Gleason Score and Prostate Cancer Aggressiveness

Determining the Gleason Score

• The Gleason score is determined by a pathologist who examines tissue samples from a prostate biopsy under a microscope, evaluating how much the cancer cells differ from normal prostate cells, with scores ranging from 6 to 10 1
• The score is calculated by adding the grades of the two most common cancer patterns seen in the biopsy, with each pattern scored from 1 to 5, and a higher score indicating more aggressive cancer cells 2, 3

Understanding Gleason Score Ranges

• Gleason score 6 (3+3) indicates well-differentiated cancer cells that look similar to normal cells and tend to grow slowly, according to the American Academy of Family Physicians 2, 3
• Gleason score 7 indicates moderately differentiated cancer cells with intermediate aggressiveness, as stated by the American Academy of Family Physicians 2
• Gleason scores 8-10 indicate poorly differentiated cancer cells that look very different from normal cells and tend to grow more rapidly, as reported by the American Academy of Family Physicians and the Mayo Clinic Proceedings 2, 3

Prognosis and Treatment Decisions

• With each increase in Gleason score, there is an increase in cancer aggressiveness, and the Gleason score is one of several factors used to determine the risk category (low, intermediate, or high risk), according to The Journal of Urology and the American Academy of Family Physicians 1, 2
• The Gleason score, along with PSA level and clinical stage, helps determine the risk category, which guides treatment recommendations, such as active surveillance, surgery, or radiation for low-risk patients, as recommended by the American Academy of Family Physicians 2, 4

Prostate Cancer Treatment Planning Based on Gleason Score

Role of Gleason Score in Treatment Decision-Making

• The National Comprehensive Cancer Network algorithm recommends treatment based on Gleason score, PSA level, and clinical stage, with very low risk (Gleason ≤6, <3 cores positive, PSA <10 ng/mL) patients eligible for observation if life expectancy <20 years, and definitive treatment if ≥20 years 5
• According to the National Comprehensive Cancer Network, low risk (Gleason ≤6) patients can opt for observation if life expectancy <10 years, and observation or definitive treatment if ≥10 years 5
• Intermediate risk (Gleason 7) patients can choose between observation or treatment options if life expectancy <10 years, and definitive treatment is recommended if ≥10 years 5
• High risk (Gleason 8-10) patients are eligible for observation only if life expectancy <5 years, and radical prostatectomy or radiation therapy (with or without hormone therapy for 2-3 years) if ≥5 years 5

Treatment Options Based on Gleason Score

• For Gleason 6 (low risk) patients, the American Family Physician recommends active surveillance, radical prostatectomy, or radiation therapy options 5
• For Gleason 7 (intermediate risk) patients, radical prostatectomy or radiation therapy (with or without brachytherapy; with or without hormone therapy for 4-6 months) is recommended 5
• For Gleason 8-10 (high risk) patients, radical prostatectomy or radiation therapy (with or without brachytherapy; with or without hormone therapy for 2-3 years) is recommended 5

Gleason Grading System: Structure, Scoring, and Clinical Implications

Grading System Structure

• Gleason grades (1 = least aggressive to 5 = most aggressive) are assigned by pathologists based on how much cancer cells deviate from normal prostate architecture, and the combined grades form a Gleason score that predicts tumor aggressiveness and patient outcomes. 6
• Grade 2 is defined as moderately differentiated cancer with some architectural distortion. 6
• Grade 4 is defined as poorly differentiated cancer with fused, cribriform, or poorly formed glands. 7

Score Calculation Rules

• The Gleason score is calculated by adding the two most predominant grade patterns identified in the biopsy specimen. 6, 8
• The primary grade represents the most common pattern; the secondary grade represents the second most common pattern. 6
• If the highest grade present is not among the primary or secondary patterns, the score combines the most predominant pattern with that highest grade. 6
• When three grades are present, the final score uses the highest grade together with the dominant (most prevalent) grade. 8, 7
• Example: a tumor composed of 60 % grade 3, 35 % grade 4, and 5 % grade 5 is reported as 3 + 4 with a tertiary grade 5. 6

Prognostic Significance

• Each incremental increase in Gleason score is directly associated with greater tumor aggressiveness. 6

Integration into Risk Stratification

• Gleason grade, together with PSA level and clinical stage, defines prostate‑cancer risk categories:
  
  • Low risk – Gleason ≤ 6, PSA ≤ 10 ng/mL, clinical stage T1c–T2a. 6
  • Intermediate risk – Gleason 7 or PSA 10–20 ng/mL or clinical stage T2b. 6
  • High risk – Gleason 8–10 or PSA > 20 ng/mL or clinical stage T2c. 6

Pathology Reporting Requirements

• Reports must include the Gleason score (sum of the two dominant grades). 6
• Length of tumor involvement in each biopsy core must be documented. 7
• The proportion of Gleason grades 4 and 5 (the “modified Gleason score”) must be reported. 9, 8
• Presence or absence of extraprostatic extension must be recorded. 7
• Number and anatomical location of positive cores must be specified. 7

Caveats in Grading

• Gleason grading should not be performed on specimens from patients who have received radiotherapy or hormonal therapy, because treatment‑induced changes obscure the original differentiation pattern. 8, 7
• The modified Gleason score, reflecting the percentage of grade 4‑5 disease, provides additional prognostic information and is recommended for comprehensive reporting. 9, 8

Contemporary Grade Group System

• Grade Group 4 corresponds to Gleason 8 (patterns 4 + 4, 3 + 5, or 5 + 3). 6

Gleason Scoring and Grade Group System for Prostate Cancer

Gleason Scoring System

• The Gleason score is a histopathologic grading system ranging from 6 to 10 that predicts prostate cancer aggressiveness; higher scores indicate more aggressive disease and poorer prognosis. 10
• When a specimen contains > 95 % poorly formed, fused, or cribriform glands (or lacks glandular formation), any < 5 % component of well‑formed glands is excluded from the grading calculation. 10

Grade Group Classification (International Society of Urological Pathology)

• The ISUP introduced a five‑tier Grade Group system that maps directly to Gleason scores, providing clearer prognostic stratification. 10
• Grade Group 1: Gleason ≤6 (only discrete, well‑formed glands). 10
• Grade Group 2: Gleason 3 + 4 = 7 (predominantly well‑formed glands with a lesser component of poorly formed/fused/cribriform glands). 10
• Grade Group 3: Gleason 4 + 3 = 7 (predominantly poorly formed/fused/cribriform glands with a lesser component of well‑formed glands). 10
• Grade Group 4: Gleason 8 (patterns 4 + 4, 3 + 5, or 5 + 3; composed of poorly formed/fused/cribriform glands or mixed patterns). 10
• Grade Group 5: Gleason 9–10 (absence of gland formation, with or without necrosis). 10

Prognostic Outcomes (Validated Cohort)

• In a validation cohort of > 26,000 patients, each incremental increase in Grade Group was associated with a stepwise decline in 5‑year biochemical recurrence‑free survival after radical prostatectomy:
  
  • Grade Group 1 – 96 % survival. 10
  • Grade Group 2 – 88 % survival. 10
  • Grade Group 3 – 63 % survival. 10
  • Grade Group 4 – 48 % survival. 10
  • Grade Group 5 – 26 % survival. 10

Risk Stratification Incorporating Gleason Grade (Guideline Framework)

• Gleason grade, together with prostate‑specific antigen (PSA) level and clinical stage, defines prostate cancer risk categories that guide therapeutic decisions. 11
• Low‑risk disease: Grade Group 1 (Gleason ≤6), PSA < 10 ng/mL, clinical stage T1–T2a. 11
• Intermediate‑risk disease: Any Gleason 7 (Grade Groups 2–3) or PSA 10–20 ng/mL or clinical stage T2b–c. 11
  
  • Favorable intermediate: Grade Group 2 (3 + 4 = 7) with < 50 % of biopsy cores positive. 11
  • Unfavorable intermediate: Grade Group 3 (4 + 3 = 7) or the presence of multiple intermediate‑risk factors. 11
• High‑risk disease: Grade Groups 4–5 (Gleason 8–10), PSA > 20 ng/mL, or clinical stage T3–T4. 11