Surgical Management of Colorectal Cancer

Radical surgery with curative intent is the treatment of choice in the majority of colorectal cancers. The basic surgical principles are removal of the major vascular pedicle feeding the tumor along with its lymphatics, obtaining a tumor-free margin, and en bloc resection of any organs or structures attached to the tumor. True colonic mucosal recurrences are rare. More common are para-anastomotic recurrences reflecting possibly an inadequate lymphadenectomy. In colon cancer, it is recommended that at least a 5 cm margin of normal bowel be obtained on either side of the tumor in order to minimize the possibility of a local recurrence. For right-sided tumors, the length of ileum apparently does not influence the local recurrence rate. In rectal cancer surgery, retrospective studies have demonstrated that inadvertent perforation at the time of surgery occurs in approximately 7 to 25% of the cases and statistically reduces survival and increases local recurrence.

Curative resections in rectal cancer may require a permanent colostomy. As technology has advanced, so have the efforts to preserve sphincter function without compromising cure. A distal surgical margin of at least 2 cm in the fresh specimen is desired in rectal cancer resections. Rarely, rectal adenocarcinomas will have distal submucosal spread.

In patients with distal rectal adenocarcinomas at least a 1 cm margin of resection is desirable. Some authors have reported margins less than 1 cm in patients who received neoadjuvant chemoradiation and underwent sphincter saving procedures without compromising either recurrence or disease-free survival.

Performance of an adequate lymphadenectomy cannot be overemphasized. Adequate lymph node resection is imperative for staging and selection of patients for adjuvant treatment. In colon cancer, a minimum of 12 negative lymph nodes should be examined to confirm node-negative disease. In rectal cancer, there is no evidence that high ligation of the inferior mesenteric artery offers any benefit over ligation at the level of the origin of the superior rectal artery. Even though it has been recommended that a minimum of 4 lymph nodes be examined for entry into adjuvant rectal trials, Tepper and colleagues reported that 14 lymph nodes need to be sampled to accurately define nodal status in rectal cancer accurately. Four cm of attached distal mesorectum should be obtained with the resected specimen. Routine extended lateral pelvic node dissection is not recommended in rectal cancer surgery. Metastases to these lymph nodes occur in about 10% of patients and imply a dire prognosis. If clinically indicated, an attempt to remove these lymph nodes at the time of surgery is warranted.

Sentinel lymph node mapping has changed the management of melanoma and breast cancer. At this time it appears not to have a major effect in altering therapy in colorectal cancer. By identifying the sentinel lymph node(s), immunohistochemical and molecular techniques can be utilized to evaluate for the presence of micrometastases otherwise not diagnosed by conventional pathology. In both single- and multi-institutional studies, it has been shown that lymphatic mapping is feasible in colon cancer patients and indeed may upstage 14 to 18% lymph node negative tumors to node positive status. Not all studies have been encouraging. In a multi-institutional trial, Bertagnolli and colleagues reported that the sentinel node evaluated with multilevel sectioning failed to predict nodal status in 54% of patients. The authors concluded that sentinel node examination with multilevel sectioning is unlikely to improve risk stratification for resectable colon cancer. Sentinel lymph node for rectal cancer is more tedious and has not been as extensively evaluated as in colon cancer.

The significance of lymph node micrometastases in colorectal carcinoma is not known. Similar to reports of micrometastases in the bone marrow of patients with colorectal carcinoma undergoing curative resection, a report from the Netherlands suggested that lymphatic micrometastases adversely affected prognosis. Prospective studies are needed to clarify the significance of molecular detection of lymphatic micrometastases.

Laparoscopic-assisted colectomy is a minimally invasive technique that has been gaining popularity in the management of colon and rectal cancer. The procedure consists of mobilization of the colon laparoscopically and performing an extracorporal anastomosis. In some situations, especially in the low sigmoid colon, an intracorporal anastomosis can be performed. In rectal cancer the technique is utilized to mobilize the mesorectum. The main potential benefits from laparoscopic colectomy have been earlier postoperative recovery and less narcotic use. The Clinical Outcomes of Surgical Therapy Study Group (COST) conducted a multi-institutional prospective randomized trial comparing laparoscopic-assisted colectomy with open colectomy for colorectal cancer in the United States. After 3 years of follow-up, there were no differences in recurrence rates, wound recurrence rates, survival, or complication rates. In that trial, patients undergoing laparoscopically assisted colectomy had a shorter median hospital stay and briefer use of parenteral narcotics and oral analgesics than those undergoing open colectomy. Therefore, the equivalency of laparoscopic-assisted colectomy in experienced surgeons (performing > 20 procedures) to open colectomy has been established by the COST trial. Laparoscopic rectal cancer surgery is being performed, but it has not been evaluated and reported in randomized controlled trials.

It is not uncommon for the clinician to be faced with a patient who had an invasive carcinoma in an adenoma. The treatment in these patients has to be individualized. Favorable histopathological characteristics are free margins of resection, well- or moderately well-differentiated adenocarcinoma, and no lymphatic or vascular invasion. In addition, the endoscopist has to be confident that the lesion was completely removed. If these characteristics are met, and the polyp is limited to the submucosa, the incidence of lymph node metastases is less than 5%, but not zero. There are patients who will not tolerate the risk of having lymph node metastases, and therefore will choose surgical resection. Since the majority of the surgical resections will not reveal residual cancer and/or lymph node metastases, it is important to balance the surgical risks with the benefits of the procedure and discuss them clearly with the patient. In patients who choose endoscopic follow-up, colonoscopy should be performed 3 months after endoscopic polypectomy to evaluate the area of excision. If the colonoscopy is normal, then colonoscopy follow-up is repeated in 1 year and, if normal, in 3 years time. Polyps where the cancer has invaded into the muscularis propria should not be treated by endoscopic excision unless surgery resection is contraindicated. The incidence of lymph node metastases in T2 lesions is as high as 20%.

Local therapy has been evaluated in selected patients with rectal adenocarcinoma. These therapies include electrofulguration, endocavitary radiation with or without brachytherapy, and local excision with or without external beam radiation or chemoradiation. Of these techniques, local excision has the advantage of providing a specimen for pathological evaluation. Surgical approaches to local excision include transanal, transsacral, or transsphincteric approaches. The latter two procedures are less commonly performed than transanal procedure.

Full thickness transanal local excision has been used for selected small (4cm) rectal tumors. Patients are staged clinically with history and physical exam, CAT scan of the abdomen and pelvis, and transrectal ultrasound. Patients with clinically enlarged lymph nodes or fixed tumors are not considered good candidates for local excision. Ideally the tumor should be easily palpated during rectal exam, be mobile, and should not involve greater than 40% of the bowel circumference. After full thickness excision, the histopathology is examined. Patients without disease extension to the muscularis propria (T1 tumors) and with favorable histology (moderate or well differentiated) have a local failure risk of

< 10%. Because of the low overall risk of recurrence, postoperative chemoradiation is not usually recommended. Patients who have poorly differentiated T1 tumors or T2 tumors with any differentiation have routinely been treated with postoperative chemoradiation in order to reduce the risk of pelvic recurrence. Initial reports with short follow-up were very encouraging and stimulated a significant amount of enthusiasm. Postoperative radiation is recommended among T1 tumors with unfavorable characteristics or T2 tumors because the local disease recurrence risk is about 20%.

In the Cancer and Leukemia Group B (CALGB) multi-institutional trial of local excision for T1 tumors and local excision and chemoradiation for T2 tumors, at a median 48 months follow-up, the 6-year actuarial survival and failure-free rates for the eligible T1 and T2 patients were 85% and 78%, respectively. There were 4 failures (2 local only, 1 distant only, and 1 local and distant) in 59 T1 patients. In 51 T2 patients there were 10 recurrences (5 local only, 2 local and distant, and 3 distant only). The salvage rate for local recurrences only was over 50%, but with a short follow-up reported. A retrospective analysis from the University of Minnesota revealed a recurrence rate of 18% and 37% in patients undergoing local excision alone for T1 and T2 tumors, respectively. These investigators subsequently published their results of salvage radical surgery in 29 patients after failed local excision. Twenty-three of 29 patients had surgery with curative intent. At a mean follow-up of 39 months, the disease-free survival was 59%.

Local excision has been used after preoperative (chemo) radiation in medically inoperable patients and patients who refuse abdominal perineal resection and in those patients whose tumors have had a complete or near complete clinical response after neoadjuvant chemoradiation has been reported. However, the follow-up in the latter studies is short, and there have been reports of lymph node metastases in specimens of pathologically T0 tumors after neoadjuvant chemoradiation. Another approach has been observation in patients who achieve clinical complete response to chemoradiation. There has been a single report of high local control and survival in such patients without surgery. These results require further validation. Local excision or observation after clinical complete response after neoadjuvant therapy is investigational and should be performed only in the context of a clinical trial.

Endocavitary radiation (contact therapy) is a technique that administers very high doses of radiation that is concentrated in the tumor with minimal radiation dose to surrounding tissues. This treatment is appropriate for medically inoperable patients, or patients who refuse surgery, or early small rectal tumors.

Miguel A. Rodriguez-Bigas, MD, Paulo Hoff, MD, Christopher H. Crane, MD


  • Wolmark N, Wieand HS, Kuebler JP, et al. A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: results of Protocol C-06 [abstract 3500]. Proc Am Soc Clin Oncol 2005;23.
  • Van Cutsem E, Hoff PM, Harper P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer 2004;90:1190-7.
  • Twelves C, Wong A, Nowacki M, et al. Updated efficacy findings from the X-ACT phase III trial of capecitabine (X) vs bolus 5-FU/LV as adjuvant therapy for patients (pts) with Dukes’ C colon cancer. Proc Am Soc Clin Oncol 2005;23:251.
  • Minsky BD, Conti JA, Huang Y, Knopf K. Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer. J Clin Oncol 1995;13:1409-16.
  • Valentini V, Coco C, Cellini N, et al. Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation. Int J Radiat Oncol Biol Phys 1998;40:1067-75.
  • 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 Breast and Bowel Project Protocol R-03. Dis Colon Rectum 1997;40:131-9.
  • Crane CH, Skibber JM, Feig BW, et al. Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 2003;97:517-24.
  • Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer.[comment]. N Engl J Med 2004;351:1731-40.
  • 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.
  • Janjan NA, Khoo VS, Rich TA, et al. Locally advanced rectal cancer: surgical complications after infusional chemotherapy and radiation therapy. Radiology 1998;206:131-6.
  • Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336:980-7.
  • Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer 1995;75:2269-75.
  • Holm T, Rutqvist LE, Johansson H, Cedermark B. Postoperative mortality in rectal cancer treated with or without preoperative radiotherapy: causes and risk factors. Br J Surg 1996;83:964-8.
  • Camma C, Giunta M, Fiorica F, et al. Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA 2000;284:1008-15.
  • Suwinski R, Taylor JM, Withers HR. Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy. Int J Radiat Oncol Biol Phys 1998;42:943-51.
  • Frykholm GJ, Isacsson U, Nygard K, et al. Preoperative radiotherapy in rectal carcinomaтАФaspects of acute adverse effects and radiation technique. Int J Radiat Oncol Biol Phys 1996;35:1039-48.
  • Kapiteijn E, Kranenbarg EK, Steup WH, et al. Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prospective randomised trial with standard operative and histopathological techniques. Dutch ColoRectal Cancer Group. Eur J Surg 1999;165:410-20.
  • Bosset J, Calais G, Mineur L, et al. Preoperative radiation (Preop RT) in rectal cancer: effect and timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial [abstract 3505]. J Clin Oncol 2005;23(Suppl 16):247S.
  • Gerard J, Bonnetain F, Conroy T, et al. Preoperative (preop) radiotherapy (RT) + 5 FU/folinic acid (FA) in T3-4 rectal cancers: results of the FFCD 9203 randomized trial [abstract 3504]. J Clin Oncol 2005;23(Suppl 16):S1.
  • Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324:709-15.
  • Douglass HO Jr, Moertel CG, Mayer RJ, et al. Survival after postoperative combination treatment of rectal cancer. N Engl J Med 1986;315:1294-5.
  • Prolongation of the disease-free interval in surgically treated rectal carcinoma. Gastrointestinal Tumor Study Group. N Engl J Med 1985;312:1465-72.
  • NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1444-50.
  • Wolmark N, Wieand 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.
  • O’Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994;331:502-7.
  • Meta-analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998;16:301-8.
  • Tepper JE, O’Connell MJ, Petroni GR, et al. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol 1997;15:2030-9.
  • Smalley S, Benedetti J, Williamson S, et al. Intergroup 0144тАФa phase III trial rectal surgical adjuvant trial of pelvc radiation plus 5-FU based chemotherapy (bolus 5-FU before and after PVI +XRT vs PVI before, during, and after XRT + PVI vs biochemically modulated bolus 5-FU and XRT): Mature outcome results andpelvic failure analysis [abstract 114]. Int J Radiat Oncol Biol Phys 2004;60(Suppl 1):S137.
  • Lee JH, Ahn JH, Bahng H, et al. Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: a preliminary report. J Clin Oncol 2002;20:1751-8.
  • Janjan NA, Crane C, Feig BW, et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol 2001;24:107-12.
  • Mohiuddin M, Regine WF, John WJ, et al. Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys 2000;46:883-8.
  • Sauer R, Roedel C, Martus P, et al. Prognostic factors after neoadjuvant radiochemotherapy for rectal cancer: update of the CAO/ARO/AIO-94 phase III study [abstract 3503]. J Clin Oncol 2005;16:246s
  • Gunderson LL, Nelson H, Martenson JA, et al. Intraoperative electron and external beam irradiation with or without 5-fluorouracil and maximum surgical resection for previously unirradiated, locally recurrent colorectal cancer. Dis Colon Rectum 1996;39:1379-95.
  • Wong CS, Cummings BJ, Brierley JD, et al. Treatment of locally recurrent rectal carcinomaтАФresults and prognostic factors. Int J Radiat Oncol Biol Phys 1998;40:427-35.
  • Mohiuddin M, Marks G, Marks J. Long-term results of reirradiation for patients with recurrent rectal carcinoma. Cancer 2002;95:1144-50.
  • Scheithauer W, Rosen H, Kornek GV, et al. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993;306:752-5.
  • Hoff PM, Ansari R, Batist G, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001;19:2282-92.
  • Douillard JY, Hoff PM, Skillings JR, et al. Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2002;20:3605-16.

Provided by ArmMed Media