Focused Issue of This Month What Are Some New Developments in Prostate Cancer Diagnosis? Seo Yong Park, MDHyun Moo Lee, MD Department of Urology, Sungkyunkwan University School of Medicine E - mail : besthml@medimail.co.kr J Korean Med Assoc 2010; 53(2): 107-118 Abstract The purpose of this article is to summarize up-to-date changes and policies in the diagnosis of prostate cancer. The triads of DRE (digital rectal examination), serum PSA (prostate specific antigen), and TRUS (transrectal ultrasound) that directed prostatic biopsy have been considered a gold standard in the early detection of prostate cancer. Even though PSA is a very useful test, its low specificity has made some controversy until now. Moreover, it is not verified whether PSA screening would contribute to the decline in prostate cancer mortality. TRUS directed prostate biopsy also has some criticisms. For example, appropriate number of biopsy core, determination of whether a patient should undergo a repeat biopsy and its timing remain controversial. This article presents guidelines on prostate cancer diagnosis with partial results of randomized controlled trials to verify aforementioned criticisms Since recently published trials show different results regarding the impact of prostate cancer screening on mortality, further analyses are needed to determine the specific parameters for optimal screening (i.e. the age at which screening should begin, re-screening intervals, the age at which screening should be discontinued, and novel screening biomarkers). Unless a new and effective screening biomarker is discovered, PSA will maintain a superlative position for screening of prostate cancer. Hence, we have to find an optimal cut-off value of PSA derivatives for Korean people. With respect to prostate biopsy, current literatures support the use of more extensive biopsy techniques to increase the likelihood of prostate cancer detection. Keywords: Prostate cancer; Prostate-specific antigen; Mass screening; Mortality; Biopsy 107
Park SYLee HM Figure 1. The cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; p=0.04). (Schroder, et al.(9) reproduced with permission of the publisher, NEJM). 108
What Are Some New Developments in Prostate Cancer Diagnosis? Figure 2. Number of prostate cancer deaths. Through 10 years, there was little difference between the two groups in terms of the proportion of deaths according to tumor stage. (Andriole, et al.(11) reproduced with permission of the publisher, NEJM). 109
Park SYLee HM Table 1. Up-to-date guidelines on prostate cancer screening Guideline Baseline PSA/DRE Recommendations Start (years) Interval AUA 2009* At 40 According to No longer recommends a single threshold value of PSA and initial results individualized risk assessment is needed EAU 2009 At 45 Every 2~4 yrs PSA threshold level of 2.5~3.0 ng/ml and PSAV > 0.6 ng/ml/yr are reasonable NCCN 2009 At 40 Annually Risk-based screening algorithm, including family history, race, and age. PSA threshold level of 2.5 ng/ml and PSAV 0.35 ng/ml/yr in men with PSA < 4 ng/ml ACS 2009 At 50 Annually Life expectancy of at least 10 years Earlier age in patients with high risk USPSTF 2008 Not recommended PSA screening is associated with psychological harms, and its potential benefits remain uncertain - Obscure efficacy in men 75 yrs - Against screening in men 75 yrs * AUA 2009 refer to the AUA Best Practice Statement 2009 PSA: prostate -specific antigen, PSAV: PSA velocity, DRE: digital rectal examination, AUA: American Urologic Association, EAU: European Urology, NCCN: National Comprehensive Cancer Network, ACS : American Cancer Society, USPSTF: United States Preventive Services Task Force 110
What Are Some New Developments in Prostate Cancer Diagnosis? Table 2. Comparisons of age-specific PSA reference ranges in each country Age (years) Age-specific PSA reference range (ng/ml) Caucasian(43) Japanese(74) Chinese(75) Korean(25) 40~49 2.5 2.0 1.2 1.9 50~59 3.5 3.0 2.4 2.4 60~69 4.5 4.0 3.2 3.6 70~79 6.5 5.0 3.4 5.2 PSA: prostate-specific antigen 111
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What Are Some New Developments in Prostate Cancer Diagnosis? Table 3 Prostate biopsy indications In patient more than 50 years old with more than 10 year life expectancy (age > 45 if stong family history of African American) 1. DRE (+) 2. PSA > 4 ng/dl regardless of age 3. consider biopsy if PSA > 2.5~3.0 ng/ml (age < 60~65years) 4. PSAV > 0.75 ng/dl/yr 5. % free PSA : > 25% no biopsy 10~15% consider biopsy < 10% biopsy 6. repeat biopsy 3~6mo after diagnosis of ASAP :high grade PIN is no longer considered an indication for re-biopsy PSA: prostate-specific antigen, PSAV: PSA velocity, DRE: digital rectal examination, ASAP: aty-pical small acinar proliferation, PIN: prostate intraepithelial neoplasia 113
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Park SYLee HM Peer Reviewers Commentary 118