Prostate Cancer Upgrading: Key Predictors - EMJ

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Prostate Cancer Upgrading Linked to Key Clinical Predictors

Key Summary:

  • A retrospective study assessed predictors of upgrading in biopsy Gleason 6 prostate cancer.
  • Higher prostate-specific antigen density and perineural invasion independently predicted upgrading.
  • Findings supported using multiple clinicopathological factors to assess upgrading risk.

PROSTATE cancer upgrading after radical prostatectomy was associated with elevated prostate-specific antigen density (PSAD) and perineural invasion (PNI) in men initially diagnosed with biopsy Gleason 6 disease, according to a single-centre retrospective cohort study. The findings suggested that these clinicopathological factors may help clinicians assess the likelihood of more aggressive disease being identified after surgery. 

Researchers retrospectively analysed 124 men diagnosed with Gleason 6 prostate cancer following biopsy involving at least 12 cores. All underwent radical prostatectomy between January 2018 and September 2024 without neoadjuvant treatment. The study aimed to identify preoperative clinical and pathological characteristics associated with a higher Gleason score in the prostatectomy specimen. 

Of the 124 patients, 53 experienced Gleason score upgrading after surgery, while 71 had no upgrading. The results highlight the potential value of evaluating clinical and pathological indicators when estimating the risk of underestimation at biopsy. 

PSAD and Perineural Invasion Show Independent Associations 

Higher prostate-specific antigen (PSA) levels were associated with upgrading (p=0.019), as were elevated PSAD (p=0.001) and the presence of PNI (p<0.001). In multivariable analysis, elevated PSAD and PNI remained independently associated with upgrading, indicating that these factors retained an association when considered alongside other variables in the model. 

However, PSAD alone showed only modest discriminatory performance, with an area under the receiver operating characteristic curve of 0.680. This suggests that although PSAD may contribute to risk assessment, it has limited ability to distinguish patients who will experience upgrading from those who will not when used in isolation. 

The researchers also examined the De-Ritis ratio, a measure based on the relationship between two liver enzymes. No statistically significant association with Gleason score upgrading was observed (p=0.215). 

Combined Assessment May Support Risk Stratification 

The findings indicate that PSAD and PNI may provide useful additional information when assessing men with biopsy Gleason 6 prostate cancer who are undergoing evaluation for radical prostatectomy. However, the modest predictive performance of PSAD reinforces the importance of interpreting it alongside other clinical and pathological findings rather than relying on a single marker. 

The study was limited by its retrospective design and single-centre cohort of 124 patients. Its findings therefore require cautious interpretation and may not be generalisable to all men diagnosed with Gleason 6 disease, particularly those managed without surgery. 

Overall, the results support a combined approach to assessing the risk of pathological upgrading. Further validation in larger cohorts would help clarify how reliably PSAD and PNI can inform preoperative risk stratification and clinical decision-making. 

Reference 

Öztürk A et al. Predictors of upgrading in men diagnosed with gleason 6 prostate cancer a single-center retrospective cohort study. BMC Urology. 2026;DOI:10.1186/s12894-026-02435-4. 

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