How is prostate cancer staged using the TNM classification together with serum prostate-specific antigen (PSA) level and Gleason grade?

Prostate Cancer Staging Using TNM Classification, PSA, and Gleason Grade

Prostate cancer staging integrates the 1997 TNM classification with serum PSA level and Gleason score to create a comprehensive risk stratification system that predicts pathologic stage, guides treatment selection, and estimates prognosis. 1

Core Staging Components

The three essential elements that must be combined for accurate staging are:

• TNM clinical stage determined by digital rectal examination (DRE), defining local tumor extent 1
• Serum PSA level measured in ng/mL, reflecting tumor burden 1
• Gleason score from biopsy specimens, indicating tumor differentiation and aggressiveness 1, 2

TNM Classification Framework

The 1997 TNM system modified by American Joint Cancer Committee criteria should be applied as the anatomic staging foundation 1:

• T1a: Incidental tumor in ≤5% of resected tissue (TURP or simple prostatectomy) with Gleason score <7 1
• T1b: Incidental tumor in >5% of resected tissue or any Gleason score ≥7 1
• T1c: Tumor identified by needle biopsy due to elevated PSA (nonpalpable, nonvisible) 3
• T2: Palpable tumor confined to prostate, subdivided by extent of involvement 1
• T3: Tumor extends through prostatic capsule 1
• T4: Tumor invades adjacent structures 1

Gleason Grading Rules

The Gleason system assigns grades 1-5 based on architectural patterns, with specific calculation rules 1, 2:

• Score calculation: Sum of the two most dominant grade patterns in the biopsy 1, 2
• Three-pattern rule: When three grades are present, combine the highest grade with the most dominant (prevalent) grade 1, 2
• Modified Gleason score: Document the proportion of grade 4 and 5 disease present, as this provides additional prognostic information 1, 2
• Critical caveat: Do not assess Gleason grade after radiotherapy or hormonal therapy, as treatment-induced changes obscure the original pattern 1, 2

Risk Stratification System

The NCCN risk groups integrate all three parameters to assign patients to validated prognostic categories that directly guide treatment decisions 1:

Very Low Risk

• Clinical stage T1c
• Gleason score ≤6
• PSA <10 ng/mL
• <3 positive biopsy cores
• ≤50% cancer in any core 1

Low Risk

• Clinical stage T1-T2a
• Gleason score ≤6
• PSA <10 ng/mL 1, 2

Intermediate Risk

• Clinical stage T2b OR
• Gleason score 7 OR
• PSA 10-20 ng/mL 1, 2

High Risk

• Clinical stage ≥T2c OR
• Gleason score 8-10 OR
• PSA >20 ng/mL 1, 2

Predictive Models: Partin Tables and Nomograms

Beyond risk groups, more precise individualized predictions use validated tools 1, 4:

• Partin tables combine clinical stage, Gleason score, and PSA to predict four mutually exclusive pathologic outcomes: organ-confined disease, extracapsular extension, seminal vesicle invasion, or lymph node metastasis 1, 4
• Nomograms provide superior accuracy for individual patients by incorporating continuous variable values rather than categorical cutoffs 1
• Multi-institutional validation demonstrates 72.4% accuracy in predicting pathological stage within 10% probability 4

Required Pathology Reporting Elements

The pathology report must document specific prognostic factors 1, 2:

• Biopsy core length in millimeters and quality 1
• Tumor involvement length in millimeters or percentage of core 1, 2
• Gleason score with primary and secondary patterns 1, 2
• Modified Gleason score showing proportion of grades 4 and 5 1, 2
• Number and location of positive cores 1, 2
• Extraprostatic extension presence or absence 1, 2
• Perineural invasion and tumor volume (optional but prognostically relevant) 1

Clinical Application: Staging Workup Based on Combined Parameters

The integrated staging approach determines imaging requirements 5:

• PSA <20 ng/mL AND Gleason score <6: Skeletal scintigraphy and pelvic CT unlikely to show metastases (92% sensitivity threshold); imaging can be omitted unless symptomatic 5
• PSA >20 ng/mL OR Gleason score ≥7: Bone scan and cross-sectional imaging indicated regardless of symptoms 5
• Any PSA with high-risk features: Mandatory bone scintigraphy and imaging for potential metastases 6, 7

Critical Staging Pitfalls

Important caveats to avoid misclassification:

• Heterogeneity within risk groups: Patients assigned to intermediate risk by clinical stage (T2b-T2c) have lower recurrence risk than those categorized by Gleason 7 or PSA 10-20 ng/mL 1
• PSA limitations: No PSA cutoff combined with T stage and Gleason grade can accurately rule in metastatic disease with both high sensitivity and specificity; imaging confirmation remains essential 7
• Single elevated PSA: Never proceed to biopsy or aggressive intervention based on one PSA measurement; always verify with repeat testing 8
• Post-treatment grading: Gleason scoring is invalid after radiation or hormonal therapy 1, 2

Prognostic Correlation

Each staging element independently predicts outcomes, with synergistic effects when combined 1, 4, 9:

• PSA correlation: Serum PSA increases with Gleason score (r=0.369, P<0.001) and stage (r=0.398, P<0.001) 9
• Gleason correlation: Higher scores correlate with increased stage (r=0.530, P<0.001) 9
• Combined prediction: The equation x = -3.488 + 0.041×PSA + 0.428×Gleason score predicts stage with validated accuracy 9