What are the stages of prostate cancer?

Prostate Cancer Staging

The TNM staging system is the standard classification method for prostate cancer, categorizing the disease based on primary tumor characteristics (T), regional lymph node involvement (N), and distant metastasis (M) to determine prognosis and guide treatment decisions. 1

TNM Classification

T (Primary Tumor) Classification:

• T1: Clinically inapparent tumor not palpable or visible by imaging 2

  • T1a: Incidental finding in ≤5% of resected tissue with Gleason score <7 2
  • T1b: Incidental finding in >5% of resected tissue 2
  • T1c: Tumor identified by needle biopsy due to elevated PSA 1

• T2: Tumor confined to the prostate 2

  • T2a: Tumor involves one-half of one lobe or less 2
  • T2b: Tumor involves more than one-half of one lobe but not both lobes 2
  • T2c: Tumor involves both lobes 2

• T3: Tumor extends through the prostate capsule 1

  • T3a: Extracapsular extension (unilateral or bilateral) 2
  • T3b: Tumor invades seminal vesicle(s) 2

• T4: Tumor is fixed or invades adjacent structures other than seminal vesicles (bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall) 2, 1

N (Regional Lymph Nodes) Classification:

• NX: Regional lymph nodes cannot be assessed 2
• N0: No regional lymph node metastasis 2
• N1: Metastasis in regional lymph node(s) 2

M (Distant Metastasis) Classification:

• MX: Presence of distant metastasis cannot be assessed 2
• M0: No distant metastasis 2
• M1: Distant metastasis 2
  • M1a: Non-regional lymph node(s) 2
  • M1b: Bone(s) 2
  • M1c: Other site(s) with or without bone disease 2

Gleason Score and Grade Groups

• The Gleason score is a critical component of prostate cancer staging, determined by adding the grades of the two most common histologic patterns seen in each biopsy core 2
• Each pattern is scored from 1 to 5, with 5 being the most poorly differentiated 2
• Gleason score interpretation:
  • Score 6: Well-differentiated tumor (better prognosis) 2
  • Score 7: Intermediate differentiation (4+3 is more aggressive than 3+4) 2
  • Scores 8-10: Poorly differentiated (worse prognosis) 2

Risk Stratification

Based on TNM stage, Gleason score, and PSA level, prostate cancer is stratified into risk groups 2:

• Very Low Risk: T1c, Gleason score ≤6, PSA <10 ng/mL, <3 cores positive for cancer, ≤50% cancer in any core, PSA density <0.15 2

• Low Risk: T1-T2a, Gleason score ≤6, PSA <10 ng/mL 2

• Intermediate Risk: T2b-T2c OR Gleason score 7 OR PSA 10-20 ng/mL 2

• High Risk: T3a OR Gleason score 8-10 OR PSA >20 ng/mL 2

Clinical vs. Pathological Staging

• Clinical staging (cTNM) is based on physical examination, imaging studies, and biopsy results before treatment 1
• Pathological staging (pTNM) is based on surgical specimens after radical prostatectomy and is generally more predictive of prognosis 1
• Clinical understaging occurs in more than 50% of cases, highlighting the limitations of pre-treatment assessment 3, 4

Prognostic Significance

• Extraprostatic extension (T3) and seminal vesicle involvement (T3b) are associated with significantly increased risk of disease progression 1
• Only about 25% of patients with T3b disease remain biochemically progression-free at 10 years 1
• Lymph node status is one of the most important prognostic factors, with the volume of nodal metastasis being a key determinant of outcomes 5

Recent Developments

• Integration of molecular and genetic markers with anatomical staging may enhance prognostic accuracy in the future 1
• Some experts suggest that the three-tiered T2 classification system is superfluous and that a tumor size-based substaging system may be more appropriate for future TNM classifications 5
• The current TNM system has been criticized for not adequately accounting for multifocal tumors, which occur in more than half of prostate cancer cases 6

Clinical Application

• The TNM stage, combined with Gleason score and PSA level, should guide treatment decisions 2, 1
• Organ-confined disease (T1-T2) may be suitable for curative local therapy, while locally advanced disease (T3-T4) may require multimodal approaches 1
• Node-positive disease (N1) may benefit from early hormonal therapy 1