lunes, 15 de agosto de 2016

Rectal Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Rectal Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

National Cancer Institute

Rectal Cancer Treatment (PDQ®)–Health Professional Version


General Information About Rectal Cancer

Incidence and Mortality

It is difficult to separate epidemiological considerations of rectal cancer from those of colon cancer because epidemiological studies often consider colon and rectal cancer (i.e., colorectal cancer) together.
Worldwide, colorectal cancer is the third most common form of cancer. In 2012, there were an estimated 1.36 million new cases of colorectal cancer and 694,000 deaths.[1]
Estimated new cases and deaths from rectal cancer in the United States in 2016:[2]
  • New cases of rectal cancer: 39,220.
  • New cases of colon cancer: 95,270.
  • Deaths: 49,190 (colon and rectal cancers combined).
Colorectal cancer affects men and women almost equally. Among all racial groups in the United States, African Americans have the highest sporadic colorectal cancer incidence and mortality rates.[3,4]


ENLARGEGastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, colon, small intestine, rectum, and anus.
Anatomy of the lower gastrointestinal system.
The rectum is located within the pelvis, extending from the transitional mucosa of the anal dentate line to the sigmoid colon at the peritoneal reflection; by rigid sigmoidoscopy, the rectum measures between 10 cm and 15 cm from the anal verge.[5] The location of a rectal tumor is usually indicated by the distance between the anal verge, dentate line, or anorectal ring and the lower edge of the tumor, with measurements differing depending on the use of a rigid or flexible endoscope or digital examination.[6]
The distance of the tumor from the anal sphincter musculature has implications for the ability to perform sphincter-sparing surgery. The bony constraints of the pelvis limit surgical access to the rectum, which results in a lesser likelihood of attaining widely negative margins and a higher risk of local recurrence.[5]

Risk Factors

Hereditary syndromes

Individuals with certain known single-gene disorders are at an increased risk of developing rectal cancer. Single-gene disorders related to known syndromes account for 10% to 15% of colorectal cancers. (Refer to the PDQ summary on Genetics of Colorectal Cancer for more information.)
The hereditary colorectal cancer syndromes and related genes that are involved include the following:[6-8]
Nonpolyposis disorders
  • Lynch syndrome (hereditary nonpolyposis colorectal cancer) mismatch repair genes: Defects in mismatch repair genes (involving MSH2MLH1PMS1PMS2, or MSH6) represent the most common form of hereditary colorectal cancer and account for approximately 3% to 5% of all colorectal malignancies.[7] The majority of genetically defined cases involve MSH2 on chromosome 2p and MLH1 on chromosome 3p. In affected families, 15% to 60% of family members are found to have mutations in MSH2or MLH1; the mutation prevalence depends on features of the family history.[9] (Refer to the Lynch syndrome section in the PDQ summary on Genetics of Colorectal Cancerfor more information.)
Polyposis disorders
  • Familial adenomatous polyposis: APC gene.
  • Attenuated familial adenomatous polyposis: APC gene.
  • Turcot syndrome: APC gene; mismatch repair genes.
  • Hyperplastic polyposis syndrome: BRAF and KRAS2 genes.
  • MYH-associated polyposis: MYH gene.
Ashkenazi Jews also have an increased risk of colorectal cancer related to a mutation in theAPC gene (I1307K), which occurs in 6% to 7% of the Ashkenazi Jewish population.[10]
Hamartomatous disorders
  • Peutz-Jeghers syndrome: STK11/LKB1 gene.
  • Juvenile polyposis syndrome: SMAD4/DPC4 and BMPR1A genes.
  • Cowden syndrome: PTEN gene.
  • Ruvalcaba–Myhre–Smith syndrome: PTEN gene.
  • Hereditary mixed polyposis syndrome.

Other genetic risk factors

Other factors more common than hereditary syndromes that increase the risk of rectal cancer include the following:
  • Personal history of colorectal cancer or colorectal adenomas.
  • First-degree relative (parent, sibling, or offspring) with a history of colorectal cancer or colorectal adenomas.[11]
  • Personal history of ovarian, endometrial, or breast cancer.[12,13]
These high-risk groups account for only 23% of all colorectal cancers. Limiting screening or early cancer detection to only these high-risk groups would miss the majority of colorectal cancers.[14] (Refer to the PDQ summary on Colorectal Cancer Prevention for more information.)


Evidence supports screening for rectal cancer as a part of routine care for all adults aged 50 years and older, especially for those with first-degree relatives with colorectal cancer, for the following reasons:
  • Incidence of the disease in those 50 years and older.
  • Ability to identify high-risk groups.
  • Slow growth of primary lesions.
  • Better survival of patients with early-stage lesions.
  • Relative simplicity and accuracy of screening tests.
(Refer to the PDQ summary on Colorectal Cancer Screening for more information.)

Clinical Features

Similar to colon cancer, symptoms of rectal cancer may include the following:[15]
  • Rectal bleeding.
  • Change in bowel habits.
  • Abdominal pain.
  • Intestinal obstruction.
  • Change in appetite.
  • Weight loss.
  • Weakness.
With the exception of obstructive symptoms, these symptoms do not necessarily correlate with the stage of disease or signify a particular diagnosis.[16]

Diagnostic Evaluation

The initial clinical evaluation may include the following:
  • Physical exam and history.
  • Digital rectal exam.
  • Colonoscopy.
  • Biopsy.
  • Carcinoembryonic antigen (CEA) assay.
  • Reverse-transcription polymerase chain reaction test.
  • Immunohistochemistry.
Physical examination may reveal a palpable mass and bright blood in the rectum. Adenopathy, hepatomegaly, or pulmonary signs may be present with metastatic disease.[6] Laboratory examination may reveal iron-deficiency anemia and electrolyte and liver function abnormalities.

Prognostic Factors

The prognosis of patients with rectal cancer is related to several factors, including the following:[6,17-25]
  • Tumor adherence to or invasion of adjacent organs.[17]
  • Presence or absence of tumor involvement in the lymph nodes and the number of positive lymph nodes.[6,18-21]
  • Presence or absence of distant metastases.[6,17]
  • Perforation or obstruction of the bowel.[6,25]
  • Presence or absence of high-risk pathologic features, including the following:[23,24,26]
    • Positive surgical margins.
    • Lymphovascular invasion.
    • Perineural invasion.
    • Poorly differentiated histology.
  • Circumferential resection margin (CRM) or depth of penetration of the tumor through the bowel wall.[6,22,27] Measured in millimeters, CRM is defined as the retroperitoneal or peritoneal adventitial soft-tissue margin closest to the deepest penetration of tumor.
Only disease stage (designated by tumor [T], nodal status [N], and distant metastasis [M]) has been validated as a prognostic factor in multi-institutional prospective studies.[17-22] A major pooled analysis evaluating the impact of T and N stage and treatment on survival and relapse in patients with rectal cancer who are treated with adjuvant therapy has been published and confirms these findings.[28]
A large number of studies have evaluated other clinical, pathologic, and molecular parameters.[29-35] As yet, none has been validated in multi-institutional prospective trials. For example, microsatellite instability–high, also associated with Lynch syndrome–related rectal cancer, was shown to be associated with improved survival independent of tumor stage in a population-based series of 607 patients with colorectal cancer who were 50 years old or younger at the time of diagnosis.[36] In addition, gene expression profiling has been reported to be useful in predicting the response of rectal adenocarcinomas to preoperative chemoradiation therapy and in determining the prognosis of stages II and III rectal cancer after neoadjuvant 5-fluorouracil-based chemoradiation therapy.[37,38]
Racial and ethnic differences in overall survival (OS) after adjuvant therapy for rectal cancer have been observed, with shorter OS for blacks than for whites. Factors contributing to this disparity may include tumor position, type of surgical procedure, and presence of comorbid conditions.[39]

Follow-up After Treatment

The primary goals of postoperative surveillance programs for rectal cancer are:[40]
  1. To assess the efficacy of initial therapy.
  2. To detect new or metachronous malignancies.
  3. To detect potentially curable recurrent or metastatic cancers.
Routine, periodic studies following treatment for rectal cancer may lead to earlier identification and management of recurrent disease.[40-44] A statistically significant survival benefit has been demonstrated for more intensive follow-up protocols in two clinical trials. A meta-analysis that combined these two trials with four others reported a statistically significant improvement in survival for patients who were intensively followed.[40,45,46]
Guidelines for surveillance after initial treatment with curative intent for colorectal cancer vary between leading U.S. and European oncology societies, and optimal surveillance strategies remain uncertain.[47,48] Large, well-designed, prospective, multi-institutional, randomized studies are required to establish an evidence-based consensus for follow-up evaluation.

Carcinoembryonic antigen (CEA)

Measurement of CEA, a serum glycoprotein, is frequently used in the management and follow-up of patients with rectal cancer. A review of the use of this tumor marker for rectal cancer suggests the following:[40]
  • Serum CEA testing is not a valuable screening tool for rectal cancer because of its low sensitivity and low specificity.
  • Postoperative CEA testing is typically restricted to patients who are potential candidates for further intervention, as follows:
    • Patients with stage II or III rectal cancer (every 2–3 months for at least 2 years after diagnosis).
    • Patients with rectal cancer who would be candidates for resection of liver metastases.
In one Dutch retrospective study of total mesorectal excision for the treatment of rectal cancer, investigators found that the preoperative serum CEA level was normal in the majority of patients with rectal cancer, and yet, serum CEA levels rose by at least 50% in patients with recurrence. The authors concluded that serial, postoperative CEA testing cannot be discarded based on a normal preoperative serum CEA level in patients with rectal cancer.[49,50]

Related Summaries

Other PDQ summaries containing information related to rectal cancer include the following:
  1. Ferlay J, Soerjomataram I, Ervik M, et al.: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. Lyon, France: International Agency for Research on Cancer, 2013. IARC CancerBase No. 11. Available online. Last accessed July 5, 2016.
  2. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 11, 2016.
  3. Albano JD, Ward E, Jemal A, et al.: Cancer mortality in the United States by education level and race. J Natl Cancer Inst 99 (18): 1384-94, 2007. [PUBMED Abstract]
  4. Kauh J, Brawley OW, Berger M: Racial disparities in colorectal cancer. Curr Probl Cancer 31 (3): 123-33, 2007 May-Jun. [PUBMED Abstract]
  5. Wolpin BM, Meyerhardt JA, Mamon HJ, et al.: Adjuvant treatment of colorectal cancer. CA Cancer J Clin 57 (3): 168-85, 2007 May-Jun. [PUBMED Abstract]
  6. Libutti SK, Willett CG, Saltz LB: Cancer of the rectum. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1127-41.
  7. Strate LL, Syngal S: Hereditary colorectal cancer syndromes. Cancer Causes Control 16 (3): 201-13, 2005. [PUBMED Abstract]
  8. Young J, Jenkins M, Parry S, et al.: Serrated pathway colorectal cancer in the population: genetic consideration. Gut 56 (10): 1453-9, 2007. [PUBMED Abstract]
  9. Syngal S, Fox EA, Li C, et al.: Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing. JAMA 282 (3): 247-53, 1999. [PUBMED Abstract]
  10. Locker GY, Kaul K, Weinberg DS, et al.: The I1307K APC polymorphism in Ashkenazi Jews with colorectal cancer: clinical and pathologic features. Cancer Genet Cytogenet 169 (1): 33-8, 2006. [PUBMED Abstract]
  11. Fuchs CS, Giovannucci EL, Colditz GA, et al.: A prospective study of family history and the risk of colorectal cancer. N Engl J Med 331 (25): 1669-74, 1994. [PUBMED Abstract]
  12. Weinberg DS, Newschaffer CJ, Topham A: Risk for colorectal cancer after gynecologic cancer. Ann Intern Med 131 (3): 189-93, 1999. [PUBMED Abstract]
  13. Burstein HJ, Winer EP: Primary care for survivors of breast cancer. N Engl J Med 343 (15): 1086-94, 2000. [PUBMED Abstract]
  14. Winawer SJ: Screening for colorectal cancer. Cancer: Principles and Practice of Oncology Updates 2(1): 1-16, 1987.
  15. Stein W, Farina A, Gaffney K, et al.: Characteristics of colon cancer at time of presentation. Fam Pract Res J 13 (4): 355-63, 1993. [PUBMED Abstract]
  16. Majumdar SR, Fletcher RH, Evans AT: How does colorectal cancer present? Symptoms, duration, and clues to location. Am J Gastroenterol 94 (10): 3039-45, 1999. [PUBMED Abstract]
  17. Compton CC, Greene FL: The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 54 (6): 295-308, 2004 Nov-Dec. [PUBMED Abstract]
  18. Swanson RS, Compton CC, Stewart AK, et al.: The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Ann Surg Oncol 10 (1): 65-71, 2003 Jan-Feb. [PUBMED Abstract]
  19. Le Voyer TE, Sigurdson ER, Hanlon AL, et al.: Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 21 (15): 2912-9, 2003. [PUBMED Abstract]
  20. Prandi M, Lionetto R, Bini A, et al.: Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg 235 (4): 458-63, 2002. [PUBMED Abstract]
  21. Tepper JE, O'Connell MJ, Niedzwiecki D, et al.: Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19 (1): 157-63, 2001. [PUBMED Abstract]
  22. Balch GC, De Meo A, Guillem JG: Modern management of rectal cancer: a 2006 update. World J Gastroenterol 12 (20): 3186-95, 2006. [PUBMED Abstract]
  23. Weiser MR, Landmann RG, Wong WD, et al.: Surgical salvage of recurrent rectal cancer after transanal excision. Dis Colon Rectum 48 (6): 1169-75, 2005. [PUBMED Abstract]
  24. Fujita S, Nakanisi Y, Taniguchi H, et al.: Cancer invasion to Auerbach's plexus is an important prognostic factor in patients with pT3-pT4 colorectal cancer. Dis Colon Rectum 50 (11): 1860-6, 2007. [PUBMED Abstract]
  25. Griffin MR, Bergstralh EJ, Coffey RJ, et al.: Predictors of survival after curative resection of carcinoma of the colon and rectum. Cancer 60 (9): 2318-24, 1987. [PUBMED Abstract]
  26. DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011.
  27. Wieder HA, Rosenberg R, Lordick F, et al.: Rectal cancer: MR imaging before neoadjuvant chemotherapy and radiation therapy for prediction of tumor-free circumferential resection margins and long-term survival. Radiology 243 (3): 744-51, 2007. [PUBMED Abstract]
  28. Gunderson LL, Sargent DJ, Tepper JE, et al.: Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 22 (10): 1785-96, 2004. [PUBMED Abstract]
  29. McLeod HL, Murray GI: Tumour markers of prognosis in colorectal cancer. Br J Cancer 79 (2): 191-203, 1999. [PUBMED Abstract]
  30. Jen J, Kim H, Piantadosi S, et al.: Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 331 (4): 213-21, 1994. [PUBMED Abstract]
  31. Lanza G, Matteuzzi M, Gafá R, et al.: Chromosome 18q allelic loss and prognosis in stage II and III colon cancer. Int J Cancer 79 (4): 390-5, 1998. [PUBMED Abstract]
  32. Roth JA: p53 prognostication: paradigm or paradox? Clin Cancer Res 5 (11): 3345, 1999. [PUBMED Abstract]
  33. Nishio H, Hamady ZZ, Malik HZ, et al.: Outcome following repeat liver resection for colorectal liver metastases. Eur J Surg Oncol 33 (6): 729-34, 2007. [PUBMED Abstract]
  34. Edler D, Hallström M, Johnston PG, et al.: Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer. Clin Cancer Res 6 (4): 1378-84, 2000. [PUBMED Abstract]
  35. Popat S, Chen Z, Zhao D, et al.: A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. Ann Oncol 17 (12): 1810-7, 2006. [PUBMED Abstract]
  36. Gryfe R, Kim H, Hsieh ET, et al.: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342 (2): 69-77, 2000. [PUBMED Abstract]
  37. Liersch T, Langer C, Ghadimi BM, et al.: Lymph node status and TS gene expression are prognostic markers in stage II/III rectal cancer after neoadjuvant fluorouracil-based chemoradiotherapy. J Clin Oncol 24 (25): 4062-8, 2006. [PUBMED Abstract]
  38. Ghadimi BM, Grade M, Difilippantonio MJ, et al.: Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol 23 (9): 1826-38, 2005. [PUBMED Abstract]
  39. Dignam JJ, Ye Y, Colangelo L, et al.: Prognosis after rectal cancer in blacks and whites participating in adjuvant therapy randomized trials. J Clin Oncol 21 (3): 413-20, 2003. [PUBMED Abstract]
  40. Abir F, Alva S, Longo WE, et al.: The postoperative surveillance of patients with colon cancer and rectal cancer. Am J Surg 192 (1): 100-8, 2006. [PUBMED Abstract]
  41. Martin EW Jr, Minton JP, Carey LC: CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma. Ann Surg 202 (3): 310-7, 1985. [PUBMED Abstract]
  42. Bruinvels DJ, Stiggelbout AM, Kievit J, et al.: Follow-up of patients with colorectal cancer. A meta-analysis. Ann Surg 219 (2): 174-82, 1994. [PUBMED Abstract]
  43. Lautenbach E, Forde KA, Neugut AI: Benefits of colonoscopic surveillance after curative resection of colorectal cancer. Ann Surg 220 (2): 206-11, 1994. [PUBMED Abstract]
  44. Khoury DA, Opelka FG, Beck DE, et al.: Colon surveillance after colorectal cancer surgery. Dis Colon Rectum 39 (3): 252-6, 1996. [PUBMED Abstract]
  45. Pietra N, Sarli L, Costi R, et al.: Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum 41 (9): 1127-33, 1998. [PUBMED Abstract]
  46. Secco GB, Fardelli R, Gianquinto D, et al.: Efficacy and cost of risk-adapted follow-up in patients after colorectal cancer surgery: a prospective, randomized and controlled trial. Eur J Surg Oncol 28 (4): 418-23, 2002. [PUBMED Abstract]
  47. Pfister DG, Benson AB 3rd, Somerfield MR: Clinical practice. Surveillance strategies after curative treatment of colorectal cancer. N Engl J Med 350 (23): 2375-82, 2004. [PUBMED Abstract]
  48. Li Destri G, Di Cataldo A, Puleo S: Colorectal cancer follow-up: useful or useless? Surg Oncol 15 (1): 1-12, 2006. [PUBMED Abstract]
  49. 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 165 (5): 410-20, 1999. [PUBMED Abstract]
  50. Grossmann I, de Bock GH, Meershoek-Klein Kranenbarg WM, et al.: Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma is useful even if normal levels exist before surgery. A retrospective study of CEA values in the TME trial. Eur J Surg Oncol 33 (2): 183-7, 2007. [PUBMED Abstract]
  • Updated: August 12, 2016

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