Rectal Cancer Treatment (PDQ®)–Health Professional Version

Anatomy

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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 lower likelihood of attaining widely negative margins and a higher risk of local recurrence.[5]

References

1. International Agency for Research on Cancer: Colorectal cancer fact sheet: Globocan 2020. Lyon, France: International Agency for Research on Cancer, 2020. Available online. Last accessed October 17, 2023.
2. American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. Available online. Last accessed June 21, 2024.
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. Lippincott Williams & Wilkins, 2011, pp 1127-41.
7. Johns LE, Houlston RS: A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 96 (10): 2992-3003, 2001. [PUBMED Abstract]
8. Imperiale TF, Juluri R, Sherer EA, et al.: A risk index for advanced neoplasia on the second surveillance colonoscopy in patients with previous adenomatous polyps. Gastrointest Endosc 80 (3): 471-8, 2014. [PUBMED Abstract]
9. Singh H, Nugent Z, Demers A, et al.: Risk of colorectal cancer after diagnosis of endometrial cancer: a population-based study. J Clin Oncol 31 (16): 2010-5, 2013. [PUBMED Abstract]
10. Srinivasan R, Yang YX, Rubin SC, et al.: Risk of colorectal cancer in women with a prior diagnosis of gynecologic malignancy. J Clin Gastroenterol 41 (3): 291-6, 2007. [PUBMED Abstract]
11. Mork ME, You YN, Ying J, et al.: High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer. J Clin Oncol 33 (31): 3544-9, 2015. [PUBMED Abstract]
12. Laukoetter MG, Mennigen R, Hannig CM, et al.: Intestinal cancer risk in Crohn's disease: a meta-analysis. J Gastrointest Surg 15 (4): 576-83, 2011. [PUBMED Abstract]
13. Fedirko V, Tramacere I, Bagnardi V, et al.: Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Ann Oncol 22 (9): 1958-72, 2011. [PUBMED Abstract]
14. Liang PS, Chen TY, Giovannucci E: Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis. Int J Cancer 124 (10): 2406-15, 2009. [PUBMED Abstract]
15. Laiyemo AO, Doubeni C, Pinsky PF, et al.: Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities. J Natl Cancer Inst 102 (8): 538-46, 2010. [PUBMED Abstract]
16. Lansdorp-Vogelaar I, Kuntz KM, Knudsen AB, et al.: Contribution of screening and survival differences to racial disparities in colorectal cancer rates. Cancer Epidemiol Biomarkers Prev 21 (5): 728-36, 2012. [PUBMED Abstract]
17. Ma Y, Yang Y, Wang F, et al.: Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS One 8 (1): e53916, 2013. [PUBMED Abstract]
18. 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]
19. 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]
20. 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]
21. 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]
22. 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]
23. 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]
24. 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]
25. 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]
26. 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]
27. 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]
28. 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]
29. DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011.
30. 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]
31. 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]
32. Le DT, Uram JN, Wang H, et al.: PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372 (26): 2509-20, 2015. [PUBMED Abstract]
33. Overman MJ, Lonardi S, Wong KYM, et al.: Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 36 (8): 773-779, 2018. [PUBMED Abstract]
34. André T, Shiu KK, Kim TW, et al.: Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med 383 (23): 2207-2218, 2020. [PUBMED Abstract]
35. 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]
36. 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]
37. 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]
38. 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]
39. 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]
40. Martin EW, 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]
41. 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]
42. 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]
43. Khoury DA, Opelka FG, Beck DE, et al.: Colon surveillance after colorectal cancer surgery. Dis Colon Rectum 39 (3): 252-6, 1996. [PUBMED Abstract]
44. 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]
45. 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]
46. Pfister DG, Benson AB, Somerfield MR: Clinical practice. Surveillance strategies after curative treatment of colorectal cancer. N Engl J Med 350 (23): 2375-82, 2004. [PUBMED Abstract]
47. Li Destri G, Di Cataldo A, Puleo S: Colorectal cancer follow-up: useful or useless? Surg Oncol 15 (1): 1-12, 2006. [PUBMED Abstract]
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 165 (5): 410-20, 1999. [PUBMED Abstract]
49. 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]

Adenocarcinomas account for most rectal tumors in the United States. Other histological types account for an estimated 2% to 5% of colorectal tumors.[1]

The World Health Organization classification of tumors of the colon and rectum includes:[2]

References

1. Kang H, O'Connell JB, Leonardi MJ, et al.: Rare tumors of the colon and rectum: a national review. Int J Colorectal Dis 22 (2): 183-9, 2007. [PUBMED Abstract]
2. Hamilton SR, Aaltonen LA: Pathology and Genetics of Tumours of the Digestive System. International Agency for Research on Cancer, 2000.

Accurate staging provides crucial information about the location and size of the primary tumor in the rectum, and, if present, the size, number, and location of any metastases. Accurate initial staging can influence therapy by helping to determine the type of surgical intervention and the choice of neoadjuvant therapy to maximize the likelihood of resection with clear margins. In primary rectal cancer, pelvic imaging helps determine the following:[1-7]

AJCC Stage Groupings and TNM Definitions

The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define rectal cancer.[11] The same classification is used for both clinical and pathological staging.[11] Treatment decisions are made with reference to the TNM classification system, rather than the older Dukes or Modified Astler-Coller classification schema.

Cancers staged using this staging system include adenocarcinomas, high-grade neuroendocrine carcinomas, and squamous carcinomas of the colon and rectum. Cancers not staged using this staging system include these histopathological types of cancer: appendiceal carcinomas, anal carcinomas, well-differentiated neuroendocrine tumors (carcinoids).[11] For more information, see Anal Cancer Treatment and Gastrointestinal Neuroendocrine Tumors Treatment.

Lymph node status

The AJCC and a National Cancer Institute-sponsored panel suggested that at least 10 to 14 lymph nodes be examined in radical colon and rectum resections in patients who did not receive neoadjuvant therapy. In cases in which a tumor is resected for palliation or in patients who have received preoperative radiation therapy, fewer lymph nodes may be present.[10-12] This takes into consideration that the number of lymph nodes examined is a reflection of both the aggressiveness of lymphovascular mesenteric dissection at the time of surgical resection and the pathological identification of nodes in the specimen.

Retrospective studies, such as Intergroup trial INT-0089 (NCT00201331), have demonstrated that the number of lymph nodes examined during colon and rectal surgery may be associated with patient outcome.[13-16]

A new tumor-metastasis staging strategy for node-positive rectal cancer has been proposed.[17]

Table 1. Definitions of TNM Stage 0a

Stage	TNMb,c	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
aReprinted with permission from AJCC: Colon and rectum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 251–74.
The explanations for superscripts b and c are at the end of Table 5.
0	Tis, N0, M0	Tis = Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae).	Enlarge
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)

Table 2. Definitions of TNM Stage Ia

Stage	TNMb,c	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
aReprinted with permission from AJCC: Colon and rectum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 251–74.
The explanations for superscripts b and c are at the end of Table 5.
I	T1–T2, N0, M0	T1 = Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria).	Enlarge
		T2 = Tumor invades the muscularis propria.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)

Table 3. Definitions of TNM Stages IIA, IIB, and IICa

Stage	TNMb,c	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
aReprinted with permission from AJCC: Colon and rectum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 251–74.
The explanations for superscripts b and c are at the end of Table 5.
IIA	T3, N0, M0	T3 = Tumor invades through the muscularis propria into pericolorectal tissues.	Enlarge
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
IIB	T4a, N0, M0	T4a = Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum).
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
IIC	T4b, N0, M0	T4b = Tumor directly invades or adheres to adjacent organs or structures.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)

Table 4. Definitions of TNM Stages IIIA, IIIB, and IIICa

Stage	TNMb,c	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
aReprinted with permission from AJCC: Colon and rectum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 251–74.
The explanations for superscripts b and c are at the end of Table 5.
IIIA	T1, N2a, M0	T1 = Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria).	Enlarge
		N2a = Four to six regional lymph nodes are positive.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
	T1–2, N1/N1c, M0	T1 = Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria).
		T2 = Tumor invades the muscularis propria.
		N1 = One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2 mm), or any number of tumor deposits are present and all identifiable lymph nodes are negative.
		–N1c = No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
IIIB	T1–T2, N2b, M0	T1 = Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria).	Enlarge
		T2 = Tumor invades the muscularis propria.
		N2b = Seven or more regional lymph nodes are positive.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
	T2–T3, N2a, M0	T2 = Tumor invades the muscularis propria.
		T3 = Tumor invades through the muscularis propria into pericolorectal tissues.
		N2a = Four to six regional lymph nodes are positive.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
	T3–T4a, N1/N1c, M0	T3 = Tumor invades through the muscularis propria into pericolorectal tissues.
		T4 = Tumor invades the visceral peritoneum or invades or adheres to adjacent organ or structure.
		–T4a = Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum).
		N1 = One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2 mm), or any number of tumor deposits are present and all identifiable lymph nodes are negative.
		–N1c = No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
IIIC	T3–T4a, N2b, M0	T3 = Tumor invades through the muscularis propria into pericolorectal tissues.	Enlarge
		T4 = Tumor invades the visceral peritoneum or invades or adheres to adjacent organ or structure.
		–T4a = Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum).
		N2b = Seven or more regional lymph nodes are positive.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
	T4a, N2a, M0	T4a = Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum).
		N2a = Four to six regional lymph nodes are positive.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)
	T4b, N1–N2, M0	T4b = Tumor directly invades or adheres to adjacent organs or structures.
		N1 = One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2 mm), or any number of tumor deposits are present and all identifiable lymph nodes are negative.
		–N1a = One regional lymph node is positive.
		–N1b = Two or three regional lymph nodes are positive.
		–N1c = No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues.
		N2 = Four or more regional nodes are positive.
		–N2a = Four to six regional lymph nodes are positive.
		–N2b = Seven or more regional lymph nodes are positive.
		M0 = No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. (This category is not assigned by pathologists.)

Table 5. Definitions of TNM Stages IVA, IVB, and IVCa

Stage	TNMb,c	Definition	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
aReprinted with permission from AJCC: Colon and rectum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 251–74.
b Direct invasion in T4 includes invasion of other organs or other segments of the colorectum as a result of direct extension through the serosa, as confirmed on microscopic examination (e.g., invasion of the sigmoid colon by a carcinoma of the cecum) or, for cancers in a retroperitoneal or subperitoneal location, direct invasion of other organs or structures by virtue of extension beyond the muscularis propria (i.e., respectively, a tumor on the posterior wall of the descending colon invading the left kidney or lateral abdominal wall; or a mid or distal rectal cancer with invasion of prostate, seminal vesicles, cervix, or vagina).
cTumor that is adherent to other organs or structures, grossly, is classified cT4b. However, if no tumor is present in the adhesion, microscopically, the classification should be pT1-4a depending on the anatomical depth of wall invasion. The V and L classification should be used to identify the presence or absence of vascular or lymphatic invasion whereas the PN prognostic factor should be used for perineural invasion.
IVA	Any T, Any N, M1a	TX = Primary tumor cannot be assessed.	Enlarge
		T0 = No evidence of primary tumor.
		Tis = Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae).
		T1 = Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria).
		T2 = Tumor invades the muscularis propria.
		T3 = Tumor invades through the muscularis propria into pericolorectal tissues.
		T4 = Tumor invades the visceral peritoneum or invades or adheres to adjacent organ or structure.
		–T4a = Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum).
		–T4b = Tumor directly invades or adheres to adjacent organs or structures.
		NX = Regional lymph nodes cannot be assessed.
		N0 = No regional lymph node metastasis.
		N1 = One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2 mm), or any number of tumor deposits are present and all identifiable lymph nodes are negative.
		–N1a = One regional lymph node is positive.
		–N1b = Two or three regional lymph nodes are positive.
		–N1c = No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues.
		N2 = Four or more regional nodes are positive.
		–N2a = Four to six regional lymph nodes are positive.
		–N2b = Seven or more regional lymph nodes are positive.
		M1a = Metastasis to one site or organ is identified without peritoneal metastasis.
IVB	Any T, Any N, M1b	Any T = See T descriptions above in Any T, Any N, M1a TNM stage group.
		Any N = See N descriptions above in Any T, Any N1, M1a TNM stage group.
		M1b = Metastasis to two or more sites or organs is identified without peritoneal metastasis.
IVC	Any T, Any N, M1c	Any T = See T descriptions above in Any T, Any N, M1a TNM stage group.
		Any N = See N descriptions above in Any T, Any N1, M1a TNM stage group.
		M1c = Metastasis to the peritoneal surface is identified alone or with other site or organ metastases.

References

1. Schmidt CR, Gollub MJ, Weiser MR: Contemporary imaging for colorectal cancer. Surg Oncol Clin N Am 16 (2): 369-88, 2007. [PUBMED Abstract]
2. Siddiqui AA, Fayiga Y, Huerta S: The role of endoscopic ultrasound in the evaluation of rectal cancer. Int Semin Surg Oncol 3: 36, 2006. [PUBMED Abstract]
3. Søreide K: Molecular testing for microsatellite instability and DNA mismatch repair defects in hereditary and sporadic colorectal cancers--ready for prime time? Tumour Biol 28 (5): 290-300, 2007. [PUBMED Abstract]
4. Zammit M, Jenkins JT, Urie A, et al.: A technically difficult endorectal ultrasound is more likely to be inaccurate. Colorectal Dis 7 (5): 486-91, 2005. [PUBMED Abstract]
5. 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. Lippincott Williams & Wilkins, 2011, pp 1127-41.
6. Goldstein MJ, Mitchell EP: Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Invest 23 (4): 338-51, 2005. [PUBMED Abstract]
7. Das P, Skibber JM, Rodriguez-Bigas MA, et al.: Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 109 (9): 1750-5, 2007. [PUBMED Abstract]
8. Lahaye MJ, Engelen SM, Nelemans PJ, et al.: Imaging for predicting the risk factors--the circumferential resection margin and nodal disease--of local recurrence in rectal cancer: a meta-analysis. Semin Ultrasound CT MR 26 (4): 259-68, 2005. [PUBMED Abstract]
9. 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]
10. 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]
11. Jessup J, Benson A, Chen V: Colon and Rectum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 251–74.
12. Nelson H, Petrelli N, Carlin A, et al.: Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 93 (8): 583-96, 2001. [PUBMED Abstract]
13. 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]
14. 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]
15. 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]
16. 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]
17. Greene FL, Stewart AK, Norton HJ: New tumor-node-metastasis staging strategy for node-positive (stage III) rectal cancer: an analysis. J Clin Oncol 22 (10): 1778-84, 2004. [PUBMED Abstract]

The management of rectal cancer varies somewhat from that of colon cancer because of the increased risk of local recurrence and a poorer overall prognosis. Differences include surgical technique, the use of radiation therapy, and the method of chemotherapy administration. In addition to determining the intent of rectal cancer surgery (i.e., curative or palliative), it is important to consider therapeutic issues related to the maintenance or restoration of normal anal sphincter, genitourinary function, and sexual function.[1,2]

The approach to the management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology.

References

1. 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]
2. Baxter NN, Garcia-Aguilar J: Organ preservation for rectal cancer. J Clin Oncol 25 (8): 1014-20, 2007. [PUBMED Abstract]
3. Le DT, Uram JN, Wang H, et al.: PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372 (26): 2509-20, 2015. [PUBMED Abstract]
4. Overman MJ, Lonardi S, Wong KYM, et al.: Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 36 (8): 773-779, 2018. [PUBMED Abstract]
5. André T, Shiu KK, Kim TW, et al.: Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med 383 (23): 2207-2218, 2020. [PUBMED Abstract]
6. Cercek A, Lumish M, Sinopoli J, et al.: PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med 386 (25): 2363-2376, 2022. [PUBMED Abstract]
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18. Roh MS, Colangelo LH, O'Connell MJ, et al.: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27 (31): 5124-30, 2009. [PUBMED Abstract]
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22. Rich TA, Skibber JM, Ajani JA, et al.: Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 32 (4): 1025-9, 1995. [PUBMED Abstract]
23. Chari RS, Tyler DS, Anscher MS, et al.: Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg 221 (6): 778-86; discussion 786-7, 1995. [PUBMED Abstract]
24. 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 40 (2): 131-9, 1997. [PUBMED Abstract]
25. Bosset JF, Magnin V, Maingon P, et al.: Preoperative radiochemotherapy in rectal cancer: long-term results of a phase II trial. Int J Radiat Oncol Biol Phys 46 (2): 323-7, 2000. [PUBMED Abstract]
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28. Peeters KC, van de Velde CJ, Leer JW, et al.: Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study. J Clin Oncol 23 (25): 6199-206, 2005. [PUBMED Abstract]
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30. 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]
31. 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 331 (8): 502-7, 1994. [PUBMED Abstract]
32. Smalley SR, Benedetti JK, Williamson SK, et al.: Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 24 (22): 3542-7, 2006. [PUBMED Abstract]
33. Fisher B, Wolmark N, Rockette H, et al.: Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 80 (1): 21-9, 1988. [PUBMED Abstract]
34. 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 92 (5): 388-96, 2000. [PUBMED Abstract]
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36. Conroy T, Bosset JF, Etienne PL, et al.: Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 22 (5): 702-715, 2021. [PUBMED Abstract]
37. Verheij FS, Omer DM, Williams H, et al.: Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial. J Clin Oncol 42 (5): 500-506, 2024. [PUBMED Abstract]
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41. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Medical Research Council Rectal Cancer Working Party. Lancet 348 (9042): 1610-4, 1996. [PUBMED Abstract]
42. Initial report from a Swedish multicentre study examining the role of preoperative irradiation in the treatment of patients with resectable rectal carcinoma. Swedish Rectal Cancer Trial. Br J Surg 80 (10): 1333-6, 1993. [PUBMED Abstract]
43. Dahlberg M, Glimelius B, Graf W, et al.: Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study. Dis Colon Rectum 41 (5): 543-9; discussion 549-51, 1998. [PUBMED Abstract]
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47. Kollmorgen CF, Meagher AP, Wolff BG, et al.: The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg 220 (5): 676-82, 1994. [PUBMED Abstract]
48. Martling A, Holm T, Johansson H, et al.: The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 92 (4): 896-902, 2001. [PUBMED Abstract]
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51. Koelbl O, Richter S, Flentje M: Influence of patient positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation: a prospective study using a 3D planning system and a radiobiological model. Int J Radiat Oncol Biol Phys 45 (5): 1193-8, 1999. [PUBMED Abstract]
52. Gunderson LL, Russell AH, Llewellyn HJ, et al.: Treatment planning for colorectal cancer: radiation and surgical techniques and value of small-bowel films. Int J Radiat Oncol Biol Phys 11 (7): 1379-93, 1985. [PUBMED Abstract]
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54. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
55. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
56. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
57. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
58. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
59. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
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Treatment of patients with advanced or recurrent rectal cancer depends on the location of the disease.

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16. Buyse M, Thirion P, Carlson RW, et al.: Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer. Lancet 356 (9227): 373-8, 2000. [PUBMED Abstract]
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20. Douillard JY, Cunningham D, Roth AD, et al.: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355 (9209): 1041-7, 2000. [PUBMED Abstract]
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22. Tournigand C, André T, Achille E, et al.: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22 (2): 229-37, 2004. [PUBMED Abstract]
23. Colucci G, Gebbia V, Paoletti G, et al.: Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol 23 (22): 4866-75, 2005. [PUBMED Abstract]
24. Fuchs CS, Marshall J, Mitchell E, et al.: Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 25 (30): 4779-86, 2007. [PUBMED Abstract]
25. Van Cutsem E, Twelves C, Cassidy J, et al.: Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19 (21): 4097-106, 2001. [PUBMED Abstract]
26. 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 19 (8): 2282-92, 2001. [PUBMED Abstract]
27. Díaz-Rubio E, Tabernero J, Gómez-España A, et al.: Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 25 (27): 4224-30, 2007. [PUBMED Abstract]
28. Porschen R, Arkenau HT, Kubicka S, et al.: Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 25 (27): 4217-23, 2007. [PUBMED Abstract]
29. Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350 (23): 2335-42, 2004. [PUBMED Abstract]
30. Saltz LB, Clarke S, Díaz-Rubio E, et al.: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26 (12): 2013-9, 2008. [PUBMED Abstract]
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34. Cunningham D, Humblet Y, Siena S, et al.: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351 (4): 337-45, 2004. [PUBMED Abstract]
35. Van Cutsem E, Köhne CH, Hitre E, et al.: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360 (14): 1408-17, 2009. [PUBMED Abstract]
36. Tol J, Koopman M, Cats A, et al.: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360 (6): 563-72, 2009. [PUBMED Abstract]
37. Maughan TS, Adams RA, Smith CG, et al.: Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377 (9783): 2103-14, 2011. [PUBMED Abstract]
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40. Tabernero J, Yoshino T, Cohn AL, et al.: Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 16 (5): 499-508, 2015. [PUBMED Abstract]
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42. Douillard JY, Siena S, Cassidy J, et al.: Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28 (31): 4697-705, 2010. [PUBMED Abstract]
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46. Heinemann V, von Weikersthal LF, Decker T, et al.: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15 (10): 1065-75, 2014. [PUBMED Abstract]
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53. Prager GW, Taieb J, Fakih M, et al.: Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med 388 (18): 1657-1667, 2023. [PUBMED Abstract]
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56. Fakih M, Tu H, Hsu H, et al.: Real-World Study of Characteristics and Treatment Outcomes Among Patients with KRAS p.G12C-Mutated or Other KRAS Mutated Metastatic Colorectal Cancer. Oncologist 27 (8): 663-674, 2022. [PUBMED Abstract]
57. Lee JK, Sivakumar S, Schrock AB, et al.: Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol 6 (1): 91, 2022. [PUBMED Abstract]
58. Neumann J, Zeindl-Eberhart E, Kirchner T, et al.: Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract 205 (12): 858-62, 2009. [PUBMED Abstract]
59. Henry JT, Coker O, Chowdhury S, et al.: Comprehensive Clinical and Molecular Characterization of KRAS G12C-Mutant Colorectal Cancer. JCO Precis Oncol 5: , 2021. [PUBMED Abstract]
60. Fakih MG, Salvatore L, Esaki T, et al.: Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med 389 (23): 2125-2139, 2023. [PUBMED Abstract]
61. Yaeger R, Weiss J, Pelster MS, et al.: Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med 388 (1): 44-54, 2023. [PUBMED Abstract]
62. Rothenberg ML, Eckardt JR, Kuhn JG, et al.: Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14 (4): 1128-35, 1996. [PUBMED Abstract]
63. Conti JA, Kemeny NE, Saltz LB, et al.: Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 14 (3): 709-15, 1996. [PUBMED Abstract]
64. Rougier P, Van Cutsem E, Bajetta E, et al.: Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 352 (9138): 1407-12, 1998. [PUBMED Abstract]
65. Cunningham D, Pyrhönen S, James RD, et al.: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352 (9138): 1413-8, 1998. [PUBMED Abstract]
66. Rothenberg ML, Oza AM, Bigelow RH, et al.: Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 21 (11): 2059-69, 2003. [PUBMED Abstract]
67. André T, Shiu KK, Kim TW, et al.: Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med 383 (23): 2207-2218, 2020. [PUBMED Abstract]
68. Andre T, Shiu K, Kim TW, et al.: Final overall survival for the phase III KN177 study: pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). [Abstract] J Clin Oncol 39 (15) (suppl): A-3500, 2021. Available online. Last accessed April 25, 2024.
69. Lenz H, Lonardi S, Zagonel V, et al.: Subgroup analyses of patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) treated with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line (1L) therapy: two-year clinical update. [Abstract] J Clin Oncol 39 (3) (suppl): A-58, 2021. Available online. Last accessed April 25, 2024.
70. Lenz HJ, Lonardi S, Elez E, et al.: Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Expanded efficacy analysis from CheckMate 8HW. [Abstract] J Clin Oncol 42 (Suppl 16): A-3503, 2024.
71. Overman MJ, McDermott R, Leach JL, et al.: Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 18 (9): 1182-1191, 2017. [PUBMED Abstract]
72. Valone FH, Friedman MA, Wittlinger PS, et al.: Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group. J Clin Oncol 7 (10): 1427-36, 1989. [PUBMED Abstract]
73. Erlichman C, Fine S, Wong A, et al.: A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. J Clin Oncol 6 (3): 469-75, 1988. [PUBMED Abstract]
74. Doroshow JH, Multhauf P, Leong L, et al.: Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. J Clin Oncol 8 (3): 491-501, 1990. [PUBMED Abstract]
75. Poon MA, O'Connell MJ, Wieand HS, et al.: Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. J Clin Oncol 9 (11): 1967-72, 1991. [PUBMED Abstract]
76. Wadler S, Lembersky B, Atkins M, et al.: Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study. J Clin Oncol 9 (10): 1806-10, 1991. [PUBMED Abstract]
77. Grem JL, Jordan E, Robson ME, et al.: Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. J Clin Oncol 11 (9): 1737-45, 1993. [PUBMED Abstract]
78. Wong CS, Cummings BJ, Brierley JD, et al.: Treatment of locally recurrent rectal carcinoma--results and prognostic factors. Int J Radiat Oncol Biol Phys 40 (2): 427-35, 1998. [PUBMED Abstract]
79. Crane CH, Janjan NA, Abbruzzese JL, et al.: Effective pelvic symptom control using initial chemoradiation without colostomy in metastatic rectal cancer. Int J Radiat Oncol Biol Phys 49 (1): 107-16, 2001. [PUBMED Abstract]
80. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001. [PUBMED Abstract]
81. Power DG, Healey-Bird BR, Kemeny NE: Regional chemotherapy for liver-limited metastatic colorectal cancer. Clin Colorectal Cancer 7 (4): 247-59, 2008. [PUBMED Abstract]
82. Khatri VP, Chee KG, Petrelli NJ: Modern multimodality approach to hepatic colorectal metastases: solutions and controversies. Surg Oncol 16 (1): 71-83, 2007. [PUBMED Abstract]
83. Pawlik TM, Choti MA: Surgical therapy for colorectal metastases to the liver. J Gastrointest Surg 11 (8): 1057-77, 2007. [PUBMED Abstract]
84. Adson MA, van Heerden JA, Adson MH, et al.: Resection of hepatic metastases from colorectal cancer. Arch Surg 119 (6): 647-51, 1984. [PUBMED Abstract]
85. Gayowski TJ, Iwatsuki S, Madariaga JR, et al.: Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors. Surgery 116 (4): 703-10; discussion 710-1, 1994. [PUBMED Abstract]
86. Hughes KS, Simon R, Songhorabodi S, et al.: Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery 100 (2): 278-84, 1986. [PUBMED Abstract]
87. Schlag P, Hohenberger P, Herfarth C: Resection of liver metastases in colorectal cancer--competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 16 (4): 360-5, 1990. [PUBMED Abstract]
88. Rosen CB, Nagorney DM, Taswell HF, et al.: Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. Ann Surg 216 (4): 493-504; discussion 504-5, 1992. [PUBMED Abstract]
89. Fong Y, Fortner J, Sun RL, et al.: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230 (3): 309-18; discussion 318-21, 1999. [PUBMED Abstract]
90. Scheele J, Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 77 (11): 1241-6, 1990. [PUBMED Abstract]
91. Scheele J, Stangl R, Altendorf-Hofmann A, et al.: Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 110 (1): 13-29, 1991. [PUBMED Abstract]
92. Wagman LD, Kemeny MM, Leong L, et al.: A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. J Clin Oncol 8 (11): 1885-93, 1990. [PUBMED Abstract]
93. Coppa GF, Eng K, Ranson JH, et al.: Hepatic resection for metastatic colon and rectal cancer. An evaluation of preoperative and postoperative factors. Ann Surg 202 (2): 203-8, 1985. [PUBMED Abstract]
94. Taylor M, Forster J, Langer B, et al.: A study of prognostic factors for hepatic resection for colorectal metastases. Am J Surg 173 (6): 467-71, 1997. [PUBMED Abstract]
95. Jaeck D, Bachellier P, Guiguet M, et al.: Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie. Br J Surg 84 (7): 977-80, 1997. [PUBMED Abstract]
96. Fernández-Trigo V, Shamsa F, Sugarbaker PH: Repeat liver resections from colorectal metastasis. Repeat Hepatic Metastases Registry. Surgery 117 (3): 296-304, 1995. [PUBMED Abstract]
97. Weeks JC, Nelson H, Gelber S, et al.: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 287 (3): 321-8, 2002. [PUBMED Abstract]
98. Higgins GA, Amadeo JH, McElhinney J, et al.: Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel. A Veterans Administration Surgical Oncology Group report. Cancer 53 (1): 1-8, 1984. [PUBMED Abstract]
99. Buyse M, Zeleniuch-Jacquotte A, Chalmers TC: Adjuvant therapy of colorectal cancer. Why we still don't know. JAMA 259 (24): 3571-8, 1988. [PUBMED Abstract]
100. Laurie JA, Moertel CG, Fleming TR, et al.: Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol 7 (10): 1447-56, 1989. [PUBMED Abstract]
101. Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322 (6): 352-8, 1990. [PUBMED Abstract]
102. Leonard GD, Brenner B, Kemeny NE: Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol 23 (9): 2038-48, 2005. [PUBMED Abstract]
103. Hernandez-Alejandro R, Ruffolo LI, Sasaki K, et al.: Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases. JAMA Surg 157 (6): 524-530, 2022. [PUBMED Abstract]
104. Adam R, Piedvache C, Chiche L, et al.: Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET). [Abstract] J Clin Oncol 46 (Suppl 16): A-3500, 2024.
105. Rossi S, Buscarini E, Garbagnati F, et al.: Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol 170 (4): 1015-22, 1998. [PUBMED Abstract]
106. Solbiati L, Livraghi T, Goldberg SN, et al.: Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology 221 (1): 159-66, 2001. [PUBMED Abstract]
107. Lencioni R, Goletti O, Armillotta N, et al.: Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial. Eur Radiol 8 (7): 1205-11, 1998. [PUBMED Abstract]
108. Curley SA, Izzo F, Delrio P, et al.: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 230 (1): 1-8, 1999. [PUBMED Abstract]
109. Oshowo A, Gillams A, Harrison E, et al.: Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases. Br J Surg 90 (10): 1240-3, 2003. [PUBMED Abstract]
110. Livraghi T, Solbiati L, Meloni F, et al.: Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection: the "test-of-time approach". Cancer 97 (12): 3027-35, 2003. [PUBMED Abstract]
111. Pawlik TM, Izzo F, Cohen DS, et al.: Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 10 (9): 1059-69, 2003. [PUBMED Abstract]
112. Kemeny N, Huang Y, Cohen AM, et al.: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341 (27): 2039-48, 1999. [PUBMED Abstract]
113. Kemeny MM, Adak S, Gray B, et al.: Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study. J Clin Oncol 20 (6): 1499-505, 2002. [PUBMED Abstract]
114. Kemeny N, Daly J, Reichman B, et al.: Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med 107 (4): 459-65, 1987. [PUBMED Abstract]
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117. Kemeny N, Cohen A, Seiter K, et al.: Randomized trial of hepatic arterial floxuridine, mitomycin, and carmustine versus floxuridine alone in previously treated patients with liver metastases from colorectal cancer. J Clin Oncol 11 (2): 330-5, 1993. [PUBMED Abstract]
118. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. Meta-Analysis Group in Cancer. J Natl Cancer Inst 88 (5): 252-8, 1996. [PUBMED Abstract]
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The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Treatment Option Overview for Rectal Cancer

Added text to state that total neoadjuvant therapy is also a treatment option for patients with rectal cancer.

Added Total neoadjuvant therapy as a new subsection.

Added Long-course versus short-course radiation therapy as a new subsection.

Treatment of Stages II and III Rectal Cancer

Added text about the results of the OPRA study in which 324 patients with stage II or III rectal cancer were randomly assigned to receive either induction chemotherapy followed by chemoradiation therapy or chemoradiation therapy followed by consolidation chemotherapy. Patients had the potential to omit surgery based on response assessment (cited Verheij et al. as reference 24 and Garcia-Aguilar et al. as reference 25).

Treatment of Stage IV and Recurrent Rectal Cancer

Added text about the results of the SUNLIGHT trial that included 492 patients with stage IV colorectal cancer whose cancer was refractory to up to two prior chemotherapy regimens. Patients were randomly assigned to receive either trifluridine-tipiracil monotherapy or trifluridine-tipiracil combined with bevacizumab (cited Prager et al. as reference 53 and level of evidence A1).

Added text about the results of the CheckMate 8HW study that randomly assigned 303 patients to receive either nivolumab and ipilimumab or chemotherapy alone (cited Lenz et al. as reference 70).

Added text about outcomes for patients with unresectable liver metastases who undergo liver transplant. The optimal patient cohort for this therapy is still being determined, but in general, the goal is to achieve good initial systemic control with chemotherapy, followed by transplant (cited Hernandez-Alejandro et al. as reference 103 and level of evidence C3).

Added text about the results of the TRANSMET that randomly assigned 94 patients to receive either chemotherapy and liver transplant or chemotherapy alone (cited Adam et al. as reference 104 and level of evidence A1).

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