Eleanor Zimmermann is due to start her Urology registrar training in the Southwest this October, and is a BURST Core Surgical Trainee Representative. @BURSTUrology
In this Residents’ Podcast, Eleanor discusses the NICE Guidance on complicated urinary tract infections: ceftolozane/tazobactam
BJUI Podcasts now available on iTunes, subscribe here https://itunes.apple.com/gb/podcast/bju-international/id1309570262
M Vermandere, T Kuijpers, J S Burgers, I Kunnamo, J van Lieshout, E Wallace, J Vlayen, E Schoenfeld, R A Siemieniuk, L Trevena, X Zhu, F Verermen, B Neuschwander, P h Dahm, K A O Tikkinen, K Aubrey‐Bassler, R W M Vernooij, B Aertgeerts, G E Bekkering
The role of medical expulsive therapy for uncomplicated ureteral stones remains controversial in light of new contradictory trial evidence. A Cochrane review was recently published to summarize the current best evidence on this topic.
To develop an evidence‐based recommendation concerning the use of alpha‐blockers for uncomplicated ureteral stones, based on an up‐to‐date Cochrane review.
We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice‐changing evidence with recommendations developed according to standards for trustworthy guidelines.
The panel suggests the use of alpha blockers in addition to standard care over standard care alone in patients with uncomplicated ureteral stones (weak recommendation based on low quality evidence). The panel judged that the net benefit of alpha‐blockers was small and that there was considerable uncertainty about patients’ values and preferences. This means that the panel expects that most patients would choose treatment with alpha‐blockers but that a substantial proportion would not. This recommendation applies to both patients in whom the presence of a ureteral stones is confirmed by imaging as well as patients in whom the diagnosis is made based on clinical grounds only.
The Rapid Recommendations panel suggests the use of alpha‐blockers for patients with ureteral stones. Shared decision‐making is emphasized in making the final choice between the treatment options.
This article is protected by copyright. All rights reserved.
Every Week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
If you only have time to read one article this month, it should be this one.
The aim of the present study was to review major organizational guidelines on the evaluation and management of asymptomatic microscopic haematuria (AMH). We reviewed the haematuria guidelines from: the American Urological Association; the consensus statement by the Canadian Urological Association, Canadian Urologic Oncology Group and Bladder Cancer Canada; the American College of Physicians; the Joint Consensus Statement of the Renal Association and British Association of Urological Surgeons; and the National Institute for Health and Care Excellence. All guidelines reviewed recommend evaluation for AMH in the absence of potential benign aetiologies, with the evaluation including cystoscopy and upper urinary tract imaging. Existing guidelines vary in their definition of AMH (role of urine dipstick vs urine microscopy), the age threshold for recommending evaluation, and the optimal imaging method (computed tomography vs ultrasonography). Of the reviewed guidelines, none recommended the use of urine cytology or urine markers during the initial AMH evaluation. Patients should have ongoing follow-up after a negative initial AMH evaluation. Significant variation exists among current guidelines for AMH with respect to who should be evaluated and in what manner. Given the patient and health system implications of balancing appropriately focused and effective diagnostic evaluation, AMH represents a valuable future research opportunity.
This guideline covers routine preoperative tests for people aged over 16 who are having elective surgery. It aims to reduce unnecessary testing by advising which tests to offer people before minor, intermediate and major or complex surgery, taking into account specific comorbidities (cardiovascular, renal and respiratory conditions and diabetes and obesity). It does not cover pregnant women or people having cardiothoracic procedures or neurosurgery. To Get accurate insights into your health with an at-home blood test visit https://www.numan.com/blood-tests.
This guideline updates and replaces NICE guideline CG3 (published June 2003).
People have the right to be involved in discussions and make informed decisions about their care, as described in your care [https://www.nice.org.uk/about/nice-communities/public-involvement/your-care].
We expect you to take our guidance into account. But you should always base decisions on the person you are working with.
Making decisions using NICE guidelines [https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-guidelines/using-NICE-guidelines-to-make-decisions] explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.
Guidance on consent for young people aged 16–17 is available from the reference guide to consent for examination or treatment [https://www.gov.uk/government/publications/reference-guide-to-consent-for-examination-or-treatment-second-edition] (Department of Health).
The tests covered by this guideline are:
The recommendations were developed in relation to the following comorbidities:
A colour poster version of these recommendations can be downloaded from tools and resources [https://www.nice.org.uk/guidance/ng45/resources].
Communication
Considering existing medicines
Pregnancy tests
Sickle cell disease or sickle cell trait tests
HbA1c testing for people without diagnosed diabetes
HbA1c testing for people with diabetes
Urine tests
Chest X-ray
Echocardiography
Consider resting echocardiography if the person has:
Before ordering the resting echocardiogram, carry out a resting electrocardiogram (ECG) and discuss the findings with an anaesthetist.
The following recommendations are specific to surgery grade and ASA grade.
| Surgery grades | Examples |
|---|---|
| Minor |
|
| Intermediate |
|
| Major or complex |
|
The ASA (American Society of Anesthesiologists) Physical Status Classification System [https://www.asahq.org/resources/clinical-information/asa-physical-status-classification-system] is a simple scale describing fitness to undergo an anaesthetic. The ASA states that it does not endorse any elaboration of these definitions. However, anaesthetists in the UK often qualify (or interpret) these grades as relating to functional capacity – that is, comorbidity that does not (ASA 2) or that does (ASA 3) limit a person’s activity.
| ASA 1 | A normal healthy patient |
| ASA 2 | A patient with mild systemic disease |
| ASA 3 | A patient with severe systemic disease |
| ASA 4 | A patient with severe systemic disease that is a constant threat to life |
[Yes] Offer the test
[Not routinely] Do not routinely offer the test
[Consider] Consider the test (the value of carrying out the test may depend on specific patient characteristics)
| Test | ASA grade | ||
|---|---|---|---|
| ASA 1 | ASA 2 | ASA 3 or ASA 4 | |
|
|||
| Full blood count | Not routinely | Not routinely | Not routinely |
| Haemostasis | Not routinely | Not routinely | Not routinely |
| Kidney function | Not routinely | Not routinely | Consider in people at risk of AKI1 |
| ECG | Not routinely | Not routinely | Consider if no ECG results available from past 12 months |
| Lung function/arterial blood gas | Not routinely | Not routinely | Not routinely |
| Test | ASA grade | ||
|---|---|---|---|
| ASA 1 | ASA 2 | ASA 3 or ASA 4 | |
|
|||
| Full blood count | Not routinely | Not routinely | Consider for people with cardiovascular or renal disease if any symptoms not recently investigated |
| Haemostasis | Not routinely | Not routinely | Consider in people with chronic liver disease
|
| Kidney function | Not routinely | Consider in people at risk of AKI2 | Yes |
| ECG | Not routinely | Consider for people with cardiovascular, renal or diabetes comorbidities | Yes |
| Lung function/arterial blood gas | Not routinely | Not routinely | Consider seeking advice from a senior anaesthetist as soon as possible after assessment for people who are ASA grade 3 or 4 due to known or suspected respiratory disease |
| Test | ASA grade | ||
|---|---|---|---|
| ASA 1 | ASA 2 | ASA 3 or ASA 4 | |
|
|||
| Full blood count | Yes | Yes | Yes |
| Haemostasis | Not routinely | Not routinely | Consider in people with chronic liver disease
|
| Kidney function | Consider in people at risk of AKI2 | Yes | Yes |
| ECG | Consider for people aged over 65 if no ECG results available from past 12 months | Yes | Yes |
| Lung function/arterial blood gas | Not routinely | Not routinely | Consider seeking advice from a senior anaesthetist as soon as possible after assessment for people who are ASA grade 3 or 4 due to known or suspected respiratory disease |
Every month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. There is also a podcast created by a Urology Resident.
If you only have time to read one article this week, it should be this one.
Bladder cancer is the seventh most common cancer in the UK. It is 3–4 times more common in men than in women. In the UK in 2011, it was the fourth most common cancer in men and the thirteenth most common in women. There were 10,399 people diagnosed with bladder cancer and 5081 deaths from bladder cancer in 2011. The majority of cases occur in people aged over 60. The main risk factor for bladder cancer is increasing age, but smoking and exposure to some industrial chemicals also increase risk.
Bladder cancer is usually identified on the basis of visible blood in the urine or blood found on urine testing, but emergency admission is a common way for bladder cancer to present, and is often associated with a poor prognosis.
Most bladder cancers (75–80%) do not involve the muscle wall of the bladder and are usually treated by telescopic removal of the cancer (transurethral resection of bladder tumour [TURBT]). This is often followed by instillation of chemotherapy or vaccine-based therapy into the bladder, with prolonged telescopic checking of the bladder (cystoscopy) as follow-up. Some people in this group who are at higher risk are treated with major surgery to remove the bladder (cystectomy). People with cancer in or through the bladder muscle wall may be treated with intent to cure using chemotherapy, cystectomy or radiotherapy, and those who have cancer too advanced to cure may have radiotherapy and chemotherapy.
The involvement of the urogenital tract and the nature of the treatments give this cancer a strong psychological impact, in addition to the physical impact of the disease and its treatments, which is often profound. The prevalence of the condition and the nature of its management make bladder cancer one of the most expensive cancers for the NHS.
There is thought to be considerable variation across the NHS in the diagnosis and management of bladder cancer and the provision of care to people who have it. There is evidence that the patient experience for people with bladder cancer is worse than that for people with other cancers.
This guideline covers adults (18 years and older) referred from primary care with suspected bladder cancer and those with newly diagnosed or recurrent bladder (urothelial carcinoma, adenocarcinoma, squamous-cell carcinoma or small-cell carcinoma) or urethral cancer. There was insufficient high-quality evidence on which to make specific recommendations for non-urothelial bladder cancer (adenocarcinoma, squamous-cell carcinoma or small-cell carcinoma).
It does not cover people aged under 18 or adults with bladder sarcoma, urothelial cancer of the upper urinary tract, or secondary bladder or urethral cancer (for example, bowel or cervix cancer spreading into the bladder).
The guideline assumes that prescribers will use a medicine’s summary of product characteristics to inform decisions made with individual patients.
This guideline recommends some medicines for indications for which they do not have a UK marketing authorisation at the date of publication, if there is good evidence to support that use. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. The patient (or those with authority to give consent on their behalf) should provide informed consent, which should be documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information. Where recommendations have been made for the use of medicines outside their licensed indications (‘off-label use’), these medicines are marked with a footnote in the recommendations.
Evidence-based recommendations on enzalutamide (Xtandi) for treating metastatic, hormone-relapsed prostate cancer for people in whom chemotherapy is not yet clinically indicated.
| TA377 | Appraisal title: Enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is clinically indicated | Section |
|---|---|---|
| Key conclusion | ||
|
Enzalutamide is recommended, within its marketing authorisation, as an option for treating metastatic hormone-relapsed prostate cancer:
The Committee concluded that, with its preferred assumptions, the resulting incremental cost-effectiveness ratio (ICER) for enzalutamide compared with best supportive care was likely to be between £31,600 and £34,800 per quality-adjusted life year (QALY) gained. This range was dependent on the method used to adjust survival estimates for active treatments not used in the NHS. Furthermore, it was likely to be nearer to the lower end of this range. The Committee concluded that enzalutamide is innovative, and that taking into account factors, which had not been fully accounted for in the modelling, agreed that the ICER for enzalutamide compared with best supportive care was below £30,000 per QALY gained, and enzalutamide could be considered a cost-effective use of NHS resources. |
1.1, 4.15, 4.18, 4.19 | |
| Current practice | ||
| Clinical need of patients, including the availability of alternative treatments |
Enzalutamide is a well-tolerated treatment, and people welcome having more treatment options to delay cytotoxic chemotherapy. Enzalutamide and abiraterone (taken before chemotherapy is clinically indicated) are currently available through the Cancer Drugs Fund. Although abiraterone before docetaxel is available to some people, it is not embedded within current NHS funding arrangements because its future is not guaranteed. It was therefore not considered as a comparator. There are some people who can have enzalutamide but not abiraterone in clinical practice (people who can’t take corticosteroids, people with visceral disease and people with severe liver disease). |
4.4, 4.1, 4.2, 4.18 |
| The technology | ||
|
Proposed benefits of the technology How innovative is the technology in its potential to make a significant and substantial impact on health-related benefits? |
Enzalutamide is the preferred treatment option for people with visceral disease and liver dysfunction, in whom abiraterone is contraindicated at this position in the treatment pathway, or for people who can’t take corticosteroids. Although enzalutamide is not a new treatment, it is the only treatment that can give these benefits at this position in the treatment pathway and so is innovative. | 4.18 |
| What is the position of the treatment in the pathway of care for the condition? | Enzalutamide is indicated for people with metastatic hormone-relapsed prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy, before chemotherapy is indicated. | 4.1 |
| Adverse reactions | Enzalutamide is a well-tolerated treatment. | 4.4 |
| Evidence for clinical effectiveness | ||
| Availability, nature and quality of evidence | The efficacy estimates for enzalutamide came from PREVAIL. Enzalutamide increased overall survival (OS) compared with placebo. The Committee considered that adjusting the OS estimated from the trial for subsequent life-extending treatments taken by people in the trial, but which are not available in the UK, was appropriate. | 4.6 |
| Relevance to general clinical practice in the NHS | The Committee was aware that in PREVAIL, once the disease progressed, people on enzalutamide could move on to subsequent treatments. It was also aware that the company considered that some of these treatments (such as abiraterone, enzalutamide, cabazitaxel, sipuleucel-T, cytotoxic chemotherapy other than docetaxel and investigational treatments) would not be used in England at this position in the treatment pathway. The Committee agreed that it was appropriate to adjust the survival estimates for people having these treatments. | 4.6 |
| Uncertainties generated by the evidence | The extent of adjustment needed to the OS estimates (to account for subsequent treatments that people had in PREVAIL that are not available in clinical practice in England) was uncertain. It was unclear which of the methods the company had used for adjustment (the Inverse Probability of Censoring Weights or the two-stage method) was better, however IPCW was associated with fewer assumptions. | 4.7 |
| Are there any clinically relevant subgroups for which there is evidence of differential effectiveness? | None identified. | – |
| Estimate of the size of the clinical effectiveness including strength of supporting evidence | Enzalutamide increased OS compared with placebo, but the extent of the difference was uncertain because some people went on to have further active treatments in both study arms. The company tried to adjust for this but there was uncertainty about which method of adjustment was appropriate. | 4.6, 4.7 |
| Evidence for cost effectiveness | ||
| Availability and nature of evidence | The company developed a new model and needed to extrapolate OS and time to treatment discontinuation from the trial data in its model. | 4.9. 4.11, 4.12 |
| Uncertainties around and plausibility of assumptions and inputs in the economic model |
The model structure was appropriate in terms of the sequence of treatments people would have in clinical practice in England, but there was uncertainty about whether time spent on treatments after enzalutamide reflected clinical practice. The Committee was concerned that that the company had not further checked the validity of the extrapolated data. This was particularly important because of the immaturity of the trial data and because of the small population at risk at the end of the trial follow-up (those who had not died or had been otherwise censored). This meant that a large proportion of the estimated survival benefit was based on the extrapolated period rather than the trial data. |
4.9, 4.11 |
|
Incorporation of health-related quality-of-life benefits and utility values Have any potential significant and substantial health-related benefits been identified that were not included in the economic model, and how have they been considered? |
The Committee considered whether the model captured the benefits of delaying chemotherapy, which is important to patients. The Committee agreed that the model predicted that people having enzalutamide had more time with better utility than people on best supportive care, but it was unclear whether the benefit of delaying chemotherapy had been fully captured by the utility values included in the modelling. The Committee concluded that enzalutamide is innovative. | 4.18, 4.19 |
| Are there specific groups of people for whom the technology is particularly cost effective? | None. | – |
| What are the key drivers of cost effectiveness? | The data cut-offs from PREVAIL that are used in the modelling and the utility value estimates. | 4.11, 4.12, 4.13 |
| Most likely cost-effectiveness estimate (given as an ICER) | The most plausible ICER for enzalutamide compared with best supportive care was nearer to £31,600 than to £34,800 per QALY gained. The Committee also concluded that enzalutamide is innovative and taking into account factors, which had not been fully accounted for in the modelling, agreed that the ICER for enzalutamide compared with best supportive care was below £30,000 per QALY gained. | 4.15, 4.18, 4.19 |
| Additional factors taken into account | ||
| Patient access schemes (PPRS) |
The company has agreed a patient access scheme with the Department of Health. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS. The company revised its patient access scheme over the course of this appraisal to increase the discount to the cost of enzalutamide for the NHS. |
2.3, 4.14 |
| End-of-life considerations |
The company did not make a case for enzalutamide meeting end-of-life criteria. The Committee considered that the first criterion for end of life (the treatment is indicated for patients with a short life expectancy, normally <24 months) had not been met. Therefore, the Committee did not consider the other criteria and concluded that enzalutamide did not meet end-of-life criteria for treating metastatic hormone-relapsed prostate cancer in people for whom chemotherapy is not yet indicated. |
4.17 |
| Equalities considerations and social value judgements | No equality issues were raised. | – |
Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.
If you only have time to read one article this week, it should be this one.
This National Institute for Health and Care Excellence (NICE) guidance is the current, unaltered NICE guidance at time of publication. BJUI publishes selected NICE guidance relevant to urologists to extend their distribution and promote best practice.
There is currently insufficient high-quality, comparative evidence to support the routine adoption of GreenLight XPS in high-risk patients, that is those who:
NICE recommends that specialists collaborate in collecting and publishing data on the comparative effectiveness of GreenLight XPS for high-risk patients to supplement the currently limited published evidence.
