Definition

Rectal adenocarcinoma is a kind of cancer that begins in the gland cells lining the inner surface of the rectum. The rectum is the final section of the large intestine, connecting the sigmoid colon to the anal canal, which in turn leads to the anus.

Description

• The most common kind of rectal adenocarcinoma is the significant majority, around 95% of all the rectal cancers diagnosed.
• Polyps to cancer development. Generally, it progresses slowly over time from precancerous growth (adenomatous polyps) to cancer.
• When a rectal adenocarcinoma is explained as invasive, it means the carcinogenic cells have grown deeper into the mucosal layer of the rectal lining, which can spread through the rectal wall to distant organs (metastasis) or a nearby lymph node

Epidemiology

Incidence/Prevalence

• An estimated 46,950 new colorectal cancer cases occur annually in the U.S., with rectal adenocarcinoma accounting for a significant portion of these diagnoses.
• The prevalence of rectal adenocarcinoma continues to rise due to improved survival rates and ongoing detection through screening.

Age

• An overwhelming increase in rectal cancer is found in the young generation below 50 years of age.

Gender

• Males are more prone to it than females.

Race

• African Americans, Alaska natives, and American Indians show the highest consistent incidences.

Risk factors

• General
  • Physical inactivity
  • Excess body weight
  • Alcohol consumption
  • Tobacco use
  • Low vitamin D levels
  • Type 2 diabetes
• Physiological
  • Earlier history of adenomatous polyps
  • Family history
  • Inflammatory bowel disease
  • Genetic syndromes
  • Male sex

Etiology

• Individuals with a family history of colorectal cancer or hereditary syndromes like Lynch syndrome and familial adenomatous polyposis (FAP) face a substantially increased risk.
• Dietary factors, such as diets high in red and processed meats and low in fiber, fruits, and vegetables, may contribute to the development of colorectal and rectal cancers.
• Lifestyle factors such as obesity, a sedentary lifestyle, cigarette smoking, and excessive alcohol consumption contribute to increased carcinogenic changes in the colorectal mucosa.
• Most rectal adenocarcinomas develop from adenomatous polyps, which originate as pre-existing adenomas. These polyps gradually undergo dysplastic changes that eventually progress into invasive cancer.
• Chronic inflammatory disorders like ulcerative colitis and Crohn’s disease cause repeated mucosal injury, increasing malignant transformation risk.
• Metabolic factors like type 2 diabetes and insulin resistance create a pro-inflammatory, pro-growth environment, increasing cancer risk.
• Pathophysiology
  • Rectal Adenocarcinoma develops in a multistep process that involves the accumulation of epigenetic and genetic alterations, wherein benign growths transform into malignant tumors over time.
  • Genetic mutations.
  • DNA mismatch repair genes.
  • Chromosomal instability (CIN)
  • Tumor suppressor genes
  • Oncogenes
  • Adenomatous polyps (Adenomas)
  • Sessile serrated polyps (SSPs)

History

• Find out the patient’s history of changes in bowel habits like constipation, diarrhea, and feeling of incomplete bowel movement
• Rectal bleeding
• Blood in stool
• Abdominal cramping
• Abdominal fullness and bloating
• Weakness or fatigue
• Weight loss
• Loss of appetite

Physical findings on examination

In the physical findings on examination of Rectal Adenocarcinoma, these findings are generally observed:

• Appearance
  • Jaundice
  • Pallor
  • Lethargy
• Abdominal examination
  • Distension
• Digital rectal examination (DRE)
  • To examine, a doctor inserts a lubricated gloved finger into the rectum to find any abnormalities
  • Rectal mass
  • Tenderness
  • Presence of blood
  • The retroverted uterus and cervix may be palpated anteriorly in women
  • The prostate gland may be palpated anteriorly in men
• Swelling of feet and hands
• Palpation of the lymph node:
  • Inguinal lymph nodes
  • Supraclavicular lymph nodes

Laboratory Tests

• Blood tests:
  • Complete blood count (CBC)
• Chemistry panel (metabolic panel)
  • Liver function tests (LFTs)
  • Kidney function tests
  • Electrolytes
• Carcinoembryonic antigen (CEA)
• Tissue-based molecular/genetic tests
  • Microsatellite instability (MSI) / mismatch repair (MMR) status
  • RAS mutation testing (KRAS, NRAS)
  • BRAF V600E mutation testing
  • HER2 amplification/overexpression
  • NTRK gene fusion testing
• Emerging liquid biopsy (blood-based molecular tests)

Diagnostic Tests

• Endoscopic Diagnosis
  • Colonoscopy with biopsy (Gold standard for diagnosis)
  • Visualizes the tumor Allows tissue sampling for histopathology
  • Proctoscopy / Sigmoidoscopy (In some cases as initial evaluation)
• Imaging for Staging
  • Pelvic MRI (Best test for local staging – T & N stage)
  • Contrast-enhanced CT abdomen & pelvis
  • Chest CT (To evaluate lung metastasis)
  • Endorectal ultrasound (ERUS) (Useful for early rectal tumors – T1/T2)
  • PET-CT (selected cases) (For suspected metastatic disease)
• Histopathology
  • Confirms adenocarcinoma
  • Determines grade, lymphovascular invasion, perineural invasion, tumor differentiation

Differential Diagnosis

• Benign rectal and anorectal conditions:
  • Anal fissure
  • Anal fistula
  • Hemorrhoids
  • Rectal prolapse
  • Rectal polyps
  • Hypertrophied anal papilla
  • Fecal impaction
  • Proctitis
  • Solitary rectal ulcer syndrome
• Less common conditions:
  • Rectal malignancies
  • Inflammatory bowel diseases
  • Endometriosis
  • Ameboma
  • Pelvic sarcoma
  • Metastatic lesions to the pelvic / rectum

General treatment items

General treatment requires a multidisciplinary approach, involving coordinated care among surgeons, medical oncologists, radiation oncologists, radiologists, and pathologists.

Surgical Interventions

• Total Mesorectal Excision (TME) is the gold standard surgical technique for predominant rectal cancer. TME involves the precise removal of the rectum and mesorectum containing the tumor.
• Categories of surgical procedures:
  • Local Excision (Trans anal Methods):
    • Polypectomy/Endoscopic resection.
    • Trans anal Excision (TAE).
    • Trans anal Endoscopic Microsurgery (TEM) and Trans anal Minimally Invasive Surgery (TAMIS)
  • Radical Resection (Abdominal Methods):
    • Low Anterior Resection (LAR).
    • Temporary Ileostomy.
    • Abdominoperineal Resection (APR).
    • Pelvic Exenteration.
  • Surgical methods:
    • Open Surgery.
    • Minimally Invasive surgery.
    • Laparoscopic Surgery.
    • Robotic-Assisted Surgery.
  • Innovations and emerging trends in Surgical techniques:
    • Trans anal Total Mesorectal Excision (TaTME)

Adjunctive Therapies

• Adjunctive therapies improve tumor control, reduce recurrence, and enhance survival when combined with surgery.
• Neoadjuvant Therapies
  • Neoadjuvant Chemoradiation (Chemotherapy + Radiation Therapy):
  • Long-Course Chemoradiation (LCRT)
  • Short-Course Radiation Therapy (SCRT)
  • Total Neoadjuvant Therapies (TNT)
  • Neoadjuvant Chemotherapy
  • Adjuvant Radiation Therapy
• Targeted therapy:
  • VEGF inhibitors
  • HER2 inhibitors
• Immunotherapy:
  • Mismatch Repair Deficiency (DMMR) / Microsatellite Instability-High (MSI-H)

Medications indicated with specific doses

Standard Chemotherapy Protocol for Rectal Adenocarcinoma:

• FOLFOX (Oxaliplatin, Leucovorin, 5-FU)
  • Oxaliplatin: 85 mg/m² IV on Day 1
  • Leucovorin: 400 mg/m² IV on Day 1
  • 5-Fluorouracil (5-FU): 400 mg/m² IV bolus on Day 1, followed by 2400 mg/m² IV continuous infusion over 46 hours
  • Schedule: Every 2 weeks
• FOLFIRI (Irinotecan, Leucovorin, and 5-FU)
  • Irinotecan: 180 mg/m² IV on Day 1
  • Leucovorin: 400 mg/m² IV on Day 1
  • 5-FU: 400 mg/m² IV bolus on Day 1, followed by 2400–3000 mg/m² IV infusion over 46 hours
  • Schedule: Every 2 weeks
• CAPOX / XELOX (Capecitabine and Oxaliplatin)
  • Capecitabine: 1,000 mg/m² orally twice daily on Days 1–14
  • Oxaliplatin: 130 mg/m² IV on Day 1
  • Schedule: Every 3 weeks
• FOLFOXIRI (Irinotecan, Oxaliplatin, Leucovorin, and 5-FU)
  • Irinotecan: 180 mg/m² IV on Day 1
  • Oxaliplatin: 85 mg/m² IV on Day 1
  • Leucovorin: 200 mg/m² IV on Day 1
  • 5-FU: 3200 mg/m² IV infusion over 48 hours
  • Schedule: Every 2 weeks

Toxoids

• Not applicable

Immunoglobulins

• Immune Checkpoint Inhibitors (for dMMR/MSI-H tumors)
• Pembrolizumab (Keytruda):
  • Indication: Verified for metastatic MSI-H/dMMR or unresectable solid malignancies.
  • Doses: Generally given intravenously by infusion every 3 to 6 weeks. A common verified dose is 200 mg every 3 weeks or 400 mg every 6 weeks.
• Nivolumab (Opdivo):
  • Indication: Verified for MSI-H/dMMR metastatic colorectal cancer that has advanced following standard chemotherapy.
  • Doses: Can be given as a single IV infusion every 2 or 4 weeks.
• Nivolumab with ipilimumab:
  • Doses: Generally given every 3 weeks for four treatments (nivolumab and ipilimumab) followed by nivolumab alone (Dosage requirement differs, so it's essential to consult the prescribing information for accurate guidance)

Vasodilators

• Not applicable

Thrombolytic agents

• Not applicable

Dietary or Activity restrictions

• Focus on balanced meals.
• Frequent small meals.
• Prioritize protein intake.
• Prioritize plant-based food
• Cut down on processed and red meat
• Cut down on sugary drinks and sweet food
• To manage diarrhea, consume a low fiber diet
• To manage taste changes, use different herbs and spices, as well as different flavors
• Regular physical activity reduces the risk of rectal cancer
• Reduce a sedentary lifestyle
• Listen to your body

Disposition

Admission Criteria

• Diagnosis and staging
• Intestinal obstruction
• Rectal bleeding
• Severe pain
• Intestinal perforation
• Severe malnutrition and dehydration

Discharge criteria

• Adequate pain control
• Stable vital signs
• Tolerance of oral intake
• Adequate mobility
• Return of bowel function
• No active infection
• Wound care
• No acute complications

Monitoring

• Regular visits with oncologist every 3 to 6 months for 2 to 3 years, followed by 6 to 12 months for the next 5 years.
• Carcinoembryonic antigen (CEA) blood tests are monitored for 3 months and 2 years in patients with stage 2 and stage 3 rectal cancer, followed by 6 months for 3 years.
• Colonoscopy is generally recommended after 1 year of surgery to check for synchronous cancers or new polyps. Colonoscopy is done every 3 years, followed by every 5 years.
• Proctoscopy may be recommended for rectal cancer patients who have had a trans anal excision in about 3 to 6 months for the first couple of years.

Patient Education

• Goals: To assist patients and their families in understanding rectal cancer, available treatment options, and likely outcomes.
• To encourage collaborative decision-making among patients, caregivers, and the oncology team.
• General education: Aims to support treatment adherence and manage side effects.
• To enable caregivers to provide assistance in nutrition, emotional support, and post-surgical care.
• Understand medication management and dietary requirements.
• Action Plan for Patients and Families:
  • Consult with the oncologist about all available treatment options, along with their risks and benefits.
  • Arrange home support for daily routines, especially following surgery.
  • Missing doses of scheduled chemo or radiation sessions can decrease their effectiveness.
  • Follow the advice to promote gentle physical activity and bowel retraining.`

Complications

• Variability in bowel movements
• Anemia
• Pain and discomfort
• Bleeding
• Intestinal obstruction
• Intestinal perforation
• Metastasis
• Surgical Complications:
  • Anastomotic leak
  • Infection
  • Bowel obstruction
  • Pulmonary embolism (PE) and deep vein thrombosis (DVT)
  • Stoma problems
  • Damage to nearby organs
  • Sexual dysfunction
• Radiation Therapy Complications:
  • Proctitis
  • Frail pelvic bones
  • Fatigue
• Chemotherapy Complications:
  • Blood count variability
  • Neuropathy
  • Fatigue
  • Gastrointestinal issues

Prevention

• Wellness enhancements include weight management, increasing physical activity, and implementing a balanced dietary routine. Avoid high-calorie and high glycemic foods.
• Avoid tobacco and alcohol consumption.
• For specific individuals, drug therapy can be an option for chemoprevention.
• Screening Tests:
  • Colorectal cancer screening
  • Flexible sigmoidoscopy
  • Colonoscopy
  • Stool-based tests like the Guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and FIT-DNA test (multi-targeted stool DNA test, e.g., Cologuard)
  • CT colonography.

Prognosis

• General survival expectancy rates have a direct correlation with determining prognosis in earlier stages.
• Survival in stages 1 and 2 is 90 to 91%.
• Survival in stage 3, where the spread to nearby structures and lymph nodes is 73 to 74%.
• Survival in stage 4, where the spread to distant organs is 16 to 18%.
• Early screening plays a critical role in improving prognosis.

Associated conditions

• Inflammatory bowel diseases (IBD)
• Metabolic conditions
• Obesity
• Type 2 diabetes
• Genetic conditions
• Documented history of polyp formation or colorectal cancer

Synonyms

• Rectal cancer
• Bowel cancer
• Rectal tumor/mass
• Colorectal cancer

ICD-10-CM

• C20 – Malignant Neoplasm of Rectum
• C78.7 – Secondary Malignant Neoplasm of the liver

• Benson, A. B., Venook, A. P., Al-Hawary, M. M., et al. (2021). Rectal Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network, 19(5), 484–517.
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• American Cancer Society. (2024). Colorectal Cancer Facts & Figures 2024–2026.
• Vilar, E., & Gruber, S. B. (2010). Microsatellite instability in colorectal cancer—the stable evidence. Nature Reviews Clinical Oncology, 7(3), 153–162.
• American Cancer Society. (2024). Colorectal Cancer Early Detection, Diagnosis, and Staging.
• U.S. Preventive Services Task Force. (2021). Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA, 325(19), 1965–1977.