Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

Vergis, Roy; Corbishley, Catherine M.; Thomas, Karen; Horwich, A.; Huddart, Robert; Khoo, Vincent; Eeles, Rosalind; Sydes, Matthew R.; Cooper, Christopher S.; Dearnaley, David P.; Parker, Chris

doi:10.1016/j.ijrobp.2009.07.1728

Cited by 27 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many biomarkers have shown association with Gleason score and some have also been associated with outcome after radical treatment (D'Amico et al , 2008; Vergis et al , 2010; Kristiansen, 2012), but comparatively little work has been done on cohorts of prostate cancer managed conservatively, especially when the diagnosis was made by a needle biopsy where tissue is limited.…”

mentioning

confidence: 99%

Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort

et al. 2013

View full text Add to dashboard Cite

Background:Standard clinical parameters cannot accurately differentiate indolent from aggressive prostate cancer. Our previous work showed that immunohistochemical (IHC) Ki-67 improved prediction of prostate cancer death in a cohort of conservatively treated clinically localised prostate cancers diagnosed by transurethral resection of the prostate (TURP). Here, we present results in a more clinically relevant needle biopsy cohort.Methods:Biopsy specimens were microarrayed. The percentage of Ki-67 positively stained malignant cells per core was measured and the maximum score per individual used in analysis of time to death from prostate cancer using a Cox proportional hazards model.Results:In univariate analysis (n=293), the hazard ratio (HR) (95% confidence intervals) for dichotomous Ki-67 (⩽10%, >10%) was 3.42 (1.76, 6.62) χ2 (1 df)=9.8, P=0.002. In multivariate analysis, Ki-67 added significant predictive information to that provided by Gleason score and prostate-specific antigen (HR=2.78 (1.42, 5.46), χ2 (1 df)=7.0, P=0.008).Conclusion:The IHC Ki-67 scoring on prostate needle biopsies is practicable and yielded significant prognostic information. It was less informative than in the previous TURP cohort where tumour samples were larger and more comprehensive, but in more contemporary cohorts with larger numbers of biopsies per patient, Ki-67 may prove a more powerful biomarker.

show abstract

mentioning

confidence: 99%

Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Vergis et al 46 showed that overexpression of the antiapoptosis gene BCL2 is a significant, independent determinant of decreased biochemical control after ADT-IGRT (P <0.001) and suggested that BCL2 positive patients should have dose-escalation (for example 74 Gy) to offset the radioresistant phenotype in apoptosisresistant prostate cancers. However, this observation is yet to be validated by other groups and is not in clinical use during IGRT alone, or in combination with ADT.…”

Section: Occult Metastases and Adt-igrtmentioning

confidence: 99%

Synergistic action of image-guided radiotherapy and androgen deprivation therapy

et al. 2015

View full text Add to dashboard Cite

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

show abstract

“…Two additional non-RTOG tissue biomarker studies using patient samples from randomized dose escalation studies conducted by the Medical Research Council (MRC) from the United Kingdom will also be reviewed [159, 160]. The MRC RT01 trial (n=843) and the phase II pilot predecessor trial (n=127) were almost identical in design.…”

Section: Select Non-rtog Prostate Cancer Tissue Biomarker Studiesmentioning

confidence: 99%

Tissue Biomarkers for Prostate Cancer Radiation Therapy

Tran¹,

Hales²,

Zeng³

et al. 2012

CMM

View full text Add to dashboard Cite

Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissue-based molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy.

show abstract

Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

Cited by 27 publications

References 41 publications

Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort

Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort

Synergistic action of image-guided radiotherapy and androgen deprivation therapy

Tissue Biomarkers for Prostate Cancer Radiation Therapy

Contact Info

Product

Resources

About