Identification of prostate cancer-expressed microRNAs associated with clinical recurrence (cR) and prostate cancer-specific survival (PCSS) following radical prostatectomy (RP).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 21-21
Author(s):  
Eric A. Klein ◽  
Mike Kiefer ◽  
Michael Crager ◽  
Cristina Magi-Galluzzi ◽  
Sara Moscovita Falzarano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Tumor Tissue ◽  
Cox Regression ◽  
Cleveland Clinic ◽  
Messenger Rnas ◽  
Prognostic Information ◽  
Cancer Specific Survival ◽  
Clinical Recurrence ◽  
Gleason Pattern

21 Background: We previously identified messenger RNAs (mRNAs) whose expression can distinguish aggressive from indolent prostate cancer. Representing multiple key genomic pathways, these mRNAs are significantly associated with cR and PCSS after RP, providing prognostic information beyond PSA, cT stage and Gleason Score. We evaluated microRNA expression in the same specimens for association with cR and PCSS. Methods: All cT1/cT2 prostate cancer pts treated with RP at Cleveland Clinic from 1987-2004 were identified (n~2,600), of which 127 pts w/ cR and 374 pts w/o cR after RP were randomly selected using cohort sampling. RNA was purified from 2 macrodissected FPE tumor specimens per pt. Expression of 76 test and 5 reference microRNAs was quantified by RT-PCR. Cox regression and control of the false discovery rate (FDR) was used to assess reference-normalized microRNA and mRNA expression for association with cR and PCSS. Results: 106 pts with cR and 310 without cR had sufficient RNA and successful microRNA assays. Analysis of primary Gleason pattern tumor tissue for each pt identified 21 microRNAs associated with cR and 13 microRNAs associated with PCSS, with FDR at 10%; 8 microRNAs were associated with both endpoints. Similar analysis of highest Gleason pattern tumor tissue for each pt identified 22 microRNAs associated with cR (17 overlapping with those for the primary Gleason pattern) and 7 microRNAs associated with PCSS, with FDR at 10%; 4 were associated with both endpoints. miR-1, miR-21, miR-93, and miR-106b were associated with both cR and PCSS in primary and highest Gleason pattern specimens. The 76 microRNAs in this study tended to have weaker association with cR and PCSS than the 732 mRNAs. In multivariate analyses, mRNAs and microRNAs provided prognostic information beyond PSA, cT stage, and biopsy Gleason score. MicroRNAs co-express more frequently with each other than with mRNAs, which may indicate distinct biological regulation. Conclusions: Expression of some microRNAs assayed in FPE prostate tumor tissue was associated with cR and PCSS after RP in this study, and may retain prognostic value in the face of tumor heterogeneity.

scholarly journals Gleason Score and Lethal Prostate Cancer: Does 3 + 4 = 4 + 3?

2009 ◽  
Vol 27 (21) ◽  
pp. 3459-3464 ◽  
Author(s):  
Jennifer R. Stark ◽  
Sven Perner ◽  
Meir J. Stampfer ◽  
Jennifer A. Sinnott ◽  
Stephen Finn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Predictive Ability ◽  
Fold Increase ◽  
Health Study ◽  
Prognostic Information ◽  
Gleason Grading ◽  
Gleason Pattern ◽  
C Statistic ◽  
Bony Metastases

Purpose Gleason grading is an important predictor of prostate cancer (PCa) outcomes. Studies using surrogate PCa end points suggest outcomes for Gleason score (GS) 7 cancers vary according to the predominance of pattern 4. These studies have influenced clinical practice, but it is unclear if rates of PCa mortality differ for 3 + 4 and 4 + 3 tumors. Using PCa mortality as the primary end point, we compared outcomes in Gleason 3 + 4 and 4 + 3 cancers, and the predictive ability of GS from a standardized review versus original scoring. Patients and Methods Three study pathologists conducted a blinded standardized review of 693 prostatectomy and 119 biopsy specimens to assign primary and secondary Gleason patterns. Tumor specimens were from PCa patients diagnosed between 1984 and 2004 from the Physicians' Health Study and Health Professionals Follow-Up Study. Lethal PCa (n = 53) was defined as development of bony metastases or PCa death. Hazard ratios (HR) were estimated according to original GS and standardized GS. We compared the discrimination of standardized and original grading with C-statistics from models of 10-year survival. Results For prostatectomy specimens, 4 + 3 cancers were associated with a three-fold increase in lethal PCa compared with 3 + 4 cancers (95% CI, 1.1 to 8.6). The discrimination of models of standardized scores from prostatectomy (C-statistic, 0.86) and biopsy (C-statistic, 0.85) were improved compared to models of original scores (prostatectomy C-statistic, 0.82; biopsy C-statistic, 0.72). Conclusion Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival.

Oncological outcomes of surgery in very high risk pT3b prostate cancer

2011 ◽  
Vol 18 (3) ◽  
pp. 113-119
Author(s):  
Daimantas MILONAS ◽  
Giedrė SMAILYTĖ ◽  
Darius TRUMBECKAS ◽  
Mindaugas JIEVALTAS
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Cox Regression ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Oncologic Outcomes ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Surgery Outcome

Background. The aim of the study was to present the oncologic outcomes and to determine the prognostic factors of overall (OS) and cancer-specific survival (CSS) as well as disease-progression-free survival (DPFS) after surgery for pT3b prostate cancer. Materials and methods. In 2002–2007, a pT3b stage after radical prostatectomy was detected in 56 patients. Patients were divided into groups according to the prostate-specific antigen (PSA) level (20 ng/ml), lymph nodes status (N0 vs. Nx vs. N1) and the Gleason score (6–7 vs. 8–10). The Kaplan–Meier analysis was used to calculate OS, CSS and DPFS. The Cox regression was used to identify the predictive factors of survival. Results. Five-year OS, CSS and DPFS rates were 75.1%, 79.6% and 79.3%, respectively. The survival was significantly different when comparing the Gleason 6–7 and 8–10 groups. The 5-year OS, CSS and DPFS were 91.2% vs. 48.6%, 97.1% vs. 51.1% and 93.8 vs. 51.1%, respectively. There was no difference in survival among the groups with a different PSA level. The OS and CSS but not DPFS were significantly different when comparing the N0 and N1 groups. The 5-year OS and CSS was 84.4% vs. 37.5% and 87.3% vs. 47.6%, respectively. The specimen Gleason score was a significant predictor of OS and CSS. The risk of death increased up to 4-fold when a Gleason score 8–10 was present at the final pathology. Conclusions. Radical prostatectomy may offer acceptable CSS, DPFS and OS rates in pT3b PCa. However, outcomes in patients with N1 and specimen Gleason ≥8 were significantly worse, suggesting the need of multimodality treatment in such cases. Keywords: prostate cancer, locally advanced, surgery, outcome

scholarly journals Prognostic Models for Patients With Gleason Score 9 Prostate Cancer: A Population-Based Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianhui Qiu ◽  
Desheng Cai ◽  
Zixin Wang ◽  
Jingcheng Zhou ◽  
Yanqing Gong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Marital Status ◽  
Gleason Score ◽  
Cox Regression ◽  
Population Based ◽  
Competing Risk ◽  
Age At Diagnosis ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Gleason Pattern

Purpose: Gleason score (GS) system is one of the most widely used histological grading methods for prostate cancer (PCa) all over the world. GS can be obtained by adding the primary Gleason pattern (GP) and secondary GP. Different proportions of GP 4 and GP 5 in prostate specimens can both lead to GS 9. In this study, we explored whether GP 5 + 4 or GP 4 + 5 was associated with different prognoses among patients with GS 9 PCa.Materials and methods: A retrospective population-based study was conducted on 10,124 subjects diagnosed with GS 9 PCa between 2004 and 2009 from the Surveillance, Epidemiology, and End Results program. A 1:1 propensity-score matching (PSM) was performed to balance the baseline characteristics between the GP 4 + 5 and 5 + 4 groups and to compare the prognoses between the two groups. Cox regression analysis and Fine-Gray competing risk regression models were adopted to screen the covariates significantly associated with all-cause mortality (ACM) and cancer-specific mortality (CAM).Results: GP 5 + 4 was associated with higher risks of ACM and CSM before or after PSM than GP 4 + 5. In the original cohort, there were eight independent predictors for ACM, which were age at diagnosis, race, AJCC NM stage, PSA levels, treatments, GP, and marital status, confirmed by the Cox analysis; and nine independent predictors for CSM, which were age at diagnosis, race, AJCC TNM stage, PSA levels, treatments, GP, and marital status, confirmed by the competing-risk model.Conclusion: GP 5 + 4 was associated with a poorer overall survival and cancer-specific survival compared with GP 4 + 5.

scholarly journals Oncologic Outcomes of Surgery in T3 Prostate Cancer: Experience of a Single Tertiary Center

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
D. Milonas ◽  
G. Smailyte ◽  
M. Jievaltas
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Oncologic Outcomes ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Risk Of Death ◽  
Tertiary Center

Aim. The aim of this study is to present the oncologic outcomes and to determine the prognostic factors of overall survival (OS), cancer-specific survival (CSS), disease-progression-free survival (DPFS), and biochemical-progression-free survival (BPFS) after surgery for pT3 prostate cancer (PCa).Methods. Between 2002 and 2007, a pT3 stage after radical prostatectomy was detected in 182 patients at our institution. The Kaplan-Meier analysis was used to calculate OS, CSS, DPFS, and BPFS. Cox regression was used to identify predictive factors of survival.Results. pT3a was detected in 126 (69%) and pT3b in 56 (31%) of cases. Five-year OS, CSS, DPFS, and BPFS rates were 90.7%, 94%, 91.8%, and 48.4%, respectively. Survival was significantly different when comparing pT3a to pT3b groups. The 5-year OS, CSS, DPFS, and BPFS were 96% versus 72%, 98% versus 77%, 97.3% versus 79.3%, and 60% versus 24.2%, respectively. Specimen Gleason score was the most significant predictor of OS, CSS, DPFS, and BPFS. The risk of death increased up to 3-fold when a Gleason score 8–10 was present at the final pathology.Conclusions. Radical prostatectomy may offer very good CSS, OS, DPFS, and BPFS rates in pT3a PCa. However, outcomes in patients with pT3b or specimen Gleason ≥8 were significantly worse, suggesting the need for multimodality treatment in those cases.

Long-Term Prognostic Significance of Primary Gleason Pattern in Patients With Gleason Score 7 Prostate Cancer: Impact on Prostate Cancer Specific Survival

2006 ◽  
Vol 175 (2) ◽  
pp. 547-551 ◽  
Author(s):  
Matthew K. Tollefson ◽  
Bradley C. Leibovich ◽  
Jeffrey M. Slezak ◽  
Horst Zincke ◽  
Michael L. Blute
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Prognostic Significance ◽  
Cancer Specific Survival ◽  
Gleason Pattern

Predictors of overall and cancer-specific survival in patients with clinically localized prostate cancer (PC) treated with primary androgen deprivation therapy (PADT): Results from the Prostate Cancer Outcomes Study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4610-4610
Author(s):  
J. Graff ◽  
M. Mori ◽  
H. Li ◽  
M. Garzotto ◽  
D. Penson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Gleason Score ◽  
Cox Regression ◽  
Tumor Biology ◽  
High Serum ◽  
Localized Prostate Cancer ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Cancer Outcome

4610 Background: Use of PADT as sole therapy for clinically localized PC is rapidly increasing, despite little evidence to support this approach. We examined predictors of overall survival (OS) and cancer-specific survival (CSS) using the data available from the Prostate Cancer Outcome Study (PCOS). Methods: PCOS recruited 5,672 patients between 1994 and 1995, within 6 months of PC diagnosis. Vital status was last updated in 12/02. 276 patients had clinically localized PC and received PADT. We examined the relationship between baseline demographic, socio-economic, and tumor factors and OS and CSS using Kaplan-Meier and Cox regression methods implemented in the SUDAAN software. Results: Of 276 patients, 148 patients have died, 35 from PC. The median age at diagnosis was 75 (50–88). The average follow-up of censored subjects was 7.6 yrs (1.1–8.1). 5-year OS was 66% (95% CI: 69–72), while the 5-year CSS was 91% (95% CI: 86–94). In the multivariate analysis (see Table), age, serum PSA at diagnosis, and Gleason score were the only independent predictors of OS. Abnormal DRE was marginally significant. The Gleason score (≥7) was the only independent predictor of CSS (HR 4.0, p = 0.04); PSA ≥ 20 (HR 2.38, p = 0.09) approached significance. This analysis was limited by a smaller number of deaths due to prostate cancer (n = 35). Conclusions: In an analysis that included a broad range of demographic and socio-economic factors, overall survival of patients with clinically localized prostate cancer treated with PADT was predicted by age and measures of tumor biology (Gleason score) and tumor mass (serum PSA). Thus, cancer remains an important contributor to overall mortality in these patients, particularly those with high Gleason score and high serum PSA. These data can be used to inform patients regarding their individual 5-year survival if they choose PADT for the treatment of their clinically localized prostate cancer. [Table: see text] No significant financial relationships to disclose.

Oncological outcomes in high-risk prostate cancer after radical prostatectomy based on Gleason score: USC experience with 3,755 cases.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 60-60
Author(s):  
Hooman Djaladat ◽  
Weichen Xu ◽  
Jie Cai ◽  
Gary Lieskovsky ◽  
Siamak Daneshmand
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Cox Regression ◽  
Adjuvant Radiation ◽  
Recurrence Free Survival ◽  
Clinical Recurrence ◽  
Free Survival ◽  
Oncological Outcomes

60 Background: Gleason score is an important predictor of oncological outcomes after radical prostatectomy. However, it remains unclear whether there is a difference in outcomes between Gleason score (GS) 8 and 9-10 disease. We compare oncological outcomes after open radical prostatectomy for prostate cancer patients with GS of 8 versus 9-10. Methods: Of 3,755 radical prostatectomy patients (1987-2008), 360 patients with final pathology of GS 8, 9 or 10 and N0M0 were included. No significant differences between age, race and surgical margins between the two groups. Impact of GS on outcomes was controlled for preoperative PSA, pathological stage, use of adjuvant radiation therapy and use of neoadjuvant/adjuvant hormone deprivation therapy in multivariable analyses. Outcomes of interest were biochemical recurrence free survival (BCRFS), clinical recurrence free survival (CRFS) and overall survival (OS). Kaplan Meier plots, log rank tests and multivariable Cox regression model were used to analyze the data. Results: Median follow-up for GS 8 and GS 9-10 were 10.0 years and 8.6 years, respectively (p=0.43). Conclusions: Long term follow up after radical prostatectomy reveals significant differences in BCRFS and CRFS but not OS between patients with GS 8 vs. 9-10 prostate cancers. Further studies may examine sub-stratification of GS 8 tumors into a lower risk category than GS 9-10 tumors. [Table: see text] [Table: see text]

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