John R Goepel

The University of Sheffield, Sheffield, England, United Kingdom

Are you John R Goepel?

Claim your profile

Publications (9)47.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: AimThere is increasing evidence of Gleason score (GS) drift in prostatic core biopsies over the last 2 decades. The ProtecT study is a randomised controlled study and it provides an excellent cohort to study the effect of time, PSA level, perineural invasion, tumour length and age on GS.Methods and resultsThe ProtecT study recruited men in the UK between 1999 and 2010. The Gleason scores were grouped into four categories ≤3+3, 3+4, 4+3 and ≥4+4 for analysis. Data from England between 2000 and 2012 were also available. A total of 3282 biopsies containing cancer were analyzed. For each year of the ProtecT study, the odds of being diagnosed with a higher GS category increased by 4.9%. Higher GS was also associated with perineural invasion, increasing tumour length, age and PSA level. Whilst biopsy GS was incomplete from England it also showed a marked decrease in GS 5 and 6 tumours over the same period.Conclusion There was GS drift from 3+3 to 3+4 with time in the ProtecT study, but there appeared to be no significant change in percentage of GS 4+3 or higher. This drift was less dramatic when compared to GS in the rest of England.This article is protected by copyright. All rights reserved.
    Histopathology 09/2014; · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: To determine the risk of disease specific mortality (DSM) in patients with primary low-risk non-invasive (G1pTa) bladder cancer. To compare this to DSM for age and gender matched general populations. PATIENTS AND METHODS: We identified all patients with primary low-risk cancer at our institution. We excluded those with adverse pathological features and matched histopathology, pharmacy, hospital episode and Cancer Registry records. We reviewed case notes for patients with subsequent muscle invasion (progression) or DSM. Patients underwent post-resection surveillance and treatment using standard regimens. The national and regional DSM rates were calculated from appropriate data. RESULTS: In total, 699 patients met our inclusion criteria (median follow up 61 months (IQ range 24-105)). Seventeen patients (2.4%) died from bladder cancer, including 13/14 that progressed to muscle invasion and 4/19 with grade-progression to high-grade non-muscle invasive disease. Low-grade dysplasia in the initial resection specimen and tumor weight were associated with DSM (Cox regression analyses p<0.003). DSM in these patients was 5 times the background rate for matched populations. Limitations to this study include its retrospective nature and the low frequency of adverse events. CONCLUSIONS: Patients with low risk bladder cancer rarely progress to muscle invasion but do have a higher risk of DSM than the general population. Current surveillance regimens appeared ineffective in detecting progression in time to alter prognosis.
    The Journal of urology 09/2012; · 3.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The treatment of high-risk non-muscle-invasive bladder cancer (BCa) is problematic given the variable natural history of the disease. Few reports have compared outcomes for primary high-risk tumours with those that develop following previous BCas (relapses). The latter represent a self-selected cohort, having failed previous treatments. OBJECTIVE: To compare outcomes in patients with primary, progressive, and recurrent high-risk non-muscle-invasive BCa. DESIGN, SETTING, AND PARTICIPANTS: We identified all patients with primary and relapsing high-risk BCa tumours at our institution since 1994. Relapses were divided into progressive (previous low- or intermediate-risk disease) and recurrent (previous high-risk disease) cancers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcome analysed using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: We identified 699 primary, 110 progressive, and 494 recurrent high-risk BCa tumours in 809 patients (average follow-up: 59 mo [interquartile range: 6-190]). Muscle invasion occurred most commonly in recurrent (23%) tumours, when compared to progressive (20%) and primary (14.6%) cohorts (log rank p<0.001). Disease-specific mortality (DSM) occurred more frequently in patients with recurrent (25.5%) and progressive (24.6%) tumours compared to primary disease (19.2%; log rank p=0.006). Other-cause mortality was similar in all groups (log rank p=0.57), and overall mortality was highest in the progressive cohort (62%) compared with the recurrent (58%) and primary groups (54%; log rank p<0.001). In multivariable analysis, progression and DSM were predicted by tumour grouping (hazard ratio [HR]: >1.15; p<0.026), stage (HR: >1.30; p<0.001), and patient age and sex (HR: >1.03; p<0.037). Carcinoma in situ was only predictive of outcome in primary tumors. Limitations include retrospective design and limited details regarding bacillus Camille-Guérin use. CONCLUSIONS: Patients with relapsing, high-risk, BCa tumors have higher progression, DSM, and overall mortality rates than those with primary cancers. The use of bladder-sparing strategies in these patients should approached cautiously. Carcinoma in situ has little predicative role in relapsing, high-risk, BCa tumors.
    European Urology 09/2012; · 10.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single-center series. METHODS: The authors reviewed all patients with primary, high-risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow-up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log-rank analysis (2-sided; P < .05). RESULTS: In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%-18.3%) at a median of 17.2 months (interquartile range, 8.9-35.8 months), including 26.5% (95% CI, 22.2%-31.3%) of the 366 patients who had >5 years follow-up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease-specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%-21.9%) at a median of 28 months (interquartile range, 15-45 months), including 28.7% (95% CI, 24.5%-33.3%) of those who had 5 years of follow-up. Disease-specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease-specific mortality were associated with the receipt of bacillus Calmette-Guerin (P > .6). CONCLUSIONS: Within a program of conservative treatment, progression of high-risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette-Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease. Cancer 2012;. © 2012 American Cancer Society.
    Cancer 04/2012; · 5.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38-66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.
    British Journal of Cancer 08/2011; 105(7):931-7. · 5.08 Impact Factor
  • Ewa Dudziec, John R Goepel, James W F Catto
    [Show abstract] [Hide abstract]
    ABSTRACT: Urothelial carcinoma of the bladder is a common disease that arises from two distinct molecular pathways, and is one of the most expensive malignancies to manage. Accurate biomarkers that could detect tumor recurrence or predict future progression would improve the care of patients and reduce the cost of managing the disease. DNA methylation, histone modification and ncRNA expression are important epigenetic mechanisms that regulate the expression of genes. These regulatory mechanisms are altered with bladder cancer, and therefore, represent potential biomarkers and therapeutic targets owing to the reversible nature of their modification. In this article, we will discuss these epigenetic changes in bladder cancer and assess their clinical potential.
    Epigenomics 02/2011; 3(1):35-45. · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the feasibility of testing for prostate cancer and the prevalence and characteristics of the disease in unselected young men. Prospective cohort nested within a randomised controlled trial, with two years of follow-up. Eight general practices in a UK city. 1299 unselected men aged 45-49. Prostate biopsies for participants with a prostate specific antigen level of 1.5 ng/ml or more and the possibility of randomisation to three treatments for those with localised prostate cancer. Uptake of testing for prostate specific antigen; positive predictive value of prostate specific antigen; and prevalence of prostate cancer, TNM disease stage, and histological grade (Gleason score). 442 of 1299 men agreed to be tested for prostate specific antigen (34%) and 54 (12%) had a raised level. The positive predictive value for prostate specific antigen was 21.3%. Ten cases of prostate cancer were detected (2.3%) with eight having at least two positive results in biopsy cores and three showing perineural invasion. One tumour was of high volume (cT2c), Gleason score 7, with a positive result on digital rectal examination; nine tumours were cT1c, Gleason score 6, and eight had a negative result on digital rectal examination. Five of the nine eligible participants (55%) agreed to be randomised. No biochemical disease progression in the form of a rising prostate specific antigen level occurred in two years of follow-up. Men younger than 50 will accept testing for prostate cancer but at a much lower rate than older men. Using an age based threshold of 1.5 ng/ml, the prevalence of prostate cancer was similar to that in older men (3.0 ng/ml threshold) and some cancers of potential clinical significance were found. Current Controlled Trials ISRCTN20141297.
    BMJ (online) 01/2008; 335(7630):1139. · 17.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Systems thinking is a set of methodologies that facilitate analysis and predictions for a complex system in a holistic way. Prostate cancer has precursor stages that are difficult to detect and a number of different therapy options for different stages, so it is a complex disease to manage within healthcare systems. In this review we show how systems thinking, especially causal loop diagrams, can be a very valuable tool for gaining greater insight into the pathogenesis and diagnosis of prostate cancer and to predict the consequences in major changes in the pattern of healthcare for this disease, e.g. introduction of national screening programmes using serum prostate specific antigen. The systems thinking approach can be used to predict changes in histopathology workflow when other parts of the system are changed.
    Diagnostic Histopathology. 01/2008;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of TMPRSS2 fusions in prostate is the most significant advance in the molecular pathology of prostate cancer in the past 10 years. In the 2 years since this discovery was first described there has been a large amount of research investigating the detailed mechanisms, prognostic significance and diagnostic utility of these chromosomal aberrations. Taking the numbers from the 10 large published series in aggregate, TMPRSS2 fusions occur in 49% of localised prostate cancers. TMPRSS2 fusion-positive prostate cancers have a significantly worse prognosis than TMPRSS2 fusion-negative prostate cancers and certain subtypes of TMPRSS2 fusions (e.g. ‘2+Edel’) have a significantly worse prognosis within TMPRSS2 fusion-positive cancers. There are five morphological features associated with TMPRSS2 fusion-positive cancers (blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, signet-ring cell features) and if three or more of these are present there is a strong (93%) positive predictive value of the genetic abnormality. TMPRSS2 fusions are easily detected by a break-apart fluorescence in situ hybridisation assay so if the adverse prognostic significance of these fusions becomes a clinically useful datum then histopathology departments will be involved in this testing in collaboration with cytogenetics services.
    Diagnostic Histopathology. 01/2008;