Breaking down colorectal cancer stages, treatment options, and research advances

Colorectal cancer (CRC), often known as bowel cancer, is one of the most common cancers worldwide. It typically begins as noncancerous growths called polyps in the colon or rectum, which can become cancerous over time. Early detection and treatment are crucial for improving survival rates.

Image Credit: Norgen Biotek Corp.

Stages of colorectal cancer

Understanding the various stages of CRC is essential for identifying the most efficient treatment strategy.

Stage 0 colorectal cancer

At this earliest stage, abnormal cells are found only in the innermost lining of the colon or rectum and have not spread to surrounding tissues. This stage is also referred to as carcinoma in situ.

Stage 1 colorectal cancer

At this stage, cancer has spread into the deeper layers of the colon or rectum but has not reached the lymph nodes.¹ Around 34.8 % of CRCs are identified at this localized stage, with a 5-year relative survival rate of 91.1 %.²

Stage 2 (A-C) colorectal cancer

Cancer has spread through the wall of the colon or rectum but has not reached the surrounding lymph nodes. Approximately 75 % of individuals with stage II A colon cancer will be cancer-free five years post-treatment without additional chemotherapy. However, 25 % will experience recurrence.³

Stage 3 (A-C) colorectal cancer

CRC has progressed to nearby lymph nodes but has not metastasized to distant organs. According to the SEER Training Modules, the 5-year survival rate for stage III CRC ranges from 35 % to 55 %, depending on the extent of lymph node involvement.⁴

Stage 4 (A-C) colorectal cancer

At this advanced stage, CRC has spread to distant organs, most commonly the lungs or liver. The five-year relative survival rate is around 13 %, although advances in treatment are improving outcomes for some patients.⁵

For individuals whose cancer has spread only to the lungs or liver, surgery may offer a potential cure. More patients with stage IV cancer are now living longer than two years.

Treatment options for colorectal cancer

Surgery

• Polypectomy: Removal of polyps during a colonoscopy
• Colectomy: Removal of part or all of the colon containing cancer

Surgery is most beneficial when the cancer is still in its early stages and has not spread to other parts of the body.

Chemotherapy

Powerful chemicals are used to kill cancer cells. This is a systemic treatment that targets cells throughout the body.

Radiation therapy

High-energy rays are used to target and destroy cancer cells, especially in cases of rectal cancer. These rays damage the DNA within the cells, limiting their ability to divide and replicate. Radiation affects all cells, but it is particularly harmful to rapidly dividing cells, such as cancer cells.

Targeted therapy

Targeted therapies are designed to attack specific characteristics of cancer cells, preventing their growth while causing minimal damage to healthy cells.

Examples include drugs that target epidermal growth factor receptors (EGFR), such as Panitumumab; drugs that target vascular endothelial growth factor (VEGF), such as Bevacizumab; and drugs like Encorafenib, which target cancer cells with BRAF gene mutations.

Immunotherapy

Immune checkpoint inhibitors are used to enhance the immune system’s ability to target and destroy cancer cells. Immunotherapy is effective only in a subset of patients whose tumors have specific genetic alterations, such as high microsatellite instability (MSI-H) or mutations in one of the mismatch repair (MMR) genes.

Colorectal cancer screening

Early detection of colon cancer can significantly reduce mortality rates and improve 5-year survival probabilities.⁶ In the United States, the 5-year relative survival rate for stage I colon cancer is approximately 92 %. For stage IIB CRC, the 5-year relative survival rate drops to 65 %.⁷

Individuals rarely experience symptoms in the early stages of CRC, making regular screening essential. Incidence and mortality rates of CRC have decreased significantly in the United States following the implementation of effective CRC screening technologies.⁸ Screening can remove pre-cancerous polyps and help prevent the development of CRC.⁹

The U.S. Preventive Services Task Force strongly recommends that individuals aged 45 to 75 undergo regular CRC screening. Those with a higher risk of CRC due to family history, certain conditions, or genetic diseases should begin screening earlier.¹⁰

Colonoscopy, a direct visualization test, is currently the most commonly used CRC screening method in the United States.¹¹ Other visualization tests include virtual colonoscopy and sigmoidoscopy. All three are invasive and involve the injection of air into the colon.¹²

CRC stool tests are widely used around the world. Since polyps and CRC may bleed, tests such as the guaiac fecal occult blood test (gFOBT) and the fecal immunochemical test (FIT or iFOBT) can detect even small amounts of blood in the stool.¹³

Multitarget stool DNA testing (Cologuard) is an FDA-approved, stool-based test that detects both hemoglobin and specific DNA biomarkers.¹⁴

Innovative colorectal cancer detection

Biomarkers from blood

Colorectal cancer research breakthroughs are revolutionizing CRC diagnosis and treatment. Currently, the FDA has approved two blood-based assays for CRC screening. 

Epi proColon 2.0 is approved for screening individuals aged 50 and older. This test detects methylated SEPT9, a biological biomarker released by CRC cells.

Shield is approved for screening individuals aged 45 and older. It analyzes plasma DNA for the presence of harmful gene mutations and other alterations.

Biomarkers from stool

Stool tests are a non-invasive, safe, cost-effective, and simple method for screening CRC. Increasing evidence supports the effectiveness of fecal indicators in CRC screening.

Proteins, DNA mutations, epigenetic markers, microorganisms, and volatile chemical compounds have all been identified and studied as potential CRC biomarkers in stool. These biomarkers are low-risk and show great promise for transforming CRC screening and early diagnostic testing.¹⁵

The image below is adapted from an article by Quan Ding et al.¹⁵ It highlights several stool biomarkers associated with CRC.

Image Credit: Diagram adopted from an article written by Quan Ding et al (12)

Stool DNA biomarkers

DNA mutations are among the most extensively studied and widely used indicators for CRC. For example, mutated KRAS genes can lead to uncontrolled cell growth and proliferation, eventually resulting in cancer.

KRAS mutations are found in approximately 40 % of CRC cases. Mutations in the Wnt signaling pathway can also serve as CRC biomarkers. This pathway promotes the generation of new cells to replace those lost over time, which is essential for maintaining intestinal function.

Mutations in the Wnt pathway cause dysregulated cell growth and division, which can lead to cancer. Such mutations are present in more than 90 % of CRC patients. The adenomatous polyposis coli (APC) gene is the most frequently altered gene in this pathway.¹⁶

Image Credit: Diagram adopted from an article written by meng et al. (2021) (32)

Stool RNA biomarkers

Fecal microRNAs (miRNAs) show promise as non-invasive diagnostic and screening biomarkers. These miRNAs remain stable and detectable in stool samples because they are packaged in exosomes, which protect them from degradation.

Notably, fecal miRNA detection typically requires only 1 gram of stool, making the method well-suited for clinical use. Recent studies have linked specific miRNAs to CRC.

Ahmed et al. observed significant changes in miRNA expression in the feces of CRC patients. The study reported increased expression of miR-21, miR-106a, miR-96, miR-203, miR-20a, miR-326, and miR-92, along with decreased levels of miR-320, miR-126, miR-484-5p, miR-143, miR-145, miR-16, and miR-125b.¹⁷

These findings support the effectiveness of fecal miRNAs as biomarkers for CRC detection and monitoring.

Image Credit: Norgen Biotek Corp.

Another intriguing discovery that has opened new possibilities for CRC screening is the ability to profile small RNA in addition to fecal immunochemical testing (FIT).¹⁸

Birkeland et al. published a study in the journal Molecular Cancer. Using Norgen Biotek's RNA stabilizing solution and Stool Total RNA Purification Kit, the researchers demonstrated that the human miRNome can be detected in residual FIT samples across populations, and that small RNA biomarker analysis can supplement FIT in large-scale screening settings.

The researchers also found that miRNAs from residual FIT samples show varying abundances between CRC patients and healthy individuals.¹⁸

Stool microbiome biomarkers

Associative studies using metagenomic approaches have identified bacterial species that are enriched in CRC. These microorganisms may serve as biomarkers for disease screening, prognosis, and response to therapy.¹⁹

Next-generation sequencing technology has enabled the analysis of microbiomes from sources such as the human gut, allowing researchers to explore taxonomic and metabolomic links between the microbiome and cancer.

The relationship between colon cancer and the human gut microbiome has been studied extensively, with varying results. However, these studies consistently show that microbiota associated with a plant-based diet are linked to a reduced risk of colon cancer.

A plant-based diet promotes the growth of microbiota that produce short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. These SCFAs have demonstrated anti-inflammatory effects by inducing T-regulatory cells in colonic tissues.²⁰

Stool microbiome biomarkers

Norgen Biotek is a market leader in stool DNA/RNA preservation and isolation systems, specifically designed for biomarker research.

Norgen’s advanced reagents effectively stabilize nucleic acids for extended periods, resulting in consistent and reliable cancer diagnostics and research outcomes. Independent studies have shown that Norgen Biotek's stool preservative outperforms competitors in maintaining gut flora from stool samples.^21,22

Additionally, the preservative supports metabolomic studies, such as SCFA analysis.²³ Norgen Biotek's cutting-edge technology for stool DNA, RNA, and nucleotide isolation addresses two of the most common challenges in working with stool samples: the presence of humic acid and DNA fragmentation. As a result, these kits efficiently isolate high-quality DNA or RNA from fecal samples.

Beyond preservation, Norgen Biotek also offers comprehensive next-generation sequencing services for small RNA, miRNA, and metagenomics applications. Each service includes a detailed, project-specific bioinformatics report, providing researchers with actionable insights tailored to their study’s objectives.

Conclusion: A path forward

Colorectal cancer is a serious but preventable disease if detected early. Advances in diagnostics, such as biomarker analysis and innovative solutions from Norgen Biotek, are paving the way for improved outcomes. Prioritizing screenings, maintaining a healthy lifestyle, and staying informed can help reduce your risk of developing colorectal cancer.

Norgen Biotek offers diagnostic tools and solutions tailored to colorectal cancer research.

References and further reading

1. Meng, M., et al. (2021). The current understanding on the impact of KRAS on colorectal cancer. Biomedicine & Pharmacotherapy, (online) 140, p.111717. https://doi.org/10.1016/j.biopha.2021.111717.
2. OncoLink. Stage II Colon Cancer: To Treat or Not to Treat? | OncoLink. (online) Available at: https://www.oncolink.org/cancers/gastrointestinal/colon-cancer/treatments/stage-ii-colon-cancer-to-treat-or-not-to-treat.
3. Medical News Today. (2019). Stage 4 colon cancer life expectancy: Diagnosis and decisions. (online) Available at: https://www.medicalnewstoday.com/articles/325230.
4. WebMD. What’s the Outlook for Stage IV Colon Cancer? (online) Available at: https://www.webmd.com/colorectal-cancer/colon-cancer-liver-metastasis-outlook.
5. American Cancer Society (2018). Colorectal Cancer Screening Guidelines. (online). Available at: https://www.cancer.org/health-care-professionals/american-cancer-society-prevention-early-detection-guidelines/colorectal-cancer-screening-guidelines.html.
6. American Cancer Society (2023). Colorectal Cancer Screening* (%), Adults 45 Years and Older by State, 2020 Screening Prevalence. (online) Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2023.pdf.
7. Surveillance, Epidemiology, and End Results (SEER) ProgramSEER*Stat Database: Incidence – SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973–2013 varying) – Linked To County Attributes – Total U.S., 1969–2014 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2016, based on the November 2015 submission.
8. Siegel, R., et al. (2014). Cancer statistics, 2014. CA: A Cancer Journal for Clinicians, 64(1), pp.9–29. https://doi.org/10.3322/caac.21208.
9. Hall, M.J., Morris, A.M. and Sun, W. (2018). Precision Medicine Versus Population Medicine in Colon Cancer: From Prospects of Prevention, Adjuvant Chemotherapy, and Surveillance. American Society of Clinical Oncology Educational Book, (38), pp.220–230. https://doi.org/10.1200/edbk_200961.
10. Davidson, K.W., et al. (2021). Screening for colorectal cancer. JAMA, (online) 325(19), pp.1965–1977. https://doi.org/10.1001/jama.2021.6238.
11. Shapiro, J.A., et al. (2012). Patterns of colorectal cancer test use, including CT colonography, in the 2010 National Health Interview Survey. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, (online) 21(6), pp.895–904. https://doi.org/10.1158/1055-9965.EPI-12-0192.
12. National Cancer Institute (2020). Colorectal Cancer Screening (PDQ^®)–Patient Version - National Cancer Institute. (online). Available at: https://www.cancer.gov/types/colorectal/patient/colorectal-screening-pdq.
13. Ding, Q., et al. (2022). Fecal biomarkers: Non-invasive diagnosis of colorectal cancer. Frontiers in Oncology, 12. https://doi.org/10.3389/fonc.2022.971930.
14. Wong, S.H. and Yu, J. (2019). Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nature Reviews Gastroenterology & Hepatology, (online) 16. https://doi.org/10.1038/s41575-019-0209-8.
15. Birkeland, E., et al. (2023). Profiling small RNAs in fecal immunochemical tests: is it possible? Molecular Cancer, (online) 22(1), p.161. https://doi.org/10.1186/s12943-023-01869-w.
16. American Cancer Society (2023). Colorectal Cancer Statistics | How Common Is Colorectal Cancer? (online). Available at: https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html.
17. Chen, Z., et al. (2019). Impact of Preservation Method and 16S rRNA Hypervariable Region on Gut Microbiota Profiling. mSystems, (online) 4(1). https://doi.org/10.1128/mSystems.00271-18.
18. Goodman, B., & Gardner, H. (2018). The microbiome and cancer.The Journal of pathology, 244(5), 667-676. WCRF
19. Ahmed, F.E., et al. (2013). Diagnostic microRNA markers to screen for sporadic human colon cancer in stool: I. Proof of principle. Cancer genomics & proteomics, (online) 10(3), pp.93–113. Available at: https://pubmed.ncbi.nlm.nih.gov/23741026/.
20. Plauzolles, A., et al. (2022). Human Stool Preservation Impacts Taxonomic Profiles in 16S Metagenomics Studies. Frontiers in Cellular and Infection Microbiology, 12. https://doi.org/10.3389/fcimb.2022.722886.
21. Fernandez-Sanjurjo, M., et al. (2024). Dynamics of Gut Microbiota and Short-Chain Fatty Acids during a Cycling Grand Tour Are Related to Exercise Performance and Modulated by Dietary Intake. Nutrients, 16(5), pp.661–661. https://doi.org/10.3390/nu16050661.
22. Rebuildcrc (2025). Biomarkers. (online) Fight CRC. Available at: https://fightcolorectalcancer.org/resource/resource-library/guide-in-the-fight/tests-and-scans/biomarkers/ (Accessed 27 Mar. 2025).
23. World Health Organization (2023). Colorectal cancer. (online) World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer.

About Norgen Biotek Corp.

Norgen Biotek: Advancing science with best-in-class, scientist-backed innovations

Norgen Biotek is a fully integrated biotechnology company that focuses on providing complete workflows for molecular biology sample preparation and analysis. With a diverse portfolio of over 600 products, the company delivers high-performance, user-friendly, and cost-effective solutions.

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Unparalleled performance

At the heart of Norgen’s success is its patented Silicon Carbide (SiC) Technology. This proprietary resin exhibits uniform binding affinity for all RNA species, regardless of molecular weight or GC content. This ensures the full diversity of small and microRNA are captured while eliminating the need for phenol extraction. This innovative technology sets Norgen kits apart from others, positioning them as leaders in RNA purification.

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Norgen is committed to providing high-quality kits capable of processing a wide range of sample types, from ultra-low input samples such as liquid biopsies to highly impure samples like stool or soil. Our sample collection and preservation devices for stool and saliva simplify handling by rendering samples non-infectious by preventing microbial growth and inactivating viruses, while our blood and urine preservation solutions ensure the stability of highly vulnerable cell-free nucleic acids.

To meet varying research demands, we offer multiple isolation methods including, but not limited to high-throughput and automation-ready magnetic bead-based formats. Additionally, our multiple-analyte kits enable the simultaneous purification of RNA, DNA, and proteins, maximizing data extraction from a single sample.

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