surgery in the form of TME has become the standard of care for mid and distal rectal cancers. T1 and T2 rectal cancers do not require neoadjuvant therapy. For rectal cancers which are T3, T4 or any T stage and nodal disease, pre-operative radiotherapy with TME improves local control with no impact on overall survival. Pre-operative radiotherapy appears to be superior to post-operative radiotherapy with improved local control and lower toxicity. In the USA, since 1996, the rate of pre-operative radiotherapy has increased, whilst the rate of post-operative radiotherapy has begun to decline.39 Pre-operative chemoradiotherapy improves local control further, compared to radiotherapy alone and may improve sphincter preserving surgical resections.40
Local excision The standard treatment for early rectal cancer has been radical resection in the form of anterior resection or abdominoperineal excision of the rectum. These operations are associated with significant mortality (2-4%) and morbidity (20-30%) and bowel, bladder and sexual function may be impaired.41-44 Whereas in the past, local excision was only contemplated in patients who were unfit for radical surgery or for local palliation in cases of metastatic disease, there has been increasing interest over the last number of years in local treatment with curative intent in early rectal cancer. Appropriate selection of patients for local excision depends on a number of tumour and patient-related characteristics.
Tumour size For a number of years, only tumours less than 3cm in diameter were considered for local excision. Larger tumours tend to be more advanced; however, tumour size has not been found to be an independent predictor of lymph node metastases and overall survival.45 Tumour size is not a contraindication to local excision but the bigger the tumour the more technically challenging it is to excise locally.
Tumour morphology Non-exophytic (ulcerated) tumours tend to be more locally advanced than exophytic tumours.46 A recent study by Chambers et al looked at tumour morphology as a predictor of outcome after local excision of rectal cancer.47 The recurrence rate in 91 patients was 9% in patients with exophytic tumours and 40% in patients with non-exophytic tumours. The five year survival was higher in the exophytic group (91% vs 54%). However, more T1 tumours and fewer T2/T3 tumours were in the exophytic group. Morphology was not shown to be an independent predictor of outcome.
Depth of mural invasion (T stage) The T stage is vitally important because the incidence of lymph node metastases correlates directly with depth of rectal wall invasion;
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6-12% for T1 tumours, 17-22% for T2 tumours and 51-66% for T3 tumours.48,49 T stage also correlates with local recurrence following local excision, with recurrence rates of 5% with T1 tumours, 18% with T2 tumours and 22% with T3 tumours.50,51 Local excision can therefore be accepted as definitive treatment in selected T1 lesions only. Currently the most accurate method for pre-operative T staging of early rectal cancer is endorectal ultrasound or MRI with an endorectal coil.8 Although both provide clear details of the rectal wall, they are not accurate in assessing the mesorectal fascia and presence of lymph nodes and for this, phased-array MRI is at present the best technique.52
Tumour histology The incidence of lymph node positivity and local recurrence rates have been associated with the degree of tumour differentiation, poorly differentiated tumours having a higher risk of nodal metastasis and worse prognosis than well or moderately differentiated tumours.53
Lymphovascular invasion Lymphatic and blood vessel invasion can predict the presence of lymph node metastases. In a study by Blumberg et al, looking at pathological factors in T1 or T2 tumours in 318 patients, positive lymph nodes were present in 14% of tumours without lymphovascular invasion and 33% of tumours which demonstrated lymphovascular invasion.54
Mucinous tumours Tumours with mucinous or colloid histology have been associated with a higher incidence of lymph node metastases and poorer prognosis in some studies; however, there is conflicting evidence and there may be not such a difference in early rectal cancer.55,56 There are limitations with histological features of biopsy specimens as there can be a degree of inter-observer variation and the biopsy sample may not be representative of other areas of the tumour as the biopsies are usually small. It must also be considered that tumours with unfavourable histological features have a poorer prognosis irrespective of the type of surgery they undergo, but currently poor differentiation, lymphovascular invasion and an extensive mucinous component in early rectal cancers are considered contraindications to local excision.
Patient related characteristics In carefully selected patients with T1 rectal cancers and no poor prognostic histological factors, local excision with curative intent may be considered. Patients with early rectal cancers with unfavourable histology or with more advanced lesions may be candidates for local excision with or without adjuvant therapy if they have significant co-morbidities prohibiting major abdominal surgery. Patients with diffuse metastatic disease may also be managed with palliative local procedures.
Methods of local excision There are four main types of local excision: transanal, transanal endoscopic microsurgery (TEM), transsacral and transsphincteric. The transsacral (Kraske procedure) and the transsphincteric (York Mason procedure) approaches are largely historical.57,58 166 |
Transanal excision This is the most commonly performed operation, where a fullthickness excision down to perirectal fat with a 1cm circumferential margin is undertaken. The rectal wall defect is then usually closed. The literature on local excision is difficult to interpret as it consists of small, retrospective series with a heterogeneous group of patients but the current data would suggest a local recurrence rate of 5-27% for T1 lesions and 11-45% for T2 lesions, with survival ranging from 74% to 90% for T1 tumours and from 55% to 75% for T2 tumours.59,60 Salvage radical surgery for recurrence after failed local excision of early rectal cancers may not provide as good an outcome as if the patient had radical surgery at the outset.61 Some studies have suggested that immediate radical surgery after local excision of a rectal cancer with unfavourable features does not compromise outcome.62
Transanal endoscopic microsurgery (TEM) TEM which was introduced by Buess et al in the early 1980s. This technique uses a closed operating proctoscope with CO2 insufflation, binocular scope and laparoscopic type instruments (Figure 3). It offers a number of advantages over transanal excision with improved visualization and exposure, and access to more proximal lesions in the rectum. TEM appears to be equivalent to radical surgery for low-risk T1 tumours in terms of local recurrence and five year survival.64-66 Local recurrence is higher and survival poorer in patients with high-risk T1 lesions after TEM compared with radical surgery.67 TEM can have a local recurrence rate of between 25% and 45% in T2 rectal cancers and therefore TEM alone appears to be a safe option in T1 rectal cancers with favourable histology only.68
Local excision with adjuvant or neoadjuvant therapy The results of local excision and adjuvant therapy are mainly retrospective reviews of selected patients who received various irradiation doses with and without chemotherapy. The Cancer and Leukaemia Group B (CALGB) reported a multiinstitutional phase II trial on local excision alone for T1 tumours, and local excision and post-operative chemoradiotherapy (54Gy/ 30 fractions five days /week and 5-FU) for T2 tumours. In this study, 59 patients with T1 tumours had a recurrence rate of 7%, with 85% six year disease-free survival. The recurrence rate in the T2 group (51 patients) was 20% with a 78% disease-free survival.69 The Radiation Therapy Oncology Group reported a phase II trial in 65 patients who had local excision. Patients with unfavorable histology or ‘insecure’ margins were treated with 50-65Gy of radiation and 5-FU. After a median follow-up of 6.1 years they reported a recurrence rate of 4% for T1, 16% for T2 and 23% for T3 tumours.70 The results of these series suggest that when compared with local excision alone, adjuvant chemoradiation confers improvements in local recurrence and disease-free survival. There are a number of benefits of pre-operative chemoradiation including partial and complete pathological tumour response, downstaging with increased tumour respectability and sphincter preservation. There have been several series evaluating pre-operative chemoradiation and local excision.71 Kim et al reported on their experience of pre-operative chemoradiation followed by local excision in 26 patients
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Fig. 3. Transanal endoscopic microsurgery equipment with T2 and T3 rectal cancers (22 patients had a complete clinical response and four patients had a partial response). Of the 22 patients who experienced a complete clinical response, 17 had a complete pathological response and were offered no other treatment. None of these 17 patients experienced a recurrence.72 Lezoche et al in 2005 reported the results of a prospective randomized trial, in 40 patients, comparing TEM against radical surgery for T2, N0 rectal tumors following preoperative chemoradiotherapy.73 The rate of complete pathological response was 30% in each group and no difference in local recurrence or survival was demonstrated.
Summary Currently the most accurate method for pre-operative T staging in early rectal cancer is endorectal ultrasound or MRI with an endorectal coil. Although both provide clear details of the rectal wall, they are not as accurate in assessing the mesorectal fascia, the circumferential margin and the presence of lymph nodes. For these reasons phasedarray MRI is at present the best overall technique for the pre-operative staging of rectal cancer. Surgery in the form of TME has become the standard of care for mid and distal rectal cancers. The use of neoadjuvent therapy in T1 and T2 rectal cancers is currently being debated. For rectal cancers which are T3, T4 or any T stage and nodal disease, pre-operative chemoradiotherapy with TME improves local control with no impact on overall survival. Pre-operative radiotherapy appears to be superior to post-operative radiotherapy with improved local control and lower toxicity. Patients with T1 rectal cancers and favourable histology are candidates for local excision. If formal histology demonstrates a more advanced tumour or poor histological risk factors then radical surgery should be performed. The current data (small retrospective studies and relatively short periods of follow-up) suggest that patients with T2 rectal cancers can be effectively treated with local excision and chemoradiation; however, this continues to be controversial.
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table 1. TNM staging for rectal tumours Tumour T1
invades submucosa
T2
invades muscularis propria
T3
invades nonperitonealised perirectal tissue
T4
invades local structures
Lymph node N0
no lymph nodes involved
N1
up to three perirectal nodes involved
N2
more than three perirectal nodes involved
Metastasis M0
no distant metastasis
M1
distant metastasis
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23. Minsky BD, Cohen AM, Enker WE et al. Combined modality therapy of rectal cancer: decreased acute toxicity with the pre-operative approach. J Clin Oncol 1992; 10: 1218-24 24. Janjan NA, Khoo VS, Abbruzzese J et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M.D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999; 44: 1027-38 25. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Eng J Med 1997; 336:980-87 26. Kapiteijn E, Marijnen CA, Nagtegaal ID et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Eng J Med 2001; 345:638-46 27. Quirke P, Sebag-Monteore D, Steele R et al. Local recurrence after rectal cancer resection is strongly related to the plane of surgical dissection and is further reduced by pre-operative short course radiotherapy. Preliminary results of the Medical Research Council (MRC) CR07 trial. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 3512 28. Sauer R, Becker H, Hohenberger W et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Eng J Med 2004; 351:1731-40 29. Pahlman L, Glimelius B. Pre or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 1990; 211: 187-95 30. Hyams DM, Mamounas EP, Petrelli N et al. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Adjuvant Breast and Bowel Project Protocol R-03. Dis Colon Rectum 1997; 40: 131-39 31. Guillem JG, Chessin DB, Cohen AM et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005; 241: 829-38 32. Gerard JP, Chapet O, Nemoz C et al. Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer with high-dose radiation and oxaliplatin-containing regimen: the Lyon R0-04 phase II trial. J Clin Oncol 2003; 21: 1119-24 33. Dunst J, Reese T, Sutter T et al. Phase I trial evaluating concurrent combination of radiotherapy and capectabine in rectal cancer. J Clin Oncol 2002; 20: 3983-91 34. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Eng J Med 1985; 312: 1465-72 35. Fisher B, Wolmark N, Rockette H et al. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP Prortocol R-01. J Natl Cancer Inst 1988; 80: 21-29 36. Krook JE, Moertel CG, Gunderson LL et al. Effective surgical adjuvant therapy for high-risk rectal cancer. N Eng J Med 1991; 324: 709-15 37. NIH consensus conference: adjuvant therapy for patients with colon and rectal cancer. JAMA 1990; 264: 1444-50
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38. Wolmark N, Weiand HS, Hyams DM et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000; 92: 388-96 39. Baxter NN, Rothenberger DA, Morris AM et al. Adjuvant radiation for rectal cancer: Do we measure up to the standard of care? An epidemiologic analysis of trends over 25 years in the United States. Dis Colon Rectum 2005; 48: 9-15 40. Ortholan C, Francois E, Thomas O et al. Role of radiotherapy with surgery for T3 and respectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum 2006; 49: 302-10 41. Matthiessen P, Hallbook O, Rutegard J et al. Population-based study of risk fsctors for postoperative death after anterior resection of the rectum. Br J Surg 2006; 93: 498-503 42. Enker WE, Merchant N, Cohen AM et al. Safety and efcacy of low anterior resection for rectal cancer, 681 consecutive cases from a specialty service. Ann Surg 1999; 230: 544-54 43. Williams N, Seow-Cohen F. Physiological and functional outcome following ultra-low anterior resection with colon-pouch anastomosis. Br J Surg 1998; 85: 1029-35 44. Nesbakken A, Nygaard K, Bull-Njaa T et al. Bladder and sexual dysfunction after mesorectal excision for rectal cancer. Br J Surg 2000; 87: 206-10 45. Whiteway J, Nicholls RJ, Morson BC. The role of surgical excision in the treatment of rectal cancer. Br J Surg 1985; 72: 694-97 46. Michelassi F, Vannucci L, Montag A et al. Importance of tumour morphology for the long term prognosis of rectal adenocarcinoma. Am Surg 1988; 54: 376-79 47. Chambers WM, Khan U, Gagliano A et al. Tumour morphology as a predictor of outcome after local excision of rectal cancer. Br J Surg 2004; 91: 457-59 48. Sitzler PJ, Seow-Choen F, Ho YH, et al. Lymph node involvement and tumor depth in rectal cancers: an analysis of 805 patients. Dis Colon Rectum 1997; 40: 1472-76 49 Brodsky JT, Richard GK, Cohen AM et al. Variables correlated with the risk of lymph node metastasis in early rectal cancer. Cancer 1992;69: 322-26 50. Bouvet M, Milas M, Giacco GG et al. Predictors of recurrence after local excision and postoperative chemoradiation therapy of adenocarcinoma of the rectum. Ann Surg Oncol 1999; 6: 26-32 51. Graham RA, Garnsey L, Jessup JM. Local excision of rectal cancer. Am J Surg 1990; 160: 306-12 52. Beets-Tan RG, Beets GL. Rectal cancer: review with emphasis on MR imaging. Radiology 2004; 232: 335-46 53. Zenni GC, Abraham K, Harford FJ et al. Characteristics of rectal carcinomas that predict the presence of lymph node metastases: implications for patient selection for local therapy. J Surg Oncol 1998; 67: 99-103 54. Blumberg D, Paty PB, Guillem JG et al. All patients with small intramural rectal cancers are at risk for lymph node metastasis. Dis Colon Rectum 1999; 42: 881-85
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55. Minsky BD, Rich T, Recht A et al. Selection criteria for local excision with or without adjuvant radiation therapy for rectal cancer. Cancer 1989; 63: 1421-29 56. Consorti F, Lorenzotti A, Midiri G et al. Prognostic signicance of mucinous carcinoma of colon and rectum: a prospective case-control study. J Surg Oncol 2000; 73: 70-74 57. Christiansen J. Excision of mid-rectal lesions by the Kraske sacral approach. Br J Surg 1980; 67: 651-52 58. Bergman L, Solhaug JH. Posterior trans-sphincteric resection for small tumours of the lower rectum. Acta Chir Scand 1986; 152: 313-16 59. Blair S, Ellenhorn JD. Transanal excision for low rectal cancers is curative in early- stage disease with favorable histology. Am Surg 2000; 66: 817-20 60. Chakravarti A, Compton CC, Shellito PC et al. Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation. Ann Surg 1999; 230; 49-54 61. Weiser MR, Landmann RG, Wong WD et al. Surgical salvage of recurrent rectal cancer after transanal excision. Dis Colon Rectum 2005; 48: 1169-75 62. Hahnloser D, Wolff BG, Larson DW et al. Immediate radical resection after local excision of rectal cancer: an oncologic compromise? Dis Colon Rectum 2005; 48: 429-37 63. Buess G, Kipfmuller K, Ibald R et al. Clinical results of transanal endoscopic microsurgery. Surg Endosc 1988; 2: 245-50 64. Lee W, Lee D, Choi S et al. Transanal endoscopic microsurgery and radical surgery for T1 and T2 rectal cancer. Surg Endosc 2003; 17: 1283-87 65. Neary P, Makin GB, White TJ et al. Transanal endoscopic microsurgery: a viable alternative in selected patients with rectal lesions. Ann Surg Oncol 2003; 10: 1106-11 66. Winde G, Nottberg H, Keller R et al. Surgical cure for early rectal carcinomas (T1): transanal endoscopic microsurgery vs anterior resection. Dis Colon Rectum 1996; 39: 969-76 67. Heintz A, Morschel M, Junginger T. Comparison of results after transanal endoscopic microsurgery and radical resection for T1 carcinoma of the rectum. Surg Endosc 1998; 12: 1145-48 68. Moore HG, Guillem JG. Local therapy for rectal cancer. Surg Clin N Am 2002; 82: 967-81 69. Steele GD, Herndon JE, Bleday RR et al. Sphinctersparing treatment for distal rectal adenocarcinoma. Ann Surg Oncol 1999; 6: 413-15 70. Russell AH, Harris J, Rosenberg PJ et al. Anal sphincter conservation for patients with adenocarcinoma of the distal rectum: long term results of radiation therapy oncology group protocol 89-02. Int J Radiat Oncol Biol Phys 2000; 46: 313-22 71. Perretta S, Guerrero V, Garcia-Aguilar J. Surgical treatment of rectal cancer: local resection. Surg Oncol Clin N Am 2006; 15: 67-93 72. Kim JS, Kim JS, Cho MJ et al. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2002 54: 403-08 73. Lezoche E, Guerrieri M, Paganini AM et al. Transanal endoscopic versus total mesorectal laparoscopic resections of T2-N0 low rectal cancers after neoadjuvant treatment: a prospective randomized trial with a 3-years minimum follow-up period. Surg Endosc 2005; 19: 751-56
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Academic Surgical Unit, Castle Hill Hospital, Cottingham, East Yorkshire, UK 2 Division of Colorectal Surgery, University of Rochester Medical Center, Rochester, New York, USA Correspondence to: J.R.T. Monson, Department of Surgery, Division of Colorectal Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box SURG, Rochester, New York 14642, USA Tel: +15852733678 Fax: +1 5852762655 Email: john_monson@ urmc.rochester.edu
RECTAL CANCER Surgery is the cornerstone of rectal cancer treatment. Oncological cure and overall survival continue to be the main goals, but sparing of the anal sphincter mechanism and functional results are also important. The modern management of rectal cancer is a multidisciplinary approach, and pre-operative staging is of crucial importance when planning treatment in these patients. Pre-operative staging is used to determine the indication for neoadjuvant therapy prior to surgical resection or to determine whether local excision is an option in carefully selected patients with early rectal cancer. Surgery in the form of total mesorectal excision (TME) has become the standard of care for mid and distal rectal cancers. Early rectal cancers do not require neoadjuvant therapy. For locally advanced cancers of the lower two-thirds of the rectum, the combination of surgical resection with chemoradiotherapy decreases local recurrence rates and probably improves overall survival. Whereas in the past local excision was only contemplated in patients who were unt for radical surgery or for local palliation in cases of metastatic disease, over the last number of years there has been increasing interest in local treatment with curative intent in early rectal cancer. keywords: rectal cancer, pre-operative staging, adjuvant therapy, local excision Surgeon, 1 June 2009, pp. 162-9
Introduction In 2004 there were 28,837 new cases of colorectal cancer in the UK, around 63% in the colon and 37% in the rectum.1 Five thousand eight hundred and thirty patients died from rectal cancer in 2004. Rectal cancer is a very different tumour from colon cancer, because of the anatomical narrow confines of the pelvis and the proximity of the genitourinary organs and nerves and the anal sphincter mechanism. It is important, therefore, to have a clear anatomical definition of the rectum. Any tumour whose distal margin is seen at 15cm or less from the anal verge using a rigid sigmoidoscope should be classified as rectal.2 Oncological cure remains the primary aim of treatment for rectal cancer, but sparing of the anal sphincters with adequate bowel, genitourinary and sexual function must also be considered. The aim of this review is to outline some of the important surgical issues in the current management of rectal cancer, namely pre-operative staging, the role of neoadjuvant and adjuvant therapy and the role of local excision.
Pre-operative staging The T stage, N stage, circumferential resection margin and identification of any distant metastatic disease are all of crucial importance when planning curative rectal cancer resections. Traditionally the challenge for pre-operative imaging is to identify those patients most likely to benefit from neoadjuvant therapy. Current practice is to stratify patients 162
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into one of three groups: those with superficial tumours requiring surgery alone, those with operable tumours but at an increased risk of local recurrence, who can be treated with short course radiotherapy and then optimal surgery, and those with more locally advanced rectal cancers with close or involved circumferential resection margins, who require long course chemoradiotherapy followed by surgery. More recently, local excision has gained popularity as a valid alternative to radical surgery in selected patients with early rectal cancer; however, this can only be considered in the presence of reliable pre-operative staging. There are a number of modalities used in the pre-operative staging of rectal cancer as outlined below.
Digital rectal examination Digital rectal examination is vital in the assessment of a rectal tumour and a mass can be palpated in 40-80% of cases.3 Evidence suggests that this does not require specialist colorectal experience with studies showing that up to 80% of palpable rectal cancers can be detected by a general practitioner.4 Rectal tumours within reach of the index finger can be palpated for distance from the anal verge, location, size and fixity. Higher lesions in the rectum obviously require rigid sigmoidoscopy, which can be carried out easily in the outpatient setting. This may be facilitated if the patient has taken a self-administered glycerine suppository.5 © 2009 Surgeon 7; 3: 162-9
Fig. 1. Axial T2 weighted MRI of pelvis with a T3N1 mid rectal cancer.
Fig. 2. Sagital T2 weighted MRI of pelvis with a T3N1 mid rectal cancer
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If a suspected rectal cancer is seen then it can be biopsied and brushed in that same outpatient sitting. The addition of brush cytology to forceps biopsy increases the diagnostic yield in a single examination and can be a complementary method of establishing the diagnosis.6 If a rectal cancer is detected by sigmoidoscopy then complete visualisation of the colon is achieved by total colonoscopy or a double contrast barium enema as the incidence of synchronous lesions is 4-5%.
Endorectal ultrasound Endorectal ultrasound (ERUS) is an established modality for the evaluation of the T stage, with accuracies varying from 62% to 92%.7 In a meta-analysis of 11 studies it has been shown that the sensitivity can be affected by the T stage, with more accurate staging for more superficial tumours and less accurate for more advanced lesions.8 There are large variations in the accuracy for nodal detection ranging from 67% to 88%.9 ERUS is limited by its operator-dependent nature, steep learning curve and limitations in staging of bulky T3 cancers, those which are stenotic and down-staged tumours after neoadjuvant therapy.10,11
CT scan The role of pre-operative CT scanning in the local staging of rectal cancer is at best limited. In a meta-analysis of 78 studies published over a period of 18 years covering 4897 patients with rectal cancer, CT showed an accuracy of 73% for T staging with wide variations in accuracy for nodal detection ranging from 22% to 73%.12,13 The low spacial and contrast resolution of CT does not give a detailed evaluation of the rectal wall and hence is poor at evaluating superficial tumours, but it can easily identify intra-abdominal metastatic disease. Initially optimistic results were achieved with CT for staging of locally advanced rectal cancer, and this imaging modality has long been used in patients with fixed rectal cancers.14 CT has now been replaced by MR imaging for loco-regional rectal cancer staging.
MRI Initial MRI studies were performed using a body coil with overall accuracy for T stage and N stage not being any better than CT scan, and certainly less accurate than ERUS. However, newer techniques with the introduction of endoluminal coils and phased-array MRI can improve T stage accuracy to a range of 71-91%.15 Endorectal MRI can be as accurate as ERUS for staging of superficial tumours, but it does have its drawbacks. It has limited availability, is costly, has a limited field of view and can be uncomfortable for patients. Also similar to ERUS, the mesorectal fascia and relationship to other pelvic structures is difficult to visualise. It has been shown that circumferential resection margin (CRM) involvement after TME is the strongest predictor of local recurrence.16,17 Phased-array MRI is now considered the best imaging tool for the pre-operative assessment of the CRM with accuracy up to 100%.18 Unfortunately MRI is not very accurate in restaging tumours after neoadjuvant chemoradiotherapy and tends to overstage tumours. This may be due to difficulty in being able to differentiate fibrosis from viable residual tumour.19 Figure 1 shows an axial T2 weighted MRI of pelvis with a T3N1 mid rectal cancer. Figure 2 shows the same tumour in saggital section. For superficial rectal cancer, ERUS and endorectal MRI are the most accurate staging methods. Although both provide clear details of the rectal wall, they are not as accurate in assessing the mesorectal fascia and the CRM. For the more advanced cancers, phased-array MRI is at present the best technique for evaluating the CRM. 164 |
Adjuncts to surgery Neoadjuvant therapy In the past when curative resection of the rectum was performed in a non-standardised fashion, local recurrence rates varied from 15% to 45%.20 Complete excision of the mesorectum or total mesorectal excision (TME) is associated with a low rate of local recurrence of 7% or less.21 TME involves precise dissection in the ‘holy’ plane of areolar tissue between the visceral fascia that envelops the mesorectum and the parietal fascia overlying the other pelvic wall structures. TME emphasises the attainment of negative distal margins and CRM, and should be considered the gold-standard surgical technique for tumours in the lower two-thirds of the rectum. Local recurrence is associated with significant morbidity and directly affects patients’ overall survival. The combination of TME with adjuvant or neoadjuvant chemotherapy and radiotherapy has resulted in greater sphincter sparing rates, with decreased local recurrence and possibly improved overall survival. At the same time as TME was being introduced, there have been a number of large European randomized trials looking at neoadjuvant radiotherapy and chemoradiotherapy in patients with rectal cancer. There are a number of theoretical advantages to giving pre-operative therapy. There is a well defined target, the rectum with good blood supply and oxygenation. Pre-operative irradiation is more ‘dose-effective’ than post-operative treatment; that is to say that a lower dose is needed pre-operatively to reduce rates of local recurrence.22 Lack of post-operative changes and adhesions reduces small bowel toxicity.23 Tumour regression and downstaging following neoadjuvant therapy is associated with increased tumour resectability and a higher rate of sphincter preservation.24 The Swedish Rectal Cancer Trial in 1997 showed that a short course of high-dose pre-operative radiation therapy (25 Gy delivered in five fractions in one week) followed by surgery within one week reduced local recurrence rates at five years from 27% to 11% and overall five year survival rate improved from 48% in the surgery-alone group to 58% in the radiotherapy-plus-surgery group.25 However, the local recurrence rate in the surgery alone arm was unacceptably high as the surgery was non-standardised. The Dutch randomised trial addressed this issue by comparing pre-operative short course radiotherapy and TME to TME alone without radiotherapy in patients with mobile rectal cancers.26 The results showed that short course pre-operative radiotherapy reduced local recurrence rate from 8.2% to 2.4% at two years. No survival benefit was apparent. These results indicate the value of pre-operative radiotherapy when used in addition to standardised TME. There was no significant difference in morbidity and mortality between the two groups except in the patients who underwent abdominoperineal excision of the rectum ( n=485). There were increased perineal infection rates of 26% versus 18% and increased sexual difficulties (impotence and dyspareunia) in the irradiated group. The results of the Medical Research Council CR07 study have recently been published in abstract form.27 This multicentre trial involving 1350 patients compared routine short course pre-operative radiotherapy with selective post-operative chemoradiation. The results showed a benefit in local recurrence rate in the short course group irrespective of quality of TME. However, median follow-up was only three years and data concerning tumour height, tumour grade and patient morbidity are yet to be published.
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The German Rectal Cancer Study Group recently published a large (823 patients) prospective randomized trial comparing pre-operative versus post-operative chemoradiation in the treatment of T3/T4 or node-positive disease.28 All patients underwent TME. They demonstrated that, although no survival benefit was achieved between the two groups, there was a superior compliance rate, a significant reduction both in local recurrence rate (6% vs 13%) and treatment toxicity in the pre-operative group and an increased rate of sphincter preservation in this group. Two other randomized trials, the Uppsala trial and the NSABP R03 trial, have also demonstrated the superiority of pre-operative radiotherapy regimen, compared with post-operative in terms of better compliance, better local control and lower toxicity.29,30 At present preoperative chemoradiotherapy followed by TME provides the treatment standard for rectal cancer patients with T3, T4, N0 or any T stage with nodal disease.31 The use of pre-operative short course radiotherapy in T1 and T2 is becoming more widespread. This generally applies to patients with cancers in the lower two-thirds of the rectum. Cancers higher up in the rectum (i.e. above 12cm) behave more like colon cancers and are usually treated with surgical resection and then adjuvant therapy if required. The role of pre-operative chemoradiation therapy continues to evolve. Several new chemotherapeutic agents like capecitabine, irinotecan and oxaloplatin have been used successfully in patients with metastatic colorectal cancer. The combinations of these new drugs together with new radiotherapy regimens are being investigated in an attempt to optimize neoadjuvant treatment in rectal cancer.32,33
Adjuvant therapy Whereas pre-operative chemoradiotherapy is the standard treatment for T3/T4 or N1 rectal cancer in Europe, post-operative chemoradiotherapy has been the standard treatment in the USA. A number of trials have shown that for locally advanced rectal cancer, post-operative chemoradiotherapy significantly improves local control as compared with surgery alone. In 1985, the Gastrointestinal Tumor Study Group (GITSG) trial randomised 227 patients into four groups following curative resection for rectal cancer: patients who had surgery alone, patients who received post-operative irradiation, patients who received post-operative chemotherapy (5-FU and semustine) and patients who received both radio- and chemotherapy.34 The combination of chemotherapy and radiation therapy reduced disease recurrence from 55% to 33%. There was no difference in overall survival. In 1988, the National Surgical Adjuvant Breast and Bowel Project (NASBP) R-01 trial randomized 555 patients into three groups following surgery: surgery alone, post-operative chemotherapy and postoperative radiotherapy.35 Radiation therapy reduced local recurrence from 25% to 16%, without any effect on overall survival. In the North Central Cancer Treatment Group (NCCTG) trial 204 patients received post-operative irradiation alone or in combination with chemotherapy.36 After a median follow-up of more than seven years, the combined therapy reduced the rate of recurrence by 34%. The combined therapy also reduced the rate of cancerrelated deaths by 36% and reduced the overall death rate by 29%. The information from these trials prompted a National Institutes of Health consensus conference, in 1990, to recommend post-operative chemoradiotherapy as standard treatment for stage II (T3 or T4, N0) or stage III (any T stage, N1, N2) rectal cancer.37 © 2009 Surgeon 7; 3: 162-9
The NSABP R-02 trial showed that the addition of post-operative radiotherapy to chemotherapy reduced local recurrence (13% to 8% at five years) but had no effect on overall survival.38 There was an improvement in survival in the 5-FU and leucorvorin chemotherapy arm. Overall, adjuvant chemoradiation reduces locoregional recurrence by 50% and improves survival by 10-15%. However, in the above studies, surgery was not standardised in the form of TME and the toxicity from post-operative radiotherapy is significant. Surgery in the form of TME has become the standard of care for mid and distal rectal cancers. T1 and T2 rectal cancers do not require neoadjuvant therapy. For rectal cancers which are T3, T4 or any T stage and nodal disease, pre-operative radiotherapy with TME improves local control with no impact on overall survival. Pre-operative radiotherapy appears to be superior to post-operative radiotherapy with improved local control and lower toxicity. In the USA, since 1996, the rate of pre-operative radiotherapy has increased, whilst the rate of post-operative radiotherapy has begun to decline.39 Pre-operative chemoradiotherapy improves local control further, compared to radiotherapy alone and may improve sphincter preserving surgical resections.40
Local excision The standard treatment for early rectal cancer has been radical resection in the form of anterior resection or abdominoperineal excision of the rectum. These operations are associated with significant mortality (2-4%) and morbidity (20-30%) and bowel, bladder and sexual function may be impaired.41-44 Whereas in the past, local excision was only contemplated in patients who were unfit for radical surgery or for local palliation in cases of metastatic disease, there has been increasing interest over the last number of years in local treatment with curative intent in early rectal cancer. Appropriate selection of patients for local excision depends on a number of tumour and patient-related characteristics.
Tumour size For a number of years, only tumours less than 3cm in diameter were considered for local excision. Larger tumours tend to be more advanced; however, tumour size has not been found to be an independent predictor of lymph node metastases and overall survival.45 Tumour size is not a contraindication to local excision but the bigger the tumour the more technically challenging it is to excise locally.
Tumour morphology Non-exophytic (ulcerated) tumours tend to be more locally advanced than exophytic tumours.46 A recent study by Chambers et al looked at tumour morphology as a predictor of outcome after local excision of rectal cancer.47 The recurrence rate in 91 patients was 9% in patients with exophytic tumours and 40% in patients with non-exophytic tumours. The five year survival was higher in the exophytic group (91% vs 54%). However, more T1 tumours and fewer T2/T3 tumours were in the exophytic group. Morphology was not shown to be an independent predictor of outcome.
Depth of mural invasion (T stage) The T stage is vitally important because the incidence of lymph node metastases correlates directly with depth of rectal wall invasion;
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6-12% for T1 tumours, 17-22% for T2 tumours and 51-66% for T3 tumours.48,49 T stage also correlates with local recurrence following local excision, with recurrence rates of 5% with T1 tumours, 18% with T2 tumours and 22% with T3 tumours.50,51 Local excision can therefore be accepted as definitive treatment in selected T1 lesions only. Currently the most accurate method for pre-operative T staging of early rectal cancer is endorectal ultrasound or MRI with an endorectal coil.8 Although both provide clear details of the rectal wall, they are not accurate in assessing the mesorectal fascia and presence of lymph nodes and for this, phased-array MRI is at present the best technique.52
Tumour histology The incidence of lymph node positivity and local recurrence rates have been associated with the degree of tumour differentiation, poorly differentiated tumours having a higher risk of nodal metastasis and worse prognosis than well or moderately differentiated tumours.53
Lymphovascular invasion Lymphatic and blood vessel invasion can predict the presence of lymph node metastases. In a study by Blumberg et al, looking at pathological factors in T1 or T2 tumours in 318 patients, positive lymph nodes were present in 14% of tumours without lymphovascular invasion and 33% of tumours which demonstrated lymphovascular invasion.54
Mucinous tumours Tumours with mucinous or colloid histology have been associated with a higher incidence of lymph node metastases and poorer prognosis in some studies; however, there is conflicting evidence and there may be not such a difference in early rectal cancer.55,56 There are limitations with histological features of biopsy specimens as there can be a degree of inter-observer variation and the biopsy sample may not be representative of other areas of the tumour as the biopsies are usually small. It must also be considered that tumours with unfavourable histological features have a poorer prognosis irrespective of the type of surgery they undergo, but currently poor differentiation, lymphovascular invasion and an extensive mucinous component in early rectal cancers are considered contraindications to local excision.
Patient related characteristics In carefully selected patients with T1 rectal cancers and no poor prognostic histological factors, local excision with curative intent may be considered. Patients with early rectal cancers with unfavourable histology or with more advanced lesions may be candidates for local excision with or without adjuvant therapy if they have significant co-morbidities prohibiting major abdominal surgery. Patients with diffuse metastatic disease may also be managed with palliative local procedures.
Methods of local excision There are four main types of local excision: transanal, transanal endoscopic microsurgery (TEM), transsacral and transsphincteric. The transsacral (Kraske procedure) and the transsphincteric (York Mason procedure) approaches are largely historical.57,58 166 |
Transanal excision This is the most commonly performed operation, where a fullthickness excision down to perirectal fat with a 1cm circumferential margin is undertaken. The rectal wall defect is then usually closed. The literature on local excision is difficult to interpret as it consists of small, retrospective series with a heterogeneous group of patients but the current data would suggest a local recurrence rate of 5-27% for T1 lesions and 11-45% for T2 lesions, with survival ranging from 74% to 90% for T1 tumours and from 55% to 75% for T2 tumours.59,60 Salvage radical surgery for recurrence after failed local excision of early rectal cancers may not provide as good an outcome as if the patient had radical surgery at the outset.61 Some studies have suggested that immediate radical surgery after local excision of a rectal cancer with unfavourable features does not compromise outcome.62
Transanal endoscopic microsurgery (TEM) TEM which was introduced by Buess et al in the early 1980s. This technique uses a closed operating proctoscope with CO2 insufflation, binocular scope and laparoscopic type instruments (Figure 3). It offers a number of advantages over transanal excision with improved visualization and exposure, and access to more proximal lesions in the rectum. TEM appears to be equivalent to radical surgery for low-risk T1 tumours in terms of local recurrence and five year survival.64-66 Local recurrence is higher and survival poorer in patients with high-risk T1 lesions after TEM compared with radical surgery.67 TEM can have a local recurrence rate of between 25% and 45% in T2 rectal cancers and therefore TEM alone appears to be a safe option in T1 rectal cancers with favourable histology only.68
Local excision with adjuvant or neoadjuvant therapy The results of local excision and adjuvant therapy are mainly retrospective reviews of selected patients who received various irradiation doses with and without chemotherapy. The Cancer and Leukaemia Group B (CALGB) reported a multiinstitutional phase II trial on local excision alone for T1 tumours, and local excision and post-operative chemoradiotherapy (54Gy/ 30 fractions five days /week and 5-FU) for T2 tumours. In this study, 59 patients with T1 tumours had a recurrence rate of 7%, with 85% six year disease-free survival. The recurrence rate in the T2 group (51 patients) was 20% with a 78% disease-free survival.69 The Radiation Therapy Oncology Group reported a phase II trial in 65 patients who had local excision. Patients with unfavorable histology or ‘insecure’ margins were treated with 50-65Gy of radiation and 5-FU. After a median follow-up of 6.1 years they reported a recurrence rate of 4% for T1, 16% for T2 and 23% for T3 tumours.70 The results of these series suggest that when compared with local excision alone, adjuvant chemoradiation confers improvements in local recurrence and disease-free survival. There are a number of benefits of pre-operative chemoradiation including partial and complete pathological tumour response, downstaging with increased tumour respectability and sphincter preservation. There have been several series evaluating pre-operative chemoradiation and local excision.71 Kim et al reported on their experience of pre-operative chemoradiation followed by local excision in 26 patients
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Fig. 3. Transanal endoscopic microsurgery equipment with T2 and T3 rectal cancers (22 patients had a complete clinical response and four patients had a partial response). Of the 22 patients who experienced a complete clinical response, 17 had a complete pathological response and were offered no other treatment. None of these 17 patients experienced a recurrence.72 Lezoche et al in 2005 reported the results of a prospective randomized trial, in 40 patients, comparing TEM against radical surgery for T2, N0 rectal tumors following preoperative chemoradiotherapy.73 The rate of complete pathological response was 30% in each group and no difference in local recurrence or survival was demonstrated.
Summary Currently the most accurate method for pre-operative T staging in early rectal cancer is endorectal ultrasound or MRI with an endorectal coil. Although both provide clear details of the rectal wall, they are not as accurate in assessing the mesorectal fascia, the circumferential margin and the presence of lymph nodes. For these reasons phasedarray MRI is at present the best overall technique for the pre-operative staging of rectal cancer. Surgery in the form of TME has become the standard of care for mid and distal rectal cancers. The use of neoadjuvent therapy in T1 and T2 rectal cancers is currently being debated. For rectal cancers which are T3, T4 or any T stage and nodal disease, pre-operative chemoradiotherapy with TME improves local control with no impact on overall survival. Pre-operative radiotherapy appears to be superior to post-operative radiotherapy with improved local control and lower toxicity. Patients with T1 rectal cancers and favourable histology are candidates for local excision. If formal histology demonstrates a more advanced tumour or poor histological risk factors then radical surgery should be performed. The current data (small retrospective studies and relatively short periods of follow-up) suggest that patients with T2 rectal cancers can be effectively treated with local excision and chemoradiation; however, this continues to be controversial.
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table 1. TNM staging for rectal tumours Tumour T1
invades submucosa
T2
invades muscularis propria
T3
invades nonperitonealised perirectal tissue
T4
invades local structures
Lymph node N0
no lymph nodes involved
N1
up to three perirectal nodes involved
N2
more than three perirectal nodes involved
Metastasis M0
no distant metastasis
M1
distant metastasis
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