Clinical Versus Pathologic Staging for Prostate Adenocarcinoma

Cooke, Ellen W.; Shrieve, Dennis C.; Tward, Jonathan D.

doi:10.1097/coc.0b013e31821241fc

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…Improved antibodies have led to the use of IHC in the evaluation of PTEN expression as a surrogate for PTEN deletions and point mutations, and IHC fits the work‐flow of diagnostic pathology and can be readily deployed at modest cost . However, interphase FISH analyses can be performed on less than 100 tumor cells, so it is now feasible to obtain clinically useful genetic information such as PTEN status by applying FISH to tumor tissue in needle core biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, these recent data using needle core biopsies and the findings of this present manuscript draw attention to the value of PTEN as a predictive biomarker for intermediate risk prostate cancer and suggest a possible clinical workflow for assessing PTEN status. For example, initial analyses of PTEN expression could be carried out using immunohistochemistry with established methods . Regions of tumor or suspicious areas in the biopsy that are PTEN weak or otherwise indeterminate by IHC could then readily be studied by FISH using the refined probes we describe.…”

Section: Discussionmentioning

confidence: 99%

“…The vast majority of biopsies are scored as either Gleason 6 or 7 and yet up grading or down grading occurs in 14–51% and 9%, respectively when comparing the Gleason score of the biopsy to that found in the prostatectomy specimen . Likewise, clinical stage poorly estimates final pathological stage , an important predictor of clinical outcome, second only to Gleason score . There is a need for biomarkers that distinguish aggressive from indolent forms of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

et al. 2015

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BACKGROUNDLoss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study.METHODSWe used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up.RESULTSIn 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03).CONCLUSIONPTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. Prostate 75: 1206–1215, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

et al. 2015

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“…Prognostically important discordance between clinical and pathologic staging has been shown for lung and prostate cancer and affects the interpretation of studies that compare radical surgery to alternative treatments without a primary resectional component [21,22]. In bladder cancer, survival outcomes of BPT appear worse if adjusted for ‘SEER’ tumor stage because of systematic stage misclassification.…”

Section: Discussionmentioning

confidence: 99%

Radical Cystectomy versus Bladder-Preserving Therapy for Muscle-Invasive Urothelial Carcinoma: Examining Confounding and Misclassification Biasin Cancer Observational Comparative Effectiveness Research

et al. 2013

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Objectives Radical cystectomy (RC) is the standard treatment for muscle-invasive Urothelial carcinoma of the bladder (UCB). Tri-modality bladder preserving therapy (BPT) is an alternative to RC, but randomized comparisons of RC versus BPT have proven infeasible. To compare RC versus BPT, we undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. Methods We identified patients age 65 years or older diagnosed between 1995 and 2005 who received RC (n=1,426) or BPT (n=417). We examined confounding and stage misclassification in the comparison of RC and BPT using multivariable adjustment, propensity score-based adjustment, instrumental variable (IV) analysis and simulations. Results Patients who received BPT were older and more likely to have comorbid disease. After propensity score adjustment, BPT was associated with an increased hazard of death from any cause (HR 1.26; 95% CI, 1.05 – 1.53) and from bladder cancer (HR 1.31; 95% CI, 0.97 – 1.77). Using the local area cystectomy rate as an instrument, IV analysis demonstrated no differences in survival between BPT and RC (death from any cause HR 1.06; 95% CI, 0.78 – 1.31; death from bladder cancer HR 0.94; 95% CI, 0.55 – 1.18). Simulation studies for stage misclassification yielded results consistent with the IV analysis. Conclusions Survival estimates in an observational cohort of patients who underwent RC versus BPT differ by analytic method. Multivariable and propensity score adjustment revealed greater mortality associated with BPT relative to RC, while IV analysis and simulation studies suggest that the two treatments are associated with similar survival outcomes.

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“…T-stage was the weakest predictor in the PREDICT model. T-stage and also tumor grading are known to be subject to understanding by random (and extended) biopsies and digital rectal examination/transrectal ultrasound when compared to post-prostatectomy pathology results [ 27 , 28 ]. Adding MRI-based T-staging may increase the predictive accuracy of a predictive model.…”

Section: Discussionmentioning

confidence: 99%

PREDICT: model for prediction of survival in localized prostate cancer

et al. 2015

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PurposeCurrent models for prediction of prostate cancer-specific survival do not incorporate all present-day interventions. In the present study, a pre-treatment prediction model for patients with localized prostate cancer was developed. MethodsFrom 1989 to 2008, 3383 patients were treated with I-125 brachytherapy (n = 1694), external beam radiotherapy (≥74 Gy, n = 336) or radical prostatectomy (n = 1353). Pre-treatment parameters (clinical T-stage, biopsy grade, PSA and age) were related to the hazard of mortality by multivariate Cox proportional hazard analysis. The PRetreatment Estimation of the risk of Death In Cancer of the prosTate (PREDICT) model was developed. The predictive accuracy of the model was assessed by calibration and discrimination and compared to the Ash risk classification system.ResultsOf the 3383 patients analyzed, 2755 patients (81 %) were alive at the end of follow-up, 149 patients (4 %) died of prostate cancer and 365 patients (11 %) died of other causes, and for 114 patients (3 %) cause of death was unknown. Median follow-up time was 7.6 years. After correction for overoptimism, the c-statistic of the prediction model for prostate cancer-specific mortality was 0.78 (95 % CI 0.74–0.82), compared to 0.78 (95 % CI 0.75–0.81) for the risk classification system by Ash et al. The PREDICT model showed better calibration than the Ash risk classification system.ConclusionsThe PREDICT model showed a good predictive accuracy and reliability. The PREDICT model might be a promising tool for physicians to predict disease-specific survival prior to any generally accepted intervention in patients with localized prostate cancer.

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Clinical Versus Pathologic Staging for Prostate Adenocarcinoma

Abstract: Pathologic staging results in higher risk stratification than that predicted by clinical criteria in the majority of patients. Nodal positivity at diagnosis is uncommon in the current era, and the Roach formula overestimates the actual risk of node-positive disease.

Cited by 7 publications

References 25 publications

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

Radical Cystectomy versus Bladder-Preserving Therapy for Muscle-Invasive Urothelial Carcinoma: Examining Confounding and Misclassification Biasin Cancer Observational Comparative Effectiveness Research

PREDICT: model for prediction of survival in localized prostate cancer

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