5.16.11.aggressive vs. indolent prostate tumors


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5.16.11.aggressive vs. indolent prostate tumors

  1. 1. EMBARGOED FOR RELEASE UNTIL MONDAY, MAY 16, 2011 AT 9:00 A.M. Contact: Wendy Waldsachs Isett, AUA 410-977-4770, wisett@AUAnet.org PROSTATE CANCER: TO TREAT, NOT TO TREAT AND WHEN TO TREAT? Panel to Address Key Questions about Low-Risk Prostate Tumor ManagementWashington, DC, May 16, 2011—As physicians and researchers debate the merit of the prostate-specific antigen(PSA) test, questions have arisen about the test’s ability to accurately identify the presence of prostate cancer,as well as how the test may be interpreted and better used to determine which prostate cancers requiretreatment and which do not. New research presented at the 2011 AUA Annual Meeting will bring light to theinnovative possibilities for the use of PSA. A special panel, to be held on Monday, May 16, 2011 at 9:00 a.m., willdiscuss with members of the media the following studies:How Soon Can We Identify Men at High Risk for Prostate Cancer Death? An Early Surveillance Strategy forProstate Cancer (#986): A single blood test before the age of 50 could predict a man’s long-term risk of prostatecancer death, according to research from Memorial Sloan-Kettering Cancer Center in New York and LundUniversity in Malmo, Sweden. Using data from the Preventive Project, a cardiovascular study enrolling men ages33 to 50 between 1974 and 1986, and a combination of case-note review or death certificate data, researchersidentified 141 men in the study who had subsequently died of prostate cancer. Nearly half (44 percent) of thedeaths occurred in men whose PSA score fell in the top 10 percent (≥1.5 ng/ml). Researchers expanded theiranalysis to the top quartile of men, measuring free PSA and human glandular kallikrein 2 (hK2), and found thatthese markers helped to identify an additional 2.4 percent of deaths in the top 10 percent of risk. These datasuggest that early analysis of PSA, free PSA and hK2 may provide critical insight into a man’s risk of developingaggressive, life-threatening disease, enabling urologists to better assess when early intervention may benecessary.Can a Single PSA Measurement at Age 60-70 Years Identify Men Who Need No Further Prostate CancerTesting? (#2025): Eliminating prostate cancer testing after the age of 60 may be an option for some men, butothers could benefit from continued testing, according to new data being presented by Johns Hopkinsresearchers. Using data from the Baltimore Longitudinal Study of Aging, researchers identified 448 men withPSA measurements between the ages of 60 and 70, including 199 with a PSA less than 1 ng/ml. They reviewedPSA trajectory and its relationship to later diagnosis of prostate cancer (including high-risk disease, defined byPSA greater or equal to 20 ng/ml, Gleason 8-10 or confirmed prostate cancer death). In the 199 men with lowPSA (median age of 61.9 at time of test), 13 were later diagnosed – four with significant disease. These dataindicate that it may not be advisable to apply a universal cut-off point for PSA testing.Possible Pitfalls in Using Prostate-Specific Antigen Velocity for Detection of Prostate Cancer (#2032): Prostate-specific antigen velocity (PSAV) can be a strong derivative in improving the performance of the PSA blood test asa marker for prostate cancer but has limited sensitivity and specificity, according to new data from researchers
  2. 2. at Northwestern University. Researchers examined patients in two categories: those with elevated PSAV and nocancer on biopsy, and those with low PSAV with biopsy-detected cancer. Of those patients with low PSAV withbiopsy-detected disease, 4.6 percent had a Gleason 8-10 tumor, 30 percent had slow-growing tumors with aGleason score less than 6 and 54 percent had Gleason 7 tumors. Of those patients with elevated PSAV andnegative biopsy, 58 percent were later diagnosed with biopsy-detected disease, suggesting a need to closelyfollow a patient’s PSA despite an initial negative biopsy.The Worst Cancers Send Early PSA Signals that Would Allow Early Detection if Monitoring Focused onIncreasing PSA (#1197): PSAV and its rate of increase over time may be a key marker in identifying aggressivedisease and could provide valuable insight in how to interpret the PSA test, according to researchers fromMedical University Innsbruck in Austria and the University of California, San Francisco. Study authors analyzedpre-diagnosis PSA history from 94 prostate cancer patients who, following surgical treatment, suffered extra-capsular extension (EE) or recurrence, and calculated annual growth rate in cancer PSA for each. Of the menwith EE or recurrence, 98.9 percent had an increasing or constant PSAV and 95 percent had a PSA annual growthrate of 10 percent or more, suggesting that, in men with a current PSA less than 4.0 ng/ml, increased scrutiny ofannual growth rates of 1.0 ng/ml or more may be warranted.“Debate has been ongoing about the use of the PSA test in the detection of prostate cancer but the questionmay not be whether we use the test but, rather, how we use it,” said Christopher Amling, MD, who moderatedthe briefing for media. “These studies shed important light on how we might refine our use and interpretation ofthe PSA test.”NOTE TO REPORTERS: Experts are available to discuss this study outside normal briefing times. To arrange aninterview with an expert, please contact the AUA Communications Office at the number above or e-mailwisett@AUAnet.org.About the American Urological Association: Founded in 1902 and headquartered near Baltimore, Maryland, the AmericanUrological Association is the pre-eminent professional organization for urologists, with more than 17,000 membersthroughout the world. An educational nonprofit organization, the AUA pursues its mission of fostering the highest standardsof urologic care by carrying out a wide variety of programs for members and their patients. ###
  3. 3. 986HOW SOON CAN WE IDENTIFY MEN AT HIGH RISK FOR PROSTATE CANCER DEATH? AN EARLYSURVEILLANCE STRATEGY FOR PROSTATE CANCERAndrew Vickers*, Caroline Savage, New York, NY, Thomas Bjork, Axel Gerdtsson, Jonas Manjer, Peter Nilsson,Anders Dahlin, Anders Bjartell, Malmo, Sweden, Peter Scardino, David Ulmert, Hans Lilja, New York, NYINTRODUCTION AND OBJECTIVES: The Preventive Project (MPP) in Malmö, Sweden was a cardiovascular studyenrolling a representative cohort (74% participation) of men aged 33 - 50 in 1974 – 1986. Until recently, rates ofprostate-specific antigen (PSA) testing in Sweden have remained low; retrieval and analysis of archived bloodplasma from MPP was previously used to demonstrate a strong association between PSA levels measured at age44-50 and risk of advanced prostate cancer diagnosis up to 30 years subsequently. Our current objective was todetermine the degree of risk concentration, that is, the proportion of cases found in men with the highest PSAlevels.METHODS: Death from prostate cancer was determined by case note review (74%) or from death certificate data(26%). A nested case-control design was used, with three controls matched to each death. Lorenz curvemethodology was used to determine risk concentration.RESULTS: The median follow up was 27years. A total of 141 men died from prostatecancer. A single PSA at age 44 – 50 wasstrongly predictive of subsequent prostatecancer death at a median follow-up of 27years (area-under-the-curve: 0.72). Thefigure shows the Lorenz curve for riskconcentration: 44% of deaths occurred inmen with the top 10% of PSA (≥ ≈1.5 ng /ml). As alternative strategy, we took the topquartile of men (PSA ≥ ≈1 ng / ml), measuredfree PSA and hK2, and took those at highestrisk on the basis of a combined model of allmarkers. Doing so would lead toidentification of an additional 2.4% of deathsin the top 10% of risk. We repeated allanalyses using metastasis as the endpoint(215 events); the results were similar: for example, 42% of metastases occurred in top 10% of PSA with anadditional 2.5% metastases were identified by free PSA and hK2.CONCLUSIONS: Long-term risk of prostate cancer death can be predicted on the basis of a single blood test beforethe age of 50. Targeting a small proportion (10%) of men in an early intervention strategy – regular PSA screeningwith compliance monitoring, and possibly chemoprevention – could prevent almost half of all prostate cancerdeaths.Figure. Lorenz curve for death from prostate cancer based on a single PSA at age 44 - 50. The x axis shows thepercentage of the population with PSA above the indicated levels, hence the percentages run from 100 down to 0.The y axis shows the number of deaths that would be included (or missed) if we consider only men with PSA aboveany given level.Source of Funding: Supported by the National Cancer Institute (grant numbers R33 CA 127768-02 and P50-CA926290); the Swedish Cancer Society (3455); the Swedish Research Council Medicine (20095); Fundacion FedericoSA, The Tegger Foundation, and the Sidney Kimmel Center for Prostate and Urologic Cancers.
  4. 4. 2025Can a Single PSA Measurement at Age 60-70 Years Identify Men Who Need No Further PSATesting?Stacy Loeb*, John B. Eifler, E. Jeffrey Metter, Luigi Ferrucci, H. Ballentine Carter, Baltimore, MDINTRODUCTION AND OBJECTIVES: For men ages 50 to 69, there is level 1 evidence that serial PSAtesting reduces prostate cancer-specific mortality. However, Vickers et al. (BMJ 2010) recentlysuggested in a case-control analysis that men with a single PSA measurement <1 ng/ml at age 60may not require additional screening. This practice might be reasonable if these men are not at riskfor the development of prostate cancer (particularly, significant disease); whereas, if additionalscreening would help identify clinically significant prostate cancer continued PSA testing might bebeneficial.METHODS: From the Baltimore Longitudinal Study of Aging, we identified 448 men with PSAmeasurements at age 60-70 years, including 199 with a PSA level <1 ng/ml. In these men weexamined the PSA trajectory and its relationship to the later diagnosis of overall and high-riskprostate cancer (defined as PSA >20 ng/ml, Gleason score 8 to 10, or confirmed prostate cancerdeath).RESULTS: In the overall population, the median age was 62.2 years (range, 60.1-69.9) at the PSAtest, and the median PSA level was 1.1 ng/ml (range, 0.05-18.6). In the 199 men with a PSA <1ng/ml, the median age was 61.9 years (60.1-69.7) at the PSA test. Of these men, 13 (6.5%) werelater diagnosed with prostate cancer, of which 4 (31%) were high-risk. Figure 1 shows the PSAtrajectory in the non-cancer, non high-risk cancer, and high-risk groups.CONCLUSIONS: Although high-risk prostate cancer was infrequent in men with a PSA <1 ng/ml atage 60 to 70, continued PSA screening could have identified the majority of these cases.Source of Funding: This research was supported in part by the Intramural Research Program of theNIH, National Institute on Aging.
  5. 5. 2032POSSIBLE PITFALLS IN USING PROSTATE SPECIFIC ANTIGEN VELOCITY FOR DETECTION OFPROSTATE CANCERGregory Auffenberg*, Joshua Meeks, Phillip R. Cooper, Qiaoyan Hu, Cheng Li, William J.Catalona, Chicago, ILINTRODUCTION AND OBJECTIVES: Prostate Specific Antigen (PSA) is a well-documented markerfor prostate cancer (CaP). PSA velocity (PSAV) is a derivative that has been used to increase PSAperformance characteristics for CaP detection. Elevated PSAV may be an early sign of underlyingCaP, but has somewhat limited sensitivity and specificity. Explanations for false-positive PSAVinclude missed CaP on biopsy; prostatitis; or assay standardization bias. Reasons for false-negative PSAV include very low volume CaP or high grade CaP (severely de-differentiated cellsproduce less PSA); prior, resolved prostatitis; or assay standardization bias.METHODS: We assessed patients who underwent prostate biopsy after prior screening with ≥3PSA blood tests. PSAV was calculated using linear regression. Elevated PSAV was defined aschange in PSA ≥0.35 ng/mL/yr. After stratifying based on PSAV, we specifically examined: 1)patients with an elevated PSAV but no CaP on biopsy and 2) patients with low PSAV but CaP onbiopsy.RESULTS: Between 2003 and 2010, 1358 patients underwent prostate biopsy after previousscreening with ≥3 PSA tests. 106 had PSAV ≥0.35 ng/mL/yr and negative biopsy. Of these, 62(58%) had CaP on biopsy at a later date, suggesting negative biopsy at the time of elevated PSAVmay have been due to missed early, low volume CaP. 10 (9.4%) biopsies revealed prostaticintraepithelial neoplasia (PIN), also suggesting a possibly missed small CaP. 12 biopsies (11.3%)had signs of prostatitis. In the remaining 22 (20.7%), cause for elevated PSAV was not readilyapparent; transient inflammation, prostatic trauma, or assay standardization bias may haveplayed a role. 480 patients with PSAV <0.35 had CaP on biopsy. Of these, 22 (4.6%) had aGleason 8-10 tumor. 464 were treated with radical prostatectomy. Surgical pathology for 266(55.4%) revealed total CaP volume <5% of submitted tissue. Of the remaining patients,30% had possibly slow growing Gleason <6 tumors involving 6-20% of submitted tissue, and 54%had Gleason 7 tumors. In some cases, assay standardization bias or prior resolved prostatitismay have caused the spuriously low PSAV.CONCLUSIONS: Nearly 80% of patients with false-positive PSAV had an easily explainedconfounder – missed CaP or prostatitis. Nearly 60% of patients with false-positive PSAV wereeventually found to have CaP, underscoring the need to closely follow a patient’s PSA despiteinitial negative biopsy. False-negative tests can often be explained by low volume or highGleason grade disease, prior resolved prostatitis, or possible PSA assay standardization bias.Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPOREgrant (P50 CA90386-05S2) and the Robert H. Lurie Comprehensive Cancer Center Grant (P30CA60553)
  6. 6. 1197The Worst Cancers Send Early PSA Signals that Would Allow Early Detection if Monitoring Focused onIncreasing PSAJasmin Bektic*, Innsbruck, Austria, Peter Carroll, Matthew Cooperberg, San Francisco, CA, HelmutKlocker, Eberhard Steiner,Viktor Skradski, Wolfgang Horninger, Tom Neville, Innsbruck, AustriaINTRODUCTION AND OBJECTIVES: We hypothesized that most cancers with extra-capsular extension(EE) and/or recurrence (R) after treatment could have been caught earlier if monitoring focused onincreasing PSA.METHODS: We analyzed 94 cancer patients treated with surgery from the Tyrol Screening Project, UCSFand CaPSURE who had EE/R after treatment and had adequate PSA history before diagnosis (at least 5tests over 4 years) that started at a PSA of 3.0 or less. The increase in PSA from low to a pre-biopsy highwas measured. The annual growth rate in cancer PSA (PSAgr) was estimated using a consistentexponential trend plus no-cancer baseline. Trend curvature was assessed as increasing, constant(linear) or decreasing PSA velocity. Hardto react to sudden jumps in PSA werenoted if PSAgr exceeded 250% in the lastyear before detection.RESULTS: Median increase in PSA was 3.4,FIG 1, with 100% 0.3 or more, 95% 1.0 ormore and 80% 2.0 or more. Median PSAgrwas 43%, FIG 2, with 95% PSAgr 10% ormore and 80% PSAgr 19% or more.Curvature was ambiguous for 8.7%.Trends for the remaining men showed:92.9% with increasing PSAV, 6.0%constant PSAV (linear) and only 1.2% (1man) had decreasing PSAV. Jump wasambiguous for 1.1%. Of the remainingmen, only 2.2% had a jump and 97.8% didnot.CONCLUSIONS: The worst cancers (EE/R)usually send a strong PSA signal that couldhave been detected early with monitoringfor increasing PSA. Only 2.2% had a jumptoo steep for early detection. Only 5% hada PSA increase of less than 1.0. Thedominant pattern of increasing PSA wasclear: 98.9% had increasing or constantPSAV and 95% had a PSAgr of 10% ormore. For men with current PSA less than 4.0, these results suggest increased screening scrutinywhenever PSA increases by 1.0. If only two or three years of PSA tests are available then screeningintensity should increase whenever PSAV exceeds 0.20. At a median PSAgr of 43% for the worst cancers,a PSAV of 0.20 is consistent with an exponential increase in PSA of 1.0 from cancer over ten years.Source of Funding: none