What is the approach to risk stratification of prostate issues?

Risk Stratification of Prostate Cancer

Risk stratification for prostate cancer should incorporate clinical T stage, serum PSA, Grade Group (Gleason score), and tumor volume on biopsy to guide management decisions and treatment options. 1

Core Risk Stratification Parameters

• PSA Level: A key biomarker with different thresholds for risk assessment:

  • PSA levels <2.5 ng/mL suggest lower risk (screening intervals can be extended to every 2 years)
  • PSA levels ≥2.5 ng/mL warrant annual screening
  • PSA levels ≥4.0 ng/mL historically indicate referral for further evaluation or biopsy
  • PSA levels between 2.5-4.0 ng/mL require individualized risk assessment incorporating other risk factors 1

• Gleason Score/Grade Group: Critical histopathological assessment:

  • Grade Group 1 (Gleason ≤6): Lower risk
  • Grade Group 2 (Gleason 3+4=7): Favorable intermediate risk (if PSA <10)
  • Grade Group 3 (Gleason 4+3=7): Unfavorable intermediate risk
  • Grade Group 4-5 (Gleason 8-10): High risk 1

• Clinical T Stage: Determined by digital rectal examination (DRE):

  • T1-T2a: Lower risk categories
  • T2b-T2c: Intermediate risk
  • T3a and above: High risk 1

• Additional Risk Factors:

  • African American race
  • Family history of prostate cancer
  • Increasing age
  • Abnormal DRE findings
  • Prior negative biopsy (lowers risk) 1

Formal Risk Classification Systems

AUA/ASTRO Risk Groups

• Low Risk:

  • Clinical stage T1-T2a AND
  • Grade Group 1 (Gleason score ≤6) AND
  • PSA <10 ng/mL 1

• Intermediate Risk: (Further stratified into favorable and unfavorable)

  • Favorable Intermediate Risk:

    • Grade Group 2 (Gleason 3+4=7) AND
    • PSA <10 ng/mL AND
    • Less than 50% of biopsy cores positive 1

  • Unfavorable Intermediate Risk:

    • Grade Group 2 (Gleason 3+4=7) with PSA 10-20 ng/mL OR
    • Grade Group 3 (Gleason 4+3=7) with PSA <20 ng/mL 1

• High Risk:

  • Clinical stage T3a OR
  • Grade Group 4-5 (Gleason score 8-10) OR
  • PSA >20 ng/mL 1, 2

Advanced Risk Assessment Tools

• PCPT Prostate Cancer Risk Calculator:

  • Integrates multiple risk factors to predict overall risk of prostate cancer and specifically high-grade cancer
  • Applicable to men ≥55 years without prior prostate cancer diagnosis
  • Requires DRE and PSA results less than a year old 1

• Memorial Sloan Kettering Cancer Center (MSKCC) Approach:

  • Starts screening at age 45
  • Adjusts screening intervals based on initial and subsequent PSA levels
  • Aims to identify men at higher risk for lethal prostate cancer while reducing overdiagnosis 1

• Tissue-based Genomic Biomarkers:

  • May be selectively used when additional risk stratification could alter clinical decision-making
  • Not recommended for routine use in all patients
  • Examples include Prolaris, Oncotype Dx, and Decipher 1

Risk-Based Management Approach

• Low-Risk Disease:

  • Active surveillance is preferred for most patients 1
  • Definitive treatment (radical prostatectomy or radiotherapy) may be considered for patients with risk factors for progression 1

• Intermediate-Risk Disease:

  • Favorable Intermediate Risk: Active surveillance, radical prostatectomy, or radiation therapy 1, 3
  • Unfavorable Intermediate Risk: Radical prostatectomy or radiation therapy (often with short-term androgen deprivation therapy) 1, 3

• High-Risk Disease:

  • Radical prostatectomy with pelvic lymph node dissection OR
  • Radiation therapy plus androgen deprivation therapy OR
  • Combination of external beam radiation therapy plus brachytherapy with or without ADT 2, 4
  • Additional imaging recommended: bone scan AND either pelvic multi-parametric MRI or CT scan 5

Biochemical Recurrence Risk Stratification

After treatment failure, further risk stratification is essential:

• Low-Risk BCR:

  • PSA doubling time >1 year AND
  • Pathological Gleason score <8 (for post-prostatectomy) OR
  • Interval to biochemical failure >18 months AND
  • Biopsy Gleason score <8 (for post-radiation) 1

• High-Risk BCR:

  • PSA doubling time ≤1 year OR
  • Pathological Gleason score 8-10 (for post-prostatectomy) OR
  • Interval to biochemical failure ≤18 months OR
  • Biopsy Gleason score 8-10 (for post-radiation) 1

Common Pitfalls in Risk Stratification

• Overreliance on PSA Alone: PSA should be interpreted in context with other risk factors and may be affected by non-cancerous conditions 1, 6

• Failure to Consider PSA Kinetics: PSA velocity and doubling time provide important prognostic information, especially for recurrence risk assessment 1

• Ignoring Patient Life Expectancy: Treatment recommendations should consider life expectancy; the Social Security Administration Life Expectancy for a 65-year-old American man is 16 years, but this can vary significantly based on health status 1

• Overlooking Racial Disparities: Black men have higher incidence rates (173.0 vs 97.1 per 100,000 compared to White men) and may require more aggressive screening and risk assessment 7

• Neglecting Medication Effects: 5α-reductase inhibitors like finasteride reduce PSA by approximately 50% within six months of treatment, requiring PSA values to be doubled for accurate comparison 6