Medication Summary

Pharmacotherapy in rectal cancer involves the use of multiple chemotherapy agents in combination regimens, often given together with radiation therapy. Chemotherapy is given before surgery to down-stage the tumor and help induce remission, and after surgery to prevent recurrences.

In metastatic rectal cancer, biologic agents are used in combination with chemotherapy. Biologic agents used in Bevacizumab in combination with chemotherapy is indicated in patients with positive or negative resectable synchronous metastases. For colon and rectal cancer, bevacizumab in combination with chemotherapy is also indicated in patients with unresectable synchronous metastases.

FOLFOX is not indicated for good-risk or average-risk stage II patients. In patients in whom 5-fluorouracil treatment has failed, capecitabine should be avoided. Patients who experience no benefit from bevacizumab regimens should avoid continuing the therapy. Cetuximab should not be replaced with panitumumab. Patients with KRAS mutations should not be treated with cetuximab or panitumumab, as these mutations confer resistance to epidermal growth factor receptor (EGFR) inhibitors.

Class Summary

These agents inhibit cell growth and proliferation. They are generally used in combination regimens.

Fluorouracil (5-FU, Fluorouracil, Adrucil)

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Blocks methylation of deoxyuridylic acid to thymidylic acid, thereby interfering with DNA synthesis. Dose is body-weight dependent and varies with specific protocol in which patient is involved.

Vincristine (Vincasar PFS, Oncovin)

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Mechanism of action uncertain. May involve decrease in reticuloendothelial cell function or increase in platelet production. It is mitotic spindle inhibitor.

Leucovorin (Wellcovorin)

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Potentiates effects of fluorouracil. Reduced form of folic acid that does not require enzymatic reduction reaction for activation. Allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis.

Given just prior to fluorouracil.

Irinotecan (Camptosar, Camptothecin-11, CPT-11)

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Inhibits topoisomerase I, inhibiting DNA replication and, consequently, cell proliferation.

Oxaliplatin (Eloxatin)

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A platinum-based antineoplastic agent used in combination with an infusion of 5-fluorouracil (5-FU) and leucovorin for the treatment of metastatic colorectal cancer in patients with recurrence or progression following initial treatment with irinotecan, 5-FU, and leucovorin. It forms interstrand and intrastrand Pt-DNA crosslinks that inhibit DNA replication and transcription. The cytotoxicity is cell-cycle nonspecific.

Cetuximab (Erbitux)

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Recombinant human/mouse chimeric monoclonal antibody that specifically binds to the extracellular domain of human epidermal growth factor receptors (EGFR, HER1, c-ErbB-1). Cetuximab-bound EGF receptor inhibits activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased production of matrix metalloproteinase and vascular endothelial growth factor. Indicated for treating irinotecan-refractory, EGFR-expressed, metastatic colorectal carcinoma. Treatment is preferably combined with irinotecan. May be administered as monotherapy if irinotecan is not tolerated.

Bevacizumab (Avastin)

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Indicated as a first-line treatment for metastatic colorectal cancer. Murine-derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). Inhibiting new blood vessel formation denies blood, oxygen, and other nutrients needed for tumor growth. Used in combination with standard chemotherapy.

Panitumumab (Vectibix)

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Recombinant human IgG2 kappa monoclonal antibody that binds to human epidermal growth factor receptor (EGFR). Indicated to treat colorectal cancer that has metastasized following standard chemotherapy.

Tucatinib (Tukysa)

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Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro and in vivo, tucatinib inhibits the antitumor activity of HER2-expressing tumor cells and inhibits the growth of HER2-expressing tumors. The combination of tucatinib with trastuzumab showed an increase in antitumor activity in vitro and in vivo. The FDA granted accelerated approval for tucatinib in combination with trastuzumab for adults with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed after treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.

Trifluridine/tipiracil (Lonsurf)

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Trifluridine is a thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation. Tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase. The combination product is indicated, as a single agent or in combination with bevacizumab, for metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Fruquintinib

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Fruquintinib is a selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. It is indicated for metastatic colorectal cancer (mCRC) in adults who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.

Questions

[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Rectal Cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/rectal.pdf. Version 3.2022 — October 27, 2022; Accessed: January 25, 2023.
American Cancer Society. Cancer Facts & Figures 2023. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf. Accessed: January 25, 2023.
Giovannucci E, Wu K. Cancers of the colon and rectum. Schottenfeld D, Fraumeni J, eds. Cancer. Epidemiology and Prevention. 3rd ed. Oxford University Press; 2006.
Anagnostopoulos G, Sakorafas GH, Kostopoulos P, et al. Squamous cell carcinoma of the rectum: a case report and review of the literature. Eur J Cancer Care (Engl). 2005 Mar. 14(1):70-4. [QxMD MEDLINE Link].
Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30. 345(9):638-46. [QxMD MEDLINE Link].
DʼSouza N, de Neree Tot Babberich MPM, d'Hoore A, et al. Definition of the Rectum: An International, Expert-based Delphi Consensus. Ann Surg. 2019 Dec. 270 (6):955-959. [QxMD MEDLINE Link].
Heald RJ. The 'Holy Plane' of rectal surgery. J R Soc Med. 1988 Sep. 81 (9):503-8. [QxMD MEDLINE Link]. [Full Text].
Leggett BA, Devereaux B, Biden K, Searle J, Young J, Jass J. Hyperplastic polyposis: association with colorectal cancer. Am J Surg Pathol. 2001 Feb. 25(2):177-84. [QxMD MEDLINE Link].
Wheeler JM, Bodmer WF, Mortensen NJ. DNA mismatch repair genes and colorectal cancer. Gut. 2000 Jul. 47(1):148-53. [QxMD MEDLINE Link]. [Full Text].
Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, et al. Colorectal Cancer Incidence Patterns in the United States, 1974–2013. J Natl Cancer Inst. 28 February 2017. 109:[Full Text].
Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 Mar 5. [QxMD MEDLINE Link]. [Full Text].
World Health Organization. Colorectal Cancer. WHO. Available at http://gco.iarc.fr/today/data/factsheets/cancers/10_8_9-Colorectum-fact-sheet.pdf. 2020; Accessed: June 7, 2022.
Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Colorectal Cancer. National Cancer Institute. Available at http://seer.cancer.gov/statfacts/html/colorect.html. Accessed: June 7, 2022.
Yothers G, Sargent DJ, Wolmark N, et al. Outcomes Among Black Patients With Stage II and III Colon Cancer Receiving Chemotherapy: An Analysis of ACCENT Adjuvant Trials. J Natl Cancer Inst. 2011 Oct 19. 103(20):1498-1506. [QxMD MEDLINE Link]. [Full Text].
Robbins AS, Siegel RL, Jemal A. Racial disparities in stage-specific colorectal cancer mortality rates from 1985 to 2008. J Clin Oncol. 2012 Feb 1. 30(4):401-5. [QxMD MEDLINE Link].
Rothwell PM, Fowkes GR, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet. Dec 7/2010; Early online publication. [Full Text].
Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011 Dec 17. 378(9809):2081-7. [QxMD MEDLINE Link]. [Full Text].
Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012 Apr 28. 379(9826):1602-12. [QxMD MEDLINE Link].
Stitzenberg KB, Sanoff HK, Penn DC, Meyers MO, Tepper JE. Practice patterns and long-term survival for early-stage rectal cancer. J Clin Oncol. 2013 Dec 1. 31(34):4276-82. [QxMD MEDLINE Link]. [Full Text].
Eu KW, Seow-Choen F, Ho JM, Ho YH, Leong AF. Local recurrence following rectal resection for cancer. J R Coll Surg Edinb. 1998 Dec. 43(6):393-6. [QxMD MEDLINE Link]. [Full Text].
Thong MS, Mols F, Lemmens VE, et al. Impact of preoperative radiotherapy on general and disease-specific health status of rectal cancer survivors: a population-based study. Int J Radiat Oncol Biol Phys. 2011 Nov 1. 81(3):e49-58. [QxMD MEDLINE Link].
Fritz CDL, Otegbeye EE, Zong X, Demb J, Nickel KB, Olsen MA, et al. Red-flag Signs and Symptoms for Earlier Diagnosis of Early-Onset Colorectal Cancer. J Natl Cancer Inst. 2023 May 4. [QxMD MEDLINE Link].
Harrison P. Proinflammatory Diet Contributes to CRC Risk in Both Sexes. Medscape Medical News. Available at https://www.medscape.com/viewarticle/891665. January 23, 2018; Accessed: January 30, 2018.
Tabung FK, Liu L, Wang W, Fung TT, Wu K, Smith-Warner SA, et al. Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women. JAMA Oncol. 2018 Jan 18. [QxMD MEDLINE Link].
Gianfredi V, Nucci D, Salvatori T, Dallagiacoma G, Fatigoni C, Moretti M, et al. Rectal Cancer: 20% Risk Reduction Thanks to Dietary Fibre Intake. Systematic Review and Meta-Analysis. Nutrients. 2019 Jul 12. 11 (7):916-32. [QxMD MEDLINE Link]. [Full Text].
Chao A, Thun MJ, Connell CJ, et al. Meat consumption and risk of colorectal cancer. JAMA. 2005 Jan 12. 293(2):172-82. [QxMD MEDLINE Link].
Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, et al. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med. 1999 Jan 14. 340(2):101-7. [QxMD MEDLINE Link].
Ferrari P, Jenab M, Norat T, Moskal A, Slimani N, Olsen A, et al. Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2007 Nov 1. 121(9):2065-72. [QxMD MEDLINE Link].
Kabat GC, Howson CP, Wynder EL. Beer consumption and rectal cancer. Int J Epidemiol. 1986 Dec. 15(4):494-501. [QxMD MEDLINE Link].
Tsoi KK, Pau CY, Wu WK, Chan FK, Griffiths S, Sung JJ. Cigarette smoking and the risk of colorectal cancer: a meta-analysis of prospective cohort studies. Clin Gastroenterol Hepatol. 2009 Jun. 7(6):682-688.e1-5. [QxMD MEDLINE Link].
Phipps AI, Baron J, Newcomb PA. Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: The Seattle Colon Cancer Family Registry. Cancer. 2011 Nov 1. 117(21):4948-57. [QxMD MEDLINE Link]. [Full Text].
Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol. 2001 Oct. 96(10):2992-3003. [QxMD MEDLINE Link].
Burt RW. Familial risk and colorectal cancer. Gastroenterol Clin North Am. 1996 Dec. 25(4):793-803. [QxMD MEDLINE Link].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High Risk Assessment: Colorectal. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Version 2.2021 — November 20, 2020; Accessed: January 5, 2021.
Henderson D. Home-Based Stool Test Detects 79% of Colorectal Cancers. Medscape Medical News. Available at http://www.medscape.com/viewarticle/820194. Accessed: February 10, 2014.
Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med. 2014 Feb 4. 160 (3):171. [QxMD MEDLINE Link]. [Full Text].
de Wijkerslooth TR, Stoop EM, Bossuyt PM, Meijer GA, van Ballegooijen M, van Roon AH, et al. Immunochemical Fecal Occult Blood Testing Is Equally Sensitive for Proximal and Distal Advanced Neoplasia. Am J Gastroenterol. 2012 Jul 31. [QxMD MEDLINE Link].
Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001 Apr 18. 93(8):583-96. [QxMD MEDLINE Link].
Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, et al. Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy. N Engl J Med. 2012 May 21. [QxMD MEDLINE Link].
[Guideline] US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW Jr, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2016 Jun 21. 315 (23):2564-75. [QxMD MEDLINE Link]. [Full Text].
McNamara D. Evidence Backs Younger Screening for Colorectal Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/887768. October 30, 2017; Accessed: November 15, 2017.
Brounts LR, Lehmann RK, Lesperance KE, Brown TA, Steele SR. Improved rates of colorectal cancer screening in an equal access population. Am J Surg. 2009 May. 197(5):609-12; discussion 612-3. [QxMD MEDLINE Link].
Keller DS, Berho M, Perez RO, Wexner SD, Chand M. The multidisciplinary management of rectal cancer. Nat Rev Gastroenterol Hepatol. 2020 Jul. 17 (7):414-429. [QxMD MEDLINE Link].
Baxter NN, Garcia-Aguilar J. Organ preservation for rectal cancer. J Clin Oncol. 2007 Mar 10. 25(8):1014-20. [QxMD MEDLINE Link].
Cercek A, Lumish M, Sinopoli J, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 5. [QxMD MEDLINE Link]. [Full Text].
Augestad KM, Crawshaw B, Delany CP. Cancer of the Rectum: Operative Management. Fazio VW, Church JM, Delaney CP, Kiran RP, eds. Current Therapy in Colon and Rectal Surgery. 3rd ed. Philadelphia, PA: Elsevier; 2017. 146-151.
Ceelen WP, Van Nieuwenhove Y, Fierens K. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev. 2009 Jan 21. CD006041. [QxMD MEDLINE Link].
Jakobsen A, Ploen J, Vuong T, Appelt A, Lindebjerg J, Rafaelsen SR. Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses. Int J Radiat Oncol Biol Phys. 2012 May 15. [QxMD MEDLINE Link].
Wong RK, Tandan V, De Silva S, Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev. 2007 Apr 18. CD002102. [QxMD MEDLINE Link].
Cassidy RJ, Liu Y, Patel K, Zhong J, Steuer CE, Kooby DA, et al. Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Database. Cancer. March 2017. 123(5):783-793. [QxMD MEDLINE Link]. [Full Text].
Hospers G, Bahadoer RR, Dijkstra EA, et al. Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: The randomized RAPIDO trial. J Clin Oncol. 2020. 38(suppl; abstr 4006):[Full Text].
Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, et al. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol. 2018 Jun 14. 4 (6):e180071. [QxMD MEDLINE Link]. [Full Text].
Rothenberger D, Garcia-Aquilar J. Rectal cancer, local treatment. Current Therapy in Colon and Rectal Surgery. 2nd ed. Philadelphia, Pa: Mosby; 2005.
Peng J, Chen W, Venook AP, et al. Long-term outcome of early-stage rectal cancer undergoing standard resection and local excision. Clin Colorectal Cancer. 2011 Mar 1. 10(1):37-41. [QxMD MEDLINE Link].
Brooks M. Local Excision for Rectal Cancer Increasing, but Inferior. Medscape Medical News. Available at http://www.medscape.com/viewarticle/815376. December 4, 2013; Accessed: January 5, 2021.
Weiser MR, Landmann RG, Wong WD, Shia J, Guillem JG, Temple LK, et al. Surgical salvage of recurrent rectal cancer after transanal excision. Dis Colon Rectum. 2005 Jun. 48(6):1169-75. [QxMD MEDLINE Link].
Kwaan MR, Stewart Sr DB, Dunn KB. Colon, Rectum, and Anus. Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz's Principles of Surgery. 11th ed. New York, NY: McGraw-Hill Education; 2019. Vol 2: 1259-1330.
Li S, Chi P, Lin H, Lu X, Huang Y. Long-term outcomes of laparoscopic surgery versus open resection for middle and lower rectal cancer: an NTCLES study. Surg Endosc. 2011 Oct. 25(10):3175-82. [QxMD MEDLINE Link].
Green BL, Marshall HC, Collinson F, Quirke P, Guillou P, Jayne DG, et al. Long-term follow-up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer. Br J Surg. 2012 Nov 6. [QxMD MEDLINE Link].
Bonjer HJ, Deijen CL, Abis GA, Cuesta MA, van der Pas MH, de Lange-de Klerk ES, et al. A randomized trial of laparoscopic versus open surgery for rectal cancer. N Engl J Med. 2015 Apr 2. 372(14):1324-32. [QxMD MEDLINE Link].
Maurer CA, Renzulli P, Kull C, et al. The impact of the introduction of total mesorectal excision on local recurrence rate and survival in rectal cancer: long-term results. Ann Surg Oncol. 2011 Jul. 18(7):1899-906. [QxMD MEDLINE Link].
Fujita S, Akasu T, Mizusawa J, Saito N, Kinugasa Y, Kanemitsu Y, et al. Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial. Lancet Oncol. 2012 Jun. 13(6):616-21. [QxMD MEDLINE Link].
Han YD, Kim WR, Park SW, Cho MS, Hur H, Min BS, et al. Predictors of Pathologic Complete Response in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation. Medicine (Baltimore). Nov 2015. 94(45):e1971. [QxMD MEDLINE Link]. [Full Text].
Jacobs M, Verdeja JC, Goldstein HS. Minimally invasive colon resection (laparoscopic colectomy). Surg Laparosc Endosc. 1991 Sep. 1 (3):144-50. [QxMD MEDLINE Link].
Trastulli S, Cirocchi R, Listorti C, Cavaliere D, Avenia N, Gullà N, et al. Laparoscopic vs open resection for rectal cancer: a meta-analysis of randomized clinical trials. Colorectal Dis. 2012 Jun. 14 (6):e277-96. [QxMD MEDLINE Link].
van der Pas MH, Haglind E, Cuesta MA, Fürst A, Lacy AM, Hop WC, et al. Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial. Lancet Oncol. 2013 Mar. 14 (3):210-8. [QxMD MEDLINE Link].
Fleshman J, Branda M, Sargent DJ, et al. Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial. JAMA. 2015 Oct 6. 314 (13):1346-55. [QxMD MEDLINE Link]. [Full Text].
Bujko K, Rutkowski A, Chang GJ, Michalski W, Chmielik E, Kusnierz J. Is the 1-cm Rule of Distal Bowel Resection Margin in Rectal Cancer Based on Clinical Evidence? A Systematic Review. Indian J Surg Oncol. 2012 Jun. 3 (2):139-46. [QxMD MEDLINE Link]. [Full Text].
Quan D, Gallinger S, Nhan C, Auer RA, Biagi JJ, Fletcher GG, et al. The role of liver resection for colorectal cancer metastases in an era of multimodality treatment: A systematic review. Surgery. 2012 Jun. 151(6):860-70. [QxMD MEDLINE Link].
Dhir M, Lyden ER, Wang A, et al. Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis. Ann Surg. 2011 Aug. 254(2):234-42. [QxMD MEDLINE Link].
Margalit DN, Mamon HJ, Ancukiewicz M, et al. Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Int J Radiat Oncol Biol Phys. 2011 Dec 1. 81(5):e735-41. [QxMD MEDLINE Link].
Kidwell KM, Yothers G, Ganz PA, Land SR, Ko CY, Cecchini RS, et al. Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: Results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01. Cancer. 2012 May 8. [QxMD MEDLINE Link].
Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14. 372 (20):1909-19. [QxMD MEDLINE Link]. [Full Text].
Prager GW, Taieb J, Fakih M, Ciardiello F, et al. Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med. 2023 May 4. 388 (18):1657-1667. [QxMD MEDLINE Link]. [Full Text].
Cao S, Bhattacharya A, Durrani FA, Fakih M. Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Expert Opin Pharmacother. 2006 Apr. 7 (6):687-703. [QxMD MEDLINE Link].
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. 2011 Jun 18. 377(9783):2103-14. [QxMD MEDLINE Link].
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, 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. 2010 Nov 1. 28(31):4697-705. [QxMD MEDLINE Link].
Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1. 28(31):4706-13. [QxMD MEDLINE Link].
Simkens LH, Koopman M, Mol L, et al. Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy. Eur J Cancer. 2011 Nov. 47(17):2560-7. [QxMD MEDLINE Link].
Boisen MK, Johansen JS, Dehlendorff C, Larsen JS, Osterlind K, Hansen J, et al. Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer. Ann Oncol. 2013 Jul 17. [QxMD MEDLINE Link].
Nelson R. Pembro Approved for 1st-Line Use in MSI-H/dMMR Colorectal Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/933172. June 30, 2020; Accessed: July 8, 2020.
Otto MA. Tucatinib Plus Trastuzumab Approved for HER2+ Colorectal Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/987242. January 20, 2023; Accessed: January 24, 2024.
Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018 Jun 26. 319 (24):2486-2496. [QxMD MEDLINE Link]. [Full Text].
Dasari A, et al; FRESCO-2 Study Investigators. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023 Jul 1. 402 (10395):41-53. [QxMD MEDLINE Link]. [Full Text].
Ng K, Ogino S, Meyerhardt JA, et al. Relationship Between Statin Use and Colon Cancer Recurrence and Survival: Results From CALGB 89803. J Natl Cancer Inst. 2011 Oct 19. 103(20):1540-51. [QxMD MEDLINE Link]. [Full Text].
Ryan ÉJ, O'Sullivan DP, Kelly ME, Syed AZ, Neary PC, O'Connell PR, et al. Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer. Br J Surg. 2019 Jun 19. 10(9):e0138720. [QxMD MEDLINE Link].
Ebert MP, Tanzer M, Balluff B, et al. TFAP2E-DKK4 and chemoresistance in colorectal cancer. N Engl J Med. 2012 Jan 5. 366(1):44-53. [QxMD MEDLINE Link].
Hendlisz A, Van den Eynde M, Peeters M, Maleux G, Lambert B, Vannoote J, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. 2010 Aug 10. 28(23):3687-94. [QxMD MEDLINE Link].
Wasan HS, et al; FOXFIRE trial investigators., SIRFLOX trial investigators., FOXFIRE-Global trial investigators., van Hazel G, Sharma RA. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017 Sep. 18 (9):1159-1171. [QxMD MEDLINE Link]. [Full Text].
Santiago I, Barata M, Figueiredo N, Parés O, Henriques V, Galzerano A, et al. The split scar sign as an indicator of sustained complete response after neoadjuvant therapy in rectal cancer. Eur Radiol. 2019 Jul 26. [QxMD MEDLINE Link].
Song M, Wu K, Meyerhardt JA, Ogino S, Wang M, Fuchs CS, et al. Fiber Intake and Survival After Colorectal Cancer Diagnosis. JAMA Oncol. 2017 Nov 2. [QxMD MEDLINE Link]. [Full Text].
Davenport L. High Fiber Intake Tied to Improved Colon Cancer Survival. Medscape Medical News. Available at https://www.medscape.com/viewarticle/888006. November 3, 2017; Accessed: November 8, 2017.
[Guideline] Kahi CJ, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, et al. Colonoscopy Surveillance After Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2016 Mar. 150 (3):758-768.e11. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008 May-Jun. 58 (3):130-60. [QxMD MEDLINE Link].
[Guideline] American Cancer Society Guideline for Colorectal Cancer Screening. American Cancer Society. Available at https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/acs-recommendations.html. November 17, 2020; Accessed: April 6, 2021.
Wilt TJ, Harris RP, Qaseem A, High Value Care Task Force of the American College of Physicians. Screening for cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2015 May 19. 162 (10):718-25. [QxMD MEDLINE Link].
Shaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, Rex DK. ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol. 2021 Mar 1. 116 (3):458-479. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colorectal Cancer Screening. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf. Version 1.2021 — March 25, 2021; Accessed: April 6, 2021.
[Guideline] Rubenstein JH, Enns R, Heidelbaugh J, Barkun A, Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Lynch Syndrome. Gastroenterology. 2015 Sep. 149 (3):777-82; quiz e16-7. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Balmaña J, Balaguer F, Cervantes A, Arnold D, ESMO Guidelines Working Group. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2013 Oct. 24 Suppl 6:vi73-80. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Stoffel EM, Mangu PB, Gruber SB, Hamilton SR, Kalady MF, Lau MW, et al. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol. 2015 Jan 10. 33 (2):209-17. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 Feb. 110 (2):223-62; quiz 263. [QxMD MEDLINE Link]. [Full Text].
Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004 Feb 18. 96 (4):261-8. [QxMD MEDLINE Link].
[Guideline] Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2020 Mar. 158 (4):1131-1153.e5. [QxMD MEDLINE Link].
[Guideline] Rutter MD, East J, Rees CJ, Cripps N, Docherty J, Dolwani S, et al. British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines. Gut. 2020 Feb. 69 (2):201-223. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Church J, Simmang C, Standards Task Force, American Society of Colon and Rectal Surgeons, Collaborative Group of the Americas on Inherited Colorectal Cancer and the Standards Committee of The American Society of Colon and Rectal Surgeons. Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Dis Colon Rectum. 2003 Aug. 46 (8):1001-12. [QxMD MEDLINE Link].
[Guideline] Monson JR, Weiser MR, Buie WD, Chang GJ, Rafferty JF, Buie WD, et al. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum. 2013 May. 56 (5):535-50. [QxMD MEDLINE Link].
[Guideline] Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1. 29 (Supplement_4):iv263. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Meyerhardt JA, Mangu PB, Flynn PJ, Korde L, Loprinzi CL, Minsky BD, et al. Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol. 2013 Dec 10. 31 (35):4465-70. [QxMD MEDLINE Link].
[Guideline] Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandalà M, Cervantes A, et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct. 24 Suppl 6:vi64-72. [QxMD MEDLINE Link].
[Guideline] Steele SR, Chang GJ, Hendren S, Weiser M, Irani J, Buie WD, et al. Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer. Dis Colon Rectum. 2015 Aug. 58 (8):713-25. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Allegra CJ, Rumble RB, Hamilton SR, Mangu PB, Roach N, Hantel A, et al. Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015. J Clin Oncol. 2016 Jan 10. 34 (2):179-85. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug. 27 (8):1386-422. [QxMD MEDLINE Link]. [Full Text].

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Diagnostics. Staging and workup of rectal cancer patients.
Staging and treatment. Rectal cancer treatment algorithm (surgery followed by adjuvant chemotherapy and radiotherapy). Initial stages are Endorectal ultrasound staging (uT).

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Table 1. Comparison of AJCC Definition of TNM Staging System to Dukes Classification.

Rectal Cancer Stages		TNM Staging	Duke Staging	5-Year Survival
Stage I		T_1-2 N₀ M₀	A	>90%
Stage II	A	T₃ N₀ M₀	B	60%-85%
Stage II	B	T₄ N₀ M₀	B	60%-85%
Stage III	A	T_1-2 N₁ M₀	C	55%-60%
	B	T_3-4 N₁ M₀		35%-42%
	C	T_1-4 N₂ M₀		25%-27%
Stage IV		T_1-4 N_0-2 M₁		5%-7%

Table 2. Acceptable Minimal Distal and Proximal Resectional Margins for Rectal Cancer. ^{[38, 68]}

Resection Margins	Proximal Resection Margin	Distal Resection Margin
Ideal Margins	5 cm or more	2 cm or more
Minimally acceptable margins	5 cm or more	0.5-1 cm

Table 3. Common Chemotherapeutic Regimens for Colon and Rectal Cancer

Regimen	Frequency	Schedule
FOLFOX	Every 2 weeks	Oxaliplatin 85 mg/m² day 1 Leucovorin 200 mg/m² day 1 5-Fluorouracil (5-FU) 400 mg/m² IV bolus day 1 and 2 5-FU 600 mg/m² IV infusion day 1 and 2 (22 hours)
FOLFOX 4	Every 2 weeks (Four cycles)	Oxaliplatin 85 mg/m² day 1 Leucovorin 200 mg/m² day 1 5-FU 400 mg/m² IV bolus day 1 and 2 5-FU 2400 mg/m² IV infusion day 1 (46 hours)
mFOLFOX 6	Every 2 weeks (Four cycles)	Oxaliplatin 85 mg/m² day 1 Leucovorin 400 mg/m² day 1 5-FU 400 mg/m² IV bolus day 1 and 2 5-FU 1200 mg/m² IV infusion day 2 days
CapeOx	Every 3 weeks	Oxaliplatin 130 mg/m² day 1 Capecitabine 1000 mg/m² PO BID for 14 days
FOLFIRI	Every 2 weeks	Irinotecan 165 mg/m² day 1 Leucovorin 200 mg/m² day 1 5-FU 400 mg/m² IV bolus day 1 and 2 5-FU 600 mg/m² IV infusion day 1 and 2 (22 hours)
FOLFOXIRI	Every 2 weeks	Irinotecan 180 mg/m² day 1 Oxaliplatin 85 mg/m² day 1 Leucovorin 200 mg/m² day 1 5-FU 3200 mg/m² IV infusion day 1 and 2 (48 hours)
Bevacizumab	Every 2 weeks with chemotherapy	5-10 mg/kg IV
Cetuximab	With chemotherapy	400 mg/m² IV day 1, then 250 mg/m² IV weekly

Table. 1

Parameter	Organization
Parameter	ESMO (2013)^[110]	ASCO (2013)^[109]	NCCN (2019)^[1]	ASCRS (2015)^[111]
History and physical exam	Every 3-6 mo for 3 y, then every 6 -12 mo at 4 and 5 y	Every 3-6 mo for 3 y, then every 6 mo to 5 y	Every 3-6 mo for 2 y, then every 6 mo to 5 y	Every 3-6 mo for 2 y, then every 6 mo to 5 y
CEA	Every 3-6 mo for 3 y, then every 6 -12 mo at 4 and 5 y	Every 3 mo for 3 y*	Every 3-6 mo for 2 y, then every 6 mo to 5 y	Every 3-6 mo for 2 y, then every 6 mo to 5 y
Chest CT*	Every 6-12 mo for first 3 y	Every 1 y for 3 y	Every 6-12 mo to 5 y	Every 1 y for 5 y
Colonoscopy**	At y 1 after surgery, and every 3-5 y thereafter	At 1 y, then every 5 y, dictated by the findings on the previous colonoscopy	At 1 y, 3 y, and 5 y if negative	At y 1 after surgery, and every 3-5 y dictated by the findings on the first postoperative examination.
Abdominal CT*	Every 6-12 mo for first 3 y	Every 1 y for 3 y	Every 6-12 mo to 5 y	Every 1 y for 5 y
ESMO = European Society of Medical Oncology; ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network; American Society of Colon and Rectal Surgeons = ASCRS CEA = carcinoembryonic antigen; CT = computed tomography * For patients at high risk for recurrence (eg, lymphatic or venous invasion, or poorly differentiated tumors). **Colonoscopy should be performed 3-6 mo postoperatively if preoperative colonoscopy was not done, due to an obstructing lesion; otherwise, colonoscopy in 1 y; if abnormal, repeat in 1 year; if no advanced adenoma (ie, villous polyp, polyp >1 cm, or high-grade dysplasia), repeat in 3 y, then every 5 y.