Risk factors, unfavorable disease and the implications for active surveillance in early-stage prostate cancer

The authors aimed to determine the risks of unfavorable disease and predictors of adverse outcomes in men with Gleason score 3 + 4 prostate cancer and how this would affect active surveillance. The authors concluded that active surveillance is a potential treatment option in men with Gleason score 3+4, low PSA scores and low-stage cancer.

In some men, immediate active treatment for prostate cancer is not necessary. Prostate cancer can be classified into three groups – low, intermediate and high risk cancer. This classification is carried out based on certain risk factors. These factors include tumor staging (size of the tumor and the extent of cancer spread), Gleason score (GS – a system used to evaluate how aggressive the cancer is based on tumor cell appearance) and prostate specific antigen levels (PSA – protein elevated in the blood in the presence of prostate cancer). Low-risk prostate cancer can be managed using active surveillance. This is not an active treatment and involves watching the cancer to determine signs of progression. 

Intermediate-risk cancer, depending on the nature of the cancer and outcomes, can be classified as favorable or unfavorable. Unfavorable disease is defined as having two or more intermediate-risk factors. This can include a Gleason score greater than 7, PSA level of 10 to 40 ng/mL or a high percentage of cancer cells following a tissue sample from the cancer site. A GS of 3+4 indicates that some tumor cells were found to have a score of 3, while other were found to have a score of 4. These scores are combined to give a GS of 7. It is not clear what effect these unfavorable characteristics have on active surveillance.

The aim of this study was to identify the risk of unfavorable disease and adverse outcomes in patients with GS 3+4 prostate cancer and the implications on active surveillance.

1,190 patients were used in this study. All patients received prostate surgery (removal of the prostate gland). All patients had early-stage (confined to the prostate gland) prostate cancer. 13.1% of patients experienced a GS upgrade (increase in previous score indicating cancer progression) following surgery. 16.9% of patients experienced a GS downgrade (decrease in score indicating cancer is less aggressive). 24.8% of patients had unfavorable disease at prostate surgery. 17.2% of men had cancer cells beyond the prostate. 

Age, PSA levels and the percentage of tumor surface involvement were the only significant factors affecting GS upgrade.

PSA levels, higher tumor grading, percentage of positive cancer tissue samples and perineural invasion (cancer found inside the nerves of the prostate giving a higher risk of cancer spread) were significant factors in GS downgrading. The factors made it less likely the tumor would be downgraded. 

Age, tumor staging, perineural invasion and percentage of positive tissue samples were significantly associated with unfavorable disease progression. 

The authors concluded that active surveillance is a potential treatment option in men with GS 3+4, low PSA scores and low-risk cancer. However, alternative tools need to be implemented to determine GS upgrade prediction.