Rectal Cancer: An Overview of Introduction, Types, Pathogenesis, Lab Diagnosis, Treatment, Prevention, and Keynotes

1. Introduction

Rectal cancer is a malignant tumor arising from the epithelial lining of the rectum, the terminal part of the large intestine. It accounts for a significant proportion of colorectal cancers and is a major cause of cancer-related morbidity and mortality worldwide. Early detection and multimodal management have substantially improved survival outcomes.

2. Types of Rectal Cancer

Rectal cancer is classified based on histology and clinical behavior:

1. Adenocarcinoma
   • Most common type (>90%)
   • Originates from glandular epithelial cells
2. Mucinous adenocarcinoma
   • Produces excessive mucin
   • Often associated with a poorer prognosis
3. Signet ring cell carcinoma
   • Aggressive, rare subtype
   • Seen in younger patients
4. Neuroendocrine tumors (NETs)
   • Arise from neuroendocrine cells
   • Usually slow-growing
5. Squamous cell carcinoma (rare)
   • More common in the anal canal than the rectum

3. Pathogenesis

Rectal cancer develops through a multistep process involving genetic and environmental factors:

• Adenoma–carcinoma sequence
• Accumulation of genetic mutations:
  • APC gene mutation (early event)
  • KRAS activation
  • TP53 inactivation
• Microsatellite instability (MSI) in some cases
• Risk factors:
  • Chronic inflammatory bowel disease (IBD)
  • Low-fiber, high-fat diet
  • Smoking and alcohol
  • Obesity and a sedentary lifestyle
  • Family history and hereditary syndromes (FAP, Lynch syndrome)

4. Laboratory Diagnosis

Laboratory and diagnostic evaluation includes:

A. Screening and Initial Tests

• Fecal occult blood test (FOBT)
• Fecal immunochemical test (FIT)

B. Endoscopic Diagnosis

• Colonoscopy with biopsy (gold standard)
• Flexible sigmoidoscopy

C. Histopathology

• Confirmation of malignancy
• Tumor grading and staging

D. Imaging and Staging

• MRI pelvis (preferred for local staging)
• CT scan (chest, abdomen, pelvis) for metastasis
• Endorectal ultrasound (ERUS)

E. Tumor Markers

• Carcinoembryonic antigen (CEA)
  • Useful for prognosis and follow-up

5. Treatment

Management depends on tumor stage, location, and patient factors:

A. Surgery

• Low anterior resection (LAR)
• Abdominoperineal resection (APR)
• Total mesorectal excision (TME) is the standard approach

B. Chemotherapy

• Neoadjuvant or adjuvant therapy
• Common regimens:
  • FOLFOX
  • CAPOX
  • 5-Fluorouracil–based therapy

C. Radiotherapy

• Preoperative (neoadjuvant) radiotherapy reduces local recurrence
• Often combined with chemotherapy (chemoradiation)

D. Targeted and Immunotherapy

• EGFR inhibitors (e.g., cetuximab) in selected cases
• Immunotherapy in MSI-high tumors

6. Prevention

Preventive strategies focus on risk reduction and early detection:

• Regular screening colonoscopy
• High-fiber, low-fat diet
• Increased intake of fruits and vegetables
• Avoid smoking and excessive alcohol use
• Maintain a healthy body weight
• Physical activity
• Surveillance in high-risk individuals

7. Keynotes

• Rectal cancer is a major subtype of colorectal cancer with distinct management.
• Adenocarcinoma is the most common histological type.
• MRI pelvis is crucial for staging and treatment planning.
• Multimodal therapy (surgery + chemoradiation) improves outcomes.
• Early detection significantly increases survival.
• Regular screening is the cornerstone of prevention.

Further Readings

1. https://emedicine.medscape.com/article/281237-overview
2. https://www.cancer.org/cancer/types/colon-rectal-cancer/about/what-is-colorectal-cancer.html
3. https://clsjournal.ascls.org/content/ascls/early/2024/09/18/ascls.2022003206.full.pdf
4. https://www.mdpi.com/2079-4991/12/1/169
5. https://www.ncbi.nlm.nih.gov/books/NBK493202
6. https://surgicaloncology.ucsf.edu/condition/rectal-cancer
7. https://www.mdpi.com/2072-6694/17/4/588
8. https://www.gastroconsa.com/colorectal-cancer-screening-guidelines-for-2025
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC9972668
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC4431429
11. https://www.sciencedirect.com/science/article/pii/S014067362400360X
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC7768867
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC4312646