Faculty Bibliography

PURPOSE: The Prostate Cancer Prevention Trial reported that 15% of men with a prostate specific antigen less than 4 ng/ml and a normal digital rectal examination have biopsy detectable prostate cancer. However, limited published data describe the tumor features of prostate cancer detected at low prostate specific antigen levels (less than 2.5 ng/ml). MATERIALS AND METHODS: A total of 1,278 men underwent radical retropubic prostatectomy by 1 surgeon between 2003 and 2008. We describe the clinicopathological features of 77 patients with a preoperative prostate specific antigen of less than 2.5 ng/ml. RESULTS: Of the men with a low prostate specific antigen (less than 2.5 ng/ml) tumor 51 (66%) had findings suspicious for prostate cancer on digital rectal examination. Indications for prostate biopsy in the remainder of men included an increased prostate specific antigen velocity, hematospermia and abnormal transrectal ultrasound findings. Prostate cancer was detected at transurethral resection of the prostate in the remaining 8% of men. Despite having a low prostate specific antigen at diagnosis 8 (10.4%) and 20 (26%) men, respectively, had biopsy and radical retropubic prostatectomy Gleason grade 7 disease or greater, while 7 (9%) and 6 (7.8%), respectively, had extracapsular tumor extension or positive surgical margins. Compared to men with a normal digital rectal examination mean tumor volume was significantly higher in those with a suspicious digital rectal examination (3.3 vs 1.7 cc, p = 0.018). CONCLUSIONS: Despite having a prostate specific antigen of less than 2.5 ng/ml at diagnosis, a considerable proportion of men had aggressive pathological features at radical retropubic prostatectomy. Digital rectal examination remains an important component of early prostate cancer detection.

When a patient presents for assessment of prostate cancer risk, do serial measurements of PSA provide more-useful information than determination of a single PSA concentration? The authors of a new systematic review contend that the answer to this question is 'no'. Stacy Loeb cautions against hasty abandonment of PSA kinetics.

PURPOSE: Prostate specific antigen testing is common in the elderly despite evidence that older men without aggressive prostate cancer are unlikely to benefit from diagnosis and treatment. We evaluated the relationship between prostate specific antigen and the risk of aggressive prostate cancer developing in men of various ages. MATERIALS AND METHODS: This longitudinal cohort study consisted of 849 men (122 with and 727 without prostate cancer) with serial prostate specific antigen measurements participating in the Baltimore Longitudinal Study of Aging. The primary outcome measure was the proportion of men by prostate specific antigen and age who died of prostate cancer or in whom aggressive prostate cancer developed (death from prostate cancer, a prostate specific antigen 20 ng/ml or greater, or Gleason score 8 or greater). RESULTS: No participants between 75 and 80 years old with a prostate specific antigen less than 3.0 ng/ml died of prostate cancer. In contrast, men of all ages with a prostate specific antigen of 3.0 ng/ml or greater had a continually increasing probability of death from prostate cancer (Fisher's exact test p <0.001). The time to death or diagnosis of aggressive prostate cancer after age 75 years was not significantly different between the prostate specific antigen categories of 3 to 3.9 and 4 to 9.9 ng/ml (p = 0.634), whereas the time to death or diagnosis of high risk prostate cancer was significantly longer for the prostate specific antigen category of less than 3 vs 3 ng/ml or greater (p = 0.019). CONCLUSIONS: Men 75 to 80 years old with a prostate specific antigen less than 3 ng/ml are unlikely to die of or experience aggressive prostate cancer during their remaining life, suggesting that prostate specific antigen testing might be safely discontinued for these men.

This Practice Point commentary discusses the study by Gosselaar et al. that reports the performance characteristics of digital rectal examination (DRE) in men from the Rotterdam cohort of the European Randomized Study of Screening for Prostate Cancer. The authors reported that the positive predictive value of DRE for detecting the presence of prostate cancer was 48.6% in the first round of screening, decreasing to 29.9% and 21.2% in the second and third rounds, respectively. Nevertheless, an abnormal DRE was associated with a significantly increased risk of very high-grade disease during all screening rounds, indicating that it provides useful additional prognostic information. This study adds to a considerable body of evidence supporting a role for DRE in early detection of prostate cancer.

BACKGROUND: A 56-year-old man initially presented to a local urologist with severe lower urinary tract symptoms and microhematuria. He had a history of hypertension, hyperlipidemia, mild asthma, gastroesophageal reflux disease, erectile dysfunction, and pyeloplasty as a child. Investigations at this time included urinalysis, measurement of serum PSA levels, cystoscopy, urine cytology, and renal ultrasonography. The findings were suggestive of benign prostatic hyperplasia, and the patient received finasteride, tamsulosin, and underwent transurethral needle ablation of the prostate. Four years after the initial presentation, the patient presented to a tertiary institution with worsened symptoms. INVESTIGATIONS: Upon re-presentation, investigations included measurement of serum PSA levels, pelvic CT, transrectal ultrasound-guided prostate biopsy, histological examination of the biopsy specimen and immunohistochemical staining. DIAGNOSIS: Gastrointestinal stromal tumor. MANAGEMENT: Imatinib 400 mg daily followed by surgical resection.

Prostate inflammation can lead to an elevation in the serum PSA concentration and confound the use of PSA kinetics. This can have considerable clinical consequences, since these measurements form the basis for important clinical decisions. Thus, there has been investigation into ways to decrease the confounding from inflammation, including repeat PSA measurements after a period of observation or a course of empiric antibiotics. This article reviews the evidence about elevations in PSA due to prostatitis and describes the controversy over the optimal approach to reduce its confounding impact on prostate cancer screening.

The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer