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Editorial: Time to raise the bar in localised prostate cancer

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In this issue of BJUI, Ficarra et al. present the long-term (mean 81.3 months) follow-up of a case series of 183 men that underwent robot-assisted radical prostatectomy (RARP) at a single academic medical centre in Europe. To the authors’ credit, they report both cancer control and patient-reported outcomes, using well-known validated and reliable instruments to assess both urinary and sexual function. Like others before them, Ficarra et al. demonstrate that RARP is a safe and effective way to treat localised prostate cancer.

However, the question the study raises is not so much about the operation’s success rate but rather how success is defined in the first place. Throughout the prostate cancer literature, we have loosened definitions of successful urinary and sexual function to make RP more palatable to patients. In the present study, potency is effectively defined as a Sexual Health Inventory for Men (SHIM) score of >17 with or without the use of a phosphodiesterase type 5 (PDE5) inhibitor. Similarly, continence is defined as either no pad use or the use of a single pad ‘for security’. This approach certainly has face validity to us as clinicians. After all, PDE5 inhibitors are effective therapies for erectile dysfunction and the use of a single urinary liner certainly does not seem like a big deal. However, we need to consider this from the patient’s perspective. Both urinary pads and PDE5 inhibitors are costly to the patient and may represent an inconvenience and a potential embarrassment to many men. Is it really fair to tell men that they will be potent and/or continent after the operation, if they are going to require these additional interventions to achieve the desired state? I think not.

Going forward, we must set the bar higher if we are to be truly honest with our patients and optimise outcomes after RP. We must effectively ‘leave patients the way we found them’ with the critical difference being that they are now cancer-free. In other words, if a man was able to achieve an erection sufficient for intercourse preoperatively without the use of PDE5 inhibitors, he should only be considered potent postoperatively if he is in the same state, i.e. able to achieve an erection sufficient for intercourse without the use of a PDE5 inhibitor. The same holds true for urinary continence and the use of urinary liners. This will certainly make it more difficult to achieve the ‘trifecta’ but the reader should remember that the term is meant to imply ‘triple perfection’ and needing to use a PD5 inhibitor for sexual activity or having to wear a urinary pad, while acceptable to many patients, is certainly not perfect.

Some will say that I am insisting that the bar be set too high, that patients are willing to accept these reasonable but less than perfect definitions of success to be cured of their cancer. I acknowledge that there may be some validity to this argument in men with higher risk disease, where we know that cancer control and cure is necessary. However, I do not think the argument holds up in the case of men with low-risk disease, many of whom will never experience any symptoms of prostate cancer in their lifetimes and will not die of their disease if it were left untreated. In these patients, setting the bar higher would not only be more honest but it would probably increase the uptake of active surveillance and decrease overtreatment. In summary, while the use of more stringent definitions of success after RP may make our operations look ‘worse’, it will help our patients to set more realistic expectations, make more informed choices about treatment and ultimately to have better outcomes.

David F. Penson
Department of Urologic Surgery, Vanderbilt University, 2525 West End Avenue, Suite 1200, Nashville, TN, 37203, USA

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Fish Oil Causes Prostate Cancer: fact or fishy tale?

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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

Changing paradigms in the investigation of an elevated PSA level

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Changing paradigms in the investigation of an elevated PSA level

Roger Kirby, Uday Patel, Ben Challacombe and Prokar Dasgupta
The Prostate Centre, London, UK

Published as a comment article in BJU International 2013; 112: 283–285. doi: 10.1111/j.1464-410X.2012.11779.x.

Video Commentary by Roger Kirby, BJUI Associate Editor.

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The Melbourne Consensus Statement on Prostate Cancer Testing

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The final, peer-reviewed version of this Consensus Statement has now been published in BJUI. You can find it here. The full citation is Murphy, D. G., Ahlering, T., Catalona, et al. (2014), The Melbourne Consensus Statement on the early detection of prostate cancer. BJU International, 113: 186–188. doi: 10.1111/bju.12556

A consensus view on the early detection of prostate cancer, led by experts at the Prostate Cancer World Congress, Melbourne, 7–10th August 2013

Recent guideline statements and recommendations have led to further confusion and controversy regarding the use of Prostate Specific Antigen (PSA) testing for the early detection of prostate cancer. Despite high-level evidence for the use of PSA testing as a screening tool, and also for its role as a predictor of future risk, the U.S. Preventive Services Taskforce (USPSTF) has called for PSA testing to be abandoned completely [1], and many men are therefore not given the opportunity for shared decision-making. Other groups such as the American Urological Association, National Comprehensive Cancer Network , and European Association of Urology support a role for PSA screening but with somewhat conflicting recommendations. The majority of guideline statements have endorsed the role of shared decision-making for men considering PSA testing.

To address these somewhat conflicting and confusing positions, a group of leading prostate cancer experts from around the world have come together at the 2013 Prostate Cancer World Congress in Melbourne and have generated the following set of consensus statements regarding the use of PSA testing. The goal of these statements is to bring some clarity to the confusion that exists with existing guidelines, and to present reasonable and rational guidance for the early detection of prostate cancer today.

1.        Consensus Statement 1: For men aged 50–69, level 1 evidence demonstrates that PSA testing reduces prostate cancer-specific mortality and the incidence of metastatic prostate cancer. In the European Randomized Study of Screening for Prostate Cancer (ERSPC), screening reduced metastatic disease and prostate cancer-specific mortality by up to 30% and 21% respectively in the intent-to-treat analysis, with a greater reduction after adjustment for noncompliance and contamination[2,3]. In addition, the Goteborg randomized population-based randomized trial showed a reduction in metastatic disease and prostate cancer mortality with screening starting at age 50 [4]. The degree of over-diagnosis and over-treatment reduces considerably with longer follow-up, such that the numbers needed to screen and numbers needed to diagnose compare very favourably with screening for breast cancer. The boob reduction in Tri-Cities procedures are one among the very best rated and most valued cosmetic procedures among woman (and some men) within the Tri-Cities, TN area.  High patient satisfaction ratings for this procedure should come as no surprise, given the quantity of relief the operation provides to those that suffer from heavy or large breasts. With years of experience, and a diary of positive patient outcomes, Dr. Jim Brantner, M.D. can help improve your overall wellness, comfort, and confidence through a secure and effective breast reduction procedure. Breast reductions, otherwise referred to as Reduction Mammoplasties, are often a relief for thousands of men and ladies . If your breasts are causing pain or other health issues, then you’ll wish to think about a breast reduction. In a breast reduction, our surgeon improves a patient’s health by removing a predetermined amount of breast tissue, skin, and fat. This reduces the patient’s breast size overall and helps improve their neck, shoulder, back, and overall health. If you would like to understand what the procedure evolves in additional detail, please read subsequent paragraph. If you discover you are feeling squeamish, be happy to scroll to subsequent section. To remove the surplus breast tissue, your surgeon will make an incision around your nipple then downward over your breast — consider a keyhole. Our expert team will remove excess skin, tissue, and fat before adjusting your nipple for cosmetic purposes. Your surgeon may have to use drainage tubes before your incision site is sutured. Our team will then wrap your breasts during a special gauze; your doctor may recommend a surgical bra, as well. While routine population-based screening is not recommended, healthy, well-informed men in this age group should be fully counseled about the positive and negative aspects of PSA testing to reduce their risk of metastases and death. This should be part of a shared decision-making process. According to a study, it is also revealed that not every time you need a surgery, breast cancer can be also be treated easily. With the advancement of the technology, Botox injection and dermal filler injection can be used by patient of breast cancer. But for this an expert recommendation is required.  Visit the dermal fillers melbourne expert to know more.

 2.        Consensus Statement 2: Prostate cancer diagnosis must be uncoupled from prostate cancer intervention. Although screening is essential to diagnose high-risk cases within the window of curability, it is clear that many men with low-risk prostate cancer do not need aggressive treatment. Active surveillance protocols have been developed and have been shown to be a reasonable and safe option for many men with low-volume, low-risk prostate cancer [5,6]. While it is accepted that active surveillance does not address the issue of over-diagnosis, it does provide a vehicle to avoid excessive intervention. Active surveillance strategies need standardization and validation internationally to reassure patients and clinicians that this is a safe strategy.

 3.        Consensus Statement 3: PSA testing should not be considered on its own, but rather as part of a multivariable approach to early prostate cancer detection. PSA is a weak predictor of current risk and additional variables such as digital rectal examination, prostate volume, family history, ethnicity, risk prediction models, and new tools such as the phi test, can help to better risk stratify men. Prostate cancer risk calculators such as those generated from the ERSPC ROTTERDAM, the Prostate Cancer Prevention Trial (PCPT) , and from Canada , are useful tools to help men understand the risk of prostate cancer in these populations. Further developments in the area of biomarkers, as well as improvements in imaging will continue to improve risk stratification, with potential for reduction in over-diagnosis and over-treatment of lower risk disease.

4.        Consensus Statement 4: Baseline PSA testing for men in their 40s is useful for predicting the future risk of prostate cancer. Although these men were not included in the two main randomized trials, there is strong evidence that this is a group of men who may benefit from the use of PSA testing as a baseline to aid risk stratification for their likely future risk for developing prostate cancer [7], including clinically significant prostate cancer. Studies have shown the value of PSA testing in this cohort for predicting the increased likelihood of developing prostate cancer 25 years later for men whose baseline PSA is in the highest centiles above the median [8,9]. For example, those men with a PSA below the median could be spared regular PSA testing as their future risk of developing prostate cancer is comparatively low, whereas those with a PSA above the median are at considerably higher risk and need closer surveillance. The median PSA for men aged 40–49 ranges from 0.5–0.7 ng/ml, with the 75th percentile ranging from 0.7–0.9ng/ml. The higher above the median, the greater the risk of later developing life-threatening disease. We recommend that a baseline PSA in the 40s has value for risk stratification and this option should be discussed with men in this age group as part of a shared decision-making process.

 5.        Consensus Statement 5: Older men in good health with over ten year life expectancy should not be denied PSA testing on the basis of their age. Men should be assessed on an individual basis rather than applying an arbitrary chronological age beyond which testing should not occur. As life expectancy improves in many countries around the world (men aged 70 in Australia have a 15 year life expectancy), a small proportion of older men may benefit from an early diagnosis of more aggressive forms of localised prostate cancer, just as it is clear that men with many competing co-morbidities and less aggressive forms of prostate cancer are unlikely to benefit irrespective of age. Likewise, a man in his 70s who has had a stable PSA at or below the median for a number of years previously is at low risk of developing a threatening prostate cancer and regular PSA screening should be discouraged.

An important goal when considering early detection of prostate cancer today, is to maintain the gains that have been made in survival over the past thirty years since the introduction of PSA testing, while minimizing the harms associated with over-diagnosis and over-treatment. This is already happening in Australia where over 40% of patients with low-risk prostate cancer are managed with surveillance or watchful waiting [10], and in Sweden where 59% of very low risk patients are on active surveillance. This is also reflected in current guidelines from the EAU, NCCN and other expert bodies, and in a comment from AUA Guideline author Dr Bal Carter in the BJU International.

Abandonment of PSA testing as recommended by the USPSTF, would lead to a large increase in men presenting with advanced prostate cancer and a reversal of the gains made in prostate cancer mortality over the past three decades.

However, any discussion about surveillance is predicated on having a diagnosis of early prostate cancer in the first instance. As Dr Joseph Smith editorialized in the Journal of Urology following the publication of the ERSPC and PLCO trials, “treatment or non-treatment decisions can be made once a cancer is found, but not knowing about it in the first place surely burns bridges” [11]. A key strategy therefore is to continue to offer well-informed men the opportunity to be diagnosed early, while minimizing harms by avoiding intervention in those men at low risk of disease progression. This consensus statement provides some guidance to help achieve these goals.

 
Signatories:

A/Professor Declan G Murphy, University of Melbourne, Peter MacCallum Cancer Centre, Melbourne, Australia

Professor Tony Costello, University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia

Dr Patrick C Walsh, The James Buchanan Brady Urological Institute, Johns Hopkins University, USA

Dr Thomas Ahlering, University of California, Irvine, School of Medicine, USA

Dr William C Catalona, Northwestern University Feinberg School of Medicine, USA

Dr Oliver Sartor, Tulane University School of Medicine, USA

Dr Tom Pickles, British Columbia Cancer Agency, Canada

Dr Jane Crowe, Australian Prostate Cancer Research Centre, Australia

Dr Addie Wootten, Royal Melbourne Hospital, Australia

Ms Helen Crowe, Royal Melbourne Hospital, Australia

Professor Noel Clarke, Manchester University, The Christie Hospital, Manchester, UK

Dr Matthew Cooperberg, University of California San Francisco, Helen Diller Family Comprehensive Cancer Centre, USA

Dr David Gillatt, University of Bristol, Bristol Urological Institute, Bristol, UK

Dr Martin Gleave, University of British Columbia, The Vancouver Prostate Centre, Vancouver, Canada

Dr Stacy Loeb, New York University, USA

Dr Monique Roobol, Erasmus University Medical Centre, Rotterdam, The Netherlands

Footnote:

The median PSA for men aged 40–49 ranges from 0.5–0.7ng/ml. The 75th percentile ranges from 0.7–0.9ng/ml.

This blog was originally published on 7th August 2013 and was updated on 13th August 2013.

References:

[1] Moyer VA, Force USPST. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120–34.

[2] Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med. 2012;366:981–90.

[3] Schroder FH, Hugosson J, Carlsson S, Tammela T, Maattanen L, Auvinen A, et al. Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur Urol. 2012;62:745–52.

[4] Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010;11:725–32.

[5] Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol. 2013;63:597–603.

[6] Bangma CH, Bul M, van der Kwast TH, Pickles T, Korfage IJ, Hoeks CM, et al. Active surveillance for low-risk prostate cancer. Crit Rev Oncol Hematol. 2012.

[7] Loeb S. Use of baseline prostate-specific antigen measurements to personalize prostate cancer screening. Eur Urol. 2012;61:875–6.

[8] Vickers AJ, Ulmert D, Sjoberg DD, Bennette CJ, Bjork T, Gerdtsson A, et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study. BMJ. 2013;346:f2023.

[9] Lilja H, Cronin AM, Dahlin A, Manjer J, Nilsson PM, Eastham JA, et al. Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of prostate-specific antigen at or before age 50. Cancer. 2011;117:1210–9.

[10] Evans SM, Millar JL, Davis ID, Murphy DG, Bolton DM, Giles GG, et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011. Med J Aust. 2013;198:540–5.

[11] Smith JA, Jr. What would you do, doctor? J Urol. 2009;182:421–2.

Fish Oils and Prostate Cancer

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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

Twitter: @daithiquinlan

Article of the week: Dutch GPs influenced by ERSPC PSA study

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Every week the Editor-in-Chief selects the 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Miss van der Meer and Dr Blanker discussing their article.

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

Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners

Saskia Van der Meer, Boudewijn J. Kollen*, Willem H. Hirdes, Martijn G. Steffens, Josette E.H.M. Hoekstra-Weebers†, Rien M. Nijman‡ and Marco H. Blanker*

Department of Urology, Isala Clinics, Zwolle, and Departments of *General Practice, †Psychosocial services and ‡Urology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Read the full article
OBJECTIVE

• To determine the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) publication in 2009 on prostate-specific antigen (PSA) level testing by Dutch general practitioners (GPs) in men aged ≥40 years.

MATERIALS AND METHODS

• Retrospective study with a Dutch insurance company database (containing PSA test claims) and a large district hospital-laboratory database (containing PSA-test results).

• The difference in primary PSA-testing rate as well as follow-up testing before and after the ERSPC was tested using the chi-square test with statistical significance at P < 0.05.

RESULTS

• Decline in PSA tests 4 months after ERSPC publication, especially for men aged ≥60 years.

• Primary testing as well as follow-up testing decreased, both for PSA levels of <4 ng/mL as well as for PSA levels of 4–10 ng/mL.

• Follow-up testing after a PSA level result of >10 ng/mL moderately increased (P = 0.171).

• Referral to a urologist after a PSA level result of >4 ng/mL decreased slightly after the ERSPC publication (P = 0.044).

CONCLUSIONS

• After the ERSPC publication primary PSA testing as well as follow-up testing decreased.

• Follow-up testing seemed not to be adequate after an abnormal PSA result. The reasons for this remain unclear.

 

Read Previous Articles of the Week

 

Editorial: Impact of ERSPC study on PSA testing in the Netherlands

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General practitioner (GP)’s view on screening for prostate cancer in the Netherlands: the impact of a randomized trial

I am grateful to be given the opportunity to provide an editorial comment on a so-far unique publication investigating the impact of results of the European Randomized study of Screening for Prostate Cancer (ERSPC) on the attitude of Dutch GPs in requesting a serum determination of PSA in men aged >40 years. Access to data from one of the major health insurance companies and the structure and data acquisition of regional laboratories in the Netherlands provided an opportunity to carry out the project. This included the differentiation of age groups, of primary as opposed to repeat PSA testing and, in the case of the hospital database, of repeat PSA testing within 1 year, which provided the opportunity to address the primary goal of the study: the evaluation of the difference in primary PSA testing rates as well as follow-up testing before and after the 2009 publication of interim data from the ERSPC study. The fact that a Dutch translation of this publication and a recommendation by the Dutch Association of General Practitioners (Nederlands Huisartsen Genootschap, NHG) were mailed at the same time and the fact that GP guidelines had not been changed since 2005 in the Netherlands provided an important basis for the reported study.

Two different databases were used and PSA testing was evaluated 1 year before and 1 year after March 2009 (excluding the month March 2009). An overview of the data acquisition and results is given in Table 1. In brief, the data based on insurance claims show a significant decrease in PSA use before and after the 2009 publication. This decrease was less pronounced or not seen at all in men aged 70–80 or >80 years. The study selectively identified men in the ERSPC region of Rotterdam after exclusion of those assigned for re-testing in the screening arm. In line with earlier investigations, the PSA testing rate in the Rotterdam region was considerably higher then in the rest of the Netherlands. This effect was blamed on increased awareness and possibly on the motivation of men randomized into the control group of the study. The so-called ‘hospital database’ refers to a regional GP laboratory. It remains unexplained why only 2098 men of the total of 9766 men who were identified as having undergone primary PSA testing (Tables 1 and 2 in the study) were included in the analysis. These data show that there was no overall difference in testing before and after the ERSPC publication, but the proportion of re-testing decreased significantly between the two periods.

Table 1: Data acquisition and results.

Several comments can be made on this study. First, information provided on the insurance claims database allows an estimate of the proportion of men in whom PSA is evaluated (123 996/715 000 = 17.3%) and of those who undergo primary PSA testing for early diagnostic purposes (66 848/715 000 = 9.4%). The overall figure contrasts sharply with the results of a study by the Central Bureau of Statistics in the Netherlands, published in 2006. The study shows PSA use of 30–40% for the age groups 60–70 years or older.

Second, as the authors acknowledge, the differentiation between primary PSA tests for the purpose of early diagnosis and for other purposes may not be entirely reliable; however, the bias resulting from possibly incorrect assumptions is likely to be small.

Third, the sub-analysis of data coming from the Rotterdam region is likely to show the impact of greater awareness resulting from written informed consent before randomization and the effect of randomization into a control group. The data confirm an earlier evaluation of this subject (reference 7 in Van der Meer et al.) and at the same time provide a rough estimate of the level of contamination which may take place in the ERSPC study, Rotterdam region.

Fourth, it is interesting to see how age and previous PSA values influence the request for repeat PSA studies. It is counterintuitive (Table 3 in Van der Meer et al.) that even in the critical PSA range 4–10 ng/mL a significant decrease of PSA use within 1 year was seen. The multivariate analysis shows that study period before and after 2009, PSA categories and age groups are all significantly related to the decrease of PSA re-testing within 1 year.

Finally, as one of the initiators of the ERSPC study, I should like to refer to two important follow-up publications (Schröder et al., Heijnsdijk et al.) that point to the over-diagnosis and over-treatment of prostate cancer as the main reasons why the almost 30% reduction in prostate cancer mortality in screened men cannot (yet) be used for establishing population-based screening. For these reasons, the authors fully agree with the viewpoint of the Dutch GP Association and the recommendation against routine use of PSA-driven screening for prostate cancer; however, as pointed out in the last sentences of their paper instruments are now available to decrease over-diagnosis and the rate of unnecessary biopsies. In addition to that, it should be realized that men who are well informed and wish to be tested for prostate cancer cannot be refused PSA testing. To assist this process, the International Society of Urology (SIU) and the international movement ‘Movember’ have recently made available on their websites a validated decision aid for men who wish to be tested, their GPs and their treating urologists.

Fritz H. Schröder
Erasmus Medical Center, Rotterdam, The Netherlands.

Read the full article

Video: PSA testing decreased in the Netherlands after ERSPC study

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Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners

Saskia Van der Meer, Boudewijn J. Kollen*, Willem H. Hirdes, Martijn G. Steffens, Josette E.H.M. Hoekstra-Weebers†, Rien M. Nijman‡ and Marco H. Blanker*

Department of Urology, Isala Clinics, Zwolle, and Departments of *General Practice, †Psychosocial services and ‡Urology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Read the full article
OBJECTIVE

• To determine the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) publication in 2009 on prostate-specific antigen (PSA) level testing by Dutch general practitioners (GPs) in men aged ≥40 years.

MATERIALS AND METHODS

• Retrospective study with a Dutch insurance company database (containing PSA test claims) and a large district hospital-laboratory database (containing PSA-test results).

• The difference in primary PSA-testing rate as well as follow-up testing before and after the ERSPC was tested using the chi-square test with statistical significance at P < 0.05.

RESULTS

• Decline in PSA tests 4 months after ERSPC publication, especially for men aged ≥60 years.

• Primary testing as well as follow-up testing decreased, both for PSA levels of <4 ng/mL as well as for PSA levels of 4–10 ng/mL.

• Follow-up testing after a PSA level result of >10 ng/mL moderately increased (P = 0.171).

• Referral to a urologist after a PSA level result of >4 ng/mL decreased slightly after the ERSPC publication (P = 0.044).

CONCLUSIONS

• After the ERSPC publication primary PSA testing as well as follow-up testing decreased.

• Follow-up testing seemed not to be adequate after an abnormal PSA result. The reasons for this remain unclear.

 

Article of the week: Using MRI to select and monitor active surveillance CaP patients

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Every week the Editor-in-Chief selects the 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.

 

Multiparametric magnetic resonance imaging findings in men with low-risk prostate cancer followed using active surveillance

Jeffrey K. Mullins*, David Bonekamp†, Patricia Landis*, Hosne Begum†, Alan W. Partin*, Jonathan I. Epstein*‡, H. Ballentine Carter* and Katarzyna J. Macura*†

*James Buchanan Brady Urological Institute, †Russell H. Morgan Department of Radiology, and ‡Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

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OBJECTIVE

• To assess the performance of multiparametric magnetic resonance imaging (MRI) in identifying pathological-index (path-index) lesions, defined as cancer present in the same prostate sextant in two separate surveillance biopsies, in men followed within an active surveillance (AS) programme for low-risk prostate cancer (CaP) with extended follow-up.

MATERIALS AND METHODS

• A total of 50 men, representing >215 person-years of follow-up in an AS programme, who were referred for prostate MRI were randomly chosen to have their images reviewed by a radiologist with expertise in prostate MRI, who was blinded to biopsy results.

• Index lesions on MRI were defined as a single suspicious lesion ≥10 mm or >2 lesions in a given prostate sextant. Lesions on MRI were considered suspicious if ≥2 abnormal parameters co-registered anatomically. Path-index lesions were defined as cancer present in a given prostate sextant on two separate biopsy sessions.

• Sensitivity and specificity were calculated to test the performance of MRI for identifying path-index lesions.

• Clinical and pathological features were compared between men with and without a MRI-index lesion.

RESULTS

• A total of 31 path-index and 13 MRI-index lesions were detected in 22 and 10 patients, respectively.

• Multiparametric MRI demonstrated excellent specificity and negative predictive value (0.974 and 0.897, respectively) for the detection of path-index lesions. Sensitivity (0.19) and positive predictive value (0.46) were considerably lower.

• Patients with an index lesion on MRI were younger and less likely to have met the ‘Epstein’ criteria for very low-risk CaP.

• Compared with men without an MRI lesion, a significant increase in biopsy reclassification was noted for men with a MRI lesion (40 vs 12.5%, P = 0.04).

CONCLUSIONS

• A non-suspicious MRI was highly correlated with a lack of path-index lesions in an AS population.

• Multiparametric MRI may be useful in both the selection and monitoring of patients undergoing AS.

 

Read Previous Articles of the Week

 

Editorial: Multiparametric MRI in active surveillance – time to rethink our current strategy?

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Active surveillance for low-risk prostate cancer is gaining increasing acceptance. Indeed, many would argue that it is now the primary management strategy for men who have little to gain from radical therapy but who may incur some harms. However, active surveillance is far from a perfect pathway. First, many men and their physicians find it unacceptable to not treat a known cancer. Second, the burden of follow-up with clinical examinations and serum PSA testing on both men and healthcare systems is far from cost-neutral. Third, the need for repeat transrectal biopsies, which many advocate, carries harms of complications and the difficulties of inaccuracy. Fourth, there is some concern that the window of curability may be lost when men eventually go on to have radical therapy, although overall and disease-specific survival is in fact reassuringly high in the medium term.

Mullins et al. have attempted to address some of these issues by evaluating the role of multi-parametric MRI (mpMRI) in men followed using active surveillance. The results, albeit preliminary, are very encouraging. The ability of mpMRI to exclude clinically significant prostate cancer found on repeat biopsies reflects those results we have seen from other groups (J Urol 2012, BJU Int 2011). Further, they show that the presence of a lesion on mpMRI more often predicts reclassification on repeat biopsy. This has been supported by others who have demonstrated that the inclusion of mpMRI findings into a nomogram was able to predict clinically insignificant prostate cancer better than models without imaging. Mullins et al. have been appropriately guarded about their own results and point out the weaknesses of their cohort in an open manner so readers can judge the external validity of their findings; however, the significance of these results for the urological community cannot be underestimated, particularly as they point us in the direction of important research questions and clinical trials that need to be formulated to give us the answers we need to improve patient care.

There is an increasing body of evidence pointing to TRUS-guided prostate biopsy as being one of the major problems in the current prostate cancer pathway. As a test, it is both inaccurate, unreliable and has harms. It is inaccurate because about one-third of men with low-risk disease have grade or burden reclassification when a better test (template biopsy) is used. It is unreliable because the status of ‘cancer’ and ‘no cancer’ fluctuates from one biopsy to the next. It is harmful not only because it can cause complications (bleeding, sepsis and pain), but also because it detects clinically insignificant disease the treatment of which the man gains little benefit from. So, the problems with active surveillance do not stem from the fact that surveillance per se is flawed, but rather from its heavy reliance on a deeply flawed diagnostic test.

So, what are the key questions for the field of active surveillance that require a coordinated effort to deliver in a timely fashion? First, could the use of mpMRI before biopsy avoid unnecessary diagnosis of clinically insignificant prostate cancer? Second, if low grade and low-volume lesions were found on an accurate biopsy (template mapping and/or MRI-targeted), could we re-designate these lesions as something other than ‘cancer’? Combined, these two changes could in effect, make active surveillance unnecessary. Third, if mpMRI has a predilection for detecting clinically significant lesions, should the presence of a lesion on imaging lead to a man being excluded from active surveillance? Thus, should all men who are considering active surveillance undergo mpMRI and possibly template mapping biopsies? Fourth, can repeat mpMRI, as opposed to repeat transrectal biopsy, detect disease progression in men on active surveillance, and how is progression defined on imaging? Fifth, is the tissue-preserving strategy of focal therapy an alternative for men suitable for active surveillance or an alternative for those men with intermediate- and high-risk disease who stand to benefit from treatment but wish to minimise the harms of treatment?

It is clear that amongst all of these elements of research we will need to embed health economics to ensure that novel strategies are both clinically and cost-effective. Nonetheless, these are exciting times for those of us who work to innovate in clinical practice and research and improve the care of men with localised prostate cancer.

 

Hashim U. Ahmed
MRC Clinician Scientist and Clinical Lecturer in Urology, Division of Surgery and Interventional Science, University College London, London, UK

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