Key Facts

Cancer staging and grading provide standardised frameworks for describing the extent and aggressiveness of cancer. They are essential for treatment planning, prognosis, clinical trial enrolment, and communication between healthcare professionals.

Epidemiology

• Stage at diagnosis is the single most important prognostic factor for most solid tumours
• In the UK, approximately 45% of cancers are diagnosed at Stage I-II (early) and 40% at Stage III-IV (advanced)
• Routes to diagnosis affect stage: screening picks up earlier stages than emergency presentations

Aetiology

• Not applicable (classification system)

Pathophysiology

• Staging reflects the biological behaviour of the tumour: local invasion → lymphatic spread → distant metastasis
• Grading reflects the degree of differentiation: well-differentiated tumours more closely resemble normal tissue and tend to be less aggressive
• Together, stage and grade predict biological behaviour, response to treatment, and overall prognosis

Clinical Staging

• Based on physical examination, imaging, and pre-operative investigations
• May be revised after surgery (pathological staging, pTNM)

Pathological Staging

• Based on surgical specimens and histopathological examination
• More accurate than clinical staging
• Includes assessment of margins, lymphovascular invasion, perineural invasion

Red Flags Indicating Advanced Stage

• Multiple organ involvement
• Weight loss >10%
• Performance status ECOG ≥3
• Bone pain (skeletal metastases)
• Neurological symptoms (brain metastases)
• Jaundice (liver metastases or biliary obstruction)

Bedside

• Full clinical examination
• Performance status assessment (ECOG/WHO or Karnofsky)

Bloods

• FBC, U&Es, LFTs, calcium, LDH, albumin
• Tumour-specific markers (PSA, CEA, CA-125, AFP, βhCG)

Imaging

• CT chest/abdomen/pelvis: standard staging for most solid tumours
• MRI: superior for local staging (brain, spine, pelvis, liver)
• PET-CT (18F-FDG): increasingly used for staging, treatment response assessment, recurrence detection
• Bone scan: for suspected skeletal metastases (breast, prostate, lung)
• USS: for superficial lymph nodes, liver, guided biopsy

Special Tests

• Biopsy and histopathology: essential for grading and tumour characterisation
• Immunohistochemistry: tumour classification and origin
• Molecular profiling: predictive biomarkers for targeted therapy
• Sentinel lymph node biopsy: minimally invasive lymph node staging (breast, melanoma)

Non-pharmacological

• MDT discussion mandatory for all new cancer diagnoses
• Treatment decisions based on stage, grade, molecular profile, performance status, and patient preference
• Clinical nurse specialist support and holistic needs assessment

Pharmacological

• Treatment stratified by stage:
  • Early stage (I-II): curative surgery ± adjuvant therapy
  • Locally advanced (III): neoadjuvant or concurrent chemoradiotherapy
  • Metastatic (IV): systemic therapy (palliative intent in most solid tumours)
• Specific regimens are cancer-type dependent

Surgical/Interventional

• Surgery is the primary curative modality for most early-stage solid tumours
• Radiotherapy: curative for some localised cancers (cervix, head & neck, prostate)
• Interventional radiology: ablation, embolisation

Referral Criteria

• All new cancer diagnoses: MDT discussion
• Stage-appropriate treatment at specialist centres
• Clinical trial eligibility assessment

• Stage is the strongest prognostic factor for most cancers
• Stage I: 5-year survival typically 80-95% (site-dependent)
• Stage IV: 5-year survival typically 5-30% (site-dependent)
• Grade independently predicts outcome within each stage
• Performance status strongly predicts treatment tolerance and survival
• Molecular subtypes increasingly influence prognosis (e.g. HER2+ breast cancer has improved outcomes with targeted therapy)

TNM Staging Overview

ECOG Performance Status

Stage Grouping (General)