Early detection of high-grade prostate cancer using digital rectal examination (DRE) in men with a prostate-specific antigen level of <2.5 ng/mL and the risk of death


Jona Hattangadi, Brigham and Women's Hospital, Department of Radiation Oncology, 75 Francis St, L-2 Level, Boston, MA 02215, USA. e-mail: jhattangadi@partners.org


Study Type – Prognosis (inception cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

There is little data on the utility of digital rectal examination (DRE) as a diagnostic tool in the era of prostate-specific antigen (PSA) testing. Using a population-based database, we found that detection of prostate cancer while still localized among men with high-grade PSA-occult disease may result in survival benefit.


  • • To determine whether detection of high-grade prostate cancer while still clinically localised on digital rectal examination (DRE) can improve survival in men with a normal prostate-specific antigen (PSA) level.


  • • From the Surveillance, Epidemiology and End Results database, 166 104 men with prostate cancer diagnosed between 2004 and 2007 were identified.
  • • Logistic regression was used to identify factors associated with the occurrence of palpable, PSA-occult (PSA level of <2.5 ng/mL), Gleason score 8–10 prostate cancer.
  • • Fine and Gray's and Cox multivariable regressions were used to analyse whether demographic, treatment, and clinicopathological factors were associated with the risk of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM), respectively.


  • • Both increasing age (adjusted odds ratio [aOR] 1.02, 95% confidence interval (CI) 1.01–1.03; P < 0.001) and White race (aOR 1.26, 95% CI 1.03–1.54; P= 0.027) were associated with palpable, Gleason 8–10 prostate cancer. Of 166 104 men, 685 (0.4%) had this subset of prostate cancer.
  • • Significant factors associated with risk of PCSM included PSA level (adjusted hazard ratio [aHR] 0.71, 95% CI 0.51–0.99; P= 0.04), higher Gleason score (aHR 2.20, 95% CI 1.25–3.87; P= 0.006), and T3–T4 vs T2 disease (aHR 3.11, 95% CI 1.79–5.41; P < 0.001).
  • • Significant factors associated with risk of ACM included age (aHR 1.03, 95% CI 1.01–1.06; P= 0.006), higher Gleason score (aHR 2.05, 95% CI 1.36–3.09; P < 0.001), and T3–T4 vs T2 disease (aHR 2.11, 95% CI 1.38–3.25, P < 0.001)


  • • Clinically localised disease on DRE among men with PSA-occult high-grade prostate cancer was associated with improved PCSM and ACM, suggesting that DRE in this cohort (older age and White race) may have the potential to improve survival.