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

A recent European Urology Oncology study assessed the mortality risks, based on the 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 assess patients with prostate cancer. A lower score indicates that cancer cells resemble normal cells closely 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 ProtecT trial findings triggered a controversy regarding the accuracy of the Gleason grade 3 + 3 or Gleason grade group (GGG) results of prostate biopsy analysis for cancer diagnosis and outcome. The majority of the ProtecT cohort had GGG 1 disease, and among this population, only 3.1% died from PC at a median follow-up of 15 years.

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

Clinical parameters based on the contemporary combined biopsy (CBx) approach need to be identified to predict occult high-risk PC in patients with a GGG 1 diagnosis. It is also important to understand whether this information could aid in detecting 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 following RP in patients with GGG1 PC. A total of 10,228 patients were selected for the primary cohort between February 28, 1992, and September 7, 2023. These patients underwent RP for a diagnosis of biopsy GGG 1 adenocarcinoma of the prostate at the University Hospital Hamburg-Eppendorf. A total of 9,248 patients underwent a 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 biopsy GGG 1 PC.  The median age of this cohort was 62 years.

Study findings

The current study observed that patients with GGG 1 PC who were diagnosed by contemporary CBx and have percent positive biopsies (PPB) over 50% or a prostate-specific antigen (PSA) level over 20 ng/ml are at a significantly higher risk of developing adverse pathology at RP and early PSA failure. Furthermore, patients with one or both clinical risk factors and belonging to the SBx group exhibited a higher risk of PCSM and ACM.

If the ProtecT trial findings were stratified based on the presence of one or more clinical factors, higher PCSM rates could have been estimated. Consideration of clinical factors during diagnosis could help identify patients who are most likely to harbor unsampled higher-grade and higher-stage cancer that could reduce life span.  Patients with biopsy GGG 1 PC, with either PPB >50% or PSA >20 ng/ml, must be seriously considered for a systematic rebiopsy.

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

Conclusions

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