Colon Cancer Facts

  • Third most common cancer diagnosed in the United States1  
  • Rising incidence among young adults with a 2% increase every year in under 50 year olds1
  • Overall lifetime risk of developing colorectal cancer is approximately 1 in 23 for men and 1 in 25 in women1
  • Expected to cause about 52,580 deaths during 20221
  • More than 90% are adenocarcinomas5

Colon Cancer Risk Factors

  • Age: Individuals 50 or older2
  • Lifestyle: Obesity, sedentary lifestyle, a diet high in red and processed meats, cigarette smoking, and alcohol2
  • Race: More common in African Americans and Native American Indians2
  • Family History: 1st degree relative with history of colorectal cancer or adematous polyps2
  • Genetic Mutations: BRCA1, BRCA 2, Lynch syndrome/HNPCC (increases lifetime risk by 50%), FAP, Peutz Jeghers syndrome, MUTHY associated polyposis2
  • Medical history: Diagnosis of ulcerative colitis, Crohn’s disease, type II diabetes, low vitamin D levels2

Colon Cancer Testing

  • CT: Chest, abdomen, and pelvis with and without contrast
  • MRI: Abdomen, can be done in place of CT views3  
  • Colonoscopy
  • Carcinoembryonic Antigen (CEA) Test4
  • Genetic Testing: Complete multi syndrome gene panel testing on patient under 40 with positive family history of first-degree relative with Lynch syndrome cancer, family history of FAM, and Ashkenazi Jewish heritage5
  • Tumor Specific Genetic Alterations: Indicated for stage IV cancers, looking for dMMR/MSI, KRAS, BRAF, EGFR, PDL1, and HER2; if no tissue available proceed with blood test, CtDNA6
  • PET: Used if a concern for metastatic disease

Prognosis

Dependent on stage of cancer, location, grade, and histology

Tumor histology5

  • More than 90% are adenocarcinomas with a number of histologic variants including mucinous, medullary, and signet ring cell5
  • Approximately 10% are neuroendocrine
    • Other types include, squamous, adenosquamous, and spindle cell17

Staging

  • The 3 aspects used to determine stage are:
    • Tumor size and depth of invasion (T)
    • Nodal status (N) Establishes cancer spread to lymph nodes
    • Metastasis (M) No metastasis (M0), or (M1) metastatic spread7

TNM information is then used to classify staging:7

  • Stage I: Cancer invaded muscular layer of colon, no spread
    • Stage IIA: Primary tumor grown through wall of colon, no LN involvement or spread to organs/tissue
    • Stage IIB: Cancer grown through to visceral peritoneum but no LN involvement or metastasis
    • Stage IIC: Tumor spread through colon wall into nearby structures, no LN involvement or metastasis
    • Stage IIIA: Cancer grown into muscle layers of intestine and 1-3 LN involved
    • Stage IIIB: Cancer grown through bowel wall, and 1-3 LN involved
    • Stage IIIC: Spread to 4 or more LN
    • Stage IV: Cancer spread to a distant organ or tissue15

Grade7

Pathologic evaluation of tumor for the level of differentiation of cancer cells compared to healthy colon tissue.

  • Grade 1: Well-differentiated
  • Grade 2: Moderately differentiated
  • Grade 3: Poorly differentiated
  • Grade 4: Undifferentiated

Colon Cancer Survival Rates

Age may play a factor in metastatic colon cancer. Younger and older age are associated with poorer overall survival and progression-free survival.

  • 5-Year Survival Rates:8
    • Localized: Stage I and II: 89.9%
    • Regional: Stage III: 71.3 %
    • Distant: Stage IV: 14.2%

Management of Colon Cancer

Management depends on multiple factors, including stage and grade of cancer, genomic mutations, age, life expectancy, access to care barriers, provider patient experience, treatment burden, and chance of cure.19-22

  • Treatment of Localized Colon Cancer
    T1-T2, N0, M0    : Colectomy with en bloc removal of regional LN or resection with diversion9
    • Treatment of Locally Advanced Colon Cancer
      T1-T3, N1:       Neoadjuvant chemotherapy is done for 3-6 months, followed by colectomy and regional LN removal. Chemotherapy includes a fluoropyrimidine –  5 fluorouracil, or capecitabine, along with oxaliplatin.20 Other options include Irinotecan.10,11
    • Treatment of metastatic Colon cancer
      Any T, any N, M1:       Treatment is guided by patient fitness, comorbidities, and mutation status. First line treatment includes the above chemotherapy regimens, surgery, targeted therapies, and immunotherapy (alone or in combination with chemotherapy).12

Considerations of Specific Treatment Modalities

Surgery

Surgery is recommended as primary curative therapy for all stage I-III colon cancers, with colectomy and regional lymph node dissection versus ostomy placement. Chemotherapy can be added prior to surgery (neoadjuvant) to shrink size of tumor or post-surgery (adjuvant) to prevent recurrence. Post-colectomy side effects include urinary, sexual, and defecatory dysfunction. Management of ostomy, access to supplies, body image is required. There is a risk for lower-extremity edema, and post-pelvic or inguinal lymph node dissection.13

Radiation

Radiation is not generally used unless a T4 tumor is initially unresectable and the disease is not metastatic. The bowel is sensitive to radiation and damage can occur at 55gy.14

Radiation can cause diarrhea, skin irritation, and nausea. Arterially directed catheter therapy can be used in chemo-resistant refractory disease and predominant liver metastasis. Post-procedure individuals may experience pain and bloating for several days.15

Radiation can also be used for lung metastasis, bone metastasis, and pain control. Given in small doses, side effects are rare.

Systemic Therapies

Systemic therapy is used for stage 3 and 4 disease, nodal disease, and metastatic disease. The backbone of therapy is chemotherapy with 5 fluorouracil or capecitabine along with oxaliplatin.10-12

Specific considerations involve treatment-related side effects including leucopenia, infection, mucositis, palmar plantar erythrodysthesia, neuropathy, cold dysthesias, nausea, cardiac complications, and cachexia.16

EGFR inhibitors: Bevacizumab, regorafinib, ramcirumab
Side effects include: delayed wound healing, hypertension, proteinuria, skin rash, dry skin17

KRAS, NRAF, BRAF: Cetuximab, panitumumab, Sotorasib, adagrasib
Side effects include: diarrhea, MSK pain, nausea, fatigue cough, ILD, hepatotoxicity.18

BRAF V600 Mutation: Encorafinib
Side effects include: monitor for new primary malignancies, uveitis, QT prolongation, nausea, fevers, headaches.19

HER2+: Traztuzumab, pertuzumab
Side effects include: reduced EF, diarrhea, skin rash.20

NTRK: Larotrec, entrectinib
Side effects include: weight gain, dizziness, ataxia, paresthesia.21

RET: Selpercatinib
Side effects include: hepatotoxicity, ILD, Hypertension, QT prolongation, hemorrhage, hypersensitivity reaction, tumor lysis syndrome, impaired wound healing, hypothyroidism, diarrhea, pain, edema.22

MSI-H/dMMR: Immunotherapy with Nivolumab, pembrolizumab, ipilumumab
Side effects include: immune mediated skin rash, organ dysfunction, hormonal dysfunction.23

Surveillance Following Therapy: 24

All individuals diagnosed with colon cancer are monitored for 5 years post diagnosis.

  • Stage 1:
    • Colonoscopy 1 year and 3 years post-surgery, then repeated once every 5 years
  • Stage II-III:
    • History and physical with CEA, every 3-6 months for 2 years, then every 6 months for 5 years
    • CT every 6-12 months for 5 years
    • Colonoscopy 1 year and 3 years post-surgery, then repeated once every 5 years
  • Stage IV:
    • History and physical with CEA every 3-6 months for 2 years, then every 6-12 months for 5 years
    • Colonoscopy 1 year and 3 years post-surgery, then repeated once every 5 years
    • Consider PET imaging for metastatic disease

References:

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12. PMID: 35020204.
  2. Johnson CM, Wei C, Ensor JE, et al. (2013). Meta-analyses of colorectal cancer risk factors. Cancer Causes Control, 24:1207-1222. DOI: 10.1007/s10552-013-0201-5
  3. Taylor AJ, Youker JE (1991). Imaging in colorectal carcinoma Semin Oncol. 18(2):99.
  4. Thirunavukarasu P, Sukumar S, Sathaiah M, Mahan M, Pragatheeshwar KD, Pingpank JF, Zeh H 3rd, Bartels CJ, Lee KK, Bartlett DL. (2011).  C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management. J Natl Cancer Inst. 103(8):689. March 18th, 2011. DOI: 10.1093/jnci/djr078 
  5. Ballester, V., Correa, M. How and when to consider genetic testing for colon cancer? Gastroenterology, 155, (4): p959. February 7, 2017. DOI: 10.1053/j.gastro.2018.08.031
  6. Chakravarty D, Johnson A, Sklar J, et al. (2022). Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion. J Clin Oncol , 40:1231. February 7, 2017. DOI: 10.1200/JCO.21.02767
  7. Compton, C. (2022). Pathology and prognostic determinants of Colorectal cancer. Uptodate. Updated October 2022. Accessed November 15, 2022.
  8. American Cancer Society. Survival rates for Colorectal cancer. Updated March 21, 2022. Accessed on November 15, 2022.
  9. Healy, M. Surgical procedures: Surgery and staging for colon cancer. Oncolink. Updated August 11, 2022. Accessed November 28, 2022.
  10. Du Lieu C, Kennedy EB, Bergsland E, Berlin J, George TJ, Gill S, Gold PJ, Hantel A, Jones L, Mahmoud N, Meyerhardt J, Morris AM, Ruíz-García E, You YN, Baxter N.(2019). Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline. .J Clin Oncol.37(16):1436. Published April 15, 2019. DOI: 10.1200/JCO.19.00281
  11. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. (2004). Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol  22:1209. Published April 1, 2004. DOI: 10.1200/JCO.2004.11.037
  12. Goldberg RM, Rothenberg ML, Van Cutsem E, et al. (2007). The continuum of care: a paradigm for the management of metastatic colorectal cancer. The Oncologist, Volume 12, Issue 1, Pages 38–50. Published January 2007. DOI: 10.1634/theoncologist.12-1-38
  13. DeSnoo L, Faithfull S. (2006).A qualitative study of anterior resection syndrome: the experiences of cancer survivors who have undergone resection surgery. Eur J Cancer 15:244-251. Published December 20, 2005. DOI: 10.1111/j.1365-2354.2005.00647.x
  14. Mendenhall WM, Amos EH, Rout WR, Zlotecki RA, Hochwald SN, Cance WG. Adjuvant postoperative radiotherapy for colon carcinoma. Cancer. 2004;101(6):1338. August 6, 2004. DOI: 10.1002/cncr.20526
  15. No authors listed. Portal vein chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in 10 studies. Liver Infusion Meta-analysis Group. Journal of the National Cancer Institute. April, 1997. Volume: 89,Issue: 7, Page: 497-505.
  16. Holmes Gobel, B., Triest-Robinson, S., Vogel, W.H. Advanced Oncology Nursing certification. 2nd Ed. Oncology Nursing Society, Pittsburgh, Pennsylvania, 2016. pp 145-147.
  17. Weaver, C.H. Understanding side effects of EGFR inhibitors. Updated December, 2018. Accessed Nov 7, 2022
  18. Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. (2008). K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med.359(17):1757. DOI: 10.1056/NEJMoa0804385
  19. FDA. FDA approval of cetuximab, in combination with encorafenib, for patients with previously treated metastatic colorectal with a BRAF V600E mutation. Issued August 27th, 2021. Accessed on November 7,2022.
  20. Meric-Bernstam F, Hainsworth J, Bose R, et al. MyPathway HER2 basket study: Pertuzumab (P) + trastuzumab (H) treatment of a large, tissue-agnostic cohort of patients with HER2-positive advanced solid tumors (abstract). J Clin Oncol, (suppl 15; abstr 3004). Published May 20, 2021.
  21. Doebele RC, Drilon A, Paz-Ares L, et al. (2020). Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.Lancet Oncol.21(2):271. Published December 11, 2019.  DOI: 10.1016/S1470-2045(19)30691-6. 
  22. Eli Lilly and Company. Retevmo – selpercatinib capsules. Updated September 21, 2022. Accessed November 7, 2022.
  23. Ph Le DT, Kim TW, et al. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164.J Clin Oncol.;38(1):11. Published November 14, 2019. DOI: 10.1200/JCO.19.02107
  24. Benson, A.B. et al. NCCN clinical practice guidelines in Oncology- Colon cancer. Surveillance, p14. Updated February, 2022.  Accessed November 7 2022.

Author Bio:

Katie Snell is a nurse practitioner at Cancer Centers of Colorado in Denver. She has worked in oncology since 1995 and is passionate about educating patients and peers about cancer diagnosis, treatment, and side effects. She is published in the clinical journal of Oncology Nursing.

Topics:

Colon Cancer DDI