Screening for prostate cancer: time to put all the data on the table
BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i2574 (Published 25 May 2016) Cite this as: BMJ 2016;353:i2574
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We thank Dr Kole for his response to our article calling for release of the critical data that underpin the advice that Public Health England (PHE) offers to all GPs and men aged 50 and over about whether to have PSA screening. He draws attention to key points made by PHE that emphasise the current level of uncertainty that exists for doctors and patients and why this data release is so important.
The first of these PHE points that; “you are more likely to die of prostate cancer and/or to experience the complications of advanced incurable prostate cancer if you do not have PSA screening" is correct based on the ERSPC's authors incomplete analysis of the incompletely published data as we discussed in detail in our publications.
However, this trial appears to contain a number of large biases that would produce incorrect results favouring screening, as we have also discussed in detail. Furthermore, the absolute differences in prostate cancer specific mortality, even without correction for these apparent biases, were very small and showed a reduction of prostate-specific mortality of only 0.11 per 1000 person-years despite reducing this to the headline figure of a 21% reduction in relative risk of death from prostate cancer, as highlighted in his second point. To mention the large relative risk reduction of dying from prostate cancer, rather than concentrate on the very small absolute mortality reduction, with no correction for risk groups and treatment differences, is very misleading for most doctors and patients. It also diverts attention from the lack of difference in the overall mortality.
This is why the full data release from this study for independent analysis is vital and urgent. There is no longer, and has never been, any reasonable reason to continue to withhold independently verified details on all the men in the trial in each arm who died, with columns for:
1. Stage and risk-group (low, intermediate or high).
2. Treatment received out of active surveillance and watchful waiting, ADT alone and radical treatment with surgery or radiation.
These data should be easily and readily retrieved and analysed, and the continuing delay of 7 years and counting may be adding vast and unnecessary physical and financial costs to men and our communities as Dr Kole states.
A final important consideration is that the results from the three arm ProtecT study are expecteded to be published soon and these results are certain to have added influence in the decision making for men about having screening with PSA and treatment for early stage prostate cancer.
Consequently, and in it the interests of all men and their loved ones, we agree with Dr Kole and urge all doctors and professional medical groups everywhere, as well as all leading government public health groups such as PHE, to increase the pressure on ERSPC to release its detailed data from this publicly-funded clinical trial for independent analysis without further delay.
Competing interests: No competing interests
Dear Sirs,
Public health England seems to have taken quite a different route in their advice:
"Updated guidance for GPs on PSA testing for prostate cancer" [1]
I am very concerned that notwithstanding the lacking evidence, PHE has taken the the step to implicitly advise men to request screening from their GP :
"If you do not have the PSA test you are more likely to die of prostate cancer than men who do have the PSA test. You are also more likely to experience the complications of advanced incurable prostate cancer" [2]
They write in their information leaflet for GPs :
"Evidence suggests PSA screening could reduce prostate-cancer related mortality by 21%." [3]
Perhaps the authors and other authorities in this field could enlighten PHE, and prevent further pressure on General Practice to provide unevidenced PSA testing of asymptomatic patients without risk factors, with all the negative [cost/resource] implications that follow for patients and the NHS.
Yours Sincerely,
Bastiaan Kole, GP, Fulham.
1. PHE Updated guidance for GPs on PSA testing for prostate cancer
https://phescreening.blog.gov.uk/2016/03/29/updated-guidance-for-gps-on-...
2. PHE summary information sheet for men aged 50 and over: https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil...
3. PHE summary information sheet for GPs
https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil...
Competing interests: Co-Founder and partner of Resilient GP
Re: Screening for prostate cancer: time to put all the data on the table
I broadly agree with the conclusion of the article that clinical trial data should be made widely available. The ERSPC data is hardly a secret – it has after all been released to several outside groups, including my own – but there is a clear case to be made that all clinical trial data be made freely available on the web after a suitable embargo period.
That said, readers should not be mislead into thinking that this is an open call for transparency from a set of disinterested scientists active in the field. The authors do not have a track record of empirical clinical research in prostate cancer screening. However, they have made remarkable, even sensationalist, claims in media such as books, [1] articles [2] and websites. [3]
More pertinently, there are a very large number of problems with the article.
I just chose a sentence at random: "However, when the complete dataset of men between 50 and 74 years of age is used, rather than just those aged 55-69, the difference [in mortality] falls to 15%, which is not significant." Here is the appropriate text from the cited article: "In addition to the core age group [aged 55 – 69], we noted a significant reduction in prostate cancer mortality for all 181 999 men aged 50–74 years at entry".
The next paragraph starts: “These data matter because the two positive European studies are influencing many men worldwide to have regular PSA screening”. As it turns out, there is no evidence that the ERSPC results have changed screening practices. indeed PSA testing in the US has fallen since the results of these trials. The following sentence reads: “However, it has still not been established that the improved outcomes for the screened groups was due to screening rather than the apparent large imbalance in treatments used between equivalent risk patients in the study and control groups.” It is true that there was a large imbalance in treatments used in study and control groups, but this is the point of screening: you treat men curatively by finding cancer early not palliatively when finding cancer late. But the exact statement that there was a large imbalance in "equivalent risk patients" is false. See, for example, Wolters et al. Int J Cancer. 2010;126:2387-2393.
The authors then write: "Independent evaluation of the European studies have drawn attention to their apparent shortcomings and possible unintended biases, but the study authors have dismissed these evaluations without directly answering the core questions". Readers may note that 3 of the 5 references given to "independent" evaluations are by the study authors themselves, and it is simply not right that the ERSPC authors have not directly addressed critiques of their study. [4]
I could go on, but it should be apparent that a point-by-point rebuttal of this paper would take more time than I could reasonably take from my own scientific work.
References
1. Ablin RJ, Piana R. The great prostate hoax. St Martin's Press (2014)
2. https://www.nytimes.com/2014/11/26/opinion/the-problem-with-prostate-scr...
3. http://www.urotoday.com/beyond-the-abstracts/urologic-oncology/prostate-...
4. Carlsson S, Roobol MJ, Schröder FH, Hugosson J, Auvinen A. RE: Prostate-specific antigen screening trials and prostate cancer deaths: the androgen deprivation connection. J Natl Cancer Inst. 2014 Apr 26;106(5). pii: dju079. doi: 10.1093/jnci/dju079. PubMed PMID: 24771874
Competing interests: I am co-inventor or the 4Kscore, a reflex test for aggressive prostate cancer. I derive royalties from clinical use of the test. The more men get PSA tests, in theory, the more money I could make. I have spent much of my career arguing for men to get fewer PSA tests.