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.

New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

Queen Mary University | September 2019 | New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

A blood test developed by experts at Queen Mary University marks a ‘paradigm shift’ in the way prostate cancer is diagnosed. 

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The new prostate cancer test detects early cancer cells, or circulating tumor cells (CTCs), that have left the original tumour and entered the bloodstream prior to spreading around the body. By measuring intact living cancer cells in the patient’s blood, rather than the PSA protein which may be present in the blood for reasons other than cancer, it potentially provides a more accurate test for prostate cancer.

The study tested the use of the CTC test in 98 pre-biopsy patients and 155 newly diagnosed prostate cancer patients enrolled at St Bartholomew’s Hospital in London.

The research team found that the presence of CTCs in pre-biopsy blood samples were indicative of the presence of aggressive prostate cancer, and efficiently and non-invasively predicted the later outcome of biopsy results.

When the CTC tests were used in combination with the current PSA test, it was able to predict the presence of aggressive prostate cancer in subsequent biopsies with over 90 per cent accuracy, better than any previously reported biomarkers.

Additionally, the number and type of CTCs present in the blood was also indicative of the aggressiveness of the cancer. Focusing on more aggressive prostate cancer may reduce over-treatment and unnecessary biopsies for benign and non-aggressive conditions.

(Source Queen Mary University) 

Full reference: Xu, L. | 2019|Non-invasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells | Journal of Urology | https://doi.org/10.1097/JU.0000000000000475

Purpose:

PSA testing results in unnecessary biopsy and over-diagnosis with consequent over-treatment. Tissue biopsy is an invasive procedure, associated with significant morbidity. More accurate non- or minimum-invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over-diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly in predicting clinically significant prostate cancer in pre-biopsy patients.

Material and Methods:

We enrolled 155 treatment naïve prostate cancer patients and 98 pre-biopsy patients for circulating tumor cell numeration. RNA was extracted from circulating tumor cells from 184 patients for gene expression analysis. Kruskal-Wallis, Spearman’s rank, multivariate logistic regression and random forest were applied to assess the association of circulating tumor cells with aggressive prostate cancer.

Results:

In localized prostate cancer patients, 54% were scored as circulating tumor cell positive, which was associated with higher Gleason score ( p=0.0003), risk group ( p<0.0001) and clinically significant prostate cancer. In pre-biopsy group, positive circulating tumor cell score in combination with PSA predicted clinically significant prostate cancer with AUC=0.869. A 12-gene panel prognostic for clinically significant prostate cancer was also identified. Combining PSA level, circulating tumor cell-score and the 12-gene panel, AUC for clinically significant prostate cancer prediction was 0.927 and in cases with multi-parametric MRI data, adding these to multi-parametric MRI significantly increased the prediction accuracy.

Conclusions:

Circulating tumor cell analysis has the potential to significantly improve patient stratification by PSA and/or multi-parametric MRI for biopsy and treatment.

The Library can provide the full article to Rotherham NHS Staff, request here

 

See also:

Science Daily New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

New device will protect prostate cancer patients during radiation treatment

An innovation that can reduce the side-effects of radiotherapy for prostate cancer patients by over 70 per cent will be rolled out across the NHS, as part of the Long Term Plan to put cutting-edge treatments at the heart of people’s care.

Thanks to a deal struck by the NHS with manufacturer Boston Scientific, hospitals in England will now be encouraged to use its hydrogel device for all patients who could benefit, making radiotherapy a safer and less painful treatment option for many men.

The hydrogel acts as a spacer, reducing the amount of radiation that can pass through the prostate and damage the rectum during treatment, by temporarily positioning it away from the high dose radiation used in treatment.

The gel, made mostly of water, is injected before treatment starts and then remains in place during radiation therapy, before being naturally absorbed by the body after about 6 months.

In studies, its use has been shown to relatively reduce life-changing side effects, such as rectal pain, bleeding and diarrhoea, by over 70%, meaning significant improvements in quality of life for those battling prostate cancer.

Full story at NHS England

[NICE Guideline] Prostate cancer: diagnosis and management [NG131]

NICE |  May 2019 | Prostate cancer: diagnosis and management NICE guideline [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.

Full details from NICE 

Improving patient experience through stratification of the prostate cancer follow up pathway

Atlas of Shared Learning | March 2019| Improving patient experience through stratification of the prostate cancer follow up pathway

A recent addition to NHS England’s Atlas of Shared Learning is a case study that comes from nurses in the Urology Unit at The Royal Marsden NHS Foundation Trust who led the development and implementation of a new prostate cancer follow-up pathway. This pathway has significantly improved patient outcomes, experience and use of resources locally (Source: NHS England).

Read the case study at NHS England 

National Prostate Cancer Audit: Annual Report 2018

Health Quality Improvement Partnership | February 2019 | National Prostate Cancer Audit: Annual Report 2018

Health Quality Improvement Partnership (HQIP) have published the results of their national prostate cancer audit in the report National Prostate Cancer Audit: Annual Report 2018.

There are over 40,000 new diagnoses of prostate cancer every year in the UK and over 11,000 men die because of the disease. This makes prostate cancer the second most common cause of cancer-related death for men in the UK.

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Image source: hqip.org.uk

 

This report presents results for men diagnosed with prostate cancer between 1st April 2016 and 31st March 2017 in England and Wales. It reports on specific diagnostic, staging and treatment information as well as core performance indicators in order to compare diagnostic specialist MDTs or treatment centres. This is the first report which combines English and Welsh data as well as using patient-reported experience (PREMs) and outcome measures (PROMs) as performance indicators.

Reporting on a total of 14 performance indicators, the NPCA is the first national audit which is able to report on process and outcome measures from all aspects of the care pathway for men with prostate cancer (Source: HQIP).

Download it from HQIP

Radiotherapy benefits some men whose prostate cancer has spread to their bones

NIHR | January 2019 | Radiotherapy benefits some men whose prostate cancer has spread to their bones

An NIHR Signal highlights a trial part-funded by NIHR, published in October 2018, which compared the effects of standard care with or without radiotherapy to the prostate on overall survival for over 2000 men.  The standard treatment for men with metastatic prostate cancer is anti-androgen hormone therapy, and this is sometimes combined with chemotherapy. Radiotherapy of the prostate itself is only usually used for symptom relief.

The trial found that radiotherapy improved three-year survival rate from 73 to 81% in men with a limited number of metastases confined to the spine and pelvis. In this group, it also prevented any disease progression over three years in half of them compared to a third on standard care.

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STAMPEDE was a randomised controlled trial  that took place in more than 100 hospitals in Switzerland and the UK. Over 2,000 men with newly diagnosed prostate cancer with metastases, confirmed on a bone scan, were recruited to the study.

Participants were randomised to either standard care (lifelong anti-androgen hormone therapy, with or without chemotherapy using docetaxel) or standard care plus radiotherapy to the prostate.

This study adds further evidence that radiotherapy could benefit men with newly diagnosed prostate cancer with local metastases.

The trial used CT and bone scans to define low and high metastatic burden. PET scans, which can detect smaller cancer deposits, are becoming widely available and may allocate people differently.

Treating the primary once the cancer has metastasised has conventionally thought to be futile. This has been challenged by finding that in low metastatic burden prostate cancer, radiotherapy to the primary significantly improves survival and should become standard of care.

This study raises the issue whether this would apply to other cancers and interesting biological questions as to the mechanism. Is it an effect of debulking the primary?  Is it immunological?  Is it due to reducing secondary spread of aggressive clones?

It seems we have underestimated in prostate cancer, the impact of local control in the setting of metastatic disease

Professor Robert Huddart, Reader and Honorary Consultant, Royal Marsden NHS Foundation Trust 

(Source: NIHR)

NIHR Radiotherapy benefits some men whose prostate cancer has spread to their bones

 

 Parker, C.  et al | 2018| Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial|  The Lancet| 

 

Background
Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.
Methods
We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule.
Findings
Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival but not overall survival. Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy).
Interpretation
Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.