ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer specific mortality

2012 ◽  
Vol 48 (4) ◽  
pp. 538-546 ◽  
Author(s):  
Tarek A. Bismar ◽  
Michael Dolph ◽  
Liang-Hong Teng ◽  
Shuhong Liu ◽  
Bryan Donnelly
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5084-5084
Author(s):  
Evelyn M Flahavan ◽  
Kathleen Bennett ◽  
Linda Sharp ◽  
Thomas Ian Barron

5084 Background: Cyclooxygenase-2 (COX-2) expression in prostate cancer has been associated with high grade tumours and poorer prognosis. Use of aspirin, a COX-2 inhibitor, has been associated with reduced prostate cancer mortality in some studies. These studies have not, however, provided information on the dose and timing of aspirin use. Methods: National Cancer Registry Ireland data was used to identify men with stage I-III prostate cancer (ICD10 C61) diagnosed 2001-2006. Aspirin use in the year preceding prostate cancer diagnosis was identified from linked prescription refill data (General Medical Services) and stratified by dose (low ≤75mg, high >75mg) and dosing intensity (proportion of days in that year with aspirin supply available). Cox proportional hazards models, adjusted for age, smoking status, year of incidence, comorbidity score, Gleason score, tumour size, pre-diagnostic statin use, and receipt of radiation (time varying) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between aspirin use and all-cause and prostate cancer-specific mortality. Interactions with tumour characteristics were examined. Results: 2,936 men with stage I-III prostate cancer were identified (aspirin users, N=1,131; 38.5%). Median patient follow-up was 5.5 years. In multivariate analyses, aspirin use was not associated with a significant reduction in prostate cancer-specific (HR 0.90, 95% CI 0.68-1.20) or all-cause mortality (HR 0.98, 95% CI 0.84-1.15). In dose response analyses aspirin use was associated with a significantly lower risk of prostate cancer-specific mortality in men receiving >75mg of aspirin (HR 0.59, 95% CI 0.35-1.00, p=0.048) but not ≤75mg aspirin (HR 1.01, 95% CI 0.75-1.37, p=0.938). Stronger associations were also observed in men with higher aspirin dosing intensity or a Gleason score >7. Conclusions: Pre-diagnostic aspirin use, measured using objective prescription refill data, was associated with a significant reduction in prostate cancer-specific mortality in men with stage I-III prostate cancer receiving >75mg of aspirin. These results confirm previous findings, and provide important new information regarding the dose of aspirin associated with survival benefit.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
Sophie D. Fossa ◽  
Anders Widmark ◽  
Olbjorn Harald Klepp ◽  
Fredrik Wiklund ◽  
Anders Angelsen ◽  
...  

4 Background: After a median observation time of 7.6 years, Scandinavian Prostate Cancer Group VII randomized trial showed a significant 12% reduction of prostate cancer-specific mortality in patients with locally advanced or histologically aggressive prostate cancer who received three months of total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients with hormonal treatment only (Widmark et al :Lancet [2009]; 373,1174). Here we provide the 10 (15)-year survival results after a median observation time of 10.7 years. Methods: Between February 1996 and December 2002, 875 patients with locally advanced prostate cancer were randomized (Randomization ratio 1:1). Primary endpoint was prostate cancer-specific survival analyzed by intention to treat. This updated analysis is based on death registry data of the Norwegian patients (2/3 of the population), and on data recorded in CRF database available for the Swedish patients. A Swedish death registry analysis is underway, and will be included in the final analysis at the meeting. Results: Prostate cancer death occurred in 118 out of 439 of the antiandrogen treatment group and in 45 out of 436 men in the combination treatment group (p< 0.0001), with death due to any cause in 210 out of 439 and 161 out of 436 men (p=0.0006), respectively. The 10 (15) year cumulative prostate cancer-specific mortality was more than halved after combined treatment: 18.9% (30.7%) and 8.3% (12.4%) (HR=0.35;[p<4.1E-10 for 15 year results]), and overall mortality was 35.3% (56.7%) and 26.4% (43.4%) (HR=0.70; P=0.0006 for 15 year results), respectively. Conclusions: Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.


2012 ◽  
Vol 110 (7) ◽  
pp. 973-979 ◽  
Author(s):  
Andrea L. Russo ◽  
Ming-Hui Chen ◽  
Ayal A. Aizer ◽  
Jona A. Hattangadi ◽  
Anthony V. D'Amico

2004 ◽  
Vol 22 (18) ◽  
pp. 3726-3732 ◽  
Author(s):  
Anthony V. D'Amico ◽  
Andrew A. Renshaw ◽  
Kerri Cote ◽  
Mark Hurwitz ◽  
Clair Beard ◽  
...  

Purpose We investigated whether pretreatment factors predicted time to prostate cancer–specific mortality (PCSM) after conventional-dose and conformal radiation therapy (CRT). Patients and Methods Between 1988 and 2002, 421 patients with low (prostate-specific antigen [PSA] level ≤ 10 ng/mL and biopsy Gleason score ≤ 6) or favorable intermediate-risk (PSA > 10 to 15 ng/mL or biopsy Gleason score 3 + 4, but not both factors) disease underwent CRT (median dose, 70.4 Gy). Cox regression multivariable analysis was performed to determine whether the PSA level, Gleason score, T category, or the percentage of positive cores (% PC) predicted time to PCSM after CRT. After a median follow-up of 4.5 years, 117 (28%) patients have died. Results The % PC was the only significant predictor (Cox P ≤ .03). The relative risk of PCSM after CRT for patients with ≥ 50% as compared with less than 50% PC was 10.4 (95% CI, 1.2 to 87; Cox P = .03), 6.1 (95% CI, 1.3 to 28.6; Cox P = .02), and 12.5 (95% CI, 1.5 to 107; Cox P = .02) in men with a PSA ≤ 10 and Gleason score ≤ 6, PSA ≤ 10 and Gleason score ≤ 7, and PSA ≤ 15 and Gleason score ≤ 6, respectively. By 5 years after CRT, 5% to 9% compared with less than 1% (log-rank P ≤ .01) of these patients experienced PCSM if they had ≥ 50% compared with less than 50% PC, respectively. Conclusion CRT dose-escalation techniques, the addition of hormonal therapy, or both should be considered in the management of patients with low or favorable intermediate-risk disease and ≥ 50% PC.


2005 ◽  
Vol 23 (28) ◽  
pp. 6992-6998 ◽  
Author(s):  
Ping Zhou ◽  
Ming-Hui Chen ◽  
David McLeod ◽  
Peter R. Carroll ◽  
Judd W. Moul ◽  
...  

Purpose We evaluated predictors of prostate cancer–specific mortality (PCSM) after prostate-specific antigen (PSA) failure after radical prostatectomy (RP) or radiation therapy (RT). Patients and Methods A total of 1,159 men with clinically localized prostate cancer treated with RP (n = 498) or RT (n = 661) developed PSA failure, and they formed the study cohort. Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis, including post-treatment PSA doubling time (PSA-DT), Gleason score, and interval to PSA failure, could also predict time to PCSM after PSA failure. The cumulative incidence method was used to estimate PCSM after PSA failure. Results A post-RP PSA-DT of less than 3 months (hazard ratio [HR], 54.9; 95% CI, 16.7 to 180), a post-RT PSA-DT of less than 3 months (HR, 12.8; 95% CI, 7.0 to 23.1), and a biopsy Gleason score of 8 to 10 (HR, 6.1; 95% CI, 3.4 to 10.7) for patients treated with RT were significantly associated with PCSM. Post-RP estimated rates of PCSM 5 years after PSA failure were 31% (95% CI, 17% to 45%) v 1% (95% CI, 0% to 2%) for patients with PSA-DT of less than 3 months v ≥ 3 months. Post-RT estimated rates of PCSM 5 years after PSA failure were 75% (95% CI, 59% to 92%) v 35% (95% CI, 24% to 47%) for patients with a biopsy Gleason score of ≥ 8 v ≤ 7, respectively, and PSA-DT of less than 3 months; these rates were 15% (95% CI, 0.8% to 28%) v 4% (95% CI, 1% to 6%), respectively, for patients with a PSA-DT ≥ 3 months. Conclusion Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score. These parameters may be useful in identifying patients for a randomized trial evaluating hormonal therapy with or without docetaxel.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5051-5051 ◽  
Author(s):  
Ayal A. Aizer ◽  
John Phillips ◽  
Ming-Hui Chen ◽  
Danjie Zhang ◽  
Marian Loffredo ◽  
...  

5051 Background: We evaluated the risk of prostate cancer-specific mortality (PCSM) following definitive treatment in men with at least one prostate biopsy core with a Gleason score (GS) lower than the highest GS identified. This pattern termed “ComboGS” in a concurrent submission was shown to be associated with a significant reduction in the odds of upgrading at radical prostatectomy (RP). Methods: In this validation cohort 666 men with localized or locally advanced prostate cancer, men were diagnosed via a transrectal, ultrasound-guided needle prostate biopsy (median 6, IQR 5-6 cores) and treated definitively between 1989-2000 with either RP or radiation (RT) or RT and hormones (HT) at a regional radiation oncology center. Patients could be referred into this center from 6 community based hospitals in Southeastern Massachusetts and Rhode Island. Community based pathologists from these 6 health care facilities assigned the biopsy GS used for the analyses in this study. Multivariable competing risks regression was performed (Table) to assess the impact of ComboGS on the risk of PCSM adjusting for age, established PC prognostic factors, and treatment. Results: After a median follow up of 4.6 years (IQR 2.5-6.7 years), 168 men (25.2%) died, 41 (24.4%) of PC. ComboGS was associated with a decreased risk of PCSM (Adjusted Hazard Ratio (AHR) 0.40, 95% Confidence Interval (CI) 0.19-0.85, p=.017). Estimates of PCSM were significantly lower in men with versus without ComboGS when the highest GS was ≥7 (p<.001) but not 6 or less (p=.71). Specifically these 5-year estimates were 14.4% and 4.8% versus 1.9% and 2.7% respectively. Conclusions: In addition to lower odds of upgrading at RP, using an independent data set the ComboGS assessed by community based pathologists serving 6 hospitals was found to also be associated with a decreased risk of PCSM. [Table: see text]


2006 ◽  
Vol 175 (4S) ◽  
pp. 382-382
Author(s):  
Stephen J. Freedland ◽  
Elizabeth B. Humphreys ◽  
Leslie A. Mangold ◽  
Mario Eisenberger ◽  
Alan W. Partin

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