Transrectal ultrasound-guided prostate biopsies are prone to detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic pathway.
PROMIS is a prospective validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinically-significant prostate cancer who are at risk prior to first biopsy. Up to 714 men will have MP-MRI (index), 10–12 core TRUS-biopsy (standard) and 5 mm transperineal template mapping (TPM) biopsies (reference). The conduct and reporting of each test will be blinded to the others.
PROMIS will measure and compare sensitivity, specificity, and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinically-significant cancers. For the primary outcome, significant cancer on TPM is defined as Gleason grade >/= 4 + 3 and/or maximum cancer core length of ≥ 6 mm. PROMIS will also assess inter-observer variability among radiologists among other secondary outcomes. Cost-effectiveness of MP-MRI prior to biopsy will also be evaluated.
PROMIS will determine whether MP-MRI of the prostate prior to first biopsy improves the detection accuracy of clinically-significant cancer.
Prostate cancer; Transrectal ultrasound guided biopsy; Template transperineal mapping biopsy; Magnetic resonance imaging; Multi-parametric MRI; Triage diagnostic test
To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD® Soluble in patients with localized prostate cancer (LPCa).
We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD® Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6.
Month 6 negative biopsy rate was 68.4 % in the overall evaluable population (N = 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function.
Focal VTP treatment with TOOKAD® Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.
Localized prostate cancer; Focal therapy; WST11 TOOKAD® Soluble; Vascular-targeted photodynamic therapy
Previous studies have suggested that there may be long-term harm associated with postoperative complications. Uncertainty exists however, because of the need for risk adjustment and inconsistent definitions of postoperative morbidity.
We did a longitudinal observational cohort study of patients undergoing major surgery. Case-mix adjustment was applied and morbidity was recorded using a validated outcome measure. Cox proportional hazards modelling using time-dependent covariates was used to measure the independent relationship between prolonged postoperative morbidity and longer term survival.
Data were analysed for 1362 patients. The median length of stay was 9 days and the median follow-up time was 6.5 yr. Independent of perioperative risk, postoperative neurological morbidity (prevalence 2.9%) was associated with a relative hazard for long-term mortality of 2.00 [P=0.001; 95% confidence interval (CI) 1.32–3.04]. Prolonged postoperative morbidity (prevalence 15.6%) conferred a relative hazard for death in the first 12 months after surgery of 3.51 (P<0.001; 95% CI 2.28–5.42) and for the next 2 yr of 2.44 (P<0.001; 95% CI 1.62–3.65), returning to baseline thereafter.
Prolonged morbidity after surgery is associated with a risk of premature death for a longer duration than perhaps is commonly thought; however, this risk falls with time. We suggest that prolonged postoperative morbidity measured in this way may be a valid indicator of the quality of surgical healthcare. Our findings reinforce the importance of research and quality improvement initiatives aimed at reducing the duration and severity of postoperative complications.
complications; complications, morbidity; complications, neurological; surgery, non-cardiac
Focal therapy offers the possibility of cancer control, without the side effect profile of radical therapies. Early single centre prospective development studies using high intensity focused ultrasound (HIFU) have demonstrated encouraging genitourinary functional preservation and short-term cancer control. Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery. We describe the study design of an investigator-led UK multi-centre, single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer.
One-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer (PSA < 15, Gleason ≤ 7, ≤ T2cN0M0) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping (TPM) biopsies. Unilateral dominant tumours, the so-called index lesion, will be eligible for treatment provided the contra-lateral side is free of ‘clinically significant’ disease (as defined by Gleason ≥ 7 or maximum cancer core length ≥ 4 mm). Patients will receive focal therapy using HIFU (Sonablate 500®). Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months.
Primary outcome is the absence of clinically significant disease based on 36-month post-treatment TPM biopsies. Secondary outcomes address a) genitourinary function using validated patient questionnaires (IPSS, IPSS-QoL, IIEF-15, EPIC-Urinary, EPIC-Bowel, FACT-P, EQ-5D), b) the predictive validity of imaging, and c) risk factors for treatment failure.
INDEX will be the first multi-centre, medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer using the TPM-ablate-TPM strategy.
Focal therapy; High-intensity focused ultrasound; Multi-centre; Prospective study; IDEAL guidelines
Focal therapy is an emerging treatment modality for localised prostate cancer that aims to reduce the morbidity seen with radical therapy, while maintaining cancer control. Focal therapy treatment strategies minimise damage to non-cancerous tissue, with priority given to the sparing of key structures such as the neurovascular bundles, external sphincter, bladder neck and rectum. There are a number of ablative technologies that can deliver energy to destroy cancer cells as part of a focal therapy strategy. The most widely investigated are cryotherapy and high-intensity focussed ultrasound. Existing radical therapies, such as brachytherapy and external beam radiotherapy, also have the potential to be applied in a focal manner. The functional outcomes of focal therapy from several phase I and II trials have been encouraging, with low rates of urinary incontinence and erectile dysfunction. Robust medium- and long-term cancer control outcomes are currently lacking. Controversies in focal therapy remain, notably treatment paradigms based on the index lesion hypothesis, appropriate patient selection for focal therapy and how the efficacy of focal therapy should be assessed. This review articles discusses the current status of focal therapy, highlighting controversies and emerging strategies that can influence treatment outcomes for the future.
Focal ablation; focal therapy; future perspective; outcomes; prostate cancer; rationale
This retrospective study compares dynamic contrast-enhanced (DCE) MRI with the serial prostate-specific antigen (PSA) measurement for detection of residual disease following whole-gland high-intensity focused ultrasound (HIFU) therapy of prostate cancer.
Patients in whom post-HIFU DCE-MRI was followed within 3 months by ultrasound-guided transrectal biopsy were selected from a local database. 26 patients met the study inclusion criteria. Serial PSA levels following HIFU and post-HIFU follow-up MRI were retrieved for each patient. Three radiologists unaware of other investigative results independently assessed post-HIFU MRI studies for the presence of cancer, scoring on a four-point scale (1, no disease; 2, probably no disease; 3, probably residual disease; and 4, residual disease). Sensitivity, specificity and receiver operating characteristic (ROC) analysis were performed for each reader, post-HIFU PSA nadir and pre-biopsy PSA level thresholds of >0.2 and >0.5 ng ml−1.
The sensitivity of DCE-MRI for detection of residual disease for the three readers ranged between 73% and 87%, and the specificity between 73% and 82%. There was good agreement between readers (κ=0.69–0.77). The sensitivity and specificity of PSA thresholds was 60–87% and 73–100%, respectively. The area under the ROC curve was greatest for pre-biopsy PSA (0.95).
DCE-MRI performed following whole-gland HIFU has similar sensitivity and specificity and ROC performance to serial PSA measurements for detection of residual or recurrent disease.
The use of minimally invasive ablative therapies in localised prostate cancer offer potential for a middle ground between active surveillance and radical therapy.
An analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between 1 February 2005 and 15 May 2007 was carried out in two centres. Outcome data (side-effects using validated patient questionnaires, biochemical, histology) were evaluated.
A total of 172 men were treated under general anaesthetic as day-case procedures with 78% discharged a mean 5 h after treatment. Mean follow-up was 346 days (range 135–759 days). Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs 40.4%, P=0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172) with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae. In all, 78.3% achieved a PSA nadir ⩽0.5 μg ml−1 at 12 months, with 57.8% achieving ⩽0.2 μg ml−1. Then, 8 out of 13 were retreated with HIFU, one had salvage external beam radiotherapy and four chose active surveillance for small-volume low-risk disease. Overall, there was no evidence of disease (PSA <0.5 μg ml−1 or negative biopsy if nadir not achieved) after one HIFU session in 92.4% (159 out of 172) of patients.
HIFU is a minimally invasive, day-case ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Long-term outcome needs further evaluation and the inception of an international registry for cases treated using HIFU will significantly aid this health technology assessment.
HIFU; high-intensity-focused ultrasound; transrectal; prostate cancer; Sonablate500
Benign prostatic hyperplasia (BPH) is a complex disease that is progressive in many men. BPH is commonly associated with bothersome lower urinary tract symptoms; progressive disease can also result in complications such as acute urinary retention (AUR) and BPH-related surgery. It is therefore important to identify men at increased risk of BPH progression to optimise therapy. Several factors are associated with progression, including age and prostate volume (PV). Serum prostate-specific antigen level is closely correlated with PV, making it useful for determining the risk of BPH progression. Medical therapy is the most frequently used treatment for BPH. 5-alpha-reductase inhibitors impact the underlying disease and decrease PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of Avodart® and Tamsulosin (CombAT) study is currently evaluating the combination of dutasteride with tamsulosin over 4 years in a population of men at increased risk of BPH progression. A preplanned 2-year analysis has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment.
Benign prostatic hyperplasia (BPH) is a bothersome disease that can progress if left untreated. However, patient and urologist perspectives on BPH management are not fully understood. The aim of the Prostate Research on Behaviour and Education (PROBE) Survey was to assess healthcare-seeking behaviour and attitudes to BPH treatment in 502 BPH patients, and the beliefs and management practices of 100 urologists, from France, Germany, Italy, Spain and the UK.
The principal concerns of patients seeking medical advice were fear of cancer, sleep disruption, discomfort or embarrassment. The majority of BPH patients recalled receiving a digital rectal examination (61%), routine prostate-specific antigen (PSA) tests (67%) and prescription medication (72%). Eighty per cent of 5α-reductase inhibitor (5ARI) users vs. 68% of α-blocker users were satisfied with their treatment. More than half of the patients were concerned about requiring surgery or developing acute urinary retention, and > 75% would prefer a drug that provides reduction in the risk of surgery than one that provides rapid symptom relief. Most urologists performed digital rectal examinations (96%) and PSA tests (71%) on > 90% of patients presenting with BPH symptoms. Eighty-seven per cent of urologists believe that BPH progresses, and 78% believe that 5ARIs prevent BPH progression. However, most urologists prescribe α-blockers while few prescribe 5ARIs.
This study highlights discrepancies between views and beliefs of patients and physicians regarding BPH and current practice in Europe.
There is increasing recognition of the importance of the role of the patient in clinical decision-making and the importance of consideration of patient perceptions and preferences in ensuring selection of the appropriate management strategy and treatment success.A recently reported US national survey indicated that currently there are significant differences in the beliefs and attitudes of patients and physicians towards benign prostatic hyperplasia (BPH) (also known as enlarged prostate) and its management.
This article provides information on the views and beliefs of both patients and urologists towards BPH and its management, and on current practice, across five European countries.This study confirms and extends the findings of the US survey and further highlights the need for improved communication between physicians and patients and greater involvement of the patient during clinical decision-making.
OBJECTIVE: To examine the current scale of provision of patient information materials by consultant surgeons in UK NHS and private sector hospitals. DESIGN: Secondary analysis of the responses of 12,555 surgical patients to surveys evaluating surgical services provided by specific consultants. SETTING: 7 NHS Trusts and one private sector hospital distributed throughout the UK. MAIN OUTCOME MEASURES: Provision of information materials by hospital, surgeon, and case-mix. Comparison of this service with patients' evaluations of surgeons' verbal communication in the outpatient clinic. RESULTS: Great variation exists between surgeons of the same specialty, and between hospital surgical directorates as a whole in the routine provision of supportive information materials to patients undergoing surgery. This variation cannot be explained solely by clinical need. Patients treated in private hospitals were less likely to receive information materials compared to patients treated within the NHS. CONCLUSIONS: Provision of printed information materials to patients by clinicians appears to be arbitrary. With the prospect of national performance frameworks in the foreseeable future, it is reasonable to assume that not only will the content of patient information be determined by quality standards but, in addition, its availability will be decided by clinical need rather than the clinician's preferences or interests.
Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice.
OBJECTIVES--To identify strengths, weaknesses, and omissions in existing leaflets and factsheets on prostatectomy given by surgeons to patients. DESIGN--Comparison of content of leaflets and factsheets with patients' needs and discontents in a questionnaire survey as part of the national prostatectomy audit. SETTING--All NHS and independent hospitals performing prostatectomy in four health regions. SUBJECTS--87 surgeons, 53 of whom used printed material to inform patients about their operations; a total of 25 different factsheets being used. 5361 men undergoing prostatectomy were sent a closed response questionnaire about their treatment; 4226 men returned it completed. A random sample of 2000 patients was asked for further comments, of whom 807 supplied pertinent comments. MAIN MEASURES--Content of the 25 factsheets compared with patients' needs identified in the questionnaires. RESULTS--Much of the information distributed had considerable shortcomings: it lacked uniformity in form and content, topics of relevance to patients were omitted, terminology was often poor, and patients' experience was at variance with what their surgeons said. For example, only one factsheet discussed the potential consequences of malignancy. Patients wanted more information on prostate cancer (1250(29%)) and some thought that the explanation of biopsy results was inadequate (29(4%)). Only six factsheets discussed the possible changes in sexual sensation after transurethral resection of the prostate, stating that patients would feel no change. However, 1490(35%) patients reported a change and 500(12%) were worried about it. CONCLUSION--Current standards of printed information do not meet the needs and requirements of patients undergoing prostatectomy.