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Article of the Week: ERSPC risk calculators significantly outperform the PCPT 2.0 in the prediction of PCa

November 9, 2016/by admin Z.9

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study

Robert W. Foley*,†, Robert M. Maweni‡, Laura Gorman†, Keefe Murphy§,¶, Dara J. Lundon Z*,†,**, Garrett Durkan††,‡‡, Richard Power§§, Frank O’Brien¶¶, Kieran J. O’Malley**, David J. Galvin†,**,***, T. Brendan Murphy§,¶ and R. William Watson*,†

*UCD School of Medicine, University College Dublin, †UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland, ‡Croydon NHS Trust, Croydon University Hospital, London, UK, §UCD School of Mathematical Sciences, University College Dublin, ¶Insight Centre for Data Analytics, University College Dublin, **Department of Urology, Mater Misericordiae University Hospital, Dublin, ††Department of Urology, University Hospital Galway, Galway, ‡‡Department of Urology, University Hospital Limerick, Limerick, §§Department of Urology, Beaumont Hospital, Dublin, ¶¶Department of Urology, University Hospital Waterford, Waterford, and ***Department of Urology, St. Vincent’s University Hospital, Dublin, Ireland

Read the full article

Objective

To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and two iterations of the European Randomised Study of Screening for Prostate Cancer (ERSPC) Risk Calculator, one of which incorporates prostate volume (ERSPC-RC) and the other of which incorporates prostate volume and the prostate health index (PHI) in a referral population (ERSPC-PHI).

Patients and Methods

The risk of prostate cancer (PCa) and significant PCa (Gleason score ≥7) in 2001 patients from six tertiary referral centres was calculated according to the PCPT-RC and ERSPC-RC formulae. The calculators’ predictions were analysed using the area under the receiver-operating characteristic curve (AUC), calibration plots, Hosmer–Lemeshow test for goodness of fit and decision-curve analysis. In a subset of 222 patients for whom the PHI score was available, each patient’s risk was calculated as per the ERSPC-RC and ERSPC-PHI risk calculators.

Results

The ERSPC-RC outperformed the PCPT-RC in the prediction of PCa, with an AUC of 0.71 compared with 0.64, and also outperformed the PCPT-RC in the prediction of significant PCa (P<0.001), with an AUC of 0.74 compared with 0.69. The ERSPC-RC was found to have improved calibration in this cohort and was associated with a greater net benefit on decision-curve analysis for both PCa and significant PCa. The performance of the ERSPC-RC was further improved through the addition of the PHI score in a subset of 222 patients. The AUCs of the ERSPC-PHI were 0.76 and 0.78 for PCa and significant PCa prediction, respectively, in comparison with AUC values of 0.72 in the prediction of both PCa and significant PCa for the ERSPC-RC (P = 0.12 and P = 0.04, respectively). The ERSPC-PHI risk calculator was well calibrated in this cohort and had an increase in net benefit over that of the ERSPC-RC.

Conclusions

The performance of the risk calculators in the present cohort shows that the ERSPC-RC is a superior tool in the prediction of PCa; however the performance of the ERSPC-RC in this population does not yet warrant its use in clinical practice. The incorporation of the PHI score into the ERSPC-PHI risk calculator allowed each patient’s risk to be more accurately quantified. Individual patient risk calculation using the ERSPC-PHI risk calculator can be undertaken in order to allow a systematic approach to patient risk stratification and to aid in the diagnosis of PCa.

Vasectomy causes aggressive prostate cancer – HELP!!!

July 14, 2014/7 Comments/by Declan Murphy

How many of you have already had a patient get in touch about this latest scare? As one expects nowadays, I first heard about this paper on Twitter within a few minutes of it being published, but it wasn’t long after that a recent patient of mine rang my rooms to challenge me about the reassurance I had given him only last week about the lack of increased risk of prostate cancer, which he had specifically asked me about. And of course since then, we have had headlines in the mass media all over the world alerting us to the results of this 24-year study that suggests that vasectomy confers an increased risk of not just prostate cancer, but high-grade prostate cancer in men undergoing vasectomy. Here are just some of the headlines:

So what are we to make of all this? The private vasectomy counselling has always been a challenging area due to the well documented possibilities of early and late failure, and also of the ever present issue of chronic scrotal pain. And while the area of prostate cancer risk has been raised previously, I must say I have always felt comfortable saying that on balance, the increased risk of developing significant prostate cancer following vasectomy proved to be minimal. “Don’t worry about it” was my typical blithe reassurance. Do I have cause to change my advice now?

Let’s look at this paper from Siddiqui et al. The data is taken from the well-known Health Professionals Follow-up Study (HPFUS), which originally enrolled almost 50,000 men aged between 40 and 75 back in 1986. Of these, about 12,000 (25%) underwent vasectomy and 6000 of these (12.2% of population) were subsequently diagnosed with prostate cancer over the 24-year follow-up period. Of these, 811 (1.6%) died of prostate cancer. The authors calculate that vasectomy was associated with a small overall increase in the risk of prostate cancer (RR = 1.10). However the headlines are coming from the higher relative risk of 1.22 among men subsequently diagnosed with high-grade prostate cancer (Gleason 8 to 10). Also, vasectomy appeared to confer a higher relative risk (1.19) of actually dying of prostate cancer or developing distant metastases compared to men who did not undergo vasectomy. It is these findings that vasectomy appears to confer not just an increased risk of prostate cancer, but an increased risk of developing aggressive or a lethal prostate cancer, which has provoked some concern.

This topic is not new and other studies have shown that this risk does not exist or at best, the risk is minimal and the quality of evidence not good enough to change practice. Does this current paper change all that? It will certainly change the nature of counselling for men considering vasectomy as there may well be a case to consider. As the population of men presenting for vasectomy are not a typical population who would be counselled about the early detection of prostate cancer, perhaps this other difficult counselling area also needs to be broached.

HELP!!!!

Declan Murphy is a urologist at Peter MacCallum Cancer Centre in Melbourne, Australia, and Associate Editor at BJUI. Twitter @declangmurphy

Fish Oil Causes Prostate Cancer: fact or fishy tale?

August 13, 2013/4 Comments/by Amanda Chung

Following the recent fish oil and prostate controversy (which BJUI Chairman Dr David Quinlan recently blogged about, the August International Urology Journal Club discussion on Twitter was based on the recent high-profile (and controversial) paper “Plasma Phospholipid Fatty Acids and Prostate cancer risk in the Select trial”, available by advance access from the Journal of the National Cancer Institute, June 10, 2013.

In the recent weeks, many concerned patients had attended urologist and GP clinics, enquiring about the reports that fish oil supplements increase the risk of prostate cancer. This has led to lengthy discussions between patients and their doctors during consultations, and even caused some clinics to run overtime.

So, does fish oil really lubricate prostate cancer growth, or is this all just a fishy tale?

In summary, this case–cohort study set out to examine the association between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial. 834 men diagnosed with prostate cancer formed the prostate cancer group. 1393 men chosen at random, and matched according to age and race, formed the non-cancer group. The study reports that men in the lowest quartiles of LCω-3PUFA, compared with men in the highest quartile, had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Similar associations were reported for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response. This study therefore concluded that increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA was confirmed. The authors went on to say that the consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis, and that recommendations to increase LCω-3PUFA intake should consider these risks.

There has been a lot of media hype surrounding this paper, with the claim that fish oil supplements may increase one’s risk of prostate cancer. This has led to many anxious patients. It is not the first time that sensational claims of natural therapies either causing or preventing cancer has received a lot of media attention.

However, as doctors who have patients and colleagues asking us for sound advice on the matter, it is important that we don’t simply dismiss such hype (and questions from anxious patients) without looking into the matter more deeply, examining the evidence for ourselves, and forming a sensible opinion.

Early in the discussion, the methodology of the study was criticised as being observational by Kate Linton and Faisal Ahmed agreed. The study lacked a proper control group, and did not adequately address confounding factors. Associations were attributed to causation.

Stacy Loeb pointed out that the study did not record the amount of fish oil supplements ingested by any of the men in the study and instead on the basis of a single serum level. Yet the media extrapolates the study’s findings to make recommendations about fish oil supplements, which can be delivered in various formulations and doses.

There was also concern for the assay method used in measuring plasma lipids.

This study’s conclusions might have interesting commercial ramifications. I wonder whether there has been a drop in fish oil supplement sales this week?

However, it is worthwhile to note that there have been other prospective studies and metanalyses that have shown an inverse association between fish oil and prostate cancer. Helen Nicholson brought to our attention, a paper published in Cancer Epidemiology, Biomarkers and Prevention in 2007, which concluded that higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer.

To conclude the discussion, several participants stated

My take home message from the August #urojc discussion is;

1.Although interesting, this study is limited by its methodology – it was not a randomised controlled trial of fish oil supplements versus no fish oil supplements. Therefore it cannot answer this question.

2.This study does not provide sufficient evidence to confirm whether omega-3 fatty acids conclusively lead to increased risk of prostate cancer.

3.Media hype = anxious patients. But we can tell our patients the science.

The winner of the best tweet prize for the August #urojc was Kate Linton for the following tweet which highlighted a significant shortcoming of the paper.

The August #urojc prize was kindly supported by the Asian Journal of Andrology.

We thank everyone who participated in the August #urojc, and to the many other on-lookers.

We look forward to your input in the next great International Urology Journal Club discussion, in early September 2013. The topic will soon be announced. If you would like any specific papers to be discussed, please DM us @iurojc – we always welcome your suggestions and feedback.

Dr Amanda Chung is an Australian Urological Surgeon in Training, currently based at The Wollongong Hospital, New South Wales. @AmandaSJChung

Fish Oils and Prostate Cancer

August 1, 2013/11 Comments/by David Quinlan

If a Blog can be a call for help, then this is it! Since the recent high-profile paper in JNCI (https://jnci.oxfordjournals.org/content/early/2013/07/09/jnci.djt174.abstract) suggesting that Omega 3 supplements increase the risk of Prostate Cancer and induce high grade prostate cancer, I am plagued by patient and colleague concerns about whether or not men should stop taking Omega 3 supplements! I know that health care providers all over the world have been similarly inundated. What are we to say to our patients?

Let us first look at the paper. The authors used data collected as part of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to determine whether men with high levels of plasma phospholipid fatty acids (high levels of which are present in fish oil supplements), namely long-chain ω-3 polyunsaturated fatty acids ([LCω-3PUFA], were at higher risk of developing prostate cancer. The case subjects in the study were 834 men diagnosed with prostate cancer, of whom 156 had high-grade cancer. The comparison cohort consisted of 1393 men selected randomly at baseline and matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. The results? Compared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). These results are strong enough for the authors to conclude that there is increased prostate cancer risk among men with high blood concentrations of these plasma phospholipid fatty acids, and that “the consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis”.

Crikey! Fish oil supplements increase risk of prostate cancer! Is it really so?? Is the study methodology robust enough to change practice? Undoubtedly, there are a lot of patients taking these supplements, some prescribed by medical practitioners; even my lovely ophthalmologist wife tells me that nearly every patient with macular degeneration worldwide is on it! My knowledge of antioxidants is somewhat pedestrian and I feel like an amateur in advising whether or not men should discontinue Omega 3 supplements.

What should we tell those who ask us? All comments gratefully received.

Dr David Quinlan
Consultant Urologist, St Vincent’s Hospital,
Senior Lecturer, University College Dublin
Chairman, BJUI