[NICE Draft Guideline] Transperineal biopsy for diagnosing prostate cancer

NICE | February 2022 | Transperineal biopsy for diagnosing prostate cancer

Four new diagnostic devices for men with suspected prostate cancer, which reduce the chances of biopsy related sepsis, have been recommended for use by NICE.

The new diagnostics guidance looks at local anaesthetic transperineal (LATP) prostate biopsy, using the freehand needle positioning devices PrecisionPoint, EZU-PA3U device, Trinity Perine Grid, and UA1232 puncture attachment, which are recommended as options for helping to diagnose prostate cancer.

Prostate cancer is the most diagnosed cancer in men in the UK according to Cancer Research UK. It mainly affects people over 50 and the risk is higher for people of African family background and people with a family history of prostate cancer.

At present NICE guidance recommends offering people with suspected clinically localised prostate cancer a multiparametric MRI as the first-line investigation.

If prostate cancer is still suspected based on the MRI image, a prostate biopsy is offered so that samples of the prostate can be collected for analysis. There are two ways of doing a prostate biopsy. In a transrectal ultrasound guided (TRUS) biopsy samples are collected using a biopsy needle inserted through the rectal wall via the anus.

However TRUS can be associated with serious infections, sometimes requiring hospital admission and antibiotic (Source: NICE). 

NICE Transperineal biopsy for diagnosing prostate cancer

Further information and documents available from NICE

ICR responds to NICE decision not to recommend olaparib for advanced prostate cancer

Institute of Cancer Research | nd | ICR responds to NICE decision not to recommend olaparib for advanced prostate cancer

The Institute of Cancer Research, London, has expressed disappointment that NICE has decided not to recommend olaparib for previously treated, hormone-relapsed metastatic prostate cancer. 

It is the latest in a series of instances where it has not proved possible to widen availability of olaparib for additional cancer indications – highlighting the barriers that exist in taking even highly innovative treatments to patients.

Full response is available from the ICR

See also:

Medscape Experts Disappointed by NICE’s Decision to Reject Prostate Cancer Drug

National Health Executive NHS reject life-extending prostate drug due to NICE recommendations

[NICE updated guideline] Prostate cancer: diagnosis and management [NG131]

NICE | December 2021 | Prostate cancer: diagnosis and management [NG131]

This guideline covers the diagnosis and management of prostate cancer in secondary care, including information on the best way to diagnose and identify different stages of the disease, and how to manage adverse effects of treatment. It also includes recommendations on follow-up in primary care for people diagnosed with prostate cancer.

 A table of NHS England interim treatment regimens gives possible alternative treatment options for use during the COVID-19 pandemic to reduce infection risk. This may affect decisions for patients with prostate cancer. See the COVID-19 rapid guideline: delivery of systemic anticancer treatments for more details.

In December 2021, NICE reviewed the evidence and updated the recommendations on risk stratification to refer to a 5-tier model. Other recommendations were amended to reflect this change. For more information, see the update information.

Full details from NICE

The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers

Ball, R. Y. et al | 2021 | The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers | Life | 11 | 11| 1172|  https://doi.org/10.3390/life11111172

To understand how PUR-4- the highest-risk category in the The Prostate Urine Risk (PUR) biomarker, a four-group classifier related to the structure of the cancerous prostate, the researchers behind this study examined its relationship to the amounts and grade of tumor in biopsy-sampled prostates and in a series of radical prostatectomy specimens. A strong association was observed by the experts, between an increasing amount of Gleason pattern 4 cancer and increasing PUR-4 signal. These data suggest that the PUR-4 signature could provide useful additional information in determining the amount of clinically significant tumor within a prostate and thereby help guide the patient treatment pathway with essential information for triage, improved management and prognostic utility.

Abstract

The Prostate Urine Risk (PUR) biomarker is a four-group classifier for predicting outcome in patients prior to biopsy and for men on active surveillance. The four categories correspond to the probabilities of the presence of normal tissue (PUR-1), D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer. In the current study we investigate how the PUR-4 status is linked to Gleason grade, prostate volume, and tumor volume as assessed from biopsy (n equal to 215) and prostatectomy (n equal to 9) samples. For biopsy data PUR-4 status alone was linked to Gleason Grade group (GG) (Spearman’s, ρ equal to 0.58, p less than 0.001 trend). To assess the impact of tumor volume each GG was dichotomized into Small and Large volume cancers relative to median volume. For GG1 (Gleason Pattern 3 + 3) cancers volume had no impact on PUR-4 status. In contrast for GG2 (3 + 4) and GG3 (4 + 3) cancers PUR-4 levels increased in large volume cancers with statistical significance observed for GG2 (p equal to 0.005; Games-Howell). These data indicated that PUR-4 status is linked to the presence of Gleason Pattern 4. To test this observation tumor burden and Gleason Pattern were assessed in nine surgically removed and sectioned prostates allowing reconstruction of 3D maps. PUR-4 was not correlated with Gleason Pattern 3 amount, total tumor volume or prostate size. A strong correlation was observed between amount of Gleason Pattern 4 tumor and PUR-4 signature (r equal to 0.71, p equal to 0.034, Pearson’s). These observations shed light on the biological significance of the PUR biomarker and support its use as a non-invasive means of assessing the presence of clinically significant prostate cancer. (Source: Ball et al, 2021).

The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers [paper]

This article is part of a special issue in Life focusing on prostate cancer

See also:

MedScape Urine Test for Prostate Cancer Signals Amount of Aggressive Tumor [news story]

[NICE Consultation] Prostate cancer (update)

NICE | In development [GID-NG10194]| Prostate cancer | Expected publication date: 15 December 2021

This guidance will partially update the following:

• Prostate cancer: diagnosis and management (NG131)
• Suspected cancer: recognition and referral (NG12)

NICE’s consultation on prostate cancer closes at 5pm on 4 November 2021

Full details, including the consultation documents are available from NICE

NICE (draft guidance) recommends apalutamide for treating prostate cancer

NICE |  September 2021 | NICE draft guidance recommends apalutamide for treating prostate cancer

NICE has recently (8 September 2021) published final draft guidance which now recommends apalutamide (also called Erleada and made by Janssen) plus androgen deprivation therapy for treating prostate cancer in adults.

The positive recommendations follow an improved discount to the price of apalutamide offered by the company.

The draft guidance looks at treating prostate cancer in adults which no longer responds to hormone therapy and who are at high risk of the cancer spreading to other parts of their body, or is still sensitive to hormone therapy but has already spread.

Apalutamide is a type of drug called an androgen receptor inhibitor which works by blocking the effect of testosterone on prostate cancer cells.  

For both types of prostate cancer where apalutamide has been recommended, the clinical trial results suggest apalutamide plus androgen deprivation therapy increases the time until the disease gets worse and how long people with these types of prostate cancer live.

It is estimated that around 8 000 people with hormone-sensitive or hormone-relapsed prostate cancer will now be eligible for treatment with apalutamide (Source: NICE).

Full details are available from NICE

NIHR: Active monitoring in early prostate cancer prevents as many deaths as surgery or radiotherapy, new research shows

NIHR| 4 February 2021| Active monitoring in early prostate cancer prevents as many deaths as surgery or radiotherapy, new research shows

New research indicates that ‘watch and wait’ also known as active monitoring in early prostate cancer prevents as many deaths as surgery or radiotherapy. The experts involved in this trial have observed that at 10-year median follow-up of patients with early prostate cancer, there was no difference in disease-specific mortality between active monitoring, radical prostatectomy and radical radiotherapy treatments, which caused different side-effect profiles.

It stuidied over 82 000 men between the ages of 50 and 69 who agreed to have a PSA test. Some 2664 were diagnosed with localised prostate cancer, and of this group, 1643 agreed to be randomly allocated to surgery, radiotherapy, or active monitoring. Urinary and sexual function was assessed by questionnaires completed by the men.

The results showed that in the ten years following their diagnosis:

• 99% of men were alive in each of the three groups
• compared with active monitoring, surgery and radiotherapy reduced the risk of disease spreading outside the prostate by half
• urinary leakage and sexual function were worst after surgery
• sexual and bowel functions were most affected by radiotherapy
• More than half (55%) men on active monitoring moved to a radical treatment but many (44%) remained disease free and avoided the side effects of treatments.

The study found that overall, quality of life was similar across all groups. Men on active monitoring had an expected gradual decline in their urinary and sexual function over time. The researchers concluded that longer follow-up is needed to determine the most cost-effective treatment for localised prostate cancer over a man’s lifetime.

This is a practice changer for the management of prostate cancer; many academics have called it the Greatest Trial Of all Time. After years of retrospective research with uncontrollable bias, it was the first large randomised controlled trial to compare surgery to radiotherapy and active monitoring for the treatment of localised prostate cancer. It showed no difference in survival in the different treatment groups which is essential news for counselling patients with a new diagnosis of prostate cancer.

Suneil Jain, Professor and Honorary Consultant in Clinical Oncology, Queen’s University of Belfast

(Source: NIHR)

The primary paper Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT

NIHR: More precise classification of risk in prostate cancer reveals a huge variation in treatment

NIHR | September 2020 |More precise classification of risk in prostate cancer reveals a huge variation in treatment

A new study identifies huge variation in the treatment of prostate cancer in English hospitals. in some hospitals, almost all are offered radiotherapy or surgery. In other hospitals, they are much more likely to be monitored with active surveillance and spared the possible effects of treatment. The researchers included more than 60000 men diagnosed with prostate cancer in almost 130 English hospitals between 2014 and 2017.

Current NICE guidelines classify prostate cancers in three tiers: low, intermediate or high risk. These are broad tiers, and not all men in the intermediate group are at the same risk of their cancer spreading. Therefore, some can potentially avoid treatment.

The Cambridge Prognostic Group (CPG) classification splits both intermediate- and high-risk groups in two, giving five tiers in total. Intermediate-risk cancers are divided into tumours with favourable and unfavourable outlooks. This study uses the CPG classification, categorising the patients into its’ five risk groups.

As expected, men in the low-risk group were least likely to have been treated with surgery or radiotherapy and most likely to have been on active surveillance. Men in the higher risk groups were most likely to have had surgery or radiotherapy. Variation between different hospitals’ approaches is not obvious in the broad intermediate category used by NICE. But when the researchers used the more detailed, five-tier CPG classification, they were able to consider those with favourable and unfavourable outlooks separately.

They found huge variations between hospitals in the treatments offered to men with intermediate-risk cancer. This was especially true for men with favourable intermediate-risk cancer. In some hospitals, less than a quarter of these men (23%) had surgery or radiotherapy. In others, almost all (97%) had surgery or radiotherapy. This suggests there is little agreement between hospitals in how these men should be managed.

NICE issued guidelines in 2019 which used the traditional three groupings of low-, intermediate- and high-risk prostate cancer. The guidelines do not divide intermediate-risk cancers into favourable and unfavourable groups. NICE recommends that men with intermediate-risk cancers should be offered surgery or radiotherapy.

Despite growing evidence in favour of active surveillance for favourable intermediate-risk prostate cancer, this approach is not recommended by NICE as initial treatment. But the guidelines state that it can be considered for men who choose not to have immediate radical treatment.

This work suggests that some men who received treatment for prostate cancer could have been managed with active surveillance. This piece of research also underlines how differences in treatment practices in men with intermediate-risk disease (CPG2 and CPG3) and in men with high-risk disease (CPG4 and CPGP5) that are not visible when using the traditional three-tiered risk classification (Source: NIHR).

Full alert available from NIHR

Read the published paper Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation from BMC Medicine

National Prostate Cancer Audit

National Prostate Cancer Audit: Prostate Biopsy Short Report  | Healthcare Quality Improvement Partnership

This report evaluates the current national use of transperineal (TP) prostate biopsies and compares differences in the outcomes of TP and transrectal (TR) biopsies. It also examines how the risk of complications is affected by the biopsy approach.

The report finds that the proportion of men undergoing a TP biopsy has nearly doubled within 3 years (14% – 25%), highlighting the increased desire to use this biopsy in certain hospitals.

Full detail at Healthcare Quality Improvement Partnership

Early suppression of male hormones is better than delayed therapy for advanced prostate cancer on balance

NIHR | October 2019 | Early suppression of male hormones is better than delayed therapy for advanced prostate cancer on balance

Offering early hormone suppression therapy to men with advanced prostate cancer that is causing no symptoms improves outcomes compared with waiting until symptoms of cancer spread arise. Early treatment is associated with 23 to 57 fewer deaths per 1,000 men over five years, depending on the men’s baseline risk. However, this comes with an increased chance of some non-serious side effects.

Hormone suppression works by lowering levels of the male sex hormones that fuel the cancer’s growth. It is the mainstay of treatment for advanced prostate cancer, but the best time to initiate therapy has been debated. This updated Cochrane review identified 10 trials comparing early suppression therapy with delaying treatment until there was evidence that the cancer had spread or the patient developed symptoms.

Early treatment is likely to be the better strategy, particularly as findings relating to side effects are less certain. Individual treatment decisions would need to be based on informed discussion between patient and doctor (Source: NIHR).

Abstract

Background: Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer.

Objectives: To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer.

Search Methods: For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019).

Selection Criteria: We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration.

Data collection and analysis: Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse.

Main results: We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths  per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events    which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time. This corresponds to 62 fewer prostate cancer deaths per 1000 at 5 years for the moderate risk group and 24 fewer death from prostate cancer  per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations. Early AST may decrease the rate of skeletal events corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue, corresponding to 31 more men with this complaint per 1000. We downgraded for study limitations and imprecision. It may increase the risk of heart failure corresponding to 27 more events per 1000. We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations.

Authors’ Conclusions: Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.