Predicting high-risk disease using tissue biomarkers

Donovan, Michael; Cordon‐Cardo, Carlos

doi:10.1097/mou.0b013e32835f89cc

Cited by 19 publications

(11 citation statements)

References 38 publications

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“…The heterogeneous nature of this patient population highlights the need for additional risk stratification, both for accurate prognostication and for refinement of treatment recommendations. While the VHR definition represents only one possible combination of prognostic factors, and while a number of other biomarkers are in various stages of analytical and clinical validation, 18, 19 the VHR definition is attractive for its simplicity and utilization of parameters routinely collected in clinical practice. Additionally, the VHR definition likely encompasses a non-trivial fraction of NCCN high-risk men, including roughly one in three men in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

Narang

Gergis

Robertson

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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Purpose/Objectives Existing definitions of high-risk prostate cancer comprise men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of NCCN high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease, and/or ≥5 biopsy cores with Gleason sum 8–10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients. Methods and Materials All men consecutively treated with definitive radiation by a single provider from 1993–2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 (34%) patients with VHR disease. Multivariable-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariable-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. Results Men with VHR disease as compared to other NCCN high-risk men experienced higher 10-year incidences of BF (54.0% vs. 35.4%, p<0.001), DM (34.9% vs. 13.4%, p<0.001), PCSM (18.5% vs. 5.9%, p<0.001), and OM (36.4% vs. 27.0%, p=0.04). VHR men with a detectable PSA at the end-of-radiation (EOR) remained at high risk of 10-year PCSM, as compared to VHR men with an undetectable EOR PSA (31.0% vs. 13.7%, p=0.05). Conclusions NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be further explored, as should novel agents.

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Section: Discussionmentioning

confidence: 99%

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

Narang

Gergis

Robertson

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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“…However, such a stratification scheme is far from perfect and sometimes results in unnecessary treatment in patients with low risk disease and delayed treatment in patients with high risk disease. Molecular and genetic markers, used singularly or in combination, can potentially separate indolent PCa from aggressive ones and help identify patients with indolent disease who can therefore be safely followed and patients with aggressive disease who need definitive treatment…”

Section: Genetic Markersmentioning

confidence: 99%

Recent advances in prostate cancer pathology: Gleason grading and beyond

Shah¹,

Zhou

2016

Pathology International

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Since its initial description in 1966 by Dr Donald Gleason, Gleason grading has become the cornerstone in the management of prostate cancer (PCa). With widespread use of Prostate Specific Antigen (PSA) screening and needle core biopsy, the diagnosis and management of PCa have dramatically evolved. In addition, better understanding of the morphological spectrum of prostate cancer and its clinical significance have prompted the refinement of the grading criteria and reporting guidelines commensurate to contemporary practice. The modification of the Gleason grading system implemented by the International Society of Urological Pathology in 2005 and subsequent revision in 2014 has profoundly impacted how PCa is graded and managed. This review aims to provide a concise update on the refinement of the histological criteria for various Gleason patterns and problem areas of Gleason grading, and provide recommendations on how to improve the grading reproducibility. The new proposal to group Gleason scores into clinically meaningful “grade groups” will also be discussed. Finally, we will discuss how magnetic resonance imaging (MRI)‐targeted biopsy and emerging genetic markers may help improve the Gleason grading accuracy and risk stratification currently based on clinicopathological parameters.

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“…Identification of prostate malignant acini can sometimes present a diagnostic challenge for pathologists since PCa can mimic benign prostate glands [3] and the architectural or cytologic clues for the diagnosis of carcinoma may not always be seen in small foci of suspicious glands. Histopathological diagnosis of PCa can be established by transrectal ultrasound-guided (TRUS) biopsy [4] after an abnormal finding on digital rectal examination or finding an augmentation in prostate-specific antigen (PSA) level [5].…”

Section: Introductionmentioning

confidence: 99%

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

Abdelhady

El-Hindawi

Hammam

et al. 2017

Open Access Maced J Med Sci

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AIM:Prostate cancer (PCa) is the second most common cancers in men worldwide. Its incidence can be influenced by several risk factors including genetic susceptibility. Therefore the search for the expression of a certain gene (ERG) and its rearrangement could give us clues for proper identification of PCa. And the study of ERG expression and its comparison to FISH in Egyptian patients can show whether ERG immunophenotype could be used instead of FISH, as it is cheaper.MATERIALS AND METHODS:This study was performed on 85 cases of PCa, showing 30 cases with HGPIN and 30 cases of prostatic hyperplasia. All were immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC TMRPSS2-ERG).RESULTS:ERG expression was found in 26% of PCa cases and 20% of HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases showing ERG immunoexpression).CONCLUSION:Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

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Predicting high-risk disease using tissue biomarkers

Cited by 19 publications

References 38 publications

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

Recent advances in prostate cancer pathology: Gleason grading and beyond

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

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