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

318s Genitourinary Cancer
4666 General Poster Session (Board #13A), Sun, 8:00 AM-12:00 PM
Regional variation in survival after metastatic prostate cancer diagnosis.
Presenting Author: Darius Lakdawalla, University of Southern California,
Los Angeles, CA
Background: Survival after diagnosis of metastatic prostate cancer (mPC)
averages 2-3 years. Substantial regional differences in survival have been
documented for PC prior to 2000. We investigated the extent to which
regional variation exists in survival for mPC patients during 2000-2007.
Methods: Using the Surveillance, Epidemiology, and End Results (SEER)
database linked to Medicare claims, we identified men (mean age, 77.6
years) continuously enrolled in Medicare Parts A/B who were diagnosed
with mPC between 2000 and 2007 and not diagnosed with another
malignancy. The base-case model was limited to hospital service areas with
�50 patients. A Cox proportional hazards model was used to estimate
hazard ratios (HR) for overall survival (OS), adjusting for year of diagnosis,
age, marital status, poverty and education covariates, Gleason score,
comorbidities, and region covariates. Sensitivity of results was tested by
limiting the analysis to patients surviving at least 6 months after diagnosis
and by removing regional sample size limits. We report HRs for covariates,
results of a Wald test of joint significance for region effects, and percentage
difference from the mean for each region’s HR for death. Results: A total of
2696 patients with mPC met the inclusion criteria. OS was 37% at 3 years
and mean HR for death was 4.8 (sd 2.1). HRs for death were positively
correlated with age (HR�1.96, 95% CI: 1.6-2.3 for �80 years), PCspecific
comorbidity index (HR�1.2, 95% CI: 1.1-1.3), and Gleason score
(HR�6.6, 95% CI: 2.4-17.8 for poorly differentiated). Year of diagnosis,
race, and socioeconomic status were not significantly associated with
mortality. Wald test of joint significance for survival across regions of
P�.019 indicated significant differences in survival across regions and was
robust in sensitivity analyses. Patients living in regions with the worst
survival rates had HRs for death that were 20% higher than the mean
(HR�5.8) and those living in regions with the best survival rates had HRs
30% lower than the mean (HR�3.4). Conclusions: There are significant
regional differences in survival for mPC patients in the 2000s. Further
research is needed to determine if treatment differences play a role in this
disparity.
4668 General Poster Session (Board #13C), Sun, 8:00 AM-12:00 PM
Incidence-based analysis of lethal prostate cancer in Swedish counties
with high versus low incidence of prostate cancer in nationwide, populationbased
registries. Presenting Author: Pär Stattin, Department of Surgery,
Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Current data from randomized trials differ in the ratio of
benefit to harms from screening for prostate cancer (PC) using prostate
specific antigen (PSA) testing and it is further unclear if decreases in PC
mortality in the US can be attributed to introduction of screening or to
changes in treatment. The aim of this study was to investigate if rapidly
increased incidence of PC diagnosis due to early and rapidly increased rate
of PSA testing, is associated with decreased incidence of lethal PC.
Methods: In this incidence-based study using highly representative data
from nation-wide population-based registries we analysed the incidence of
lethal prostate cancer in eight Swedish counties with the most rapid and
largest increased incidence of PC diagnosis (high incidence counties) from
1995 through 2002, and six counties with the smallest increased PC
incidence (low incidence counties). We analysed the rate ratio (RR) in high
vs. low incidence counties of cases with metastatic PC at diagnosis,
(positive bone scan or PSA above 100 ng/ml), PC-specific mortality, and
excess mortality (death among PC cases regardless of cause). Participants
were men aged 50-74 years during 2000 to 2009 in the high versus low
incidence counties contributing 4,528,134 versus 2,471,373 personyears
at risk, respectively. There were 33,780 incident PC diagnoses and
1,577 PC deaths in high incidence counties and 16,377 PC cases and 985
PC deaths in low incidence counties. Results: In high vs. low incidence
counties, RR of metastatic PC was 0.85 (95% confidence interval [CI] �
0.79 to 0.92), RR of PC-specific mortality was 0.87 (95% CI � 0.81 to
0.95) and RR of excess mortality in men with PC was 0.75 (95 %CI � 0.66
to 0.86). Conclusions: Our study provides data on a population-level
indicating a decreased incidence of lethal PC in areas with rapid and large
increase in incident PC diagnosis due to increased rates of PSA testing,
early diagnosis, and treatment with curative intent.
4667 General Poster Session (Board #13B), Sun, 8:00 AM-12:00 PM
The impact of prior therapy with ketoconazole (keto) on clinical outcomes
after subsequent docetaxel treatment in metastatic castration-resistant
prostate cancer (mCRPC) patients: Results from a randomized phase III
trial (CALGB 90401). Presenting Author: Eric Jay Small, University of
California, San Francisco, San Francisco, CA
Background: Small retrospective reviews have suggested the possibility of a
decreased benefit of docetaxel in mCRPC patients (pts) previously treated
with abiraterone acetate, a novel androgen synthesis inhibitor (ASI).
CALGB 90401 was an intergroup (CALGB, ECOG) randomized phase 3 trial
in which 1050 mCRPC pts were treated with docetaxel, which offered the
opportunity to evaluate the effect of prior treatment with keto, an earlier
generation ASI, on clinical outcomes following docetaxel treatment in
mCRPC pts. Methods: Data from 1,050 men randomized on CALGB 90401
to treatment with docetaxel and prednisone with either bevacizumab or
placebo were used. Pts were chemotherapy naïve, had evidence of
progressive mCRPC, an ECOG performance status � 2, and adequate bone
marrow, hepatic and renal function. Randomization was stratified by age,
prior history of a thromboembolic event, and 24-month predicted survival
using the CALGB nomogram. The effect of prior keto use on overall survival
(OS), progression-free survival (PFS), PSA decline, and objective response
rate (RR) was estimated using proportional hazards and logistic regression
models. Results: 277/1050 pts (26%) had received prior keto. Baseline
characteristics including the 3 stratification factors, race, performance
status, measurable disease, and baseline alkaline phosphatase and Hgb
were balanced between prior keto treated pts and keto untreated pts. LDH
and PSA were higher in the keto treated patients (211 vs. 201, p � 0.01;
and 121 vs. 73, p � .0001; respectively.) There were no statistically
significant differences in keto vs. non-keto treated patients with regards to
OS (21.1 vs. 22.3 m, p � 0.643); PFS (8.1 vs. 8.6m p � 0.394 ); �50%
decline in PSA (61% vs. 66% p�.112); or objective response (39% vs.
43% p � 0.34). Conclusions: As measured by OS, PFS, PSA and RR, prior
treatment with the ASI ketoconazole has no impact on the subsequent
clinical impact of docetaxel in mCRPC pts.
4669 General Poster Session (Board #13D), Sun, 8:00 AM-12:00 PM
Association of decreased expression of protein phosphatase 2A subunit
PR55� (PPP2R2C) with an increased risk of metastases and prostate
cancer-specific mortality. Presenting Author: Elysia Sophia Spencer, Fred
Hutchinson Cancer Research Center, Seattle, WA
Background: The protein phosphatase 2A (PP2A) holoenzyme complex
negatively controls cell growth, differentiation and apoptosis. Down regulation
of PP2A activity is associated with oncogenic transformation of
papillomas and is a target for the small-T viral oncogene. The PR55�
(2R2C) subunit regulates PP2A target specificity, inhibiting c-Src activity
in some cell lines. c-Src activity enhances growth and invasion in prostate
cancer. This study evaluates whether PPP2R2C protein levels in radical
prostatectomy (RP) specimens were predictive for the development of
metastases or prostate-cancer specific mortality (PCSM). Methods: From
1954-1997, 1004 consecutive patients underwent RP at Virginia Mason
Medical Center in Seattle. Metastases were confirmed radiographically or
by tissue diagnosis. Death certificates confirmed PCSM. Patients without
stored tissue were excluded. 34 patients with metastases or PCSM were
matched to patients without recurrence (NR) at a 1:2 ratio. Paraffinembedded
tissue was stained with anti-PPP2R2C monoclonal antibody,
clone 6D1 (Abnova, Taiwan). A pathologist evaluated the percentage and
intensity of nuclei stained using a 4-point scale. Statistical analysis was
performed on SAS. Results: Mean follow up was 10.26 years. PPP2R2C was
detected in 13/18 (72.2%) PCSM, 18/22 (81.8%) metastases and 45/49
(91.8%) NR patients. Mean expression was lower in cancerous vs benign
glands, 1.74 vs 2.04 (p � 0.001). Expression intensity from PCSM vs NR
was 1.45 vs 1.80 (p � 0.041). On multivariate analysis, expression was
lower in metastases or PCSM versus NR 1.79 vs 2.35 (p � 0.002),
independent of pre-op PSA and Gleason grade. Conclusions: PPP2R2C loss
was highly correlated with metastasis and PCSM. Patients with the lowest
levels of expression were at the highest risk for PCSM. As tissue was
obtained at time of surgery, this analysis reflects a truly prognostic
biomarker, independent of Gleason grade and PSA. We have shown that
PPP2R2C scoring is a useful metric to identify patients at high risk of
developing advanced disease. With further validation may allow for more
accurate individual patient treatment plans and counseling.
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