**4.2 Modern NCCN classification system**

The modern National Comprehensive Cancer Network (NCCN) classification system includes a six-tier system, with very low-risk, low-risk, favorable intermediaterisk (FIR), unfavorable intermediate-risk (UIR), high-risk, and very high-risk (see **Figure 1**) [8].

Importantly, this new system divides the heterogenous group of intermediate-risk prostate adenocarcinoma into favorable and unfavorable classifications. This bifurcation is based on research led by Drs. Zachary Zumsteg and Michael Zelefsky at Memorial Sloan Kettering Cancer Center between 1992 and 2007, on 1208 patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (EBRT) to 81 Gy or 86.4 Gy in 1.8 Gy daily fractions with or without


**Table 1.**

*Original D'Amico three-tier classification system.*


#### **Figure 1.**

*NCCN prostate initial risk stratification and staging work-up for clinically localized disease [8].*

short-term androgen deprivation therapy (ADT) [9]. FIR prostate cancer was defined as having NCCN intermediate-risk disease and all the following: a single intermediate risk factor, Gleason 3 + 4 = 7, and < 50% of biopsy cores positive. UIR prostate cancer was classified as any intermediate-risk patient with at least one of the following: primary Gleason pattern of 4, ≥50% of biopsy cores positive, PSA ≥10, and cT2bcT2c. The results demonstrated that patients with UIR disease had a 2.4x increase in PSA recurrence, 4.3x increase in distant metastases, and 7.4x increases in prostate cancer-specific mortality; therefore, it was concluded that a bifurcation could be made within the intermediate-risk category.

## **4.3 UCSF-CAPRA scoring system**

The UCSF-Cancer of the Prostate Risk Assessment (CAPRA) score is another model developed to predict the aggressiveness of a diagnosed prostate adenocarcinoma, including primary endpoints such as prostate cancer–specific mortality, allcause mortality, and metastatic disease in patients post-treatment (see **Figure 2** and **Table 2**) [10].
