A Guide to the Diagnostic Process for Colorectal Cancer

Colorectal cancer, which includes cancers of the colon and rectum, is one of the most common types of cancer worldwide. Understanding the diagnostic and treatment process is essential for early detection and effective management. This guide offers an in-depth overview of the diagnostic process, interpretation of test results, treatment options, and strategies for managing the disease.

The Diagnostic Process for Colorectal Cancer

Colorectal cancer is often detected during routine screenings or following symptoms such as blood in stool, changes in bowel habits, or unexplained weight loss. A thorough diagnostic process is crucial to confirm the presence of cancer, determine its stage, and develop a treatment plan.

A. Symptoms That May Lead to Diagnosis

• Persistent changes in bowel habits (diarrhea, constipation, or narrow stools).
• Rectal bleeding or blood in stool (bright red or tarry black).
• Abdominal pain, bloating, or discomfort.
• A feeling of incomplete bowel evacuation.
• Unexplained weight loss or fatigue.
• Weakness or anemia without a known cause.

B. Diagnostic Tests

1. Initial Evaluation

• Medical History:
  • Family history of colorectal cancer or genetic conditions like Lynch syndrome or familial adenomatous polyposis (FAP).
  • Personal history of polyps, inflammatory bowel disease (IBD), or prior cancers.
• Physical Examination:
  • Abdominal palpation for masses or tenderness.
  • Digital rectal examination to detect rectal abnormalities.

2. Screening and Detection

• Colonoscopy:
  • The gold standard for diagnosing colorectal cancer.
  • Allows direct visualization of the colon and rectum, biopsy of suspicious areas, and polyp removal.
• Stool-Based Tests:
  • Fecal Immunochemical Test (FIT): Detects hidden blood in stool.
  • Multi-target Stool DNA Test (Cologuard): Detects abnormal DNA and blood in stool.
• Flexible Sigmoidoscopy:
  • Examines the rectum and lower colon; may identify abnormalities in a limited area.

3. Imaging Studies

• CT Colonography (Virtual Colonoscopy):
  • Non-invasive imaging alternative for screening.
• Double-Contrast Barium Enema:
  • Outdated but occasionally used when other methods are unavailable.

C. Confirming Diagnosis

A biopsy and its accompanying pathology report are critical components of the colorectal cancer diagnostic process. Understanding the details of these tests can help patients and caregivers comprehend the diagnosis, predict prognosis, and plan appropriate treatments.

What is a Biopsy?

A biopsy involves the removal of tissue from a suspicious lesion, polyp, or tumor for microscopic examination. It is typically performed during a colonoscopy but may also be done during surgery or through imaging-guided techniques if the tumor is inaccessible via colonoscopy.

Types of Biopsies

1. Endoscopic Biopsy:
   • Tissue is taken during a colonoscopy using forceps or other tools.
   • Common for detecting abnormalities in the colon or rectum.
2. Surgical Biopsy:
   • Performed when the tumor is removed surgically, either as part of treatment or for diagnosis.
   • May involve partial or full removal of the tumor.
3. Fine-Needle Aspiration (FNA) or Core Biopsy:
   • Performed under imaging guidance (CT or ultrasound) if the tumor is located in an inaccessible area or a metastatic site like the liver or lungs.

What Does the Pathologist Look For?

The biopsy sample is sent to a pathologist, who analyzes it under a microscope and generates a pathology report. The report provides crucial details about the cancer’s type, grade, and molecular characteristics.

Key Components of a Pathology Report

A. Histologic Type

• Most colorectal cancers are adenocarcinomas, which originate from the glandular cells lining the colon and rectum.
• Less common types include:
  • Mucinous Adenocarcinoma: Contains mucus-producing cancer cells.
  • Signet-Ring Cell Carcinoma: Rare and more aggressive.
  • Neuroendocrine Tumors: Arise from hormone-producing cells, often more aggressive.

B. Tumor Grade

The grade describes how much the cancer cells differ from normal cells, indicating how quickly the cancer is likely to grow and spread:

• Low-Grade (Well-Differentiated):
  • Cancer cells look similar to normal cells and grow slowly.
• High-Grade (Poorly Differentiated):
  • Cells appear abnormal and grow more aggressively.

C. Depth of Invasion

• The report details how far the cancer has grown into the layers of the colon or rectal wall:
  • Mucosa: The innermost layer.
  • Submucosa: Beneath the mucosa.
  • Muscularis Propria: Muscle layer.
  • Serosa (or Adventitia): The outermost layer.
• This information contributes to the T (tumor) stage in the TNM system.

D. Surgical Margins

• Margins are the edges of the tissue removed during surgery or biopsy.
  • Negative Margins (Clear): No cancer cells are found at the edges.
  • Positive Margins: Cancer cells are present at the edges, indicating incomplete removal and possible need for further treatment.

E. Lymph Node Involvement

• Examines whether cancer has spread to nearby lymph nodes:
  • Number of Nodes Examined: Ideally, 12 or more nodes should be tested.
  • Number of Nodes Positive: Indicates the N (node) stage in the TNM system.

F. Molecular and Genetic Testing

• Identifies specific mutations or markers that guide treatment options:
  • KRAS and NRAS Mutations: Presence of these mutations makes certain targeted therapies (like anti-EGFR drugs) ineffective.
  • BRAF Mutation: Associated with poor prognosis; may guide targeted therapy.
  • Microsatellite Instability (MSI) or Mismatch Repair (MMR) Deficiency:
    • MSI-High or dMMR tumors respond well to immunotherapy drugs like pembrolizumab (Keytruda).

G. Other Features

• Lymphovascular Invasion (LVI):
  • Indicates whether cancer has invaded blood vessels or lymphatic channels.
  • Presence of LVI increases the risk of metastasis.
• Perineural Invasion (PNI):
  • Indicates cancer involvement in or around nerves, associated with a more aggressive disease.

Common Terms in a Pathology Report

• Carcinoma in Situ: Cancer is confined to the inner lining and has not spread deeper.
• Invasive Adenocarcinoma: Cancer has spread beyond the inner lining into deeper layers.
• Hyperplasia or Dysplasia: Pre-cancerous changes that may or may not progress to cancer.
• Necrosis: Areas of dead tissue within the tumor, often seen in aggressive cancers.

How to Understand Your Pathology Report

• Focus on the Summary:
  • Look for the histologic type, grade, and whether margins are clear.
• Ask About Staging Information:
  • Confirm the TNM stage based on the pathology findings.
• Discuss Molecular Markers:
  • Ask about the presence of KRAS, NRAS, BRAF mutations, and MSI status, as these influence treatment.

The biopsy and pathology report provide the foundation for understanding colorectal cancer and tailoring treatment. By comprehensively analyzing the type, grade, and molecular features of the cancer, doctors can determine the best therapeutic approach. Patients and caregivers should discuss these findings thoroughly with their healthcare team to make informed decisions about the treatment journey.

D. Staging of Colorectal Cancer

The staging of colorectal cancer describes the size of the tumor, the involvement of nearby lymph nodes, and the presence of distant metastasis. The TNM system (Tumor, Node, Metastasis) developed by the American Joint Committee on Cancer (AJCC) is commonly used.

A. TNM Staging System

• T: Tumor
  • Tis (Tumor in Situ): Cancer is confined to the inner lining (mucosa) and hasn’t invaded deeper layers.
  • T1: Tumor has invaded the submucosa (beneath the mucosa).
  • T2: Tumor has invaded the muscularis propria (muscle layer of the colon wall).
  • T3: Tumor has grown through the muscularis propria into the outermost layers.
  • T4: Tumor has invaded nearby structures or organs:
    • T4a: Penetrated the serosa (outermost layer of the colon or rectum).
    • T4b: Invaded nearby organs or tissues.
• N: Nodes
  • N0: No regional lymph nodes are involved.
  • N1: Cancer has spread to 1-3 nearby lymph nodes.
    • N1a: 1 lymph node is involved.
    • N1b: 2-3 lymph nodes are involved.
    • N1c: No lymph nodes involved, but tumor deposits are found in nearby tissue.
  • N2: Cancer has spread to 4 or more lymph nodes.
    • N2a: 4-6 lymph nodes involved.
    • N2b: More than 6 lymph nodes involved.
• M: Metastasis
  • M0: No distant metastasis.
  • M1: Cancer has spread to distant organs:
    • M1a: Metastasis to one organ or site (e.g., liver or lung).
    • M1b: Metastasis to more than one organ or site.
    • M1c: Metastasis to the peritoneum (lining of the abdominal cavity).

B. Stages of Colorectal Cancer

• Stage 0 (Carcinoma in Situ):
  • Cancer is confined to the mucosa and hasn’t spread deeper.
• Stage I:
  • Cancer has invaded the submucosa (T1) or muscularis propria (T2) without lymph node involvement (N0).
• Stage II:
  • Cancer has spread through the wall of the colon or rectum but hasn’t reached lymph nodes:
    • Stage IIA: T3, N0.
    • Stage IIB: T4a, N0.
    • Stage IIC: T4b, N0.
• Stage III:
  • Cancer has reached nearby lymph nodes but not distant sites:
    • Stage IIIA: T1-T2, N1.
    • Stage IIIB: T3-T4a, N1; T1-T2, N2.
    • Stage IIIC: T3-T4b, N2.
• Stage IV:
  • Cancer has metastasized to distant organs:
    • Stage IVA: M1a (metastasis to one site).
    • Stage IVB: M1b (metastasis to more than one site).
    • Stage IVC: M1c (peritoneal metastasis).

C. Importance of Staging

• Treatment Planning:
  • Early stages (0-I) may only require surgery.
  • Advanced stages (III-IV) typically require a combination of surgery, chemotherapy, radiation, and targeted therapy.
• Prognosis:
  • Higher stages are associated with lower survival rates, but advances in treatment have improved outcomes.

E. Advanced Imaging Tests

Imaging tests are vital for staging colorectal cancer, detecting metastasis, and monitoring treatment response.

A. Types of Advanced Imaging Tests

1. CT Scan (Computed Tomography)

• Purpose:
  • Creates detailed cross-sectional images of the body.
  • Identifies the spread of cancer to nearby lymph nodes, liver, lungs, or other organs.
• Process:
  • Patient may receive contrast dye (oral or IV) to enhance imaging.
• Key Findings:
  • Tumor size and location.
  • Enlarged lymph nodes.
  • Liver or lung metastasis.

2. MRI (Magnetic Resonance Imaging)

• Purpose:
  • Provides high-resolution images of soft tissues, particularly useful for rectal cancer staging.
• Process:
  • Uses magnetic fields and radio waves; may include contrast dye.
• Key Findings:
  • Tumor depth (important for rectal cancer surgery planning).
  • Involvement of nearby structures like blood vessels or organs.

3. PET Scan (Positron Emission Tomography)

• Purpose:
  • Detects active cancer cells using a radioactive tracer (e.g., FDG).
• Process:
  • Patient receives an injection of a radioactive sugar tracer, and cancer cells absorb more tracer than normal cells.
• Key Findings:
  • Identifies metastatic or recurrent cancer.
  • Highlights areas of high metabolic activity indicating active disease.

4. Endorectal Ultrasound (ERUS)

• Purpose:
  • Used for rectal cancer to determine the depth of tumor invasion and lymph node involvement.
• Process:
  • A probe is inserted into the rectum, emitting sound waves to create detailed images.
• Key Findings:
  • Tumor penetration into rectal layers.
  • Nearby lymph node involvement.

5. Liver Ultrasound

• Purpose:
  • Screens for liver metastasis, which is common in colorectal cancer.
• Process:
  • Non-invasive, using sound waves to create liver images.
• Key Findings:
  • Detects liver masses or abnormalities suggestive of cancer spread.

B. When Are Imaging Tests Performed?

• At Diagnosis:
  • To stage the cancer and determine if it has spread.
• Before Surgery:
  • To guide surgical planning and assess resectability of the tumor or metastases.
• After Treatment:
  • To monitor for recurrence or assess the effectiveness of therapy.

C. Limitations of Imaging Tests

• False Positives:
  • Enlarged lymph nodes may not always indicate cancer.
• False Negatives:
  • Microscopic metastases may not be visible on scans.
• Interpretation:
  • Requires skilled radiologists to differentiate cancerous tissue from normal variations or benign conditions.

Conclusion

Staging and advanced imaging are cornerstones of colorectal cancer diagnosis and management. Together, they provide a clear picture of the disease’s extent, enabling doctors to tailor treatment plans to the patient’s specific needs. Understanding these diagnostic tools empowers patients to engage in their care and make informed decisions about their treatment journey.

Going through the diagnostic progress and need to understand treatment options? See Wellnest's guide for Treatment Options for Colorectal Cancer, Managing Side Effects of Colorectal Cancer Treatment, Must-Have Items for Going Through Treatment, and Questions to Ask the Doctor.