Category Archives: Screening

Summary of PHTwitJC #2: Prostate-Specific Antigen Concerntration at age 60

Participants and followers of #PHTwitJC voted on their preferred topic to discuss and critique, from a selection of case-control papers put forward.  It was intended for this paper to be discussed on 28th August, however due to low participation it was re-run.

On Sunday September 11th #PHTwitJC discussed a paper by Vickers, A et al ((2010) Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study).  The transcript of discussions can be accessed here.

Q1 – This paper uses a case-control study design – was this appropriate for this topic?

Participants agreed that a case-control design was appropraite as the outcome was suitably rare (death from prostate cancer).  Cases and controls were identified from a previous cohort study (otherwise known as a nested case-control study design); it was suggested that using a clearly defined closed cohort strengthened the design.

Q2 – Did recruitment for cases and controls affect selection bias?

It was unclear from the paper how participants were recruited in the original cohort study, therefore it is difficult to ascertain the probability of selection bias.  It was questioned whether a bias was created through the different inclusion criteria for cases and controls (i.e. cases were dead, but controls were all alive). This is likely to cause a sample selection bias within the control group by discounting those who were dead.  Participants discussed what the implications of this bias would be upon the effect size.

Q3 – What confounding factors could be present?  Have these been accounted for?

A number of potential confounding factors (such as socio-economic status (SES), ethnicity, family history and other health conditions) were not accounted for in this paper.

Q4 – Study concluded that “a single measure of PSA at age 60 is associated with a man’s lifetime risk of death from prostate cancer” – are these results valid?

Participants questioned whether the results of this study were clinically useful, for example

“Stats hold up but can you predict when someone needs treating ie at 60 or 80? Would treat at 60 prolong life?” (@TwitttwooSue)

Participants did not feel confident that a single measure can infer lifetime risk of death from prostate cancer, especially as the study does not consider other causes of death (sample selection bias).  It was noted that the authors used different thresholds for different parts of the analysis, which can be considered problematic.

Q5 – What are the PH implications of this study? How might these influence future practice/policy?

It was noted that other RCT evidence have demonstrated that prostate-specitic antigen can identify cancers, but it has not been shown to prolong life (all-casue mortality).  Although the authors stated that the findings should inform screening programmes, it was noted that this was not discussed in the paper.

A query was raised questioning why investment in research for evidence to support prostate cancer screening continues, despite evidence to date suggesting that prostate cancer is not suitable to a screening programme.  @carotomes wondered whether there was political weight attached to the research due to the lack of male screening programmes, however @TwittwooSue pointed out that the male-only screening programme for Abdominal Aortic Aneurysm (AAA) screening is due to be launched soon.

Overall it was felt that this paper provided insufficient evidence to support the use of PSA as an effective screening tool for prostate cancer.  #PHTwitJC participants agreed that this paper shouldn’t influence change in public health policy or practice.

Critical Appraisal of Prostate Screening #PHTwitJC Paper

In preparation for this weeks #PHTwitJC I thought it would be a good idea to 1) read the paper in it’s entirety, then 2) critically appraise the paper using the CASP framework for case-control designs.  My theory is the more familiar I am with the paper, the easier it will be to chair the discussions.

(Also – critical appraisal will be tested for within the Part A exam, plus it’s relevant to LO 2.14… so one piece of work can tick a few boxes.  And I’m hoping that practice will make it easier and quicker to do…).  Now for a prostate screening related cartoon:

Critical appraisal of Vickers et al (2010) Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study, BMJ 2010;341:c4521

1 – Did the study address a clinically focused issue?

Yes.  Population = Swedish men (data taken at age 60 and followed-up outcomes at age 85).  Risk factor studied = PSA concerntration at age 60.  Study assessed association between PSA concerntration and outcome of death from prostate cancer, or prostate cancer metastatis.

2 – Did the authors use an appropraite method?

Prostate cancer in men is relatively high (estimate is that close to 40% of 70 year old men have detectable cancer in the prostate at autopsy), yet death from prostate cancer is relatively low.  Therefore the outcome of ‘death from prostate cancer’ is suitably rare for a case-control study design, as used in this study.  The key question of this paper was whether prostate cancer is likely to cause symptoms or shorten life, not whether a man has prostate cancer.

3 – Were the cases recruited in an acceptable way?

Cases were obtained from the ‘Malmo Preventive Project‘ Cohort (subjects were invited to participate in a broad health-screening programme, including a physical examination and a panel of laboratory tests – the objective of the project was to identify individuals with high-risk of cardiovascular disease and alcohol abuse).  As a large representative sample of the population, with health information and stored samples, on face value this appears to be a convenient and appropriate recruitment method.  The paper described the cohort as:

The cohort reported here includes 1167 men born in 1921, constituting 71% of the eligible population, who gave blood and completed medical history and lifestyle questionnaires in 1981-2

According to the MPP website link and numbers there was a large drop-out rate (as often the case in cohort studies); only 40% had completed the study in full.  I’m not sure what ‘eligible population‘ refers to – men born in Malmo in 1921?  Cohort population who had completed health data? Is ‘cohort reported here’ different from MPP?  Important to know precisely what population is being referred to.  Also – there is likely to be a healthy-participant selection bias as participants would have agreed to tests to be taken and to participate in the topic of the research (CVD and Alcohol).

Case selection: cases were defined precisely and verified by blinded/independent clinicians.  Number of cases selected was all meeting case definitions within cohort.  Case identification was reliant upon Cancer Registry records, which are reported to be very reliable in Sweden.  No power calculation was apparent.

4 – Were the controls recruited in an acceptable way?

We used a nested case-control design to analyse data from the cohort. Separate matches were conducted for each of the three study events: clinically diagnosed prostate cancer, prostate cancer metastasis, and death from prostate cancer.

Cases were matched 3:1 (which is excellent!) from the same cohort population (therefore the same healthy-participant selection bias applies).  For each case, controls were selected at random (precise randomisation method omited) from a group of men who were alive and event-free at the time of the event in the case.  They were matched on date of birth and date of base-line blood sample (with a 3 month window).

I guess three questions arise here. 1 – what impact would a healthy-participant selection bias have upon the study? Is this group different to the general population? This population is probably more likely to engage in any screening programmes, but do we know whether the incidence of life-threatening prostate cancer is comparable from this group to the general population?  2 – (and this may be a silly question, but) why did cases need to be alive at the time of the case-event? Does this not contradict the point of controls; for them to be exactly the same (date of birth, blood sample) apart from their outcomes (e.g. prostate cancer or metastatis is cases and diseases-free or death in controls).  What effect does exclusion of dead controls (at time of case-event) have upon study?  3 – (again, this may be a silly question, but) would it be realistic and/or useful at all to match cases and controls to PSA levels?

5 – Was the exposure accurately measures to minimise bias?

Case-control studies normally have a disadvantage of reliying upon historical records and memory/recall for exposure measurements.  However, this study design overcomes such problems as the exposure (PSA) was measured prior to the events.  Furthermore, the exposure samples were assayed in anticoagulated blood plasma (stored at −20°C) and re-tested and ‘determined as previously reported’.  Identical objective methods were used to assess PSA concerntration levels for both cases and controls.  It was not mentioned whether the re-test were done by someone blinded or independent to this investigation, but that would’ve increased the reliability of such concerntration measures.

The use of PSA as a valid marker for prostate cancer was discussed by the authors.

6 – What confounding factors have the authors accounted for? Were these accounted for in the design/analysis?

Main factors which concern me relate to the original cohort recruitment.  Although the authors of this study have reported the age and clinical exposure and outcomes of participants (both cases and controls), no consideration seems to have been given to their socio-economic status, ethnicity (men with african-heritage are more at risk), family history (risk doubles when prostate cancer present in immediate family), and other health conditions (such as men with diabetes mellitus appear to have a lower risk of developing prostate cancer).  (For further information on Epidemiology of Prostate Cancer go here)

None of these potential confounders were acknowledged or accounted for in this paper.

7 – What were the results of this study?

There were 43 cases of metastasis and 35 deaths from prostate cancer. Concentration of prostate specific antigen at age 60 was associated with prostate cancer metastasis (area under the curve 0.86,  95% confidence interval 0.79 to 0.92; P<0.001) and death from prostate cancer (0.90, 0.84 to 0.96; P<0.001)… Although only a minority of the men with concentrations in the top quarter (>2 ng/ml) develop fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Conversely, men aged 60 with concentrations at the median or lower (≤1 ng/ml) were unlikely to have clinically relevant prostate cancer (0.5% risk of metastasis by age 85 and 0.2% risk of death from prostate cancer).

8 – How precise are the results?

Can’t fault reporting of ROC curves, tables, 95% confidence intervals with associated p-values.  I found the results quite straightforward and easy to understand.

*However*… one cannot rule out the effect of counfounders; the participant characteristics were not reported, acknowledged or discussed, nor adjusted for.

As well as considering the influence of participant characteristics within cohort, important to also consider charactertistics of non-responders/drop-outs… this is particularly important when drop-out is high (i.e. 60% in the MPP).  The author should not assume that all readers are familiar with the MPP study, and moreover they should report the charactertistics of their participants as this is highly relevant to the interpretation of their reported findings.

9 – Do you believe the results?

The results appear to be positive – it is easy to be swayed due to the positive correlation between PSA concerntration and prostate cancer outcome.  The author has reported a significant p-value, therefore the results are unlikely to be due to chance.  The effect of bias and confounding cannot be ruled out…

The study design and methods are well reported and objective, but the study has been let down in it’s reporting of participant (and non-participant) charactertistics.  Therefore even if the results were valid, one could not be sure whether these results are applicable to local and general populations.

10 – Can the results be applied to the local population?

Insufficient description of cohort population (aside from nationality and age) to make comparisons to local population.  Authors acknowledge further research on PSA and race would be useful, yet no description of the ethnic classifications is provided in this study.

11 – Do the results of this study fit with other available evidence?

Screening is associated with considerable overdiagnosis, and many men need to be screened to save one life.  PSA is a common screening tool for prostate cancer and this study seeks to stratify risk of adverse-event prostate cancer with PSA as meansured at age 60.

Screening: Health Knowledge Interactive Learning Module

For those preparing for the FPH Part A exams, I strongly advise having a look around the Health Knowledge website.  It has pretty much *everything* we’ll need, including the ‘public health textbook’ (which correlates identically to the Part A syllabus) as well as a variety of self-taught modules.  There are plenty of further resources and it’s also user friendly.  Thumbs up from me!

Today, I thought I would re-familiarise myself with screening via the interactive module.

Chapters 1-5 cover the basic concepts, which is a bit simplistic if you’ve studied screening during a masters.  Chapters 6-8 I found interesting practical exercises and tips of how to apply knowledge and use public health skills (such as commissioning and working with media) and chapter 9 was an interview with Muir Grey where he described the changes and improvements made to screening programmes in the UK since the 70s.  Overall, quite a time-consuming unit!  A good overview, but feel I probably need to make notes explicitly related to the syllabus points to obtain the level of knowledge needed to survive a Part A question on screening.

What was refreshing however, was the practical element of this module.  Compared to the academic learning environment which prioritises test accuracy, today I learnt about the new (to me) concept of programme accuracy.  The main point to learn being a screening tool/test is only as good as the programme it is set in.  You may have a very accurate test, but if attention is not paid to training of staff who obtain the sample, communication between different agencies (such as labs, primary care…etc) is inadequate, and failsafe systems are not enforced, at best a screening programme is ineffective and at worst a serious incident (SI) can occur.