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Posts tagged ‘Prostate Cancer Diagnosis’

Dr Benjamin J. Davies, an academic urologist at the University of Pittsburgh today castrated the media over their coverage of the Prostate Cancer Intervention versus Observation Trial (PIVOT).

Pivot Prostate Cancer Trial Conclusion

In an article titled “Prostate Cancer: Lessons from PIVOT lost in media hype” published in the News and Views section of Nature Reviews Urology, Dr Davies states, “we must be careful to ensure the less-newsworthy facts and limitations of high-profile trials, such as PIVOT, are not lost in the media hype.

Davies goes on to say,

“an odious meme is circulating in the medical media, suggesting that prostate cancer is universally diagnosed, that PSA screening causes more harm than help, and that urologists should disregard basic epidemiologic data.”

Strong words perhaps, but those who follow Davies on twitter (@daviesbj) will know that he does not mince words and is not lost for an opinion.

However, in writing for a publication such as Nature Reviews Urology, which is probably not on the reading list of the private practice urologist or member of the mass media, he is preaching to the converted, namely academic-orientated physicians like Davies himself.

All clinical trials have their limitations, and Davies makes valid points that the PIVOT trial has a number of noticeable weaknesses.  Attention was also drawn to this in the accompanying editorial when the data was recently published in the New England Journal of Medicine.  I encourage you to read his review.

I reported the presentations of the PIVOT data from the plenary sessions at the 2011 annual meeting of the American Urological Association (AUA) and the 2012 congress of the European Association of Urology (EAU) on this blog and do take exception to Davies’ implied assertion that ALL the media coverage of the PIVOT trial was “hype.”

Experienced Healthcare journalists such as Scott Hensley (@scotthensley) provided fair and evenly balanced coverage on NPR Shots, for example.

If the media coverage of the PIVOT trial data was not as balanced or did not contain the message that Davies wanted to hear, then rather than shoot the media messenger the urology community should ask themselves why they did not obtain it?

Interestingly, at AUA 2011 and EAU 2012 there were no press conferences on the PIVOT trial data, yet it was an important topic and a plenary presentation.  Press conferences allow the media to ask questions of a panel of speakers and the opportunity to gain a variety of perspectives.  Why did the leading urologists who organize these major medical congresses not provide this access?

It is the responsibility of the urology community to reach out and educate the media if you think we don’t understand the nuances of the data.

Davies singles out the PIVOT trial for critical review, but in so doing he touches upon the wider issue of the lack of quality clinical trial data to support treatment and practice in urology.  It is for this reason that those clinical trials that are published, whatever their limitations, have disproportionate impact.

As I wrote from EAU 2012, why is there no level 1 evidence-based medicine that shows the benefits of robot assisted radical prostatectomy?  Are academic physicians unable to do high quality and robust clinical trials that justify their practice?

In his article, Davies goes beyond criticizing the PIVOT trial to castigating the media over their coverage of PSA screening, for which he is an ardent proponent.

Unfortunately, he ignores the reality that mass media don’t generate the data, they only report what organizations such as the United States Preventative Services Task Force (USPSTF) recommend.  If academic urologists believe the USPSTF got it wrong, then the failure is theirs in their inability to generate compelling data or influence the recommendations.

Finally, when Davies says, “no doubt urologists have not helped themselves by overscreening and overtreating” he touches on what I believe is the underlying cause of much of the problem associated with PSA screening.

Academic urologists need to educate their community colleagues.  Influencing everyday practice and treatment decisions will do more to help patients in the long run than being critical of the media, however justified that may be in some cases.

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EAU-2012-Congress-Media-Briefing-Professor-Jelle-Barentsz“The Mannogram – Yes we scan” Jelle Barentsz, Professor of Radiology at Radbound University, Nijmegen, The Netherlands told the assembled media at the recent European Association of Urology (EAU) annual Congress in Paris.

Professor Barentsz described how advances in magnetic resonance imaging (MRI), and in particular multi-parametric MRI (Mp-MRI) offer the potential for the improved detection and characterization of prostate cancer.

In the same way there is a mammogram that women use for breast cancer screening, Professor Barentsz raised the possibility that using magnetic resonance imaging, men could have a mannogram to screen and diagnose prostate cancer.

Some of the advantages of multi parametric MRI he highlighted include:

  • Prediction of tumor aggression
  • Prediction of low vs intermediate or high grade prostate cancer correctly in 95% of men in a trial as compared to 54% with TRUS (trans-rectal ultrasound guided) biopsy
  • In cases where there was a negative TRUS biopsy initially, mp-MRI and MR guided biopsy detected prostate cancer in 41% (108/265 of trial participants), with 87% of the prostate cancer detected being significant.

It is beyond the scope of this post to go into the physics of multi-parametric MRI or discuss in more detail the imaging trial data on which the above conclusions are based.  However, for those interested in this area, I have included details of some of the references Professor Barentsz kindly provided at the end of the post.

Why do we need new techniques for prostate cancer diagnosis? 

During their lifetime 1 in 6 men will be clinically diagnosed with prostate cancer.  There are 899,000 new cases and 258,000 deaths per year in Europe.

The current diagnostic tools of digital rectal examination (DRE), serum prostate specific antigen (PSA) and trans-rectal ultrasound guided (TRUS) biopsy have a number of limitations for prostate cancer detection.

This includes a lack of specificity (PSA = 36%), insensitivity (DRE = 37%) or failure to detect cancer due to sampling error with TRUS biopsy (more than 20% of cancers are not detected on first biopsy).

The result is that we end up with large numbers of men with elevated men or rising PSA, who have repeat biopsies. This comes at a high cost to health care providers, the uncertainty of diagnosis and the discomfort that comes with a TRUS biopsy (TRUS-Bx).

Many men undergo diagnostic procedures only to find they don’t have prostate cancer. One of the key issues in the prostate cancer screening debate is this unacceptable harm/benefit ratio.

Prostate biopsy to confirm cancer diagnosis is an invasive procedure as Professor Jenny Donovan, Head of the School of Social  and Community Medicine, at the University of Bristol told the EAU Congress.

In a plenary session, Prof Donovan described some of the initial findings from the PROBE (Prostate Biopsy Effects study), which looked at 1,147 men who received a TRUS-Bx.

“The majority of men tolerated biopsy reasonably well – over 60% experience minor symptoms. However, around one third experience symptoms that bothered them,” she said.

Professor Donovan went on to give examples of some of the feedback on the biopsy experience that researchers obtained:

“I found it incredibly painful and distressing – biopsy with a nail gun,” one man in the PROBE study said.

Data presented by Professor Donovan showed that after the procedure, 11% of men would not want another biopsy (this rose to 20%) seven days later.

Magnetic Resonance Imaging Guided Biopsy may offer benefits

Given the discomfort that many men experience with TRUS biopsy, and the fact a negative biopsy does not automatically mean no cancer (there’s a risk of sampling error), the use of MR guided biopsy may offer significant benefits.

One is that instead of 12 cores being sampled by the TRUS-Bx, only 2 cores are obtained using the MR guided biopsy technique that Professor Barentsz described.

Personally, I would prefer to have two precise cores samples taken from me through imaged based guidance, than have a TRUS biopsy that is like a nail gun that shoots in 12 sampling rods into the target area of the prostate.  This would be like the difference between a sniper rifle and a blunderbuss, metaphorically.

One of the practice implications of this is that radiologists may end up performing MR guided biopsies instead of urologists performing TRUS biopsies.

Urologists in private practice or those who are paid per procedure may not be happy about the practice changing implications that may result.

The MR imaging research that Professor Barentsz described at EAU is not without its limitations and one concern is the reproducibility of advanced imaging techniques outside of an expert university or academic setting.  I put this question to Professor Barentsz in the media briefing and have included an excerpt of his reply that you can listen to:

According to Professor Barentsz, the imaging techniques for MR guided prostate biopsy are readily reproducible outside the academic environment with guidelines already in place for standardized acquisition protocols and structured interpretation of results.

We are now at the point that the standardization of prostate MRI as well as the standardization of reporting with all kind of computer assistance is a fact and not fiction anymore,” said Barentsz.

The European Society of Urogenital Radiology (ESUR) recently published MR guidelines, that include a structured reporting system, called PI-RADS (prostate imaging, reporting, and data system).  This has been adopted in the United States by the American College of Radiology (ACR).

Before men with prostate cancer can expect to see these advanced imaging techniques used outside of expert centers, however, urologists and radiologists will need to agree on the benefits they offer and adapt their practice accordingly. Urologists may be reluctant to move away from TRUS biopsy, so it is likely widespread implementation will take some time and require education, and explanation of the evidence based medicine that supports the proposed change in practice.

The conclusion from Professor Barentsz’s EAU presentation is that imaging looks likely to play an increasing role in the diagnosis of prostate cancer.

It will be an exciting area to watch. The idea of a Mannogram has the potential to become a reality that would benefit the 1 in 6 men who will be diagnosed with Prostate Cancer during their lifetime.


ResearchBlogging.orgHambrock, T., Somford, D., Huisman, H., van Oort, I., Witjes, J., Hulsbergen-van de Kaa, C., Scheenen, T., & Barentsz, J. (2011). Relationship between Apparent Diffusion Coefficients at 3.0-T MR Imaging and Gleason Grade in Peripheral Zone Prostate Cancer Radiology, 259 (2), 453-461 DOI: 10.1148/radiol.11091409

Hoeks, C., Schouten, M., Bomers, J., Hoogendoorn, S., Hulsbergen-van de Kaa, C., Hambrock, T., Vergunst, H., Sedelaar, J., Fütterer, J., & Barentsz, J. (2012). Three-Tesla Magnetic Resonance–Guided Prostate Biopsy in Men With Increased Prostate-Specific Antigen and Repeated, Negative, Random, Systematic, Transrectal Ultrasound Biopsies: Detection of Clinically Significant Prostate Cancers European Urology DOI: 10.1016/j.eururo.2012.01.047

Barentsz, J., Dickinson, L., & Sciarra, A. (2011). Re: Axel Heidenreich. Consensus Criteria for the Use of Magnetic Resonance Imaging in the Diagnosis and Staging of Prostate Cancer: Not Ready for Routine Use. Eur Urol 2011;59:495–7 European Urology, 60 (1) DOI: 10.1016/j.eururo.2011.03.013

Hambrock, T., Hoeks, C., Hulsbergen-van de Kaa, C., Scheenen, T., Fütterer, J., Bouwense, S., van Oort, I., Schröder, F., Huisman, H., & Barentsz, J. (2012). Prospective Assessment of Prostate Cancer Aggressiveness Using 3-T Diffusion-Weighted Magnetic Resonance Imaging–Guided Biopsies Versus a Systematic 10-Core Transrectal Ultrasound Prostate Biopsy Cohort European Urology, 61 (1), 177-184 DOI: 10.1016/j.eururo.2011.08.042

Barentsz, J., Richenberg, J., Clements, R., Choyke, P., Verma, S., Villeirs, G., Rouviere, O., Logager, V., & Fütterer, J. (2012). ESUR prostate MR guidelines 2012 European Radiology, 22 (4), 746-757 DOI: 10.1007/s00330-011-2377-y

The recent announcement from the United States Preventative Services Task Force (USPSTF) on prostate cancer screening has stimulated a lot of debate.  “Dr Len’s Cancer Blog” from the American Cancer Society has a thoughtful piece about the “to screen or not to screen” dilemma. It is reminiscent of the breast cancer mammography debate.

Scott Hensley’s post on “Shots”, the NPR health blog also provides a good overview of the debate and issues. I confess I was surprised by the vehemence of the response from some practising urologists on twitter such as Dr Benjamin J. Davies (@daviesbj), Assistant Professor of Urology at the University of Pittsburgh School of Medicine:

What do the US Preventative Task Force authors say? In the findings published in the October 7, 2011 issue of the Annals of Internal Medicine, the conclusion from their peer-review of the literature is that:

“screening based on PSA identifies additional prostate cancers, but most trials found no statistically significant effect on prostate cancer–specific mortality.”

This is nothing new – the evidence in favor of Prostate-Specific Antigen (PSA) screening for prostate cancer has for sometime been inconclusive at best. Research published in the British Medical Journal earlier this year suggested that indiscriminate screening for prostate cancer may not be of value until we obtain more sensitive biomarkers.

All the USPSTF have done is a retrospective literature review that confirms our current state of knowledge.

Despite the amount of $$$ that have been spent on PSA clinical studies, no convincing data in support of it as a screening tool for all men has been developed. That’s not to say that it has no utility or benefit.

If PSA screening does detect some prostate cancers and early treatment may save lives particularly in those with an aggressive form of the disease, then it’s hard not ask:

  • What is the alternative if PSA screening is now discouraged?
  • Will this mean more men will not be screened, even those at high risk, with a consequent increase in prostate cancer mortality or lower overall survival?
  • Will insurers refuse to cover PSA testing moving forwards?
  • Will family physicians actively discourage PSA testing?

One limitation of the USPSTF report that struck me while reading through the analysis and recommendations, was the absence of data from the Prostate Cancer Intervention versus Observation (PIVOT) trial that was presented in the plenary session at the American Urological Association (AUA) annual meeting earlier this year.

I wrote in a previous blog post about the PIVOT data presented at AUA 2011 by Dr Wilt. This VA/NCI/AHRQ randomized clinical trial showed in a 12 year follow-up of over 5000 men with localized prostate cancer, no benefit from radical prostatectomy in low risk early stage patients.

In my opinion it is practice changing data that sadly has not yet been published in a peer-reviewed journal which is why it was not included in the USPSTF analysis. A few photographs that I took at the presentation of the PIVOT data are shown below:

The 12 year survival data showed that in those patients with PSA <=10 ng/ml there was no significant difference in survival over observation versus RP.

However in those patients with PSA > 10ng/ml there was a significant difference in mortality (p=0.03 HR=0.36) suggesting that in the small sub-group of patients with high PSA, RP did provide a benefit over “watchful waiting.” PSA measurements may therefore help in the treatment and ongoing management of patients.

If one of the challenges of PSA screening is the issue of the harms from treatment, then the PIVOT data that showed no difference in mortality through watchful waiting over radical prostatectomy (RP) except for high risk patients is important.

Roger Chou and his colleagues in their Annals paper did note this:

“When available, results from the Prostate Cancer Intervention Versus Observation Trial, which compared prostatectomy with watchful waiting for screening-detected cancer, may help clarify which patients would benefit from prostatectomy or other active treatments, potentially reducing harms from unnecessary treatment.”

The issue may, therefore, not be one that PSA screening per-se is the problem, but that in too many men, a raised PSA results in unnecessary surgery or overtreatment with its consequent risks and harms.

As reported by Alemozaffar and colleagues in the September 21, 2011 issue of the Journal of the American Medical Association (JAMA), 2 years after RP only 35% of men could maintain a functional erection.

“At 2 years after treatment, erectile dysfunction was reported by 619 of 987 (63% [95% CI, 60%-66%]) men (334/511 [65% {95% CI, 61%- 69%}] in the prostatectomy group”

That’s depressing news when coupled with other side-effects from RP or other interventions such as incontinence or problems with bowel function.

It adds further support to the idea that the potential risks versus benefits from prostate cancer surgery and deciding who should actually have surgery or other intervention, is where there’s also a need for more debate.

Men need to be able to make an informed decision. Some urologists may not be unbiased in their treatment recommendations given they have a vested interest in earning money from surgery or maintaining utilization rates of expensive robotics. Data from the PIVOT trial, when published, is evidence-based medicine that will impact their practice.

Use of prostate cancer risk calculators to assess those patients at high risk who might benefit from RP or other intervention could also help lower the harms that currently impact the utility of PSA screening.

How will men approach the PSA screening debate? Despite the USPSTF recommendations I will still be asking my physician for an annual PSA test, so long as it remains covered by my health insurance. The PSA test and digital rectal exam remain the main ways we have to detect prostate cancer early.

Psychologically I value the risk of picking up a disease early higher than the downside of a false positive. I would, however, not rush into any surgery or radiotherapy absent a clear finding that the benefits of intervention outweighed the potential harm.

My approach towards prostate cancer PSA screening again reminds me of the debate over mammography.  We all want to discover cancer early, and have the best possible treatment options as a result.

Hopefully, as our understanding of the biology of prostate cancers and associated biomarkers develop we may be able to generate new screening tests that have fewer false positives than PSA and provide for more accurate early diagnosis.

ResearchBlogging.orgAlemozaffar, M., Regan, M., Cooperberg, M., Wei, J., Michalski, J., Sandler, H., Hembroff, L., Sadetsky, N., Saigal, C., Litwin, M., Klein, E., Kibel, A., Hamstra, D., Pisters, L., Kuban, D., Kaplan, I., Wood, D., Ciezki, J., Dunn, R., Carroll, P., & Sanda, M. (2011). Prediction of Erectile Function Following Treatment for Prostate Cancer JAMA: The Journal of the American Medical Association, 306 (11), 1205-1214 DOI: 10.1001/jama.2011.1333

Roger Chou, MD, Jennifer M. Croswell, MD, MPH, Tracy Dana, MLS, Christina Bougatsos, BS, Ian Blazina, MPH, Rongwei Fu, PhD, Ken Gleitsmann, MD, MPH, Helen C. Koenig, MD, MPH, Clarence Lam, MD, MPH, Ashley Maltz, MD, MPH, J. Bruin Rugge, MD, MPH, & Kenneth Lin, MD (2011). Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force Annals of Internal Medicine, E-375 (October 7)

As many of you know, I previously wrote up on this blog the results from the Prostate Cancer Intervention versus Observation trial (PIVOT) that were presented during the plenary session at the recent American Urological Association (AUA) 2011 annual meeting.

Other science bloggers who were at the meeting also wrote about the presentation (see Scott Hensley’s excellent post on NPR’s health blog).

In fact anyone in the press room at AUA (I had a media pass as a science blogger) could have reviewed a copy of Dr Wilt’s presentation immediately afterwards and written about it.

However, what surprises me is that the data from this trial, which to many was the highlight of the AUA meeting and may be practice changing for urologists, has had relatively little or no pick-up by the mainstream news media.  The only reason I can think for this is due to the fact there is no abstract available, press release or other information for the media to use as reference.  Why is this?

As a scientist it makes no sense to me to present the results of a landmark study in the plenary session of a major scientific congress and not to share the data, especially when the data could have a major impact for men diagnosed with early prostate cancer and the practice of evidence based medicine.  Are urologists seriously supposed to rely on the notes they made from a rushed presentation or blog posts to guide them?

While it is common for abstracts to be delayed till the day of the presentation for groundbreaking or late-breaking research, there is no reason why an abstract with the main findings from the PIVOT trial should not have been released.

A cooperative study sponsored by government institutions such as the VA/NCI/AHRQ should be prepared to disseminate data, or else why present it at AUA?

Instead, the problem may be more due the fact that Dr Wilt, as Scott Hensley pointed out in his NPR blog post, has not submitted a manuscript of the data he presented at AUA for publication, so may be trying not to fall foul of the so-called “Ingelfinger rule” that medical journals insist upon.

This rule was named after the New England Journal of Medicine editor who established it.  In its simplicity, it states that data will not be accepted for publication if it has been published elsewhere.

However, with no disrespect to a full Professor of Medicine at a major medical school who has published numerous papers, it’s unfair to the scientific community to want to have your cake and eat it  i.e. have the glory of a plenary presentation without allowing the scientific community to use the data until you get round to writing a paper.  Clearly, it would have made more sense to have a manuscript in press before agreeing to present at the AUA plenary.

I am also troubled by the fact that what constitutes publication of the data does not include presentation at the plenary session of a major scientific congress.  If this isn’t publication, what is?  While technically a plenary presentation is not a peer-reviewed publication in the sense of having been through the rigors of a journal’s peer-review process (the value of which may not be as much as we believe), there is some implied peer review of scientific merit, or else why would it be given a plenary?

According to the Journal of the American Medical Association (JAMA) policy on dissemination of information, it’s OK to make a presentation at a scientific meeting, but not to disseminate further information to the media or the press.  I’m sorry but this makes no sense to me.  In other words it appears it’s OK for Dr Wilt to present the data, but not share it, but if you were at the meeting you can report it.  However, if you were not at the meeting, then you can’t obtain a copy of what was presented?

You can read the tangled logic of the JAMA policy below, and each journal is slightly different in how it views this:

Presentation of research findings during, or publication of an abstract for, an open scientific or clinical meeting does not preclude consideration of the study for publication in JAMA.

News media reports based on coverage that occurs during the usual course of presentation of a scientific or clinical paper does not preempt a manuscript from consideration for publication.

However, authors presenting papers at such meetings are advised to refrain from providing additional information beyond that covered during the course of their presentation and exchange with meeting attendees.

Yet, here we have the results of a major 12 year study which for the first time establishes evidence based medicine on the use of radical prostatectomy in early stage prostate cancer patients, and nobody wants to share the data with the public?

In the light of the presentation that was made at the AUA plenary and the lack of any further information while we wait for Dr Wilt to submit a manuscript through the peer-review process of a major journal, which can take several months, I think it’s important for this data to be shared.

Since media reports of data presented at meetings appear to not to forego the opportunity of publishing the results, at least according to the JAMA policy, I hope that we will see further news reports about Dr Wilt’s AUA plenary presentation.

The results from the PIVOT study are important to scientists, urologists and men talking to their doctor about prostate cancer.  This data may help them better judge whether they should undertake watchful waiting or undergo radical prostatectomy surgery.  The data slides and Dr Wilt’s conclusions speak for themselves, as you can see in my earlier post.  I look forward to reading the full scientific paper when it is eventually published.

Update May 23, 2011

A webcast with audio and slides of Dr Wilt’s plenary presentation of the PIVOT data is now available on the AUA website.


Data from the Prostate Cancer Intervention versus Observation Study (PIVOT) presented today in the plenary session of the 2011 annual meeting of American Urological Association (AUA) will have a major impact on the practice of Urology.

The VA/NCI/AHRQ cooperative study, initiated in 1994, was designed to assess the effect of radical prostatectomy (RP) compared to observation only or “watchful waiting” in men with localized prostate cancer.

What makes the PIVOT study so important is that it is the first randomized trial in the United States to look at RP versus “watchful waiting.”  In all, 13,022 men were screened at 52 US centers, from which 5023 men were deemed eligible.  Surprisingly, 4292 declined randomization and 731 men were enrolled in the trial.

The primary endpoint was all-cause mortality and the secondary endpoint, Prostate Cancer (PCa) mortality.  The two groups of patients were comparable between the observation and RP groups (mean age 66.8, 67.0 years); PSA Mean (10.2, 10.1), Gleason Score < 6 (70.1%, 69.8%).

Timothy Wilt (Minnesota) presented the results today at AUA 2011 (Abstract#407)

All-Cause Mortality

  • Absolute Risk Reduction (ARR) between Observation & RP = 2.9%,
  • Hazard Ratio = 0.88 (95% 0.71-1.08), P=0.22



Prostate Cancer Mortality – all patients

  • AR = 2.7%  (95% CI -1.3 to 6.2)
  • Hazard Ratio=0.63 (95% CI 0.36-1.09), p=0.09

In other words looking at the groups as a whole there was no benefit of RP on survival.  Wilt presented further analysis on subgroups with low-risk local pathology, intermediate risk-local pathology and high risk PSA>10.

Only in the high-risk groups (PSA>10) was there a significant benefit to RP, in terms of lowering Prostate Cancer Mortality.

  • HR= 0.36 (0.15 to 0.89); p=0.03
  • ARR = 7.2% (0 to 14.8)

Wilt’s conclusion from the data was that compared to observation, RP produced

“reductions in all-cause and prostate cancer mortality that were not significant and less than 3% in absolute terms over 12 years.”

He added that:

“Surgery did not reduce mortality more than observation in men with low PSA or low risk from Prostate Cancer”

However, these “results suggest a benefit from surgery in men with higher PSA or higher risk of disease.”

The PIVOT trial provides evidence-based medicine results that will directly influence how urologists treat early stage prostate cancer.  Several urologists and others at AUA tweeted about the PIVOT data.  Using Storify, these provide some sentiments and perspective from practicing urologists in the live audience.

The conclusion from this data is that low risk, early stage prostate cancer patients should be observed by “watchful waiting” rather than undergo radical prostatectomy (RP).  This may have a financial impact on urologists who previously may have favored RP in low risk patients.

Update May 23, 2011

A webcast with audio and slides of Dr Wilt’s plenary presentation of the PIVOT data is now available on the AUA website.

Update March 6, 2012

Dr Wilt presented an update on the PIVOT trial at the 2012 European Association of Urology (EAU) Congress in Paris. You can read my blog post from the meeting:

PIVOT data continues to show no survival benefit for prostatectomy over watchful waiting in men with low to medium risk early prostate cancer.”

 Update July 18, 2012

The data from the PIVOT trial presented in the plenary sessions at AUA 2011 and EAU 2012 has finally been published online first (July 18, 2012) in The New England Journal of Medicine.NEJM PIVOT trial prostate cancer


One of the sessions that I attended at the 2011 annual meeting of the American Urological Association (AUA) focused on research into advanced prostate cancer.  A particularly thought provoking presentation was:

Time trends of biochemical recurrence (BCR) following radical prostatectomy (RP) among 1574 BCR patients (Abstract #639)

Presented by Alex Haese from Hamburg, Germany, this paper was a retrospective analysis of 1,574 patients who had a biochemical recurrence (PSA > 0.2 mg/dl) following RP. Researchers looked at clinical progression and cancer specific survival rates and compared their findings to published United States data.

The results appeared to be somewhat depressing for European patients who experience a BCR, with a time to BCR of 1.8 years, compared to 2.1 years in the US research by Pound from Johns Hopkins and 2.4 years in the data published by Hull, at Memorial Sloan Kettering Cancer Center (MSKCC).

Once a BCR is experienced, the time to metastases is faster in Europe, 4.7 years in the research presented by Haese at AUA, as compared to 8 years in US research by Pound. Risk factors for metastasis free survival include time to BCR i.e.

“The longer the interval between RP and BCR, the greater the probability of being met-free.”

In other words delaying time to progression is associated with longer survival.

Following BCR, time to Prostate Cancer death was 6.0 years in the 1,574 European patients, compared to 13 years in the US Pound research.  Again, the data presented showed that,

“The longer the interval between RP and BCR, the greater the probability of being alive.”

This research must be put into context, as metastasis and death in BCR patients are rare (92% of the 1,574 patients with BCR were free of metastases at 5 years, 81% at 10 years).  However, for those patients who did progress, the results appear significantly different between the US and Europe.

What could explain this?

The presentation left this question unanswered, although in Q&A it was briefly touched upon. One person raised the question of whether differences in screening could be the difference in Europe vs. US?

Other questions that come to mind are whether the subject populations in the Hull and Pound data were comparable.  The German data also had more patients (1574) compared to 304 in the Pound research and 147 (Hull) raising the question that the larger sample size may be more accurate data?

Other factors that might possibly explain the difference include:

  • Androgen deprivation therapy (ADT)
  • Radiotherapy
  • Supportive care (eg bisphosphonates)

All of which tend to be more aggressively pursued as treatment options in the USA.

Overall, this presentation raised the interesting question of US/European differences in Prostate Cancer progression that hopefully will be answered by future research.

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