Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 07/2012; 30(24):3020-5. DOI: 10.1200/JCO.2012.43.3441
Source: PubMed


An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer.

Clinical context:
Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection.

Recent data:
Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic.

In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.

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    • "However, the recent decline in PC related mortality rates is now being discussed to be partially explained by the improved treatment and earlier diagnosis due to a broad standard PSA screening in economically developed countries [4, 5]. As the standard PSA screening in the early diagnosis of human PC remains a very controversial issue, novel, reliable molecular PC markers are needed [6–8]. "
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    ABSTRACT: Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.
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    • "The prostate cancer pathway from screening and diagnosis to treatment has recently been critically questioned in light of level 1 evidence pointing to pathway-related harms that may outweigh the benefits in many men. As a consequence, recent guidelines have recommended limiting the systematic use of prostate cancer screening based on prostate-specific antigen (PSA) testing to avoid overdiagnosis and overtreatment [1–4]. There is a clear requirement to improve the current therapeutic ratio of the entire diagnostic and therapeutic pathway with novel interventions. "
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    ABSTRACT: New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes.
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    • "It is generally accepted that PSA provides the highest diagnostic performance for PCa and that its application to clinical practice has revolutionized the management of this disease [2]. However, the major drawback is its lack of cancer specificity and the lack of an upper or lower threshold value [9,10]. False elevations in noncancerous conditions not only result in unnecessary biopsies that lead to potential complications, but often mask aggressive forms of cancer that may lead to substantial harm [1]. "
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    ABSTRACT: To evaluate the predictive performance of various parameters derived from volume-adjusted prostate-specific antigen (PSA) values in detecting prostate cancer (PCa) and high-grade (Gleason score≥7) PCa according to treatment with a 5α-reductase inhibitor (5ARI). The results of 3,520 prostate biopsies performed between May 2006 and January 2013 were retrospectively assessed. With adjustment for age, 291 patients who had received 5ARI treatment for more than 6 months were identified and matched 1:3 to patients naïve to 5ARIs, resulting in a total of 873 patients. Peripheral zone (PZ) and transition zone (TZ) volumes were determined by transrectal ultrasonography. Receiver-operating characteristic (ROC) curve analysis was used to compare predictive performances of PSA, PSA density (PSAD; PSA/prostate volume), PZPSAD (PSA/PZ volume), and TZPSAD (PSA/TZ volume) for detecting PCa and high-grade PCa for each group. The area under the ROC curve (AUC) was higher for PSAD than for PSA in the 5ARI group (0.751 vs. 0.677) and in the 5ARI-naïve group (0.649 vs. 0.582), respectively (P<0.001). In the 5ARI group, the AUC for PZPSAD was even higher than that for PSAD (0.781 vs. 0.751, P=0.038); in the 5ARI-naïve group, however, PZPSAD failed to achieve significant superiority (0.652 vs. 0.649, P=0.321). All volume-adjusted PSA indexes showed higher predictive accuracies for detecting PCa than did PSA in both groups. For detecting high-grade cancer, PZPSAD also revealed the highest predictive value in the 5ARI group, whereas PSA revealed the highest predictive value in the 5ARI-naïve group. The diagnostic performance of PSAD in the detection of PCa is superior to that of PSA. For patients receiving 5ARI for more than 6 months, PZPSAD confers additional benefits for detecting both PCa and high-grade PCa.
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