Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
1.
Urol Oncol ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33563540

RESUMO

PURPOSE: To investigate the value of second-opinion evaluation of multiparametric prostate magnetic resonance imaging (MRI) by subspecialised uroradiologists for the detection of significant cancer in transperineal fusion prostate biopsy. METHODS: The evaluated data included age, PSA (ng/ml), PSA density, Gleason score, digital rectal examination (DRE), prostate volume of 149 patients. Twenty-seven patients (18%) had no previous prostate biopsy, 114 patients (77%) had a previous negative biopsy, and 8 patients (5%) were on active surveillance. Using PI-RADS v2 scores for mpMRI a second report was performed by a specialist uroradiologist. In all cases a subsequent transperineal biopsy was performed with at least 2 cores per target and additional background systemic cores. Initial and second-opinion radiology reports were evaluated for detection of any cancer and Gleason score (GS) 7-10 cancer, including positive predictive value and negative (NPV) and compared by Fisher's exact test. RESULTS: At transperineal biopsy, 51 % (76/149) of patients had a GS 6-10 prostate cancer (PCa), 27 % (40/149) of patients had a GS 3 + 3 PCa and 12 % (18/149) a GS 3 + 4 and 12 % (18/149) had a GS ≥4 + 3 PCa. Agreement between initial and second-opinion reads was observed in 57.7% (86/149; kappa value = 0.32). The detection of clinically significant cancers with second-opinion reads was significantly higher (0.61; 17/28) compared to initial reads (0.35; 17/49); P = 0.034. CONCLUSIONS: Second reading of prostate mpMRIs by subspecialised uroradiologists significantly improved the positive predictive value for detection of clinically significant prostate cancer and showed a trend towards improved NPV for MRI-negative cases where biopsy could be safely avoided. Urologists should be aware that the experience of the reporter will affect the report when making decisions if and how to obtain biopsies. Reporter experience may help to reduce overcalling and avoid over-targeting of lesions.

2.
J Urol ; : 101097JU0000000000001700, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33617330

RESUMO

PURPOSE: To identify and validate known predictors of disease reclassification at 1 or 4 year(s) to support risk-based selection of patient suitable for AS. MATERIALS AND METHODS: An individual participant data meta-analysis using data from 25 established cohorts within the Movember Foundations GAP3 consortium. In total 5,530 men were included. Disease reclassification was defined as any increase in Gleason grade group (GGG) at biopsy at 1 and 4 years. Associations were estimated using random effect logistic regression models. The discriminative ability of combinations of predictors was assessed in an internal-external validation procedure using the area under the ROC (AUC). RESULTS: Among the 5,570 men evaluated at 1 year, we found 815 reclassifications to higher GGG at biopsy (pooled reclassification rate 13%, range 0%-31%). Important predictors were age, prostate-specific antigen (PSA), prostate volume, T-stage, and number of biopsy cores with PCa. Among the 1,515 men evaluated at 4 years, we found 205 reclassifications (pooled reclassification rates 14%, range 3%-40%), with similar predictors. The average AUCs at internal-external validation were 0.68 and 0.61 for 1 and 4-year reclassification respectively. CONCLUSIONS: Disease reclassification occurs typically in 13-14% of biopsies at 1 and 4 years after start of AS, with substantial between study heterogeneity. Current guidelines might be extended by considering prostate volume to improve individualized selection for AS. Additional predictors are needed to improve patient selection for AS.

3.
Lancet Digit Health ; 3(3): e158-e165, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33549512

RESUMO

BACKGROUND: Accurate prognostication is crucial in treatment decisions made for men diagnosed with non-metastatic prostate cancer. Current models rely on prespecified variables, which limits their performance. We aimed to investigate a novel machine learning approach to develop an improved prognostic model for predicting 10-year prostate cancer-specific mortality and compare its performance with existing validated models. METHODS: We derived and tested a machine learning-based model using Survival Quilts, an algorithm that automatically selects and tunes ensembles of survival models using clinicopathological variables. Our study involved a US population-based cohort of 171 942 men diagnosed with non-metastatic prostate cancer between Jan 1, 2000, and Dec 31, 2016, from the prospectively maintained Surveillance, Epidemiology, and End Results (SEER) Program. The primary outcome was prediction of 10-year prostate cancer-specific mortality. Model discrimination was assessed using the concordance index (c-index), and calibration was assessed using Brier scores. The Survival Quilts model was compared with nine other prognostic models in clinical use, and decision curve analysis was done. FINDINGS: 647 151 men with prostate cancer were enrolled into the SEER database, of whom 171 942 were included in this study. Discrimination improved with greater granularity, and multivariable models outperformed tier-based models. The Survival Quilts model showed good discrimination (c-index 0·829, 95% CI 0·820-0·838) for 10-year prostate cancer-specific mortality, which was similar to the top-ranked multivariable models: PREDICT Prostate (0·820, 0·811-0·829) and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram (0·787, 0·776-0·798). All three multivariable models showed good calibration with low Brier scores (Survival Quilts 0·036, 95% CI 0·035-0·037; PREDICT Prostate 0·036, 0·035-0·037; MSKCC 0·037, 0·035-0·039). Of the tier-based systems, the Cancer of the Prostate Risk Assessment model (c-index 0·782, 95% CI 0·771-0·793) and Cambridge Prognostic Groups model (0·779, 0·767-0·791) showed higher discrimination for predicting 10-year prostate cancer-specific mortality. c-indices for models from the National Comprehensive Cancer Care Network, Genitourinary Radiation Oncologists of Canada, American Urological Association, European Association of Urology, and National Institute for Health and Care Excellence ranged from 0·711 (0·701-0·721) to 0·761 (0·750-0·772). Discrimination for the Survival Quilts model was maintained when stratified by age and ethnicity. Decision curve analysis showed an incremental net benefit from the Survival Quilts model compared with the MSKCC and PREDICT Prostate models currently used in practice. INTERPRETATION: A novel machine learning-based approach produced a prognostic model, Survival Quilts, with discrimination for 10-year prostate cancer-specific mortality similar to the top-ranked prognostic models, using only standard clinicopathological variables. Future integration of additional data will likely improve model performance and accuracy for personalised prognostics. FUNDING: None.

4.
Br J Cancer ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33288843

RESUMO

Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation.

5.
Int J Clin Pract ; : e13977, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33369808

RESUMO

AIMS: To evaluate the diagnostic yield of investigations performed on patients with a history of urinary tract infections (UTI). METHODS: A retrospective review was conducted on patients who underwent cystoscopy and imaging for a history of UTI between 2014 and 2019 in a single UK teaching hospital. Data were collected on demographics, cystoscopy and radiological findings requiring further management. The cohort was stratified by age, gender and a confirmed history of recurrent UTI (rUTI). The subsequent algorithm was re-tested in a second cohort to validate its use. RESULTS: Seven hundred patients were included in the primary analysis-427 female and 273 males. Three hundred and thirty-one met the criteria of rUTI. The median age was 64 years (18-97). Imaging abnormalities were equally frequent in men 6.3% (15/241) and women 8% (30/380) and the majority noted in patients aged ≥55 years, 30/45 (66.7%). Amongst those who did not meet the definition of rUTI, abnormal imaging was identified in 5%-7% regardless of age group and gender. Cystoscopy abnormalities (n = 24) were twice more likely in males, 5.5%(15/273) than females, 2%(9/427). About 88%(21/24) were identified in patients ≥55 years. There were no positive findings in women <55 years. Applying baseline imaging but confining cystoscopy to those aged ≥55 years and men with a confirmed history of rUTI would have saved 44% of procedures, missed no abnormalities with an overall diagnosis detection rate of 9.8% (69/700). This algorithm was validated in a separate cohort of 63 patients; applying it would have saved 46% (29/63) of cystoscopies with a positive diagnostic rate of 9.5% and no missed findings. CONCLUSION: To our knowledge this is one of the largest studies reporting the outcomes of investigations for UTI and rUTI. Our result suggests that imaging is a useful baseline assessment, but cystoscopy should be limited to specific subgroups. We propose and validate a simple decision algorithm to manage investigations for referrals for UTI in secondary care.

6.
Eur Radiol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196886

RESUMO

OBJECTIVES: To assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS). METHODS: A total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS. RESULTS: Progression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74-0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05). CONCLUSION: The PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS. KEY POINTS: • PRECISE scores 1-3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4-5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time.

7.
Sci Rep ; 10(1): 20475, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33235229

RESUMO

Magnetic resonance fingerprinting (MRF) is a rapidly developing fast quantitative mapping technique able to produce multiple property maps with reduced sensitivity to motion. MRF has shown promise in improving the diagnosis of clinically significant prostate cancer but requires further validation as part of a prostate multiparametric (mp) MRI protocol. mpMRI protocol mandates the inclusion of dynamic contrast enhanced (DCE) imaging, known for its significant T1 shortening effect. MRF could be used to measure both pre- and post-contrast T1 values, but its utility must be assessed. In this proof-of-concept study, we sought to evaluate the variation in MRF T1 measurements post gadolinium-based contrast agent (GBCA) injection and the utility of such T1 measurements to differentiate peripheral and transition zone tumours from normal prostatic tissue. We found that the T1 variation in all tissues increased considerably post-GBCA following the expected significant T1 shortening effect, compromising the ability of MRF T1 to identify transition zone lesions. We, therefore, recommend performing MRF T1 prior to DCE imaging to maintain its benefit for improving detection of both peripheral and transition zone lesions while reducing additional scanning time. Demonstrating the effect of GBCA on MRF T1 relaxometry in patients also paves the way for future clinical studies investigating the added value of post-GBCA MRF in PCa, including its dynamic analysis as in DCE-MRF.

8.
J Clin Urol ; 13(5): 364-370, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33072331

RESUMO

Objectives: To report the prospective multicentre clinical evaluation of a first-in-man disposable device, Cambridge Prostate Biopsy Device, to undertake local anaesthetic outpatient transperineal prostate biopsies. Material and methods: Disposable single-use Cambridge Prostate Biopsy devices were manufactured based on a previous prototype. The lead site developed a user training course and disseminated the method to other sites. The Cambridge Prostate Biopsy Device (CamPROBE) was offered as an alternative to transrectal ultrasound guided biopsy to men due for a biopsy as part of their clinical management. Data on safety (infections and device performance), clinical utility, patient reported experience, biopsy quality and cancer detection were collected. Procedure time and local anaesthetic use was recorded in the lead site. The study was funded by a United Kingdom National Institute for Health Research (NIHR) i4i product development award. Results: A total of 40 patients were recruited (median age 69 y) across six sites; five sites were new to the procedure. Overall, 19/40 were first prostate biopsies and 21/40 repeat procedures. Both image-targeted and systematic biopsy cores taken. There were no infections, device deficiencies or safety issues reported. The procedure was well tolerated with excellent patient-reported perception and low pain scores (median of 3, scale 0-10). Histopathology quality was good and the overall cancer diagnosis rate (first diagnostic procedures) was 68% (13/19) and for significant cancers (⩾ histological Grade Group 2), 47% (9/19). In the lead centre (most experienced), median procedure time was 25 minutes, and median local anaesthetic use 11 ml (n=17). Conclusions: Data from this device evaluation study demonstrate that the United Kingdom-developed Cambridge Prostate Biopsy Device/method for transperineal biopsies is safe, transferable and maintains high diagnostic yields. The procedure is well tolerated by patients, suited to the local anaesthetic outpatient setting and could directly replace transrectal ultrasound guided biopsy. Level of evidence: Level III.

9.
Science ; 370(6512): 75-82, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004514

RESUMO

The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted (n = 1914 microbiopsies), whole-exome (n = 655), and whole-genome (n = 88) sequencing. We found widespread positive selection in 17 genes. Chromatin remodeling genes were frequently mutated, whereas mutations were absent in several major bladder cancer genes. There was extensive interindividual variation in selection, with different driver genes dominating the clonal landscape across individuals. Mutational signatures were heterogeneous across clones and individuals, which suggests differential exposure to mutagens in the urine. Evidence of APOBEC mutagenesis was found in 22% of the microbiopsies. Sequencing multiple microbiopsies from five patients with bladder cancer enabled comparisons with cancer-free individuals and across histological features. This study reveals a rich landscape of mutational processes and selection in normal urothelium with large heterogeneity across clones and individuals.


Assuntos
Genes Neoplásicos , Mutagênese , Seleção Genética , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária/patologia , Urotélio/patologia , Desaminases APOBEC/genética , Adulto , Idoso , Biópsia , Montagem e Desmontagem da Cromatina/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênicos/análise , Mutação
10.
BMJ Open ; 10(9): e036024, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907896

RESUMO

OBJECTIVES: Active surveillance (AS) enables men with low risk, localised prostate cancer (PCa) to avoid radical treatment unless progression occurs; lack of reliable AS protocols to determine progression leaves uncertainties for men and clinicians. This study investigated men's strategies for coping with the uncertainties of active monitoring (AM, a surveillance strategy within the Prostate testing for cancer and Treatment, ProtecT trial) over the longer term and implications for optimising supportive care. DESIGN: Longitudinal serial in-depth qualitative interviews every 2-3 years for a median 7 (range 6-14) years following diagnosis. SETTING: Four centres within the UK Protect trial. PARTICIPANTS: Purposive sample of 20 men with localised PCa: median age at diagnosis 64 years (range 52-68); 15 (75%) had low-risk PCa; 12 randomly allocated to, 8 choosing AM. Eleven men continued with AM throughout the study period (median 7 years). Nine received radical treatment after a median 4 years (range 0.8-13.8 years). INTERVENTION: AM: 3-monthly serum prostate-specific antigen (PSA)-level assessment (year 1), 6-12 monthly thereafter; increase in PSA ≥50% during previous 12 months or patient/clinician concern triggered review. MAIN OUTCOMES: Thematic analysis of 73 interviews identified strategies to accommodate uncertainty and anxiety of living with untreated cancer; implications for patient care. RESULTS: Men sought clarity, control or reassurance, with contextual factors mediating individual responses. Trust in the clinical team was critical for men in balancing anxiety and facilitating successful management change/continued monitoring. Only men from ProtecT were included; men outside ProtecT may have different experiences. CONCLUSION: Men looked to clinicians for clarity, control and reassurance. Where provided, men felt comfortable continuing AM or having radical treatments when indicated. Clinicians build patient trust by clearly describing uncertainties, allowing patients control wherever possible and being aware of how context influences individual responses. Insights indicate need for supportive services to build trust and patient engagement over the long term. TRIAL REGISTRATION NUMBER: ISRCTN20141297; Pre-results.

11.
J Natl Cancer Inst ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853339

RESUMO

BACKGROUND: There is an urgent need to identify factors specifically associated with aggressive prostate cancer (PCa) risk. We investigated whether rare pathogenic, likely pathogenic, or deleterious (P/LP/D) germline variants in DNA repair genes are associated with aggressive PCa risk in a case-case study of aggressive versus non-aggressive disease. METHODS: Participants were 5,545 European-ancestry men, including 2,775 non-aggressive and 2,770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Samples were assembled from 12 international studies and germline sequenced together. Rare (minor allele frequency<0.01) P/LP/D variants were analyzed for 155 DNA repair genes. We compared single variant, gene-based, and DNA repair pathway-based burdens by disease aggressiveness. All statistical tests are two-sided. RESULTS: BRCA2 and PALB2 had the most statistically significant gene-based associations, with 2.5% of aggressive and 0.8% of non-aggressive cases carrying P/LP/D BRCA2 alleles (OR = 3.19, 95% CI = 1.94 to 5.25, P = 8.58x10-7) and 0.65% of aggressive and 0.11% of non-aggressive cases carrying P/LP/D PALB2 alleles (OR = 6.31, 95% CI = 1.83 to 21.68, P = 4.79x10-4). ATM had a nominal association, with 1.6% of aggressive and 0.8% of non-aggressive cases carrying P/LP/D ATM alleles (OR = 1.88, 95% CI = 1.10 to 3.22, P=.02). In aggregate, P/LP/D alleles within 24 literature-curated candidate PCa DNA repair genes were more common in aggressive than non-aggressive cases (carrier frequencies=14.2% versus 10.6%, respectively; P = 5.56x10-5). However, this difference was statistically non-significant (P=.18) upon excluding BRCA2, PALB2, and ATM. Among these 24 genes, P/LP/D carriers had a 1.06-year younger diagnosis age (95% CI=-1,65 to 0.48, P = 3.71x10-4). CONCLUSIONS: Risk conveyed by DNA repair genes is largely driven by rare P/LP/D alleles within BRCA2, PALB2, and ATM. These findings support the importance of these genes in both screening and disease management considerations.

12.
Health Technol Assess ; 24(37): 1-176, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32773013

RESUMO

BACKGROUND: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. OBJECTIVES: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years. DESIGN: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. SETTING: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. PARTICIPANTS: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. INTERVENTIONS: The interventions were active monitoring, radical prostatectomy and radical radiotherapy. TRIAL PRIMARY OUTCOME MEASURE: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. SECONDARY OUTCOME MEASURES: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. RESULTS: There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). LIMITATIONS: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. CONCLUSIONS: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20141297. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

13.
Br J Cancer ; 123(7): 1063-1070, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32669672

RESUMO

BACKGROUND: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. METHODS: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. RESULTS: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. CONCLUSIONS: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

15.
Br J Radiol ; 93(1112): 20200298, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32479105

RESUMO

OBJECTIVE: To compare the performance of Likert and Prostate Imaging-Reporting and Data System (PI-RADS) multiparametric (mp) MRI scoring systems for detecting clinically significant prostate cancer (csPCa). METHODS: 199 biopsy-naïve males undergoing prostate mpMRI were prospectively scored with Likert and PI-RADS systems by four experienced radiologists. A binary cut-off (threshold score ≥3) was used to analyze histological results by three groups: negative, insignificant disease (Gleason 3 + 3; iPCa), and csPCa (Gleason ≥3 +4). Lesion-level results and prostate zonal location were also compared. RESULTS: 129/199 (64.8%) males underwent biopsy, 96 with Likert or PI-RADS score ≥3, and 21 with negative MRI. A further 12 patients were biopsied during follow-up (mean 507 days). Prostate cancer was diagnosed in 87/199 (43.7%) patients, 65 with (33.6%) csPCa. 30/92 (32.6%) patients with negative MRI were biopsied, with an NPV of 83.3% for cancer and 86.7% for csPCa. Likert and PI-RADS score differences were observed in 92 patients (46.2%), but only for 16 patients (8%) at threshold score ≥3. Likert scoring had higher specificity than PI-RADS (0.77 vs 0.66), higher area under the curve (0.92 vs 0.87, p = 0.002) and higher PPV (0.66 vs 0.58); NPV and sensitivity were the same. Likert had more five score results (58%) compared to PI-RADS (36%), but with similar csCPa detection (81.0 and 80.6% respectively). Likert demonstrated lower proportion of false positive in the predominately AFMS-involving lesions. CONCLUSION: Likert and PI-RADS systems both demonstrate high cancer detection rates. Likert scoring had a higher AUC with moderately higher specificity and lower positive call rate and could potentially help to reduce the number of unnecessary biopsies performed. ADVANCES IN KNOWLEDGE: This paper illustrates that the Likert scoring system has potential to help urologists reduce the number of prostate biopsies performed.


Assuntos
Imagem por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
BMC Med ; 18(1): 139, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32539712

RESUMO

BACKGROUND: PREDICT Prostate is an endorsed prognostic model that provides individualised long-term prostate cancer-specific and overall survival estimates. The model, derived from UK data, estimates potential treatment benefit on overall survival. In this study, we externally validated the model in a large independent dataset and compared performance to existing models and within treatment groups. METHODS: Men with non-metastatic prostate cancer and prostate-specific antigen (PSA) < 100 ng/ml diagnosed between 2000 and 2010 in the nationwide population-based Prostate Cancer data Base Sweden (PCBaSe) were included. Data on age, PSA, clinical stage, grade group, biopsy involvement, primary treatment and comorbidity were retrieved. Sixty-nine thousand two hundred six men were included with 13.9 years of median follow-up. Fifteen-year survival estimates were calculated using PREDICT Prostate for prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). Discrimination was assessed using Harrell's concordance (c)-index in R. Calibration was evaluated using cumulative available follow-up in Stata (TX, USA). RESULTS: Overall discrimination of PREDICT Prostate was good with c-indices of 0.85 (95% CI 0.85-0.86) for PCSM and 0.79 (95% CI 0.79-0.80) for ACM. Overall calibration of the model was excellent with 25,925 deaths predicted and 25,849 deaths observed. Within the conservative management and radical treatment groups, c-indices for 15-year PCSM were 0.81 and 0.78, respectively. Calibration also remained good within treatment groups. The discrimination of PREDICT Prostate significantly outperformed the EAU, NCCN and CAPRA scores for both PCSM and ACM within this cohort overall. A key limitation is the use of retrospective cohort data. CONCLUSIONS: This large external validation demonstrates that PREDICT Prostate is a robust and generalisable model to aid clinical decision-making.

17.
Nanoscale ; 12(17): 9647-9652, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32319508

RESUMO

Easy monitoring of prostate specific antigen (PSA) directly from blood samples would present a significant improvement as compared to conventional diagnostic methods. In this work, a split mode thin film bulk acoustic resonator (TFBAR) device was employed for the first time for label-free measurements of PSA concentrations in the whole blood and without sample pre-treatment. The surface of the sensor was covalently modified with anti-PSA antibodies and demonstrated a very high sensitivity of 101 kHz mL ng-1 and low limit of detection (LOD) of 0.34 ng mL-1 in model spiked solutions. It has previously been widely believed that significant pre-processing of blood samples would be required for TFBAR biosensors. Importantly, this work demonstrates that this is not the case, and TFBAR technology provides a cost-effective means for point-of-care (POC) diagnostics and monitoring of PSA in hospitals and in doctors' offices. Additionally, the accuracy of the developed biosensor, with respect to a commercial auto analyser (Beckman Coulter Access), was evaluated to analyse clinical samples, giving well-matched results between the two methods, thus showing a practical application in quantitative monitoring of PSA levels in the whole blood with very good signal recovery.

18.
BMC Med ; 18(1): 95, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32299423

RESUMO

BACKGROUND: The clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI (mpMRI pre-biopsy). mpMRI however remains a resource-intensive test and is highly operator dependent with variable effectiveness with regard to its negative predictive value. Here we tested the use of the phi assay in standard clinical practice to pre-select men at the highest risk of harbouring significant cancer and hence refine the use of mpMRI and biopsies. METHODS: A prospective five-centre study recruited men being investigated through an mpMRI-based prostate cancer diagnostic pathway. Test statistics for PSA, PSA density (PSAd) and phi were assessed for detecting significant cancers using 2 definitions: ≥ Grade Group (GG2) and ≥ Cambridge Prognostic Groups (CPG) 3. Cost modelling and decision curve analysis (DCA) was simultaneously performed. RESULTS: A total of 545 men were recruited and studied with a median age, PSA and phi of 66 years, 8.0 ng/ml and 44 respectively. Overall, ≥ GG2 and ≥ CPG3 cancer detection rates were 64% (349/545), 47% (256/545) and 32% (174/545) respectively. There was no difference across centres for patient demographics or cancer detection rates. The overall area under the curve (AUC) for predicting ≥ GG2 cancers was 0.70 for PSA and 0.82 for phi. AUCs for ≥ CPG3 cancers were 0.81 and 0.87 for PSA and phi respectively. AUC values for phi did not differ between centres suggesting reliability of the test in different diagnostic settings. Pre-referral phi cut-offs between 20 and 30 had NPVs of 0.85-0.90 for ≥ GG2 cancers and 0.94-1.0 for ≥ CPG3 cancers. A strategy of mpMRI in all and biopsy only positive lesions reduced unnecessary biopsies by 35% but missed 9% of ≥ GG2 and 5% of ≥ CPG3 cancers. Using PH ≥ 30 to rule out referrals missed 8% and 5% of ≥ GG2 and ≥ CPG3 cancers (and reduced unnecessary biopsies by 40%). This was achieved however with 25% fewer mpMRI. Pathways incorporating PSAd missed fewer cancers but necessitated more unnecessary biopsies. The phi strategy had the lowest mean costs with DCA demonstrating net clinical benefit over a range of thresholds. CONCLUSION: phi as a triaging test may be an effective way to reduce mpMRI and biopsies without compromising detection of significant prostate cancers.

19.
Eur Radiol ; 30(7): 4039-4049, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32166495

RESUMO

PURPOSE: To assess the added value of dynamic contrast-enhanced (DCE) in prostate MR in clinical practice. METHODS: Two hundred sixty-four patients underwent prostate MRI, with T2 and DWI sequences initially interpreted, prior to full multiparametric magnetic resonance imaging (mpMRI) interpretation using a Likert 1-5 scale. A prospective opinion was given on likely benefit of contrast prior to review of the DCE sequence, and retrospectively following full mpMRI review. The final histology result following targeted and/or systematic biopsy of the prostate was used for outcome purposes. RESULTS: Biparametric magnetic resonance imaging (bpMRI) and mpMRI were assigned the same score in 86% of cases; when dichotomising to a negative or positive MRI (Likert score ≥ 3), concordance increased to 92.8%. At Likert score ≥ 3 bpMRI detected 89.9% of all cancers and 93.5% clinically significant prostate cancers (csPCa) and mpMRI 90.7% and 94.6%, respectively. mpMRI had fewer false positives than bpMRI (11.4% vs 18.9%) and a lower Likert 3 rate (8.3% vs 17%), conferring higher specificity (74% vs 67%), but similar sensitivity (95% versus 94%) and ROC-AUC (90% vs 89%). At a positive MRI threshold of Likert ≥ 4, mpMRI had a higher sensitivity than bpMRI (89% versus 80%) and detected more csPCa (89.2% versus 79.6%). DCE was prospectively considered of potential benefit in 27.3%, but readers would only recall 11% of patients for DCE sequences, mainly to assess score 3 peripheral zone lesions. Following full mpMRI review, DCE was considered helpful in 28.4% of cases; in 23/75 (30.6%) of these cases this only became apparent after reviewing the sequence, reasons included increased confidence, presence of "safety-net" lesions or inflammatory lesions. CONCLUSION: BpMRI has equivalent cancer detection rates to mpMRI; however, mpMRI had fewer Likert 3 call rates and increased specificity and was subjectively considered of benefit by readers in 28.4% of cases. KEY POINTS: • bpMRI has similar cancer detection rates to the full mpMRI protocol at a positive MRI threshold of Likert 3. • mpMRI had fewer intermediate category 3 calls (8.3%) than bpMRI (17%) and fewer false positives than bpMRI (11.4% vs 18.9%), conferring higher specificity (74% vs 67%). • Readers considered DCE beneficial in 28.4% of cases, but in a relatively high number (30.6%) this only became apparent after reviewing the sequence.


Assuntos
Meios de Contraste/administração & dosagem , Imagem por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias da Próstata/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Br J Radiol ; 93(1108): 20190929, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31971823

RESUMO

OBJECTIVE: To introduce capped biparametric (bp) MRI slots for follow-up imaging of prostate cancer patients enrolled in active surveillance (AS) and evaluate the effect on weekly variation in the number of AS cases and total MRI workload. METHODS: Three 20 min bpMRI AS slots on two separate days were introduced at Addenbrooke's Hospital, Cambridge. The weekly numbers of total prostate MRIs and AS cases recorded 15 months before and after the change (Groups 1 and 2, respectively). An intergroup variation in the weekly scan numbers was assessed using the coefficient of variance (CV) and mean absolute deviation; the Mann-Whitney U test was used for an intergroup comparison of the latter. RESULTS: In AS patients, a shift from considerable to moderate variation in weekly scan numbers was observed between the two groups (CV, 51.7 and 26.8%, respectively); mean absolute deviation of AS scans also demonstrated a significant decrease in Group 2 (1.28 vs 2.58 in Group 1; p < 0.001). No significant changes in the variation in total prostate MRIs were observed, despite a 10% increased workload in Group 2. CONCLUSION: A significant reduction in weekly variation of AS cases was demonstrated following the introduction of capped bpMRI slots, which can be used for more accurate long-term planning of MRI workload. ADVANCES IN KNOWLEDGE: The paper illustrates the potential of introducing capped AS MRI slots using a bp protocol to reduce weekly variation in demand and allow for optimising workflow, which will be increasingly important as the demands on radiology departments increase worldwide.


Assuntos
Imagem por Ressonância Magnética/estatística & dados numéricos , Vigilância da População , Neoplasias da Próstata/diagnóstico por imagem , Carga de Trabalho/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...