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Editorial: How active should active surveillance be?

February 18, 2015/1 Comment/by Scott Eggener

Many investigators, including those from Johns Hopkins University (JHU) and the Prostate cancer Research International: Active Surveillance project (PRIAS), have provided meaningful data to strongly support the increasing use of active surveillance (AS) across the world. There are a multitude of strategies to minimise excessive rates of prostate cancer over detection and overtreatment. After the diagnosis of prostate cancer, the single best is AS for appropriately selected men.

For decades, the concept of not treating a prostate cancer in otherwise healthy men, even if low-grade and low-volume was typically considered nihilistic and heretical, particularly in the USA. Thankfully, data have largely made this line of thinking anachronistic. The era of sensibly applied AS is upon us, and single-institution series with intermediate-term follow-up are excellent, with exceedingly low rates of metastasis or cancer-related death. However, we await longer-term (>10 years) outcomes from the contemporary PSA screening era.

The ‘success’ of AS is largely dependent on the entry criteria, follow-up strategies, and indications for curative intervention. Highly restrictive inclusion criteria, rigorous biopsy based follow-up and strict definitions of reclassification triggering treatment have produced superb outcomes. Critics appropriately argue these criteria exclude a significant proportion of men with a low rate of requiring treatment or having metastases, if allowed on AS. Conversely, other programmes with looser entry criteria, more lax follow-up, and relaxed indications for intervention will be more inclusive and have lower rates of immediate or delayed intervention but must be counterbalanced against the expected higher rate of metastases or death.

The current study [1] evaluates two different AS follow-up strategies from JHU and PRIAS. In general, JHU uses annual biopsies with progression defined as a new PSA density >0.15 ng/mL/mL or increasing tumour volume or grade beyond a certain threshold, while PRIAS recommends less frequent biopsies (years 1, 4, and 7) while relying on serological (PSA doubling time, PSADT) alongside histological indicators for defining progression and recommending treatment.

Not surprisingly, different strategies lead to varying expected outcomes. Among the JHU patients, 38% were reclassified at a median of 2.1 years. Nearly two-thirds of the reclassified would have been identified at the PRIAS year 1 or triennial biopsies with 16% identified between PRIAS biopsies at a median delay of 1.9 years. The unanswerable but incredibly important question is whether this delay is essentially a non-issue, perhaps a favourable attribute (more AS time without compromising cure rates), or clinically disastrous (patients no longer curable).

PRIAS relies heavily on PSA kinetics, which can be a double-edged sword. Among men in the JHU programme with >5 years follow-up, 11% would have delayed reclassification compared with PRIAS at a median time of 4.7 years. Additionally, 12% would have undergone intervention due to PRIAS-defined PSADT but not progressed based on the JHU protocol. It is convenient and perhaps intuitive that PSA kinetics should predict progression and meaningful clinical events for men on AS; however, the data from multiple studies have simply not supported this concept [2, 3].

The JHU programme has restrictive entry rules compared with most other programmes, a rigorous biopsy based follow-up protocol, and strict criteria to treat, which is exactly why no metastasis or death have been reported among 769 men, some with up to 15 years follow-up[4]. Guidelines are needed but should not be overly prescriptive or rigid. For example, a surveillance biopsy showing a single core of Gleason 6 encompassing 60% of the total core or three cores of Gleason 6 with total cancer length of 3 mm would lead to a recommendation of treatment according to published JHU criteria. Many of us would not be phased with these biopsy reports and comfortably recommend ongoing AS.

Data from AS series are very encouraging but it is highly likely we can do even better. For example, 10-year cancer-specific survival is 97% in the Sunnybrook AS experience and all five cancer-related deaths occurred in patients that would not meet most contemporary AS entry criteria [5, 6]. I am hopeful and confident that emerging data incorporating MRI imaging, serum biomarkers (e.g. prostate health index), or tissue-based biomarkers (e.g. Prolaris, Oncotype Dx) will provide us with a more comprehensive understanding of these men’s cancer such that tailored, evidence-based recommendations can be even more accurate.

There is much yet to be learned about AS and this study [1] adds to our knowledge. Surveillance for prostate cancer is definitely active, but it is also dynamic and evolving.

Read the full article

Scott Eggener

Associate Professor of Surgery, University of Chicago, Chicago, IL, USA

References

1 Kates M, Tosoian JJ, Trock BJ, Feng Z, Carter HB, Partin AW. Indications for intervention during active surveillance of prostate cancer:

a comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) protocols. BJU Int 2015; 115: 216–22

2 Whitson JM, Porten SP, Hilton JF et al. The relationship between prostate speciﬁc antigen change and biopsy progression in patients on active surveillance for prostate cancer. J Urol 2011; 185: 1656–60

3 Fall K, Garmo H, Andrén O et al. Prostate-speciﬁc antigen levels as a predictor of lethal prostate cancer. JNatlCancerInst2007; 99: 526–32

4 Tosoian JJ, Trock BJ, Landis P et al. Active surveillance program for prostate cancer: an update of the Johns Hopkins experience. J Clin Oncol 2011; 29: 2185–90

5 Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28: 126–31

6 Krakowsky Y, Loblaw A, Klotz L. Prostate cancer death of men treated with initial active surveillance: clinical and biochemical characteristics. J Urol 2010; 184: 131–5

Video: Indications for Intervention During Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and PRIAS Protocols

February 18, 2015/by admin Z.9

Indications for Intervention During Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and PRIAS Protocols

Max Kates, Jeffrey J. Tosoian, Bruce J. Trock, Zhaoyong Feng, H. Ballentine Carter and Alan W. Partin

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

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OBJECTIVE

To analyse how patients enrolled in our biopsy based surveillance programme would fare under the Prostate Cancer Research International Active Surveillance (PRIAS) protocol, which uses PSA kinetics.

PATIENTS AND METHODS

Since 1995, 1125 men with very-low-risk prostate cancer have enrolled in the AS programme at the Johns Hopkins Hospital (JHH), which is based on monitoring with annual biopsy. The PRIAS protocol uses a combination of periodic biopsies (in years 1, 4, and 7) and prostate-specific antigen doubling time (PSADT) to trigger intervention. Patients enrolled in the JHH AS programme were retrospectively reviewed to evaluate how the use of the PRIAS protocol would alter the timing and use of curative intervention.

RESULTS

Over a median of 2.1 years of follow up, 38% of men in the JHH AS programme had biopsy reclassification. Of those, 62% were detected at biopsy intervals corresponding to the PRIAS criteria, while 16% were detected between scheduled PRIAS biopsies, resulting in a median delay in detection of 1.9 years. Of the 202 men with >5 years of follow-up, 11% in the JHH programme were found to have biopsy reclassification after it would have been identified in the PRIAS protocol, resulting in a median delay of 4.7 years to reclassification. In all, 12% of patients who would have undergone immediate intervention under PRIAS due to abnormal PSA kinetics would never have undergone reclassification on the JHH protocol and thus would not have undergone definitive intervention.

CONCLUSIONS

There are clear differences between PSA kinetics-based AS programmes and biopsy based programmes. Further studies should address whether and how the differences in timing of intervention impact subsequent disease progression and prostate cancer mortality.

Article of the week: Guideline of guidelines: prostate cancer screening

September 10, 2014/8 Comments/by admin Z.9

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The introduction 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.

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

Guideline of guidelines: prostate cancer screening

Stacy Loeb
Department of Urology and Population Health, New York University, New York, NY, USA

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INTRODUCTION

Prostate cancer screening is one of the most controversial topics in urology [1]. On one hand, there is randomised data showing that PSA screening results in earlier stages at diagnosis, improved oncological outcomes after treatment, and lower prostate cancer mortality rates. However, the downsides include unnecessary biopsies due to false-positive PSA tests, over-diagnosis of some insignificant cancers, and potential side-effects from prostate biopsy and/or prostate cancer treatment. The ongoing controversy is highlighted by the divergent recommendations on screening from multiple professional organisations. The purpose of this article is to summarise the recent guidelines on prostate cancer screening from 2012 to present.

New technology for prostate cancer…beyond robotics!

May 8, 2014/12 Comments/by Addie Wootten

Urology has led the way introducing new technology for men with prostate cancer. Robotic surgery, focal therapy, nanoknife, cyberknife – the list goes on. But have we fully embraced the everyday technology we all have access to in our care for men with prostate cancer? There are a growing number of Apps designed to support prostate cancer patients and improve quality of life. If you type ‘prostate’ into the iTunes App store about 82 results are found, but many of these are fundraising events, journals and staging tools, many of which are not patient friendly. Whilst there is an increasing appetite for patient-centered tools – focused on supporting and empowering patients in managing their health and wellbeing – we still have some way to go in this regard.

As a clinical psychologist working in urology, I often hear patients and their families describing their feelings of uncertainty and loss of control. Furthermore, Australia is a huge country with vast rural and remote areas and many patients that live in these areas find it very difficult to access the information, advice and support they require to ensure optimal outcomes from their prostate cancer.

The benefits of harnessing technology in the pursuit of improved health and wellbeing via improved patient engagement and access to services are clear; so why not use this technology to improve the care we provide to men with prostate cancer?

We have developed an online prostate cancer portal www.PROSTMATE.org.au

PROSTMATE provides tailored information, access to self-help interventions, a personal record of treatments and other milestones, a PSA graphing function and a regular check-up that records self-reported ratings across 5 quality of life domains and graphs these over time. PROSTMATE also offers telehealth (web-enabled video) consultations with prostate cancer nurses and allied health clinicians.

A complex and dynamic algorithm has been designed to tailor the extensive library of information to match the user type and stage of treatment for each person using PROSTMATE. Recommended library information is delivered to the user via their private dashboard and this information automatically updates when information has been read. This aspect of PROSTMATE was designed to help prostate cancer patients navigate to the information most relevant to them and their circumstances, and to reduce the often overwhelming feeling of information overload.

The timeline provides an opportunity for patients to record all their prostate cancer milestones including their treatments, test results, medical appointments, personal journal entries and more. The timeline’s graphical illustration of PSA results and self-reported quality of life over time also allows users to keep track of things as simply as possible.

The telehealth consultations are one of the most exciting aspects of PROSTMATE as they connect men, and their families with expert prostate cancer nurses and psychologists (and hopefully in the future exercise physiologists and physiotherapists) whom they may not have had access to in their routine care. We know that many men, particularly men from rural and remote areas, find it very difficult to access allied health services and we hope that delivering clinical consultations via telehealth will facilitate improved access to services as well as overall improvements in quality of life in the long-term; not to mention the potential savings made through reduced travel time, time off work and reductions in patient loads in busy outpatient clinics.

PROSTMATE launched to the general public in November 2013 and since then has attracted more than 700 new members. We have received overwhelming feedback supporting the use of technology in the care of everyone affected by prostate cancer. It’s surprising how many men and family members feel isolated by the traditional medical model and we are delighted that we can harness the power of technology to empower and connect people to their health and wellbeing.

PROSTMATE is free to join and has been supported by generous philanthropic funding. Our program is continually evolving as we learn what is most useful to our members, and through this, we intend to expand and develop new components and functionality in the near future. You can become a member yourself by selecting health professional in the sign up pages to see what PROSTMATE might offer your patients.

Visit www.PROSTMATE.org.au and follow us on Twitter @PROSTMATE

Dr. Addie Wootten
Clinical Psychologist
eHealth Research Manager
Australian Prostate Cancer Research
Twitter: @addiewootten @PROSTMATE

Valentine’s Day PSA

February 14, 2014/1 Comment/by Prokar Dasgupta

A few years ago Barrack Obama, the President of the USA, is supposed to have said on Valentine’s Day – “Gentlemen – do not forget!”

He was apparently speaking “from experience”. Not remembering that important day can have catastrophic consequences for many men. On that occasion, PSA stood for public service announcement.

The headline, however, could easily have been mistaken for Prostate Specific Antigen. One could argue whether the PSA test is as important to men as Valentine’s Day. Most men probably do not bother, especially if they are less than 40 years old. The PSA debate swings around like a sine wave. Despite the best possible randomised controlled trials for and against PSA screening, there seem to be no clear answers with deep divisions amongst men and their urologists.

This February, the BJUI adds to the PSA debate by publishing the Melbourne Consensus Statement [1]. It was an attempt to bring some sense to a thorny subject. When published as a blog on www.bjui.org, most of our readers liked it, but certainly not all. The usual heated debate was inevitable. Earlier last summer Bal Carter, one of our BJUI Executive Members, chaired the AUA panel that recommended shared decision making for asymptomatic men between 55–69 years as far as PSA screening was concerned. They carefully analysed over 300 studies to make these recommendations [2]. I congratulated Bal on this milestone on the very morning this made headline news. However, such was the controversy that he had to present the findings twice – one appearance on the AUA podium was just not enough.

In a well-informed man, over diagnosis is not necessarily a problem as long as it does not lead to over treatment. I find myself treating a number of men in their 40s with strong family histories of prostate cancer. It is very difficult to deny them a PSA test when they seek it. This discussion is likely to become redundant in years to come when better risk stratification with genomic tools and improved imaging will complement the PSA test, rather than relying on it alone. In the meantime I leave it to our knowledgeable readers to make up their own minds.

Not everyone is interested in the PSA test in the month of February. If you belong to this category, perhaps we could grab your attention with a multi-institutional collaborative study showing disease free and overall survival rates of over 90% following LESS partial nephrectomy, a challenging procedure, even for technically accomplished surgeons [3]. Khurshid Guru’s group also present data to show that urinary and bowel domains take about 6 months to recover after robotic cystectomy; sexual domains even longer [4].

I have no illusions that none of the above may be of the slightest importance to some readers. In which case you may wish to head to the best florist in town. Forget that at your peril …

Prokar Dasgupta, Editor in Chief, BJUI
Guy’s Hospital, King’s College London

References

Murphy DG, Ahlering T, Catalona WJ et al. The Melbourne Consensus Statement on the Early Detection of Prostate Cancer. BJU Int 2014; 113: 186–188
Carter HB. American Urological Association (AUA) Guideline on prostate cancer detection: process and rationale. BJU Int 2013;112: 543–547
Springer C, Greco F, Autorino R et al. Analysis of oncological outcomes and renal function after laparoendoscopic single site partial nephrectomy: a multi-institutional outcome analysis. BJU Int 2014; 113: 266–274
Poch MA, Stegemann AP, Rehman S et al. Short-term patient reported health-related quality of life (HRQL) outcomes after robot-assisted radical cystectomy (RARC). BJU Int 2014; 113: 260–265

Article of the week: Rethinking inflammation in PCa

October 23, 2013/by admin Z.9

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.

Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate-specific antigen (PSA) concentration in the Finnish prostate cancer screening trial

Tytti H. Yli-Hemminki*^†, Marita Laurila*, Anssi Auvinen^‡, Liisa Määttänen^§, Heini Huhtala^‡, Teuvo L.J. Tammela^¶ and Paula M. Kujala*

*Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, ^†Department of Pathology, Seinäjoki Central Hospital, Seinäjoki, ^‡School of Health Sciences, University of Tampere, Tampere, ^§Finnish Cancer Registry, Helsinki, and ^¶Department of Urology, Tampere University Hospital and University of Tampere, Tampere, Finland

T. H. Y.-H. and M. L. contributed equally to this study.

Read the full article

OBJECTIVE

• To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate-specific antigen (PSA) concentrations and benign initial biopsy.

MATERIALS AND METHODS

• Study subjects were men aged 54–67 years with an elevated PSA (≥4 ng/mL or 3–4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996.

• A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation.

• Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry.

• The median length of follow-up was 10.5 years.

• Cox regression analysis was used to assess PCa risk after the initial benign biopsy.

RESULTS

• Histological inflammation was found in 66% of the biopsies.

• Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35–1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46–1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42–1.07; P = 0.092).

CONCLUSIONS

• Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance.

• Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.

Read Previous Articles of the Week

Editorial: Does inflammation reduce the risk of prostate cancer?

October 23, 2013/1 Comment/by Roger Kirby

Chronic inflammation is thought to play an aetiological role in tumorigenesis in several cancers including bladder, oesophagus and liver [1]. Molecular studies show that it plays a critical role in several stages of the carcinogenic process including tumour initiation, promotion, metastases and response to therapy. However the role in prostate cancer is less clear and to date, clinical studies are inconclusive.

The article in this issue of BJUI by Yli-Hemminki et al. [2] appears to show an inverse association with histological inflammation and the risk of prostate cancer. Using data from the Finnish subgroup of the European Randomised Study of Prostate Cancer Screening (ERSPC) study they examined 293 patients with previous negative biopsies over a 10.5-year period and reported an 18% risk of prostate cancer in men with inflammation on initial biopsy (34 of 101 men) as opposed to 27% in those without inflammation (51 of 192 men). Perhaps somewhat surprisingly, histological inflammation did not appear to be significantly associated with PSA concentration, although it did appear that the free/total PSA ratio was higher in men with inflammation.

One potential confounding factor is that inflammation may also play a role in the pathogenesis of BPH. A large scale study showed that the odds ratio for BPH was 8.0 with a history of prostatitis [3]. Furthermore, the Medical Therapy of Prostatic Symptoms (MTOPS) study showed that men with inflammation had a significantly higher risk of BPH progression and acute urinary retention. These factors may impact on PSA levels and the chance of a subsequent prostate biopsy. However, the authors report that the inverse association of prostate cancer and inflammation did not alter when corrected for prostate volume, PSA level and age.

Significantly, those patients who screened positive at first biopsy were already excluded as were those with a suspicion of prostate cancer, such as a small atypical focus. Despite this, the study group probably represents high-risk patients, as they had all previously met the criteria for the first round of biopsies. This is borne out by the fact that the risk of prostate cancer was significantly increased when the men with inflammation on biopsy were compared with the initially screened negative men (hazard ratio 4.3). Unfortunately, we do not know what the rate of inflammation was in the control arm as they were screened negative and hence no biopsies were taken.

The significance of PSA level or prostatic intraepithelial neoplasia was not specifically investigated, although the reported rates were 32.1% and 7.5% respectively. Overall the incidence of inflammation was reported as 65%, but this included both acute and chronic inflammation. A smaller number of patients were given grade 2/3 chronic inflammation (80 and 20 patients, respectively) and only 14 patients had grade 2/3 acute, indicating most had milder degrees of inflammation. Whether this is a representative sample is not entirely clear. As the authors comment, published rates of histological inflammation do vary significantly from 8 to 99% and this does appear to vary according to detection method.

Several case-control studies and a meta-analysis [4] have shown that there is a significant increase in the relative risk of prostate cancer in men with prostatitis; however, these epidemiological studies all suffer from selection bias, in that men with clinical symptoms are more likely present and to be investigated and followed up by a Urologist. This study [2] only examines the role of histological inflammation and, at least partially, removes the selection bias associated with clinical symptoms, although it could still be argued that men with clinical prostatitis may be more likely to present for screening. This study represents a highly selected group of patients that are high risk for prostate cancer and no firm conclusions can be drawn on the general population. As inflammation is so common in prostate specimens, further high-quality large-scale studies are needed with similar long-term follow-up.

Miles A. Goldstraw and Roger S. Kirby
The Prostate Centre, London, UK

Read the full article

References

Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 860–867
Yli-Hemminski T, Laurila M, Auvinen A et al. Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate-specific antigen (PSA) concentration in the Finnish prostate cancer screening trial. BJU Int 2013; 112: 735–741
Alcarez A, Hammerer P, Tubaro A, Schroder FH, Castro R. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur Urol 2009; 55: 864–875
Dennis LK, Lynch CF, Torner JC. Epidemiologic association between prostatitis and prostate cancer. Urology 2002; 60: 78–83

Article of the week: The AUA speaks: prostate cancer detection guideline

September 4, 2013/1 Comment/by admin Z.9

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

American Urological Association (AUA) Guideline on prostate cancer detection: process and rationale

H. Ballentine Carter

The Johns Hopkins University School of Medicine, Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA

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ABSTRACT

To review the process and rationale for the American Urological Association (AUA) guideline on prostate cancer detection. The AUA guideline on detection of prostate cancer involved a systematic literature review of >300 studies that evaluated outcomes important to patients (prostate cancer, incidence/mortality, health-related quality of life, diagnostic accuracy and harms of testing). A multidisciplinary panel interpreted the evidence and formulated statements to assist the urologist and the asymptomatic average-risk man in decision-making about prostate cancer detection. Other than prostate-specific antigen (PSA)-based prostate cancer screening, there was no evidence to address the outcomes of interest to patients. The strongest evidence that benefits may outweigh harms was in men aged 55–69 years undergoing PSA-based screening. This led the panel to recommend shared decision-making for these men at average risk, but recommend against routine screening for other age groups at average risk. Further, to reduce the harms associated with screening (false positive tests, over diagnosis, over treatment), the panel recommended against annual screening for those who choose to be screened. A panel under the auspices of the AUA recommended shared decision-making for the average risk asymptomatic man aged 55–69 years considering PSA-based screening for prostate cancer detection.

Read Previous Articles of the Week

Changing paradigms in the investigation of an elevated PSA level

August 7, 2013/by Roger Kirby

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.

Read the article

The Melbourne Consensus Statement on Prostate Cancer Testing

August 7, 2013/61 Comments/by Declan Murphy

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, 7–10^th 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 75^th 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 75^th 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.