Before your doctor considers any form of treatment, the most important considerations are:

Anatomic extent of disease (tumor, node, metastasis [TNM] stage);
Histologic grade (Gleason score/grade group) and molecular characteristics of the tumor;
Serum PSA level;
Estimated outcome with different treatment options;
Potential complications with each treatment approach;
The patient's general medical condition, age, and comorbidity, as well as individual preferences;

Histologic grade is obtained from the biopsy and is one of the most important considerations. The Gleason grades for the two most prevalent differentiation patterns are combined to create the Gleason score, and Gleason score is now incorporated into the newly adopted grade group system, the ISUP grade score. In the grade group system, tumors are separated into five categories based upon the primary and secondary Gleason pattern:

Grade group 1 (Gleason score 3+3)
Grade group 2 (Gleason score 3+4)
Grade group 3 (Gleason score 4+3)
Grade group 4 (Gleason score 4+4, 3+5, or 5+3)
Grade group 5 (Gleason score 4+5, 5+4, or 5+5)

The Gleason grade is based solely on the architectural features of prostate cancer cells and correlates closely with clinical behavior. A higher score indicates a greater likelihood of having non-organ-confined disease, as well as a worse outcome after treatment of localized disease. Based on the growth pattern and degree of differentiation, tumors are graded from 1 to 5, with grade 1 being the most and grade 5 the least differentiated.

Why is there a sum of two numbers? Because the Gleason score is derived by adding together the numerical values of the two most prevalent differentiation patterns (a primary grade and a secondary grade). The ISUP score is a new grade group system not designed to replace the Gleason grading system but to provide a more accurate risk stratification. In this last system, tumors are separated into five categories based on the primary and secondary Gleason patterns. It is recommended for the two scores to appear on the pathology report as the current practice.

Grade group 1 prostatic adenocarcinoma of a small volume can be considered an early phase of prostate cancer and can be clinically insignificant because very few are associated with subsequent development of metastatic disease, and these may represent sampling error in the original needle biopsy.

In Grade group 2 most cells still look similar to normal prostate cells. The cancer is likely to grow slowly.

However, Grade group 3 (Gleason 7 (4+3) represents men with Gleason 4+3 tumors (where grade 4 is more prevalent than grade 3) that have a less favorable outcome than do those with Gleason 3+4 disease (grade group 2), where grade 3 is more prevalent. In this situation the cells look less like normal prostate cells and the cancer is likely to grow at a moderate rate.

Grade group 4 (Gleason score 8) includes patients with Gleason score 4+4 disease as well as those with Gleason score 3+5 or 5+3 prostate cancer. The presence of a component of Gleason grade 5 (either 3+5 or 5+3) was associated with an increased risk of prostate cancer mortality compared with Gleason score 4+4 disease. Some cells look abnormal and the cancer might grow quickly or at a moderate rate.

In grade group 5 (Gleason score 9 or 10 (or 4 + 5 = 9, 5 + 4 = 9 or 5 + 5 = 10), the cells look very abnormal. The cancer is likely to grow quickly.

Beware the presence of special subtypes of cancer that coexist with conventional prostatic adenocarcinoma that are associated with a poor prognosis, which may require special management:

Cribriform pattern
Ductal adenocarcinoma
Small cell carcinoma
A sarcomatoid component along with the carcinoma (carcinosarcoma or sarcomatoid carcinoma)

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