Annual Meeting Proceedings Part 1 - American Society of Clinical ...

316s Genitourinary Cancer
4658 General Poster Session (Board #12A), Sun, 8:00 AM-12:00 PM
Prostate-specific antigen (PSA) screening in the United States: Patterns of
use and PSA outcomes in screened versus unscreened men. Presenting
Author: Ian M. Allen, UNC-CH School of Medicine, Chapel Hill, NC
Background: PSA screening is a subject of substantial controversy. We
examined patterns of PSA screening using a recent cohort from the
population-based National Health and Nutrition Examination Survey
(NHANES) study and compared PSA levels of previously screened vs. never
screened men. Methods: NHANES is a cross-sectional study which collects
health-related information (including cancer screening history, family
history and socioeconomic variables) and blood samples from nationally
representative samples of the US population. We included 2,078 previously
screened men and 1,902 never screened men surveyed from 2003-8.
Statistical analysis accounted for sampling weights. Results: 25% of men
age 40-49 years had prior PSA screening; 56% age 50-59, and 72% age
60-69. Screening rates were higher for men with family history (68% vs.
50% no history, p�.001), health insurance (58% vs. 21% no insurance,
p�.001), and Caucasians (59% vs. 44% non-Caucasian, p�.001). No
significant differences were seen in the PSA values of screened vs. never
screened men stratified by age (Table), or by race/ethnicity, insurance
status, or family history. Conclusions: Rates of PSA screening in the US
differ by age, family history, race/ethnicity and insurance status. However,
no significant differences were seen in PSA values of screened vs.
unscreened men, and very few patients under 60 years of age had PSA
values �10. Despite questions about the appropriate role of PSA testing,
population-based prostate cancer screening is routinely conducted among
Caucasian and non-Caucasian men 50 years of age and older.
PSA in screened versus unscreened individuals stratified by age.
Screened (%) Unscreened (%) p value
Age 49-49
PSA 0-3.99 98.9 98.7 0.927
PSA 4-9.99 0.7 0.9
PSA >10 0.3 0.3
Age 50-59
PSA 0-3.99 92.9 94.6 0.066
PSA 4-9.99 6.4 4.1
PSA >10 0.6 1.2
Age 60-69
PSA 0-3.99 81.9 83.3 0.136
PSA 4-9.99 15.7 12.2
PSA >10 2.3 4.4
4660 General Poster Session (Board #12C), Sun, 8:00 AM-12:00 PM
A first-in-human phase I imaging study using hyperpolarized 1c-13 pyruvate
(h-Py) in patients (pts) with localized prostate cancer (l-PCa).
Presenting Author: Andrea Lynne Harzstark, University of California, San
Francisco, San Francisco, CA
Background: Preclinical studies demonstrated that the conversion of h-Py to
hyperpolarized 13C lactate (h-lac) is detectable on MRI-spectroscopy and is
a useful marker of differentiation in PCa. H-Py MRI provides more than
10,000-fold enhancement in signal to noise ratio (SNR), allowing for rapid
detection of metabolic alterations in vivo. Hyperpolarized compounds have
not been previously studied in man. Methods: Pts with biopsy-proven
untreated l-PCa were enrolled in a phase I study of h-Py MRI. Following a
modified 3�3 design, 6 pts were enrolled at each dose level (0.14, 0.28
and 0.43 mL/Kg): 3 to monitor kinetics of h-Py, and 3 to evaluate the
spatial distribution of metabolism in PCa and normal prostate (nl-P). An
expansion cohort of 15 pts explored the biological variability of metabolism.
A dynamic nuclear polarization (DNP) system, the first human system
anywhere, generated and delivered 230 mM sterile h-Py. IV injection of
h-Py was followed by imaging with a 3T MR scanner with custom transmit
and receive coils. Monitoring included EKG, vital signs, and laboratory
testing. Results: 31 pts were imaged. 23 pts had Gleason (G) 6, 6 pts G7,
and 2 pts G8 PCa. Median age was 63 years (range 45-75); median PSA
was 5.9 ng/mL (1.88-20.2). No dose limiting toxicities or �grade (gr) 2
toxicity was observed. Toxicity included: gr 1dysgeusia (6 pts), gr 1
hypokalemia, gr 1 hypocalcemia, gr 1 dizziness, and gr 2 diarrhea (1 pt
each). Median time from dissolution of the agent to delivery into patients
was 66 seconds (43-88). Signals from h-Py and h-Lac were seen in PCa
and nl-P at all doses; 0.43 mL/Kg showed the best SNR and discrimination
between PCa and nl-P and was therefore established as the phase II dose.
There appeared to be an association between h-Lac levels and PCa grade.
Conclusions: H-py metabolic imaging has minimal toxicity and provides the
ability to discriminate Ca from nl-P based on increased levels of h-lac. The
correlation with grade and changes with therapy require further study.
4659 General Poster Session (Board #12B), Sun, 8:00 AM-12:00 PM
Prevalence of nonmetastatic (M0) prostate cancer (PC) patients on continuous
androgen deprivation therapy (ADT) in the United States. Presenting
Author: Karynsa Cetin, Center for Observational Research, Amgen Inc,
Thousand Oaks, CA
Background: ADT is the cornerstone treatment of metastatic PC, but the
nature and extent of its use in the M0 setting is less well-described. We
sought to estimate the current prevalence of M0 PC patients actively
receiving continuous ADT (�6 months) in the US. Methods: Two pointprevalent
cohorts on 12/31/2008 with continuous insurance coverage in
2008 were assembled: men aged 45-64 years (yrs) enrolled in commercial
health plans (MarketScan) and men aged �67 yrs enrolled in fee-forservice
(FFS) Medicare (Medicare 5% sample). Among those with evidence
of PC and no evidence of metastases, we selected men who had continuous
exposure to gonadotropin-releasing hormone agonists during at least the
last 6 months of 2008 or received bilateral orchiectomy prior to 7/1/2008.
The number of prevalent ADT users was extrapolated to the entire national
commercially insured population aged 45-64 yrs and to the entire Medicare
FFS population aged �65 yrs using person-level weights. Applying agespecific
prevalence estimates to the US Census population on 12/31/
2008, we estimated the number of prevalent ADT users in the total US
male population aged �45 yrs. Results: An estimated 11,935 (95%
confidence interval [CI]: 11,310-12,561) commercially insured men aged
45-64 yrs and 115,468 (95% CI: 112,304-118,633) Medicare FFS men
aged �65 yrs were M0 PC patients actively receiving continuous ADT for
�6 months on 12/31/2008. Extrapolated to the total US male population
aged �45 yrs, this estimate was 188,916 (95% CI: 184,104-193,727).
Age-specific prevalence (N [95% CI]) on 12/31/2008 is presented in the
table. Conclusions: We projected nearly 190,000 US men with M0 PC were
actively receiving continuous ADT for �6 months at the end of 2008, and
the vast majority (91%) of these men were aged �65 yrs. Additional work
will address timing of initiation, duration, and other aspects of ADT use in
this large population of M0 PC patients.
Age, yrs Commercial and FFS Medicare males US males
45-64 11,935 (11,310-12,561) 17,163 (16,264-18,062)
65-74 28,087 (26,272-29,902) 43,851 (41,017-46,686)
75-84 51,541 (49,549-53,532) 76,157 (73,214-79,100)
>85 35,841 (34,195-37,487) 51,745 (49,368-54,121)
4661 General Poster Session (Board #12D), Sun, 8:00 AM-12:00 PM
Correlation of UHRF1 expression in primary prostate cancer patients with
adverse prognosis. Presenting Author: Enrico Roggero, IOSI International
Prostate Research Group, Bellinzona, Switzerland
Background: Cancer of the prostate is a leading cause of cancer death in
western countries. There is a great need to understand the clinical course of
the disease and to distinguish the indolent tumors from those with
aggressive behavior. Epigenetic mechanisms play an essential role in
cancer initiation and progression. Our groups have recently provided
evidence that over-expression of UHFR1 (ubiquitin-like with PHD and ring
finger domain) leads to prostate cancer progression by activating a robust
epigenetic switch involving silencing of a network of tumor suppressor
genes. The purpose of this study was to evaluate in a clinical setting the
prognostic impact of UHFR1 expression. Methods: In a series of 225
eligible patients (median age 63 years, range 44-75) with prostate cancer
treated in a single institution with prostatectomy between 1990 and 1999
we evaluated the tumor nuclear expression of UHRF1 by immunohistochemistry
(IHC). Clinical and histological data of the series were also reviewed.
The UHFR1 expression (evaluated in tissue microarrays by immunohistochemistry)
and prognostic factors were analyzed using univariate analyses
and multivariate logistic regression analysis to identify association with
overall survival (OS). Results: The median FU for the series was 137 months
(range 1-229), eighty-one patients died (median FU 85 months). In
Ninety-seven patients (43%) the UHRF1 expression was positive. In
univariate analyses Gleason Score (�7 vs 7-9), Stage Risk Group (TNM
Stage �III vs Stage III and/or N�) and UHFR1 expression (negative vs
positive) were significant prognostic factors for OS with p-value �0.0001.
In multivariate analyses Gleason Score, Stage Risk Group and UHFR1
expression were independent predictors for OS with respectively HRs of
2.77 (95% CI 1.72-4.46) p�0.0001, HRs of 1.96 (95% CI 1.14-3.37)
p�0.014 and Hrs 1.35 (95% CI 1.02-1.78) p�0.030. Conclusions: Our
results indicate that expression of UHFR1 protein, independently from
historical prognostic factors, is linked with adverse prognosis for overall
survival in a homogeneous primary prostate cancer treated group with
long-term follow-up.
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