What are the stages of cancer and how is cancer diagnosed?

Cancer Staging and Diagnosis

Cancer staging is defined using the TNM Classification system, which describes the anatomical extent of disease based on three components: T (tumor size/extent), N (regional lymph node involvement), and M (distant metastasis), and this classification must be recorded at initial diagnosis and remain unchanged in medical records. 1

Understanding the TNM Classification System

The TNM system is the universally accepted standard for recording anatomical disease extent, maintained by the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC). 1 This system serves multiple critical functions:

• Guides treatment planning by precisely defining disease extent 2, 3
• Establishes prognosis for individual patients 1, 3
• Facilitates clinical trial eligibility and stratification 1
• Enables communication between clinicians and cancer registries 1, 4

The Three TNM Components

T Category (Tumor): Describes the size and local extent of the primary tumor. 1, 2

N Category (Node): Defines the extent of regional lymph node involvement. 1, 2

M Category (Metastasis): Indicates the presence or absence of distant metastatic disease. 1, 2

Critical terminology note: These should be called "T category," "N category," and "M category"—NOT "T stage," "N stage," or "M stage," because the term "stage" is reserved exclusively for the aggregated roman numeral stage groups (Stage I, II, III, IV). 1

Two Types of TNM Classification

Clinical Classification (cTNM)

Clinical staging is determined before any treatment intervention and is based on: 1

• Physical examination findings 1
• Imaging studies (CT, MRI, PET-CT) 5
• Endoscopy results 1
• Laboratory findings 2
• Surgical exploration (when performed for diagnostic purposes) 1

Pathological Classification (pTNM)

Pathological staging incorporates all clinical information PLUS additional evidence from surgery and pathological examination of surgical specimens. 1 This requires collaboration between clinicians and pathologists—it cannot be determined by the pathologist alone without full clinical information. 1

Stage Groups and Prognostic Classifications

The TNM categories are combined into roman numeral stage groups (Stage I, II, III, IV) that reflect overall prognosis. 1 However, modern staging increasingly incorporates non-anatomical prognostic factors:

• Anatomical stage groups: Based solely on TNM components 1
• Prognostic stage groups: Integrate anatomical extent with biomarkers and other prognostic factors 1

Example: Breast Cancer Staging Evolution

The AJCC 8th edition for breast cancer now incorporates biological markers (ER, PR, HER2 status, tumor grade) into prognostic stage groups, representing a major advancement beyond pure anatomical staging. 6 The Oncotype DX Recurrence Score is also integrated for ER+/HER2-/node-negative or 1-3 positive node disease. 6

Special Staging Scenarios and Prefixes

Cancer stage must be defined at initial diagnosis and remain unchanged in the medical record, even if disease extent changes during treatment. 1 However, restaging uses specific prefixes to maintain clarity:

Restaging Prefixes 1

• "y stage": Used after neoadjuvant (preoperative) therapy 1
• "r stage": Applied after documented disease-free period with later recurrence, or after surveillance period (as in prostate/thyroid cancer) 1

Important Terminology Distinctions 1

• Downstaging: Reduction in T or N category after neoadjuvant therapy 1
• Downsizing: Reduction in tumor volume after neoadjuvant therapy 1
• Stage migration: Change in proportion of T, N, or M categories within a population following introduction of new diagnostic methods 1
• Stage shift: Change in stage distribution within a population due to screening programs (shift to lower stages) or limited access to care (shift to higher stages) 1

Cancer Diagnosis Process

Stage-Specific Diagnostic Workup

For early-stage breast cancer (Stage I-IIA), the diagnostic workup includes: 6

• History and physical examination 6
• Complete blood count and liver function tests 6
• Alkaline phosphatase 6
• Bilateral diagnostic mammography with ultrasound 6
• Core needle biopsy with marker placement 6
• No routine systemic staging unless signs/symptoms present 6

For locally advanced disease (Stage III), add: 6

• Chest CT 6
• Abdominal/pelvic CT or MRI 6
• Bone scan or sodium fluoride PET/CT 6
• Optional FDG-PET/CT 6

Pathological Assessment Requirements

Mandatory pathological evaluations include: 6

• ER/PR status using standardized immunohistochemistry 6
• HER2 testing per ASCO-CAP guidelines 6
• Tumor grade using WHO classification 6
• Sentinel lymph node biopsy with accurate documentation of involved nodes 6

Nasopharyngeal Cancer Example

For nasopharyngeal cancer staging, the diagnostic approach requires: 5

• Nasopharyngoscopy 5
• MRI of nasopharynx/skull base/neck (preferred over CT when available) 5
• PET-CT for distant metastases (most sensitive and specific method) 5

Common Pitfalls to Avoid

The literature demonstrates widespread inconsistent use of staging terminology—87.5% of surveyed experts confirmed this problem. 1 Avoid these errors: 1

• Mixing T, N, M categories with grouped stages incorrectly 1
• Confusing downstaging with downsizing 1
• Combining patients with primary, recurrent, and metastatic disease in prognostic analyses 1
• Mixing baseline and non-baseline factors in prognostic models 1
• Using "upstaging" or "understaging" terms (lack precision) 1

Registry and Documentation Standards

Cancer registries must record both individual T, N, M categories AND roman numeral stage groups at initial diagnosis. 1 Clinical and pathological TNM categories should both be documented when available. 1 The original stage designation remains permanent in medical records regardless of subsequent disease progression. 1