Prostate cancer is one of the most commonly diagnosed cancers in men globally, highlighting the importance of accurate and timely diagnosis. Once the cancer is identified, doctors use a process called risk stratification to categorize the tumor based on its potential for growth and spread. This categorization dictates the appropriate course of action, ranging from simple monitoring to aggressive treatment. Within this system, the “unfavorable intermediate-risk” category represents a specific subset of tumors that require careful attention and often a more intensive treatment approach.
Understanding Intermediate-Risk Prostate Cancer
Risk stratification in prostate cancer relies on three primary clinical factors to group tumors: the Prostate-Specific Antigen (PSA) level, the Grade Group (derived from the Gleason score), and the clinical T-stage, which describes the physical extent of the tumor within the prostate. Intermediate-risk prostate cancer is broadly defined by specific parameters that place it between the least aggressive low-risk and the most aggressive high-risk categories. Generally, a patient falls into the intermediate-risk group if they have a PSA level between 10 and 20 nanograms per milliliter (ng/mL), or a Grade Group 2 or 3, corresponding to a Gleason score of 7.
The third defining factor is the clinical T-stage, where the tumor is confined to the prostate but may be felt on examination, such as T2b (cancer in more than half of one lobe) or T2c (cancer in both lobes). This intermediate classification encompasses a highly varied group of patients, which is why it must be further refined into favorable and unfavorable subgroups. Distinguishing between these two intermediate subsets is essential because their prognoses and recommended treatments differ significantly.
Specific Criteria Defining Unfavorable Risk Status
The designation of Unfavorable Intermediate-Risk (UIR) is assigned when a tumor exhibits features suggesting a higher probability of aggressive behavior compared to a Favorable Intermediate-Risk (FIR) tumor. This distinction is made based on the number and severity of the adverse clinical and pathological indicators present. A tumor is typically classified as UIR if it meets one or more of a few well-defined criteria.
One of the most significant criteria is the specific composition of the Grade Group 3 tumor, which is a Gleason score of 4+3=7. Although a Gleason score of 7 is in the intermediate range, the 4+3 designation indicates that the pattern 4, which represents a more aggressive cell structure, is the predominant pattern, suggesting a more biologically aggressive tumor than a 3+4=7 tumor. Another criterion for UIR status is the presence of multiple intermediate-risk factors simultaneously, such as having both a T2b T-stage and a PSA level near the upper limit of the intermediate range.
A high volume of cancer found during the biopsy procedure can push a patient into the unfavorable category. Specifically, if 50% or more of the biopsy cores taken from the prostate contain cancer, the tumor is considered to have a higher burden and thus a greater risk of progression. Tumors with a higher clinical stage, such as T2c, where the tumor is found in both sides of the prostate, are also generally categorized as unfavorable.
Contextualizing Unfavorable Intermediate Risk
The UIR designation helps guide patient expectations and treatment intensity within the overall spectrum of prostate cancer risk. Compared to tumors in the Low-Risk category, UIR disease carries a substantially higher risk of recurrence and disease-specific mortality. Low-risk patients often qualify for active surveillance, where treatment is deferred, but this approach is rarely appropriate for a UIR diagnosis due to the elevated risk of progression.
Conversely, while UIR tumors are more aggressive than their favorable counterparts, they typically have a slightly better prognosis than those classified in the High-Risk category. High-risk tumors are often defined by a Gleason score of 8 to 10 or a PSA greater than 20 ng/mL, suggesting a much greater likelihood of spread outside the prostate. The UIR group, therefore, represents a heterogeneous middle ground where the potential for progression is significant, but often still localized enough to be potentially cured with definitive, intensive local therapy.
Standard Treatment Strategies
The standard management for Unfavorable Intermediate-Risk prostate cancer generally involves definitive local treatment, moving beyond the monitoring often considered for lower-risk disease. For patients with a life expectancy of ten years or more, the primary options are radical prostatectomy or a combination of radiation therapy and short-term hormone therapy. Radical prostatectomy involves the surgical removal of the entire prostate gland, often with the removal of nearby lymph nodes to accurately stage the disease and eliminate the cancer.
The main alternative is definitive radiation therapy, which can be delivered through External Beam Radiation Therapy (EBRT) or a combination of EBRT and brachytherapy. Brachytherapy involves implanting small radioactive seeds directly into the prostate to deliver a high dose of radiation to the tumor. A distinguishing feature of treatment for UIR tumors is the required use of short-term Androgen Deprivation Therapy (ADT) in conjunction with radiation.
ADT, which lowers male hormone levels, is typically administered for a duration of four to six months alongside the radiation regimen. This combined approach is supported by evidence showing that the hormone suppression enhances the effectiveness of the radiation in controlling the tumor and improving long-term outcomes. Treatment selection is ultimately personalized, taking into account the patient’s age, overall health, specific tumor characteristics, and their personal preferences regarding the side effect profiles of surgery versus radiation.