LBA02-09 A HIGH THROUGH-PUT TEST INTERROGATING 442 SMALL NON-CODING RNAS (SNCRNA) EXTRACTED FROM URINE EXOSOMES ACCURATELY IDENTIFIES AND STRATIFIES PROSTATE CANCER INTO LOW-, INTERMEDIATE- OR HIGH-RISK DISEASE

PURPOSE We identified (1) differences in localized prostate cancer (PCa) risk group at presentation and (2) disparities in access to initial treatment for Asian American, Native Hawaiian, and Pacific Islander (AANHPI) men with PCa after controlling for sociodemographic factors. METHODS We assessed all patients in the National Cancer Database with localized PCa with low-, intermediate-, and high-risk disease who identified as Thai, White, Asian Indian, Chinese, Vietnamese, Korean, Japanese, Filipino, Hawaiian, Pacific Islander, Laotian, Pakistani, Kampuchean, and Hmong. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment or active surveillance with intermediate- or high-risk disease, adjusting for sociodemographic and clinical factors. RESULTS Among 980,889 men (median age 66 years), all AANHPI subgroups with the exception of Thai (AOR = 0.84 [95% CI, 0.58 to 1.21], P > .05), Asian Indian (AOR = 1.12 [95% CI, 1.00 to 1.25], P > .05), and Pakistani (AOR = 1.34 [95% CI, 0.98 to 1.83], P > .05) men had greater odds of presenting at a progressively higher PCa risk group compared with White patients (Chinese AOR = 1.18 [95% CI, 1.11 to 1.25], P < .001; Japanese AOR = 1.36 [95% CI, 1.26 to 1.47], P < .001; Filipino AOR = 1.37 [95% CI, 1.29 to 1.46], P < .001; Korean AOR = 1.32 [95% CI, 1.18 to 1.48], P < .001; Vietnamese AOR = 1.20 [95% CI, 1.07 to 1.35], P = .002; Laotian AOR = 1.60 [95% CI, 1.08 to 2.36], P = .018; Hmong AOR = 4.07 [95% CI, 1.54 to 10.81], P = .005; Kampuchean AOR = 1.55 [95% CI, 1.03 to 2.34], P = .036; Asian Indian or Pakistani AOR = 1.15 [95% CI, 1.07 to 1.24], P < .001; Native Hawaiians AOR = 1.58 [95% CI, 1.38 to 1.80], P < .001; and Pacific Islanders AOR = 1.58 [95% CI, 1.37 to 1.82], P < .001). Additionally, Japanese Americans (AOR = 1.46 [95% CI, 1.09 to 1.97], P = .013) were more likely to receive treatment compared with White patients. CONCLUSION Our findings suggest that there are differences in PCa risk group at presentation by race or ethnicity among Asian American, Native Hawaiian, and Pacific Islander subgroups and that there exist disparities in treatment patterns. Although AANHPI are often studied as a homogenous group, heterogeneity upon subgroup disaggregation underscores the importance of further study to assess and address barriers to PCa care.

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Use of the Prostate Health Index for the Detection of Aggressive Prostate Cancer at Radical Prostatectomy

Urologia Internationalis ◽

10.1159/000379758 ◽

2015 ◽

Vol 95 (4) ◽

pp. 390-399 ◽

Cited By ~ 5

Author(s):

Luigi Mearini ◽

Elisabetta Nunzi ◽

Carla Ferri ◽

Guido Bellezza ◽

Carolina Lolli ◽

...

Keyword(s):

Prostate Cancer ◽

Lymph Node ◽

High Risk ◽

Radical Prostatectomy ◽

Gleason Score ◽

Health Index ◽

Final Pathology ◽

High Risk Disease ◽

Prostate Health Index ◽

Prostate Health

Introduction: In current study, we compared the accuracy of the PSA isoform p2PSA and its derivatives, the percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI) in the detection of prostate cancer (PC) characteristics at the ﬁnal pathology with respect to reference standards. Materials and Methods: This was an observational prospective study evaluating 43 consecutive PC patients treated with laparoscopic/robotic radical prostatectomy (RP). Logistic regression models were ﬁtted to test the predictors of pT3 stage, pathologic Gleason score ≥8 or Gleason score upgrading, margin status, lymph node invasion, and the presence of high-risk disease (pT3 disease and/or Gleason score ≥8 and/or positive lymph node). The comparative base model included tPSA, clinical stage, biopsy Gleason score, and percentage of positive core. Results: Seventeen patients (39.5%) were affected by pT3 disease or had a pathologic Gleason score ≥8; positive margins were detected in 12 patients (27.9%), lymph node invasion was found in 2 patients (4.7%), and 15 patients (34.8%) harbored high-risk disease. In the univariate analysis, p2PSA, %p2PSA, and PHI were signiﬁcant predictors of pT3 disease, pathologic Gleason score, and the presence of high-risk disease (all p < 0.05), whereas only PHI was an independent predictor of pT3 disease, margin status, and presence of high-risk disease, increasing the accuracy of a base multivariable model by 6.3% (p < 0.05) and 4.2% (p < 0.05) for the prediction of pT3 and high-risk disease, respectively. Conclusions: p2PSA and its derivatives, primarily PHI, were signiﬁcant predictors of unfavorable PC characteristics as detected at the ﬁnal pathology, thus improving the clinical performance of standard prognostic factors for aggressive disease.

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Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2010.07.1975 ◽

2011 ◽

Vol 81 (5) ◽

pp. 1279-1285 ◽

Cited By ~ 15

Author(s):

Almudena Zapatero ◽

Feliciano García-Vicente ◽

Carmen Martín de Vidales ◽

Alfonso Cruz Conde ◽

Yamile Ibáñez ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Long Term Results ◽

High Dose ◽

High Risk Disease

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PSA-detected prostate cancer in the United States: A population-based study of 70,345 men with AJCC stage T1cN0M0 disease.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.50 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 50-50

Author(s):

Hong Zhang ◽

Lois B. Travis ◽

Edward M. Messing ◽

Ollivier Hyrien ◽

Rui Chen ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Gleason Score ◽

Prostate Cancer Screening ◽

Specific Antigen ◽

The United States ◽

Population Based ◽

Population Based Study ◽

Ajcc Stage ◽

High Risk Disease

50 Background: The U.S. Preventive Services Task Force (USPSTF) recently recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. This recommendation has heightened the debate about risks and benefits of prostate cancer screening, and underscored our limited understanding of PSA-detected prostate cancer. The purpose of this study was to determine the frequency of various risks of prostate cancer based on patient characteristics and PSA levels. Methods: This population-based study used the Surveillance, Epidemiology, and End Results (SEER) program to identify men with AJCC stage T1cN0M0 disease diagnosed between 1/2004 and 12/2008. Multivariate logistic regression was conducted to model the probability of developing low (PSA <10 mg/L and Gleason score ≤6), intermediate (PSA between 10 mg/L to 20 mg/L and/or Gleason score 7), and high risk diseases (PSA ≥20 mg/L, and/or Gleason score ≥8). Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were evaluated. Among them, 47.6%, 35.9% and16.5% had low, intermediate, or high risk disease, respectively. Odds ratios (OR) of having intermediate or high risk disease in patients ≥75 years old were 4.47 (95% confidence interval (CI) 3.81 to 5.26, p<0.01) and 9.39 (95% CI 7.25 to 12.16, p<0.01), respectively, when compared with patients aged <50. Also, black men had increased ORs for intermediate and high risk disease compared with white men (OR 1.50, 95% CI 1.42 to 1.58, p<0.01 for intermediate risk disease; OR 1.84, 95% CI 1.72 to 19.97, p<0.01 for high risk disease). While men aged >75 accounted for 11.8% of the population at risk, they accounted for 24.3% of intermediate and 26.1% of high risk disease. Conclusions: A substantial number of PSA-detected prostate cancer patients have either intermediate or high risk disease at diagnosis. Men age >75 or of black race have the highest risk of presenting with intermediate or high risk disease.

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Periprostatic fat tissue transcriptome reveals a signature diagnostic for high-risk prostate cancer

Endocrine Related Cancer ◽

10.1530/erc-18-0058 ◽

2018 ◽

Vol 25 (5) ◽

pp. 569-581 ◽

Cited By ~ 7

Author(s):

Stefano Mangiola ◽

Ryan Stuchbery ◽

Geoff Macintyre ◽

Michael J Clarkson ◽

Justin S Peters ◽

...

Keyword(s):

Prostate Cancer ◽

Adipose Tissue ◽

High Risk ◽

Cross Validation ◽

Validation Cohort ◽

Second Phase ◽

High Risk Prostate Cancer ◽

Diagnostic Potential ◽

High Risk Disease ◽

Risk Prostate Cancer

Evidence suggests that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. In this study, we investigated the adipose transcriptional profiles of low- and high-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue from patients categorised as having prostate cancer with either a low or high risk of progression based on tumour characteristics at prostatectomy and profiled by RNA sequencing. The expression of selected genes was then quantified by qRT-PCR in a cross-validation cohort. In the first phase, a total of 677 differentially transcribed genes were identified, from which a subset of 14 genes was shortlisted. In the second phase, a 3 gene (IGHA1,OLFM4,RERGL) signature was refined and evaluated using recursive feature selection and cross-validation, obtaining a promising discriminatory utility (area under curve 0.72) at predicting the presence of high-risk disease. Genes implicated in immune and/or inflammatory responses predominated. Periprostatic adipose tissue from patients with high-risk prostate cancer has a distinct transcriptional signature that may be useful for detecting its occult presence. Differential expression appears to be driven by a local immune/inflammatory reaction to more advanced tumours, than any specific adipose tissue-specific tumour-promoting mechanism. This signature is transferable into a clinically usable PCR-based assay, which in a cross-validation cohort shows diagnostic potential.

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Outcome and patient-reported toxicity in localised prostate cancer treated with dose-escalated hypofractionated intensity-modulated radiotherapy

Journal of Radiotherapy in Practice ◽

10.1017/s146039691200043x ◽

2013 ◽

Vol 12 (4) ◽

pp. 326-333

Author(s):

David Thomson ◽

Sophie Merrick ◽

Ric Swindell ◽

James Wylie ◽

Richard Cowan ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

High Risk ◽

Intensity Modulated Radiotherapy ◽

Late Toxicity ◽

Phase Iii ◽

Patient Questionnaire ◽

Intensity Modulated ◽

High Risk Disease ◽

Cause Specific Survival

AbstractObjectiveTo report outcomes and late toxicity for a hypofractionated dose-escalated radiotherapy schedule in patients treated using intensity-modulated radiotherapy (IMRT) for localised prostate cancer.Materials and methodsEighty-eight men with localised prostate cancer were treated with 57 Gy in 19 daily fractions over 4 weeks. A total of 70 out of 88 had high-risk disease. Overall survival, cause-specific survival and biochemical progression-free survival (bPFS, Phoenix definition) were reported. Toxicity was measured retrospectively using Radiation Therapy Oncology Group (RTOG) criteria and assessed prospectively with a validated Late Effects in Normal Tissues Subjective, Objective, Management and Analytic (LENT/SOMA) patient questionnaire.ResultsAt 5 years, overall survival was 84%, cause-specific survival 88% and bPFS 65%. In patients with high-risk disease, 5-year bPFS was 62%. There was no RTOG toxicity above grade III. LENT/SOMA questionnaires were returned by 74% patients. Median scores for bowel and urinary function were <1. Maximum bowel and urinary toxicity scores ≥2 were reported by 64% and 59% of patients, respectively. The median score for sexual function was 1·5, but nearly all (96%) patients recorded a toxicity score ≥2 for at least one question.ConclusionsDose-escalated hypofractionated radiotherapy delivered using IMRT has promising outcomes and acceptable late toxicity. This fractionation schedule is being compared with conventional treatment within an on-going multicentre phase III clinical trial.

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Association of radical prostate cancer therapy with a survival benefit in the older man.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.66 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 66-66

Author(s):

Paul Cathcart ◽

Amundeep Johal ◽

Jan van der Meulen ◽

Mark Emberton

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Cancer Therapy ◽

Survival Benefit ◽

Older Men ◽

Prostate Cancer Therapy ◽

High Risk Disease ◽

Specific Mortality ◽

Radical Therapy ◽

Cancer Specific Mortality

66 Background: Data from several recent randomised controlled trials have suggested that older men have little to gain from radical prostate cancer therapy. In contrast, observational studies have suggested that older men might be at increased risk of prostate cancer related death than their younger counterparts. Using a national cancer registry, we sought to explore this issue further. Methods: English national mortality records for an 11 year period between 1997 and 2008 were linked to national hospital admission records together with national cancer registration records to generate a working dataset. Complete data were available on 75,735 men. Competing risks regression analysis was employed to identify the effect of age on Prostate Cancer Specific mortality. Results: Older men were more likely to have high-grade prostate cancer (<70 yrs: 20% v’s >79 yrs: 36%) and be staged with locally advanced (<70 yrs: 20% v’s >79 yrs: 35%) or metastatic disease (<70 yrs: 18% v’s >79 yrs: 25%). Older men were less likely to receive radical therapy (<70 yrs: 46% v’s >79 yrs: 4%) although they were more likely to die of their disease. 8-year overall mortality for low, intermediate and high risk disease in men <70 was 8%, 11% and 31% compared to 34%, 36% and 54% for men >79. Comparable figures for 8-year prostate cancer specific mortality were 1%, 5% and 22% for men <70 and 8%, 10% and 32% for men >79.The Number Needed to Treat (NNT) to save one prostate cancer related death for men with low risk disease aged less than 70 was 100 compared to 20 and only 6 for men aged <70 with intermediate and high risk disease respectively. For men aged between 75 and 79, radical prostate cancer therapy was only associated with a survival benefit in men with high risk disease (OR: 0.49, 95% CI 0.36-0.66, p<0.001) for which the NNT was 5. Conclusions: Older men present with more advanced and more aggressive prostate cancer and as such are more likely to die from their disease. Radical therapy was associated with a survival benefit up to the age of 80 providing therapy was targeted to those with higher risk disease.

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Current clinical presentation and treatment of localized prostate cancer in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.116 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 116-116

Author(s):

Usama Mahmood ◽

Lawrence B. Levy ◽

Paul Linh Nguyen ◽

Andrew Lee ◽

Deborah A. Kuban ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Clinical Presentation ◽

Local Treatment ◽

Multivariable Analysis ◽

Sociodemographic Factors ◽

Low Risk ◽

Localized Prostate Cancer ◽

High Risk Disease ◽

The Us

116 Background: This year, the Surveillance, Epidemiology, and End Results (SEER) database released individual patient clinical Gleason score (GS) at the time of biopsy/transurethral resection of the prostate (TURP), which, along with the previously available clinical stage and prostate-specific antigen (PSA), allows a unique opportunity to study the clinical presentation and treatment selection of prostate cancer in the US. Methods: The SEER database was used to identify men diagnosed with localized prostate cancer in 2010 who were then assigned National Comprehensive Cancer Network (NCCN) risk group based on clinical factors at diagnosis. We determined sociodemographic factors associated with having high-risk disease and analyzed the impact of NCCN risk, along with sociodemographic factors, on local treatment selection. Results: A total of 42,403 men were identified of which 16,171 (38%) had low-risk, 16,990 (40%) had intermediate-risk, and 9,242 (22%) had high-risk disease. Older, non-white, and non-married patients living in counties with higher poverty rates, were most likely to be diagnosed with high-risk disease on multivariable analysis. Of the 38,634 men for whom prostate cancer was the first malignancy, 8,832 (23%) had no local treatment, 15,421 (40%) had prostatectomy, 13,855 (36%) had radiation treatment (including external beam radiation and/or brachytherapy), and 526 (1%) had another form of local tumor destruction (predominantly cryotherapy). In total, 29% of low-risk, 16% of intermediate-risk, and 25% of high-risk patients received no local treatment (p < 0.001). On multivariable analysis, older, non-white, and non-married patients living in counties with higher poverty rates who had low-risk disease, were least likely to receive local treatment. Conclusions: Our analysis provides information regarding the current clinical presentation and treatment of localized prostate cancer in the US. We note persistent disparities in the presentation and treatment of prostate cancer according to sociodemographic factors and potential under treatment of high-risk disease.

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Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers to detect clinically significant disease: Results from the initial screening round of the IMPACT study.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.8 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 8-8

Author(s):

Christos Mikropoulos ◽

Elena Castro ◽

Elizabeth Bancroft ◽

Elizabeth Page ◽

Natalie Taylor ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Brca2 Mutation ◽

Psa Testing ◽

Mutation Carriers ◽

High Risk Disease ◽

Brca1 Carriers ◽

Clinically Significant ◽

The Impact ◽

Significant Disease

8 Background: Men with germline BRCA1/2 mutations have a higher risk of developing prostate cancer (PrCa) than non-carriers. IMPACT is an international consortium of 62 centers in 20 countries evaluating the use of targeted PrCa screening in men with BRCA1/2 mutations. This analysis reports the first year’s screening results for all men at enrolment in the study. Methods: We recruited men aged between age 40 and 69 with germline BRCA1/2 mutations and a control group that tested negative for a BRCA1/2 mutation. All men underwent prostate-specific antigen (PSA) testing at enrollment and those with a PSA of greater than 3ng/ml threshold were offered prostate biopsy. All men are offered a biopsy irrespective of PSA level after five years of screening. Results: We recruited 2,481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls) of whom 199 (8%) presented with a PSA greater than 3ng/ml. We performed a total of 162 biopsies and diagnosed 59 PrCas (18 BRCA1 carriers, ten BRCA1 controls; 24 BRCA2 carriers, seven BRCA2 controls); 66% of the tumors were classified as intermediate or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3·0ng/ml in BRCA2 mutation carriers was 48%, double that reported in population screening studies. A significant difference in detecting intermediate or high-risk disease was observed in BRCA2 carriers using this threshold. Conclusions: The IMPACT screening network will be useful for targeted PrCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this yields a high proportion of aggressive disease. Early data indicate that the majority of BRCA1/2 mutation carriers diagnosed with prostate cancer at biopsy had developed clinically significant disease (requiring radical treatment). Clinical trial information: NCT00261456.

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Clinical-genomic sub-classification of high-risk prostate cancer: Implications for tailoring therapy and clinical trial design.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.337 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 337-337

Author(s):

Vinayak Muralidhar ◽

Mohammed Alshalalfa ◽

Daniel Eidelberg Spratt ◽

Yang Liu ◽

R. Jeffrey Karnes ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Risk Stratification ◽

High Risk Prostate Cancer ◽

High Risk Disease ◽

Risk Prostate Cancer ◽

Risk Patients ◽

Genomic Risk ◽

Clinical Genomic ◽

Very High

337 Background: Current risk stratification schema have limited prognostic performance in predicting outcome within National Comprehensive Cancer Network (NCCN) high-risk to very high-risk prostate cancer. Methods: Two multicenter high-risk cohorts were used for training (n = 214) and validation (n = 151) of a novel RNA microarray-based integrated clinical-genomic Classifier Optimized for Outcome in High-risk Prostate cancer (COOHP) to classify patients as COOHP favorable high-risk, standard high-risk, or very high-risk. Cox analysis was used to model metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Model performance was compared to prior sub-classification systems using time-dependent c-indices. Results: Among NCCN high/very high-risk patients in the training cohort, 11% were classified as COOHP favorable high-risk, 70% as COOHP standard high-risk, and 18% as COOHP very high-risk. Patients with COOHP favorable high-risk disease had better rates of 5-year MFS compared to those with COOHP standard high-risk disease (94% vs 76%, hazard ratio [HR] 0.10, p = 0.02), and patients with COOHP very high-risk disease had worse 5-year MFS compared to those with COOHP standard high-risk disease (34% vs 76%, HR 3.5, p < 0.0001). Similarly, patients with COOHP very high-risk disease had worse 10-year PCSS compared to those with COOHP standard high-risk disease (36% vs 82%, HR 4.4, p < 0.0001). The c-indices for 5-year MFS and 10-year PCSS in the training cohort were 0.80 and 0.74, significantly improved compared to prior clinical and clinical-genomic risk stratification systems (0.62-0.69 for 5-year MFS and 0.56-0.63 for 10-year PCSS). These results were consistent in the validation cohort, where 5-year MFS significantly varied among the three COOHP subgroups (100% vs 89% vs 79%, p = 0.020), as did 10-year OS (100% vs 71% vs 53%, p = .040). Conclusions: A clinical-genomic risk stratification system specifically designed to discriminate prognosis in high-risk prostate cancer better identified favorable high-risk and very high-risk subsets of disease compared to prior clinical and clinical-genomic stratification systems.

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