Researchers identify two risk factors that indicate a higher risk of aggressive prostate cancer

Recent European Urological Oncology The study assessed mortality risks, based on Gleason score and clinical parameters, in patients with prostate cancer (PC).

Prostate cancer and Gleason score

The Gleason score is a grading system ranging from 6 to 10 that 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. Clinicians use the Gleason score to formulate effective treatment for prostate cancer, which could lead to a better prognosis.

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

As mentioned, participants in the ProtecT trial were randomly assigned to active monitoring (AM) and radical therapy. Patients received different treatments for prostate cancer, including androgen deprivation therapy (ADT), radical prostatectomy (RP) or radiation therapy (RT). About 61% of patients randomized to AM eventually received radical treatment by 15 years of follow-up. These patients were at higher risk of developing metastatic disease. There is a possibility that a subgroup of the ProtecT cohort may have benefited from prior treatment despite having a GGG 1 PC biopsy.

Clinical parameters based on the modern combined biopsy (CBx) approach need to be determined to predict high-risk occult PC in patients diagnosed with GGG 1. It is also important to understand whether this information could help 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 unspecified high-risk PC, PCSM, and ACM after RP in patients with GGG1 PC. A total of 10,228 patients were recruited for the main cohort between February 28, 1992 and September 7, 2023. These patients underwent RP for a biopsy diagnosis of GGG 1 adenocarcinoma of the prostate 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 biopsy diagnosis of GGG 1 PC. The median age of this cohort was 62 years.

Study findings

The current study observed that patients with GGG 1 PC diagnosed with contemporary CBx and having percentage positive biopsies (PPB) above 50% or prostate specific antigen (PSA) level above 20 ng/ml are at significantly higher risk of developing adverse 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 ProtecT trial findings were stratified by the presence of one or more clinical factors, higher rates of PCSM could have been calculated. Examining clinical factors at diagnosis could help identify patients who are more likely to have higher-grade and higher-stage cancer without a sample that could shorten life expectancy. Patients with biopsy GGG 1 PC, either with PPB >50% or PSA >20 ng/ml, should be seriously considered for systematic repeat biopsy.

A reduced PC-related mortality rate was attributed to early intervention with RP. Listing a GGG 1 result as benign could significantly delay the time the cancer is diagnosed and treated. In this study, the SBx group was ideal for assessing long-term mortality risk because the CBx technique is relatively new and has been commonly used for only five years. Considering this, the authors indicated the possibility of PCSM and ACM results overestimating the true risks if a CBx approach had been used. This could be the reason for the 2.47% lower incidence of adverse pathology in RP in the CBx group compared to the SBx group.

conclusions

This study observed that patients categorized as GGG 1, with either PPB >50% or PSA >20 ng/ml, are at higher risk of adverse pathology, early PSA failure, and risk of mortality. This information should assist clinicians in identifying patients with GGG 1 who may be at higher risk of severe PC or have an increased risk of mortality.