Urinary exosomal microRNA profiling in intermediate-risk prostate cancer

AbstractMicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA.

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Association of risk of clinical recurrence (CR) and prostate cancer death (PCD) with a 17-gene genomic prostate score (GPS) value <20.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5074 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5074-5074 ◽

Cited By ~ 1

Author(s):

Phillip G. Febbo ◽

Michael Crager ◽

Emily Burke ◽

H. Jeffrey Lawrence ◽

Jennifer Cullen ◽

...

Keyword(s):

Prostate Cancer ◽

Cox Regression ◽

Intermediate Risk ◽

Regression To The Mean ◽

Sampling Weights ◽

Clinical Recurrence ◽

Hazard Ratios ◽

Risk Prostate Cancer ◽

Prostate Cancer Death

5074 Background: Over-treatment of localized prostate cancer (PC) can result from over-estimation of a patient’s risk of CR and PCD. GPS (scale 0-100) has been validated to predict adverse pathology, biochemical recurrence, metastasis, and PCD and provides a more accurate overall assessment of patient risk than clinical risk factors alone. A recent validation study found that no patients with AUA Low- or Intermediate-risk disease and a GPS of <20 developed PC metastases or PCD. Here, 2 large longitudinal PC cohorts were analyzed to estimate the risk of CR and PCD for GPS <or >20 units. Methods: Data from Klein et al. European Urology (EU) 2014 and Cullen et al. EU 2014 were analyzed to establish the risk of CR and PCD associated with a pre-established GPS cut-point of 20. Patients were divided based on the value of GPS (≤20, >20). Cox regression analyses accounted for cohort sampling weights. Since GPS was developed using Klein et al, standardized hazard ratios (std HR, HR for 1 SD change in the covariate) for GPS and CR and PCD survival curves for the 2 groups were estimated correcting for regression to the mean (RM). Results: Of the 402 patients in Cullen et al. (median follow up 5.2 years), only 5 patients developed metastases; all 5 had GPS >20. For Klein et al., of 426 patients with a median follow up of 6.6 years, there were 109 CR (metastasis and local recurrence) and 39 PCD; only one patient with events had a GPS <20. Overall 28% of patients had GPS <20. GPS was a significant predictor for both CR (std HR 2.50 (95%CI 1.99, 3.15, p <0.001, RM-corrected std HR 2.16, FDR <0.1%) and PCD (std HR 2.90 (95% CI 2.06,4.06, p<0.001, RM-corrected std HR 1.96, FDR <0.1%) after adjustment for AUA group. Men with intermediate risk prostate cancer and a GPS score of < 20 have a 2.6% and 0.7% 10-year RM-corrected risk of CR and PCD, respectively (Table 1). Conclusions: GPS strongly predicts risk of CR and PCD in men with AUA Low- or Intermediate-risk PC. Patients with a GPS score <20 have a very low risk of CR or PCD and should be considered for AS. [Table: see text]

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99 Serum Cytokine Profiling as a Potential Biomarker in Intermediate Risk Prostate Cancer: An Exploratory Study

Radiotherapy and Oncology ◽

10.1016/s0167-8140(19)33391-2 ◽

2019 ◽

Vol 139 ◽

pp. S44

Author(s):

Aruz Mesci ◽

Stanley Liu ◽

Hans Chung

Keyword(s):

Prostate Cancer ◽

Exploratory Study ◽

Intermediate Risk ◽

Serum Cytokine ◽

Potential Biomarker ◽

Risk Prostate Cancer ◽

Cytokine Profiling

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External validation of a nomogram for identification of pathologically favorable disease in intermediate risk prostate cancer patients

The Prostate ◽

10.1002/pros.23348 ◽

2017 ◽

Vol 77 (8) ◽

pp. 928-933 ◽

Cited By ~ 3

Author(s):

Jean-Baptiste Beauval ◽

Bastien Cabarrou ◽

Giorgio Gandaglia ◽

Pierre-Marie Patard ◽

Adil Ouzzane ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

External Validation ◽

Intermediate Risk ◽

Risk Prostate Cancer

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Is there a relationship between testosterone levels at the end of short-term androgen deprivation therapy and outcomes in intermediate risk prostate cancer? Prospective data from a phase III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.78 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 78-78 ◽

Cited By ~ 1

Author(s):

Abdenour Nabid ◽

Marie-Pierre Garant ◽

Eric Vigneault ◽

Luis Souhami ◽

Celine Lemaire ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Testosterone Level ◽

Cox Regression ◽

Androgen Deprivation ◽

Phase Iii ◽

Intermediate Risk ◽

Short Term ◽

Testosterone Levels ◽

Risk Prostate Cancer

78 Background: The purpose of this analysis was to assess whether the testosterone level measured at the end of short term androgen deprivation therapy (STADT) and prostate radiotherapy (RT) has an impact on treatment outcomes in patients with intermediate risk prostate cancer (IRPC) treated on a randomized trial (PCS III ClinicalTrials.gov #NCT00223145). Methods: From December 2000 to September 2010, 400 patients with IRPC received 6 months of STADT (bicalutamide 50mg die and goserelin 10.8mg x 2) and RT. Castrate level of testosterone was defined as <1.7 nmol/L: lower level <0.7 and upper level 0.7-1.7. In 347/400 patients, testosterone levels were available at the end of STADT and were divided into 3 groups based on measured testosterone levels: <0.7, 0.7 to 1.7 and >1.7 nmol/L. Patient’s characteristics were compared with ANOVA and Fisher’s exact test. Biochemical failure, prostate cancer recurrence and death were compared with Cox regression. Results: Patient’s characteristics were well balanced between the 3 groups with no statistical difference for age, performance status, PSA at start, Gleason score and stage. At the end of STADT 55.3% (192/347) presented testosterone levels <0.7 and 38.9% (135/347) levels between 0.7 and 1.7 for a total of 94.2% (327/ 347) reaching castrate levels ≤1.7 nmol/L. In 5.8% of patients (20/347) a castrate testosterone level was not achieved. With a median follow-up of 8.1 years, outcomes are shown in the table. Conclusions: In IRPC patients treated with STADT and RT, the majority of patients (94.2%) achieve a castrate level of testosterone (<1.7 nmol/L). Although we could not show a difference in outcomes between castrate and non-castrate patients, these data have to be viewed with caution given the small number of non-castrate patients studied. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: NCT00223145. [Table: see text]

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