Biopsy follow-up of prostate-specific antigen tests.
ABSTRACT A prostate-specific antigen (PSA) level above 4 ng/mL has historically been recognized as an appropriate threshold to recommend biopsy; however the risk of high-grade disease observed among men with lower PSA levels in the Prostate Cancer Prevention Trial has led to calls to change the criteria for biopsy referral.
To aid providers when discussing aggressiveness of biopsy by cataloging available community biopsy patterns and determine whether lower PSA thresholds are being used to recommend biopsy.
Laboratory and biopsy records were reviewed among 59,764 men in a large Washington State health plan between 1998 and 2007. Follow-up in the 12-month period after a test was categorized as biopsy, urology visit without biopsy, additional PSA testing with no urology visit, or no PSA-related follow-up. Data analysis occurred between 2010 and 2011.
Twenty-eight percent of tests with PSA levels ≥4.0 ng/mL, 2.9% of tests with levels between 2.5 and 4.0 ng/mL, and 0.4% of tests with levels <2.5 ng/mL were followed with a biopsy within 12 months. More than 40% of elevated tests (≥4.0 ng/mL) were followed by a urologist visit without a biopsy, and more than 30% of tests ≥4.0 did not have any PSA-related follow-up within 12 months. PSA velocity, defined as annualized rate of change in PSA level, was strongly associated with biopsy, especially when absolute PSA was <4.0 ng/mL. There appear to be no discernable temporal trends in biopsy thresholds or practice patterns based on PSA lower levels or velocity.
Despite recent calls to more aggressively recommend biopsy at lower PSA thresholds, the practice in this large health plan has remained consistent over time.
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ABSTRACT: Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein.Acta Pharmacologica Sinica 06/2014; · 2.50 Impact Factor
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ABSTRACT: IMPORTANCE Despite ongoing controversies surrounding prostate-specific antigen (PSA) screening, many men 65 years or older undergo screening. However, few data exist that quantify the chain of events following screening in clinical practice to better inform decisions. OBJECTIVE To quantify 5-year downstream outcomes following a PSA screening result exceeding 4.0 ng/mL in older men. DESIGN AND SETTING Longitudinal cohort study in the national Veterans Affairs health care system. PARTICIPANTS In total, 295 645 men 65 years or older who underwent PSA screening in the Veterans Affairs health care system in 2003 and were followed up for 5 years using national Veterans Affairs and Medicare data. MAIN OUTCOME MEASURES Among men whose index screening PSA level exceeded 4.0 ng/mL, we determined the number who underwent prostate biopsy, were diagnosed as having prostate cancer, were treated for prostate cancer, and were treated for prostate cancer and were alive at 5 years according to baseline characteristics. Biopsy and treatment complications were also assessed. RESULTS In total, 25 208 men (8.5%) had an index PSA level exceeding 4.0 ng/mL. During the 5-year follow-up period, 8313 men (33.0%) underwent at least 1 prostate biopsy, and 5220 men (62.8%) who underwent prostate biopsy were diagnosed as having prostate cancer, of whom 4284 (82.1%) were treated for prostate cancer. Performance of prostate biopsy decreased with advancing age and worsening comorbidity (P < .001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men 85 years or older, those with a Charlson-Deyo Comorbidity Index of 3 or higher, and those having low-risk cancer. Among men with biopsy-detected cancer, the risk of death from non-prostate cancer causes increased with advancing age and worsening comorbidity (P < .001). In total, 468 men (5.6%) had complications within 7 days after prostate biopsy. Complications of prostate cancer treatment included new urinary incontinence in 584 men (13.6%) and new erectile dysfunction 588 men (13.7%). CONCLUSIONS AND RELEVANCE Performance of prostate biopsy is uncommon in older men with abnormal screening PSA levels and decreases with advancing age and worsening comorbidity. However, once cancer is detected on biopsy, most men undergo immediate treatment regardless of advancing age, worsening comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA screening.JAMA Internal Medicine 04/2013; · 13.25 Impact Factor