Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘PIVOT trial’

PIVOT-prostate-cancer-intervention-versus-observation-trial-dataTimothy J. Wilt MD, MPH presented an update on the VA, NCI, AHRQ Prostate cancer Intervention Versus Observation Trial (PIVOT) on the final day of the 2012 European Association of Urology (EAU) Congress in Paris.

I previously wrote on this blog about the PIVOT data presented by Professor Wilt in the plenary session at the 2011 American Urological Association Annual meeting.

The PIVOT trial objective according to Dr Wilt, was to answer the following question:

Among men with clinically localized prostate cancer detected during the early PSA era, does the intent to treat with radical prostectomy reduce all-cause & prostate cancer mortality compared to observation?

PIVOT enrolled 731 men from 1994 to 2002 who were randomized to either receive radical prostatectomy or undergo just observation.

The results from the trial provide level 1 evidence based medicine (highest standard) concerning the survival benefits conferred by radical prostactectomy (with the potential for quality of life impacts such as incontinence & erectile dysfunction), as compared to not undertaking surgery, but instead doing observation only in the form of watchful waiting or active monitoring.

Dr Wilt told the urologists in the EAU 2012 Congress plenary session, that after a median follow-up of 10 years (interquartile range = 7.3 to 12.6), the median survival was 12.7 years. Wilt told the audience that:

“Prostate cancer mortality was uncommon occurring in only 7.1% of men, it did not vary considerably by patient age, race, comorbidities or health status, but did vary considerably by tumor risk status ranging from 3 % in men with low risk disease to 13 % in men with high risk disease.”

PIVOT Prostate Cancer Mortality Results

No of Deaths: 52/731 (7.1%)

    • Low risk  (3.4%)
    • High risk (8.4%)
    • High risk (13.3%)

In the men who had death judged to be due to prostate cancer, absolute differences between treatments were less than 1%,” Wilt said.

As far as I could determine, the data presented at EAU 2012 was no different from the PIVOT data presented at AUA 2011 other than being another year mature.

A subgroup analysis showed that surgery conferred no survival benefit over watchful waiting except for high-risk patients.  In his EAU 2012 presentation, Dr Wilt described the subgroup findings in more detail (emphasis added):

Low Risk Prostate Cancer

“In men with low risk prostate cancer, disease mortality occurred in less than 3% and did not differ between radical prostatectomy and observation”  (HR=1.48; ARR=1.4, P=0.54). This favored observation.”

High Risk Prostate Cancer

“Among men with high risk tumors, prostate cancer mortality occurred in approximately 13%. Radical prostatectomy produced a 60% relative risk reduction  (HR = 0.4, ARR = 8.4) of borderline significance (P=0.04).

Intermediate Risk Prostate Cancer

“Among men with intermediate risk prostate cancer, we found a non-significant reduction of 4.6%.”

PSA <= 10ng/ml

“In men with PSA <= 10ng/ml there was no significant difference between radical prostatectomy and watchful waiting.” (HR = 0.92, ARR=0.3%, P=0.82).  The findings were virtually identical throughout the course of the study. The lines are essentially superimposable for prostate cancer mortality in men treated with observation or with radical prostatectomy.”

PSA > 10ng/ml

“Among men with baseline PSA > 10ng/ml, radical prostatectomy reduced prostate cancer death by a relative 64% and an absolute difference of 7.2%. You can see the curves begin to separate at approximately 7 years.” (HR=0.36, ARR= 7.2%, P=0.03)

PIVOT-Prostatectomy-versus-observation-data-conclusion-2012Dr Wilt’s conclusion based on the latest study data was that:

“In men with localized prostate cancer detected during the early PSA era, radical prostatectomy compared to observation did not significantly reduce all-cause and prostate cancer mortality. Absolute differences through at least 12 years were less than 3%” 

These results are important findings that should impact the treatment of men diagnosed with early stage, low risk prostate cancer.

The fact that the survival curves do not diverge except for high-risk patients presenting with a PSA > 10ng/mL, may also have an impact on the ongoing PSA prostate screening debate.

If the PIVOT data results in more men being put on watchful waiting/active monitoring, then it should lower the overtreatment that screening currently produces.  Urologists will, however, need to be prepared to counsel their patients accordingly and forego the economic benefits that undertaking surgery affords many of them.

Urologists at the EAU in Paris greeted the PIVOT trial data in silence and an absence of social media interaction (I did not see any urologists tweet enthusiastically about it).

Many urologists who have trained many years to perform complex surgical techniques may find the idea of watchful waiting an anathema.

Adopting a policy of watchful waiting in many prostate cancer patients may also place economic pressures placed on those urologists who need a throughput of patients to recover or amortize the cost of expensive technology such as the da Vinci robotic system.

The PIVOT trial data is, however, level 1 evidence based medicine that cannot be ignored.

Hopefully, this analysis of the PIVOT trial data will be published in a peer-reviewed journal in the not too distant future so that it can reach a wider audience than those urologists who attended the AUA 2011 and EAU 2012 plenary sessions.

Update July 18, 2012

The results of the PIVOT trial presented at AUA 2011 and EAU 2012 have been published in the New England Journal of Medicine (online first, July 18, 2012).

NEJM PIVOT prostate cancer

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

error: Content is protected !!