Prostate cancer requires precise classification to guide appropriate treatment decisions. Doctors and patients rely on specialized grading systems to assess how aggressive cancer cells appear and their likelihood of growth or spread. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) Grade Group system is the current standard for classifying prostate cancer aggressiveness. This system provides a clear, uniform method for pathologists to categorize tumors and for clinicians to discuss the prognosis.
The Shift to Grade Groups
The current WHO/ISUP Grade Group system was developed to address limitations in the older Gleason Score system. Under the traditional system, the lowest score assigned was 6, which often led patients to believe their tumor was moderately aggressive (6 out of 10 points). This perceived high score frequently resulted in patient anxiety and contributed to the potential for overtreatment of slow-growing tumors. Clinicians recognized the need for a simplified, intuitive method that better reflected the tumor’s biological behavior.
The International Society of Urological Pathology (ISUP) introduced a new five-tier scale in 2014, later adopted by the WHO. This scale, known as the Grade Group system, ranges from 1 (least aggressive) to 5 (most aggressive). Establishing Grade Group 1 as the lowest grade reduces the psychological burden on patients diagnosed with very low-risk disease. This reclassification improves prognostic accuracy and supports better communication regarding the disease.
What Defines Grade Group 2
Grade Group 2 identifies prostate cancer classified into the intermediate-risk category. A diagnosis of Grade Group 2 corresponds specifically to a Gleason Score of 7, derived from the specific pattern combination of \(3+4=7\). This score is determined by analyzing the two most common architectural patterns of the cancer cells found in the prostate tissue sample. The first number (3) represents the primary or most prevalent pattern, while the second number (4) is the secondary pattern.
Pattern 3 signifies cancer cells arranged in relatively well-formed, distinct glandular structures, which look closer to normal prostate tissue. Pattern 4 indicates that the cells are more disorganized, appearing as poorly formed, fused, or cribriform glands, which is a sign of greater cellular abnormality. Therefore, Grade Group 2 signifies a tumor where the majority of the cancer cells are the lower-grade Pattern 3, but a substantial minority are the more aggressive Pattern 4. This specific composition is distinct from Grade Group 3, which also sums to a Gleason Score of 7, but with the more aggressive pattern being dominant (\(4+3=7\)).
How the Grade is Determined
Assigning the WHO/ISUP Grade Group begins with acquiring prostate tissue, typically through a transrectal ultrasound (TRUS-guided) biopsy. Multiple small tissue cores are extracted from the prostate gland to ensure adequate sampling of the potentially heterogeneous tumor. These samples are then sent to a pathology laboratory for detailed microscopic examination.
The pathologist analyzes the architectural arrangement of the cancer cells, assigning a numerical pattern score from 1 to 5 based on how much the cells deviate from normal glandular structure. The two most common patterns are identified, and their respective scores are added together to calculate the final Gleason Score. For a Grade Group 2 diagnosis, the pathologist identifies Pattern 3 as the most common arrangement and Pattern 4 as the second most common, resulting in the \(3+4=7\) score. This Gleason Score is then converted directly into the five-tier WHO/ISUP Grade Group system for final classification.
Prognosis and Management Options
A Grade Group 2 diagnosis places the patient into the broad “intermediate-risk” category for prostate cancer. This means the tumor is more aggressive than low-risk cases but less aggressive than high-risk cases. This intermediate category is not uniform and is further subdivided to better predict the likelihood of disease progression. Patients are classified as having either “favorable intermediate-risk” or “unfavorable intermediate-risk” disease based on a combination of factors.
Favorable Intermediate-Risk
Favorable factors often include having only one intermediate-risk criterion, a lower tumor volume, and a lower Prostate-Specific Antigen (PSA) level. Patients in this favorable subgroup may have outcomes similar to low-risk patients and might be considered candidates for Active Surveillance (AS). Active Surveillance involves a structured program of regular monitoring, including repeat PSA tests, digital rectal exams, and periodic repeat biopsies, to defer or avoid definitive treatment while ensuring the cancer does not progress undetected.
Unfavorable Intermediate-Risk
Unfavorable intermediate-risk disease is characterized by features such as a higher PSA level (10-20 ng/mL), a more advanced clinical stage (T2b or T2c), or the presence of multiple intermediate-risk factors. These patients have a higher chance of disease progression and are typically directed toward definitive treatment options. Definitive treatments commonly include surgical removal of the prostate (radical prostatectomy) or various forms of radiation therapy, such as external beam radiation or brachytherapy. The specific choice depends on the patient’s overall health, age, life expectancy, and the specific characteristics of their tumor.