Unfavorable intermediate-risk prostate cancer is a more aggressive form of intermediate-risk disease with a higher chance of progression or recurrence. It is defined by having multiple intermediate-risk factors (e.g., PSA 10–20 ng/mL, Gleason 7, or stage T2b–T2c), a Gleason score of 4+3=7 (Grade Group 3), or ≥50% of biopsy cores involved.

These patients are at greater risk than those with favorable intermediate disease and usually require definitive treatment, such as external beam radiation therapy with 4–6 months of androgen deprivation therapy (ADT) or radical prostatectomy. Active surveillance is generally not recommended due to the higher likelihood of progression.