Archive for category: Learning

Resident’s Podcast: NICE Guidance – ceftolozane & tazobactam for complicated UTIs

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

 

Alpha‐blockers for uncomplicated ureteral stones: a clinical practice guideline

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

Abstract

Background

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.

Aim

To develop an evidence‐based recommendation concerning the use of alpha‐blockers for uncomplicated ureteral stones, based on an up‐to‐date Cochrane review.

Method

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.

Results

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.

Conclusion

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.

NICE Guidance – Prostate artery embolisation for lower urinary tract symptoms caused by benign prostatic hyperplasia

1 Recommendations

  • 1.1 Current evidence on the safety and efficacy of prostate artery embolisation for benign prostatic hyperplasia is adequate to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent and audit.
  • 1.2 Patient selection should be done by a urologist and an interventional radiologist.
  • 1.3 This technically demanding procedure should only be done by an interventional radiologist with specific training and expertise in prostatic artery embolisation.

2 The Condition, Current Treatments and Procedure

The Condition

  • 2.1 Benign prostatic hyperplasia is common in older men. Stromal and epithelial cells increase in number, causing the prostate to increase in size. It often occurs in the periurethral region of the prostate, with large discrete nodules compressing the urethra. Symptoms include hesitancy during micturition, interrupted or decreased urine stream (volume and flow rate), nocturia, incomplete voiding and urinary retention.

Current Treatments

  • 2.2 Mild symptoms are usually managed conservatively. Drugs may also be used, such as alpha blockers and 5‐alpha‐reductase inhibitors. If other treatments have not worked, then surgical options include transurethral resection of the prostate, transurethral vaporisation of the prostate, holmium laser enucleation of the prostate or prostatectomy (see the NICE guideline on lower urinary tract symptoms in men https://www.nice.org.uk/guidance/cg97). Insertion of prostatic urethral lift implants has been introduced more recently as an alternative treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Potential complications of surgical procedures include bleeding, infection, strictures, incontinence and sexual dysfunction.

The Procedure

  • 2.3 Prostate artery embolisation for benign prostate hyperplasia is usually done using local anaesthesia. Under X‐ray guidance, the prostate is approached through the left or right femoral artery. Super‐selective catheterisation of the small prostatic arteries is done using fine microcatheters through the pelvic arteries. Embolisation involves the introduction of microparticles to completely block the prostatic vessels. Embolisation agents include polyvinyl alcohol (PVA) and other newer synthetic biocompatible materials.
  • 2.4 The aim of prostate artery embolisation is to reduce the prostate’s blood supply, causing some of it to undergo necrosis and shrink. It is common for patients to experience pelvic pain during and after the procedure. This does not usually last more than 1 to 3 days. The potential benefits of prostate artery embolisation compared with surgery include fewer complications, avoiding a general anaesthetic and it may be done as a day case procedure.

3 Committee Considerations

The Evidence

  • 3.1 To inform the committee, NICE did a rapid review of the published literature on the efficacy and safety of this procedure. This comprised a comprehensive literature search and detailed review of the evidence from 10 sources, which was discussed by the committee. The evidence included 1 systematic review, 2 randomised controlled trials (also included in the systematic review), 1 non‐randomised comparative study (also included in the systematic review), 2 case series, 3 case reports, and data provided by the UK‐ROPE register and is presented in table 2 of the interventional procedures overview (https://www.nice.org.uk/guidance/IPG611/evidence). Other relevant literature is in the appendix of the overview.
  • 3.2 The specialist advisers and the committee considered the key efficacy outcomes to be: quality of life, urinary symptoms as measured by the International Prostate Symptom Score, and improvement in urodynamics.
  • 3.3 The specialist advisers and the committee considered the key safety outcomes to be: inadvertent embolisation of other sites, urinary retention, prostatic bleeding (haematuria and haematospermia), groin haematoma, pain, retrograde ejaculation, and no loss of sexual function.
  • 3.4 Four commentaries from patients who had experience of this procedure were received, which were discussed by the committee.

Committee Comments

  • 3.5 The evidence showed a relatively high incidence of urinary retention after the procedure.
  • 3.6 The committee was informed that this procedure involves extensive imaging, which may result in significant radiation exposure.

Article of the Week: NICE Guidance. Sepsis – recognition, diagnosis and early management

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.

Sepsis: recognition, diagnosis and early management

 

Overview
This guideline covers the recognition, diagnosis and early management of sepsis for all populations. The guideline
committee identied that the key issues to be included were: recognition and early assessment, diagnostic and prognostic value of blood markers for sepsis, initial treatment, escalating care, iden tifying the source of infection, early monitoring, information and support for patients and carers, and training and education.
Who is it For?
People with sepsis, their families and carers.
Healthcare professionals working in primary, secondary and tertiary care. Recommendations
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].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-decisionsexplains 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.

 

More Information
You can also see this guideline in the NICE pathway on sepsis [https://pathways.nice.org.uk/pathways/sepsis].
To nd out what NICE has said on topics related to this guideline, see our web page on infections [https://www.nice.org.uk/guidance/conditions-and-diseases/infections]See also the guideline committees discussion and the evidence reviews (in the full guideline [https://www.nice.org.uk/Guidance/NG51/evidence]), and information about how the guideline was developed [https://www.nice.org.uk/Guidance/NG51/documents], including details of the committee. Recommendations for Research The guideline committee has made the following recommendations for research.

 

© NICE (2017) Sepsis: recognition, diagnosis and early management

 

Guideline of guidelines: Asymptomatic Microscopic Haematuria

Abstract

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.

NICE Guidance: Routine preoperative tests for elective surgery

Overview

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.

Who is it for?

  • Healthcare professionals
  • People having elective surgery, their families and carers

This guideline updates and replaces NICE guideline CG3 (published June 2003).

Recommendations

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:

  • chest X-ray
  • echocardiography (resting)
  • electrocardiography (ECG; resting)
  • full blood count (haemoglobin, white blood cell count and platelet count)
  • glycated haemoglobin (HbA1c) testing
  • haemostasis tests
  • kidney function (estimated glomerular filtration rate, electrolytes, creatinine and sometimes urea levels)
  • lung function tests (spirometry, including peak expiratory flow rate, forced vital capacity and forced expiratory volume) and arterial blood gas analysis
  • polysomnography
  • pregnancy testing
  • sickle cell disease/trait tests
  • urine tests.

The recommendations were developed in relation to the following comorbidities:

  • cardiovascular
  • diabetes
  • obesity
  • renal
  • respiratory.

Recommendations relevant for all types of surgery

A colour poster version of these recommendations can be downloaded from tools and resources [https://www.nice.org.uk/guidance/ng45/resources].

  • 1.1

    Communication

    • 1.1.1
      When offering tests before surgery, give people information in line with recommendations (including those on consent and capacity) made in the NICE guideline on patient experience in adult NHS services [https://www.nice.org.uk/guidance/cg138].
    • 1.1.2
      Ensure that the results of any preoperative tests undertaken in primary care are included when referring people for surgical consultation.
  • 1.2

    Considering existing medicines

    • 1.2.1
      Take into account any medicines people are taking when considering whether to offer any preoperative test.
  • 1.3

    Pregnancy tests

    • 1.3.1
      On the day of surgery, sensitively ask all women of childbearing potential whether there is any possibility they could be pregnant.
    • 1.3.2
      Make sure women who could possibly be pregnant are aware of the risks of the anaesthetic and the procedure to the fetus.
    • 1.3.3
      Document all discussions with women about whether or not to carry out a pregnancy test.
    • 1.3.4
      Carry out a pregnancy test with the woman’s consent if there is any doubt about whether she could be pregnant.
    • 1.3.5
      Develop locally agreed protocols for checking pregnancy status before surgery.
    • 1.3.6
      Make sure protocols are documented and audited, and in line with statutory and professional guidance.
  • 1.4

    Sickle cell disease or sickle cell trait tests

    • 1.4.1
      Do not routinely offer testing for sickle cell disease or sickle cell trait before surgery.
    • 1.4.2
      Ask the person having surgery if they or any member of their family have sickle cell disease.
    • 1.4.3
      If the person is known to have sickle cell disease and has their disease managed by a specialist sickle cell service, liaise with this team before surgery.
  • 1.5

    HbA1c testing for people without diagnosed diabetes

    • 1.5.1
      Do not routinely offer HbA1c testing before surgery to people without diagnosed diabetes.
  • 1.6

    HbA1c testing for people with diabetes

    • 1.6.1
      People with diabetes who are being referred for surgical consultation from primary care should have their most recent HbA1c test results included in their referral information.
    • 1.6.2
      Offer HbA1c testing to people with diabetes having surgery if they have not been tested in the last 3 months.
  • 1.7

    Urine tests

    • 1.7.1
      Do not routinely offer urine dipstick tests before surgery.
    • 1.7.2
      Consider microscopy and culture of midstream urine sample before surgery if the presence of a urinary tract infection would influence the decision to operate.
  • 1.8

    Chest X-ray

    • 1.8.1
      Do not routinely offer chest X-rays before surgery.
  • 1.9

    Echocardiography

    • 1.9.1
      Do not routinely offer resting echocardiography before surgery.
    • 1.9.2

      Consider resting echocardiography if the person has:

      • a heart murmur and any cardiac symptom (including breathlessness, pre-syncope, syncope or chest pain) or
      • signs or symptoms of heart failure.

Before ordering the resting echocardiogram, carry out a resting electrocardiogram (ECG) and discuss the findings with an anaesthetist.

Recommendations for specific surgery grades (minor, intermediate, and major or complex) and ASA grades

The following recommendations are specific to surgery grade and ASA grade.

Surgery grades
Surgery grades Examples
Minor
  • excising skin lesion
  • draining breast abscess
Intermediate
  • primary repair of inguinal hernia
  • excising varicose veins in the leg
  • tonsillectomy or adenotonsillectomy
  • knee arthroscopy
Major or complex
  • total abdominal hysterectomy
  • endoscopic resection of prostate
  • lumbar discectomy
  • thyroidectomy
  • total joint replacement
  • lung operations
  • colonic resection
  • radical neck dissection
ASA grades

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
Key to recommendations in tables

[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)

Table 1. Minor surgery
Test ASA grade
ASA 1 ASA 2 ASA 3 or ASA 4
  1. AKI, acute kidney injury. 1See recommendation 1.1.8 of the NICE guideline on acute kidney injury [https://www.nice.org.uk/guidance/cg169/chapter/1-Recommendations#assessing-risk-factors-in-adults-having-surgery].

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
Table 2. Intermediate surgery
Test ASA grade
ASA 1 ASA 2 ASA 3 or ASA 4
  1. AKI, acute kidney injury. 1Note that currently the effects of direct oral anticoagulants (DOACs) cannot be measured by routine testing. 2See recommendation 1.1.8 of the NICE guideline on acute kidney injury [https://www.nice.org.uk/guidance/cg169/chapter/1-Recommendations#assessing-risk-factors-in-adults-having-surgery].

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

  • If people taking anticoagulants need modification of their treatment regimen, make an individualised plan in line with local guidance
  • If clotting status needs to be tested before surgery (depending on local guidance) use point-of-care testing1
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
Table 3. Major or complex surgery
Test ASA grade
ASA 1 ASA 2 ASA 3 or ASA 4
  1. AKI, acute kidney injury. 1Note that currently the effects of direct oral anticoagulants (DOACs) cannot be measured by routine testing. 2See recommendation 1.1.8 of the NICE guideline on acute kidney injury [https://www.nice.org.uk/guidance/cg169/chapter/1-Recommendations#assessing-risk-factors-in-adults-having-surgery].

Full blood count Yes Yes Yes
Haemostasis Not routinely Not routinely Consider in people with chronic liver disease

  • If people taking anticoagulants need modification of their treatment regimen, make an individualised plan in line with local guidance
  • If clotting status needs to be tested before surgery (depending on local guidance) use point-of-care testing1
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

Article of the Month: Bladder cancer: diagnosis and management of bladder cancer

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.

Introduction

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).

Medicines

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.

NICE Guidance: Enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated

Overview

Evidence-based recommendations on enzalutamide (Xtandi) for treating metastatic, hormone-relapsed prostate cancer for people in whom chemotherapy is not yet clinically indicated.

Summary of Appraisal Committee’s Key Conclusions

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:

  • in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated
  • and only when the company provides it with the discount agreed in the patient access scheme.

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.

 

Article of the Month: GreenLight XPS for treating benign prostatic hyperplasia

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.

GreenLight XPS for treating benign prostatic hyperplasia

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.

 

 Recommendations

  • 1.1
    The case for adopting GreenLight XPS for treating benign prostatic hyperplasia is supported in non-high-risk patients. GreenLight XPS is at least as effective in these patients as transurethral resection of the prostate (TURP), but can more often be done as a day-case procedure, following appropriate service redesign.

 

  • 1.2

    There is currently insufficient high-quality, comparative evidence to support the routine adoption of GreenLight XPS in high-risk patients, that is those who:

    • have an increased risk of bleeding or
    • have prostates larger than 100 ml or
    • have urinary retention.

    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.

 

  • 1.3
    Cost modelling indicates that in non-high-risk patients, cost savings with GreenLight XPS compared with TURP are determined by the proportion of procedures done as day cases. Assuming a day-case procedure rate of 36%, and that the GreenLight XPS console is provided at no cost to the hospital (based on a contracted commitment to fibre usage), the estimated cost saving is £60 per patient. NICE’s resource impact report estimates that the annual cost saving for the NHS in England is around £2.3 million. In a plausible scenario of 70% of treatments being done as day cases, the cost saving may be up to £3.2 million.

 

  • 1.4
    NICE recommends that hospitals adopting GreenLight XPS plan for service redesign to ensure that day-case treatment can be delivered appropriately.

 

 

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