Risk Stratification of Intermediate‑Risk Prostate Cancer

Definitions of Favorable Intermediate‑Risk Disease

The NCCN defines favorable intermediate‑risk prostate cancer as requiring all three of the following: predominant Gleason grade 3 (Gleason 3+4 = 7, Grade Group 2), < 50 % of biopsy cores positive, and ≤ 1 NCCN intermediate‑risk factor (clinical stage T2b‑c, PSA 10–20 ng/mL, or Gleason 7). 1
The AUA/ASTRO guideline classifies favorable intermediate‑risk disease as either (a) Grade Group 1 with PSA 10–<20 ng/mL or stage T2b‑c and < 50 % positive cores, or (b) Grade Group 2 with PSA < 10 ng/mL or stage T1‑2a and < 50 % positive cores. 4

According to the NCCN, a patient is categorized as unfavorable intermediate‑risk when any of the following is present: primary Gleason pattern 4 (Gleason 4+3 = 7, Grade Group 3), ≥ 50 % positive biopsy cores, or > 1 NCCN intermediate‑risk factor present simultaneously. 1
The AUA/ASTRO guideline similarly defines unfavorable intermediate‑risk as (a) Grade Group 1 with PSA 10–<20 ng/mL and stage T2b‑c, or (b) Grade Group 2 with PSA 10–<20 ng/mL and/or stage T2b‑c and/or ≥ 50 % positive cores, or (c) Grade Group 3 with PSA < 20 ng/mL. 4

Patients classified as unfavorable intermediate‑risk experience significantly lower PSA recurrence‑free survival compared with favorable intermediate‑risk patients. 1
Distant metastasis at 5 years occurs in 5.4 % of unfavorable versus 1.6 % of favorable intermediate‑risk patients, indicating a markedly higher risk. 1
Prostate‑cancer‑specific mortality is increased in the unfavorable group relative to the favorable group. 1

When MRI‑targeted biopsies are performed, multiple cores obtained from the same targeted lesion should be counted as a single core to avoid inflating the percentage of positive cores. 4
The percentage of positive cores is calculated as:

The NCCN states that favorable intermediate‑risk patients may be managed with active surveillance (with close monitoring), as their outcomes are comparable to low‑risk disease. 1
Unfavorable intermediate‑risk patients should not be offered active surveillance; they require definitive therapy, often including treatment intensification such as longer‑duration androgen‑deprivation therapy combined with radiation. 1

Clinicians should not rely solely on the Gleason 3+4 versus 4+3 distinction without evaluating the other risk factors; a Gleason 3+4 tumor can still be classified as unfavorable intermediate‑risk if ≥ 50 % of cores are positive or multiple intermediate‑risk factors are present. 1
Accurate risk categorization demands integration of primary Gleason pattern, percentage of positive cores, and the number of NCCN intermediate‑risk factors to avoid misclassification. 1