Background
Early intervention is potentially lifesaving for a range of conditions. A key cause of death
from cancer and other causes is late presentation and there are key barriers to early access
such as low education levels, difficult access to primary care (for example due to
anti-social working hours) as well as lack of knowledge of relevant symptoms that might
trigger referral and investigation. The Man Van project seeks to address some of these
reasons for late presentation and started with an initial focus on prostate cancer. The
project has now broadened to include a range of conditions that are major causes of mortality
and morbidity in men such as heart and liver disease, other urological cancers (penile,
testicular, bladder, kidney). The Man Van clinics will be focused on populations at risk of
delayed presentation to healthcare systems such as men in manual or low skill jobs and
workplaces with high numbers of black and ethnic minority employees.
Prostate cancer is the most common cancer in men in the United Kingdom (UK), with over 50,000
new cases diagnosed and 15,000 lives lost to prostate cancer in the UK each year 1. This is
of particular concern for black African and African Caribbean men who carry a 1 in 4 risk of
developing prostate cancer, and for men with a family history of the disease. Another
challenge is that, typically, men tend to approach their GP for men's health issues when
symptoms are severe. Around 20-25% of men with prostate cancer still present to A&E with
retention. At this late-stage treatment is less likely to be successful and certainly will
carry more morbidity for the patient and cost for the health care system. The recent COVID-19
pandemic has further exacerbated this issue with routine referrals to cancer diagnostics
clinics dropping by around a third (in house data, Royal Marsden Hospital), suggesting a
growing reservoir of un-diagnosed cancer in the community.
Till date there is no consensus on the modality of prostate cancer screening, but most
studies have focussed on PSA as a screening tool, with MRI scanning and biopsies as adjuncts
to this. PSA itself has a controversial history in screening for prostate cancer with studies
showing differing results. A key issue in using PSA as a screening tool comes from the
definition of what a 'normal' PSA is. PSA increases with age and with benign growth of the
prostate but can also be elevated in urinary tract infections or prostatic inflammation.
Oesterling's age specific PSA ranges from 1993 are still in use today. Prostate cancer is of
course another cause of PSA elevation. Having a higher PSA threshold for investigation
increases the positive predictive value for detecting prostate cancer but lowers the negative
predictive value, and the reverse is true as well. A study by Gerstenbluth documented a
positive predictive value of 98.5% for PSA in detecting prostate cancer with a PSA of 50ng/ml
or above.
The evidence for screening is also controversial resulting in differing guidance around the
world. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial from the USA
looked at systematic vs opportunistic screening in over 76000 men. Using a PSA threshold of
over 4 and 7-10 years of follow-up no significant difference in mortality from prostate
cancer was found between the screened and non-screened arms. However, the study had high
rates of contamination between the two groups with an estimated 74% of the control group
subject to at least one routine PSA test during the trial (95% in the intervention arm) and
around 50% of men in the control group tested each year.
The European Randomized Study of Screening for Prostate Cancer (ERSPC) has been studying
186,000 men aged 55 to 69 in Europe since 1992. Now in its 16th year of follow-up6 results
show a 20% reduction in cancer specific survival, and the numbers needed to treat was now
below that which is observed in breast cancer strengthening the argument for some form of
screening. A total of seven studies in different regions of Europe were included, with each
study utilising different screening criteria and treatment protocols, interval timing, and
PSA cut-offs (between 3 and 4), again muddying the waters. As a result of this conflicting
evidence the National Institute of Clinical Excellence (NICE) guidelines suggest a risk
stratified approach along with patient counselling. The guidelines recommend giving a PSA
test to any man over the age of 50 years who requests it as well as offering it to men with
lower urinary tract symptoms, haematuria, erectile dysfunction or symptoms that may suggest
advanced prostate cancer such as unexplained bone pain or weight loss. However, routine
systematic screening is not recommended.
Rationale
The rationale behind the introduction of the Man Van mobile outreach service is to increase
patient access and support to cancer investigation pathways. This is particularly important
in patient groups from lower socio-economic and high risk groups where delay in early
intervention can result in delayed presentation and adverse health outcomes. We hope to
demonstrate the feasibility and applicability of such a service to improve patient outcomes
and hope to gather important qualitative and DNA based data for further research.
This research project will analyse the clinical data obtained from each patient's routine
health screening and long-term follow-up data from NHS Digital and other healthcare
providers, to make a full assessment of how effective the Man Van mobile outreach model is in
diagnosing prostate and other male cancers by making a comparison with the current detection
rates from diagnoses made under the traditional screening and diagnosis pathway. It is
anticipated that the results of this study will provide further evidence for the
commissioning of targeted outreach programmes for early detection of prostate and other male
cancers.
Point of care testing (MV-POCT)
Point of care blood testing is a feature of the van that will allow instant results to be
given to patients, preventing the need for follow-up appointments and speeding up diagnoses.
Both PSA and HbA1c tests are currently carried out on the van using formal laboratory blood
tests which are then sent via courier to the Royal Marsden biochemical laboratory.
As well as a formal laboratory validation process which is required before any point of care
machine can be used (which is not part of the research protocol) we will determine what
effect the difference between laboratory and point of care testing may have on the decision
making process for patients.
The clinical decision making from PSA testing will be whether an onwards referral for
prostate cancer investigation is recommended by the clinical team. For HbA1c it will be
whether a primary care referral for diabetic management is recommended by the clinical team.
The laboratory value will be taken as the 'true' value in this instance as all final clinical
decision making based on this.
Qualitative questionnaire (MV-QualQ)
As the Man Van provides a new clinical model for assessing patients, the patients'
perspective on the model, and comparisons to existing clinical services is important. Going
into more detail than a service evaluation questionnaire, a qualitative study has been
developed to better understand how patients feel about and react to the service. A
qualitative questionnaire has been developed following discussion group input via a modified
Delphi process.
The Delphi method is a commonly used method for achieving a consensus of opinion of real
world knowledge from experts in the field. It was developed by Dalkey and Helmer at the Rand
Corporation in the 1950s and is aimed at problem-solving, idea-generation, or determining
priorities.
The complexity of issues that prevent men from seeking or finding healthcare and our lack of
understanding is the key driver for this study. This is particularly relevant for men from
ethnic minorities and lower socio-economic groups. Understanding the barriers and
facilitators to healthcare access may provide further support of the Man Van project and may
help develop further research themes aimed at increasing healthcare access.
In-depth qualitative patient interviews will be carried out on at least 5 patients to further
delineate themes which arise from the questionnaires. With permission interviews will be
recorded and transcribed to aid thematic analysis.
Health Economic Analysis (MV-Eco)
A key element of the Man Van project is its long-term use as a novel method of targeted
screening and improving health care outcomes. Like all NHS funded services a cost-benefit
analysis is integral to supporting the case for this project into the future. Health economic
arguments form key parts of discussion for NICE and NHS England commissioning groups.
The health economic arguments for prostate cancer screening remain unclear as they do for
various diseases, however a combined approach that targets high risk patients and assess for
prostate cancer, bladder/renal cancer, diabetes, hypertension and other diseases assessed for
in the Man Van may make for a stronger economic argument.
Polygenic risk scores (MV-PRS)
Prostate cancer is the commonest cancer in men in the Western world, with over 40,000 new
cases per annum. However, its aetiology remains very poorly understood. The substantial
variation in incidence rates worldwide suggests that lifestyle risk factors are important
however, no definite lifestyle risk factors have been identified till date.
Family history has been identified as a significant risk factor for prostate cancer, as it is
in many other cancers and diseases. Although this is likely due to inherited genetic
pre-disposition, causation is yet to be fully established.
Although gene mutations have been discovered as being causative factors for many diseases PRS
allow for the amalgamation of greater variants in order to explain a larger proportion of
diseases rather than single low penetrance variants. PRS has the potential to enhance risk
susceptibility to a greater proportion of the population and offer new avenues in patient
screening and disease prevention.
The clinical application of PRS is subject of intense debate and ongoing research. We hope to
add to this area of ongoing study, in particular with the combination of offering lifestyle
modification advice in the context of PRS. PRS scores will be generated from saliva samples
of DNA. As is common with many studies the under recruitment and under representation of
ethnic minority patients remains an issue, resulting in less representative polygenic risk
scores for patients of non-white ethnicities. We hope to address this via the Man Van by
recruiting higher proportions of other ethnicities.
DNA Collection (MV-DNA)
Genetic studies have become a key part of cancer research, both for early diagnosis and
prognostic reasons. A key issue for studies is trial recruitment, with significant issues in
the recruitment of ethnic minorities to trials, which is particularly relevant when a disease
may affect a particular ethnicity more (for example prostate cancer in Black men). DNA
collection with either blood or saliva samples can help to build a database which can be used
for further genetic studies.
Urinary Circulating Tumour DNA collection (MV-UctDNA)
Despite much research into the development of novel urinary biomarkers for bladder cancer,
the mainstay of diagnosis remains invasive with a flexible (or rigid) cystoscopy. Even
cystoscopy is only carried out after a red flag symptom triggers a referral (haematuria or
recurrent infections). Several tests exist but none has replaced cystoscopy as the gold
standard either for diagnosis of new bladder cancer or disease recurrence. Circulating tumour
DNA (ctDNA) from urine has potential as a new avenue of development of diagnostic tests for
bladder cancer and also prostate cancer.