Scientists have identified two risk factors that indicate a higher risk of developing aggressive prostate cancer.

Recent European Oncological Urology study assessed the risk of death, based on Gleason score and clinical parameters, in patients with prostate cancer (PC).

Prostate Cancer and Gleason Score

The Gleason score is a scoring system that ranges from 6 to 10 and is used to evaluate patients with prostate cancer. A lower score indicates that the cancer cells are very similar to normal cells and are more likely to spread slowly. Doctors exploit the Gleason score to formulate effective treatments for prostate cancer, which can lead to a better prognosis.

The results of the ProtecT trial have generated controversy regarding the accuracy of prostate biopsy Gleason score 3 + 3, or Gleason group (GGG), for the diagnosis and outcome of cancer treatment. The majority of the ProtecT cohort had GGG 1 disease, and in this population, only 3.1% died of PC at a median follow-up of 15 years.

As noted, participants in the ProtecT study were randomly assigned to dynamic monitoring (AM) or radical treatment. Patients received a variety of prostate cancer treatments, including androgen deprivation therapy (ADT), radical prostatectomy (RP), or radiotherapy (RT). Approximately 61% of patients who were randomly assigned to AM ultimately received radical treatment by year 15 of follow-up. These patients were at higher risk for metastatic disease. It is possible that a subset of the ProtecT cohort may have benefited from prior treatment despite GGG 1 PC biopsy.

Clinical parameters based on the contemporary combined biopsy (CBx) approach should be identified to predict occult high-risk PC in patients diagnosed with GGG 1. It is also critical to understand whether this information can facilitate detect patients with GGG 1 who are at higher risk of PC-specific mortality (PCSM) and all-cause mortality (ACM).

About the study

The current study investigated the association of clinical factors with unsampled high-risk PC, PCSM, and ACM after RP in patients with GGG1 PC. A total of 10,228 patients were recruited into the primary cohort between February 28, 1992, and September 7, 2023. These patients underwent RP for the diagnosis of GGG1 prostate adenocarcinoma biopsy at the University Hospital Hamburg-Eppendorf. A total of 9,248 patients underwent 12-core TRUS-guided systematic biopsy (SBx). The median age of the study cohort was 63 years.

Another cohort was designed with 980 additional patients who underwent RP between July 2, 2013, and September 7, 2023, for a diagnosis of GGG 1 PC biopsy. The median age of this cohort was 62 years.

Findings

In the current study, we observed that patients with GGG 1 PC diagnosed with contemporary CBx and having a positive biopsy rate (PPB) of more than 50% or prostate-specific antigen (PSA) level of more than 20 ng/ml had a significantly higher risk of developing unfavorable pathology in RP and early PSA failure. Furthermore, patients with one or both clinical risk factors and belonging to the SBx group showed a higher risk of PCSM and ACM.

If the ProtecT study results had been stratified by the presence of one or more clinical factors, higher rates of PCSM could have been estimated. Consideration of clinical factors at diagnosis could facilitate identify patients who are most likely to develop unsampled higher-grade, higher-stage tumors, which could shorten life expectancy. Patients with a GGG 1 PC biopsy, with a PPB >50% or PSA >20 ng/mL, should be seriously considered for systematic rebiopsy.

The reduced mortality rate associated with PC was attributed to early intervention with RP. Defining a GGG score of 1 as benign may significantly delay the time to diagnosis and treatment of cancer. In this study, the SBx group was ideal for assessing long-term mortality risk because the CBx technique is relatively fresh and has been routinely used for only five years. Taking this into account, the authors pointed out the possibility of overestimating PCSM and ACM scores relative to the true risks if the CBx approach were used. This may be the reason for the 2.47% lower incidence of adverse pathology in RP in the CBx group compared with the SBx group.

Conclusions

In this study, patients classified as GGG 1, having PPB >50% or PSA >20 ng/ml, were observed to be at increased risk of adverse pathology, early PSA failure, and risk of death. This information should facilitate physicians identify patients with GGG 1 who may be at increased risk of severe PC or have an increased risk of death.