Now the ball bounces back....advantage to PSA screening

It's reasonable to expect that a life will be extended on a study due to lead time bias. If a person was going to die at 70 because of PC and it was found at 65 due to psa screening and would have been found at 69 without it the stats would show an increase in 48 months of life when nothing at all had changed. There are many things that affect life extension including better treatment and earlier detection. Just because there is a correlation doesn't mean there is causation.
It is reasonable to expect that psa screening does extend lives, but to what extent is still unknown. To take this study as evidence and ignore all the others that show a minimal effect of screening is not good science and shows humans come to a belief and look at evidence supporting those beliefs while rejecting all evidence that doesn't support it.
I'm not opposed to screening, especialy for those in a high risk catagory and for younger men, which may benefit more from screening. But I see no evidence at this time to support mass screening of an entire population. 75% of all biopsies are negative and 60% of positive biopsies are for cancers that would never kill anyone. In only a very small percentage of patients would screening and treatment make a difference in extending lives.
In the history of cancers the most effective programs have been prevention programs and not screening and treatment programs. (Abspestos, smoking, lifestyle changes, injections to stop cervical virius ect.)

Instead of just tracking deaths, I wonder if there is a study the follows QOL issues (ED and incontinence) after treatment as a function of post diagnosis time. In other words, Does earlier diagnosis and treatment reduce the number of side effects?

For example, my PCa was diagnosed when my very first PSA results came back at ~20, Bx 7/12 - up to 70%. PNI, EPE. I had surgery and ended up with both side effects. The surgeon even told me "I had to cut wide to get it all."
What would have happened if my doc had ordered a PSA test 2 years earlier when my PSA was (theoretically) 5, Bx 2/12 - up to 10% involvement on one side. No EPE. Would I have the same side effects as I do now? I'm don't know for sure, but it sure feels that way.
Maybe it is just as well. I could have suffered a heat attack while performing a now impossible act in the bedroom.
Forget about deaths. We already know the numbers are small. Years from now we are likely to find that early detection through PSA screening actually reduced the number of men with side effects.

Jeff - a "Late Detection" data point. (Late Detection is definitely not GFMPH)

Statistics are meaningless in a population of one, which is what we all are. No matter what any study says, I will still believe that knowing sooner rather than later offers the best chance for effective treatment.

Not to be dense about it, but how can anyone debate whether screening saves lives after looking at this chart?

www.scielo.br/img/revistas/ibju/v30n1/1a02f01.gif

The total population death rate started going down dramatically at the same time that PSA testing become common. No other cancer shows the same decline in death rate. I've never heard the anti-screening crowd offer a credible alternative explanation for this data.

The diagnosis of prostate cancer is an emotionally-charged issue, which starts for the typical newcomer with a dose of “cancer hysteria” rooted in the historical perception that the “big-C” is going to bring certain misery and death.   The reality is, and the evidence shows, that PC is one of the most common and least lethal forms of cancer producing a large population of survivors. One benefit that newcomers have in encountering an experienced and knowledgeable cadre of survivors such as the “veterans” at HW is that we vets can draw focus and expose newcomers to the many evidence-based findings which may initially appear counterintuitive .   For example… The notion that PSA screening has been the primary driver to the improvement in PC mortality and increased longevity for metastatic patients (the topic of the original poster’s article) naively ignores the evidence and actual history.   Newcomers who are just coming up-to-speed in their knowledge and education on PC should not be expected to understand the details; PC veterans should know better. It is simplistic to look at the improved mortality roughly coincident with the “PSA-era” and say “this must have caused that.”   Anyone who has taken a sophomore-level science class, however, will tell you that the correlation between two variables does not automatically imply that one causes the other; and in fact, the opposite belief that correlation proves causation is specifically known as a “logical fallacy.” The article referenced by the original poster compares longevity of newly diagnosed men with metastatic PC between 1985 and 2009.   The original Journal of Urology authors (not the novice Yahoo article authors) were very, very careful to note that while the increase in survival benefit occurred during the “PSA-era” it was not possible to know exactly why it had occurred.   Reading through the haze of one’s “cancer hysteria,” however, a newcomer could quickly gloss-over this inconvenient message. PSA screening is generally acknowledged to have contributed a small fraction of the improvement.   Improved forms of imaging testing and drug treatments are seen as the significant contributors to greater longevity and decreased mortality .   The timeframe generally associated with the “PSA-era” has, in fact, also been known as the so-called “ golden age for prostate cancer drug discovery .”   Those who make the implication that the improvements must have been primarily PSA screening-based generally ignore these medical break-throughs: For historical completeness, let’s start with 1985 — the first year of the comparisons in the Journal’s article.   Lupron was first FDA approved for PC in 1985, but took several years   to become wide-spread.   Zoladex was first FDA approved for PC in 1989.   Casodex approved in 1995.   Both Nilutamide and Flutamide in 1996.   Viadur in 2000,   Eligard in 2002.   Leupromur, Firmagon, Ketocanazole, abiraterone acetate & prednisone and TAK-700 all approved since then.   Think that these new novel, targeted HT treatments didn’t make a difference…?   What about Ozarelix, ARN-509 and MDV3100? What about the chemotherapies that have been approved since 1985?   Taxatere (Docetaxel), XL184 (Cabozantinib)?   What about Zytiga (abiraterone) which was so effective while under evaluation that the trial was stopped and the new drug was provided to all patients where were intitally on placebo.   What about Provenge?   Radium-223, Affirm, Tasquinimod, Mitoxanatrone, Vinorelbine, Cytoxan and others? This very long list of continuous improvements in treatments in the fight against PC have made the significant difference in improved mortality and longevity for metastatic patients diagnosed in 1985 versus 2009…not PSA screening.   PSA screening has primarily contributed the well-recognized “ stage shifting ” that has taken place, and the lead-time bias as previously discussed.   This is not to say that PSA testing should be eliminated — nobody has impled that, we can do a better, more targetted screening to younger, high risk men to be more effective. When the PSA-era began, it was primarily used as a means to detect advanced PC ( not early stage), and it was originally administered primarily to those in the far upper age groups.   Lots of 75+ year olds (the Medicare population) with advanced PC were being operated on (the rate of radical porstatectomies nearly tripled between 1989 and 1992) and a significant number of men were dying on the operating table or within 30 days, contributing to the spike in mortality 20-years ago.   Then in 1992, Medicare changed the fee structure for PC treatment services and launched an investigation into RPs performed on high risk, co-morbid men.   This corresponds directly to the tipping point in the PC-reported deaths in the SEER data (see the link to the chart, posted above).   As Medicare reimbursement rates started dripping in 1992, the rate of surgery amond the medicare population dropped by 1/3 between 1992-1995.   Private insurance continued to pay high rates for RPs, and the rates of diagnosis and surgery among younger men started rising... Improved mortality and longevity due primarily to PSA screening…that’s a naively simplistic view, and it is not the view of the Journal of Urology article authors.  

PC mortality is decreasing in 21 countries; 2 of those countries have widespread screening.

see also: http://mecc.cancer.gov/5.Bouchardy_2008.pdf

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Added later as an edit:  I should reiterate that nobody says that PSA screening has had zero effect on longevity/mortality; it's just not the big impact that seems intuitive with a simple, surface-level perspective...

 

 

 

 

 

 

Post Edited (Casey59) : 8/27/2012 3:42:42 PM (GMT-6)

ralf,

i still find your proofs on this subject totally convincing, and my opinion mirrors yours on this subject
thanks for chiming in, as usual

david

I think these studies on how or if psa testing effects survival times are missing a big point,if one is concerned about finding cures for this disease. Let's say the "decider" ( some panel) holds sway and stops psa testing, that is, stops Medicare and some or all private insurance stops paying as well. So cancer screening as we know it is eliminated. What, now it would be just DRE?, and the average cancer detected would be well advanced as compared to now.

Point being missed here is we would be swapping to a much smaller and sicker pool to study for new cures. The markets for and in turn the research for developing new drugs would be a lot different, smaller and sicker, than now exists. I like the idea of as a large a pool as possible to be studied for research. Perhaps the larger pool that includes a smaller percent of very sick people would be more representative of the people who actually have this disease would help maintain the representative interest in drugs for early stage and even for drugs to prevent it in the first place.

Let me say something about the PIVOT trial. Finally Dr. Wilt and co-authors reported findings from the Prostatectomy Versus Observation Trial (PIVOT) for localized prostate cancer. The trial began early in the era of PSA testing (November 1994 through January 2002), when little information was available about the relative effectiveness of prostatectomy versus observation in men with screen-detected localized prostate cancer.

Beginning with an accrual target of 2,000 patients, after many years, PIVOT ended with 731 men enrolled by investigators at 44 Veterans Affairs sites and eight National Cancer Institute sites. Primary entry criteria included age <75, clinically localized prostate cancer (T1-T2NxM0) PSA <50 ng/mL, negative bone scan, and life expectancy of at least 10 years.

The patients were randomized to radical prostatectomy (technique at surgeon discretion) or observation. Men assigned to observation were offered palliative therapy or chemotherapy for symptomatic or metastatic progression.

All patients were followed for a minimum of 8 years from randomization, and the trial had a median follow-up of 10 years.The study population had a mean age of 67 and median PSA value of 7.8 ng/mL. Blacks accounted for almost a third of the patients, almost half had stage T1c (nonpalpable) disease, and 25% had Gleason scores =7.

Among men with complete data, 40% had low-risk cancers, 34% intermediate risk, and 21% high risk.

The primary endpoint was overall mortality, and the secondary endpoint was prostate cancer mortality. When the trial ended, 47% of patients in the prostatectomy arm had died compared with 49.9% in the observation arm. Median overall survival was 13.0 and 12.4 years in the prostatectomy and observation groups, respectively.

Prostate cancer-specific mortality was 5.8% with prostatectomy and 8.4% with observation.

Subgroup analysis identified only one group of men who had a survival benefit with radical prostatectomy: the subgroup with PSA values >10 ng/mL (about a third of the study population).

Because of the poor recruitment of participating patients many researchers noted that the study lacked statistical power to show a survival advantage, which the authors acknowledged.

William Catalona, MD, a urologic surgeon at Northwestern University in Chicago, said the results cannot be extrapolated to the general population because VA patients differ from those seen outside the VA system, including older age and more coexisting health problems. He also noted that the trial showed that surgery substantially reduced suffering.

"The goal of radical prostatectomy is to prevent suffering and death from prostate cancer," Catalona said by email. "In this regard, careful inspection of the data reveals that the occurrence of metastases was 60% lower and the prostate cancer mortality rate was 37% lower in men treated with surgery (40% lower at 12 years). In fact, most of the outcomes in their forest plots favor surgery over observation."

Ruth Etzioni, PhD, a biostatistics researcher at the Fred Hutchinson Cancer Center in Seattle, expressed concern about misinterpretation of the results as an indictment of surgery.

"If this study is reported in the press the way it has been reported in the journal – as indicating that radical prostatectomy is not beneficial when compared with watchful waiting – then this will represent a further unsound nail in the coffin of important efforts to manage this most common of male malignancies," Etzioni said in a written response:

"When one takes the PIVOT study results as reported, together with the [US Preventive Services Task Force] recommendations regarding PSA screening, one could then easily conclude that we should not be screening for or treating prostate cancer. This would be a mistake.

"Screening and treatment of primary tumors with treatments like radical prostatectomy plausibly account for about two-thirds of the almost 50% drop in prostate cancer deaths in this country since the early 1990s."

It is an incredible misinterpretation to say that surgery did not prevent PCa deaths, but Dr. Wilt went ahead and said anyway even when his long awaited results said otherwise...

good post Casey and I concur...Hopefully it will give doctors a wake up call but in the end it all seems to be about money.

Bottom line is since Psa testing began it has resulted in thousands of men being over treated for a cancer they would die with but not of. Thousands of men are experiencing incontinence and early ED as a byproduct who never needed to. Yes it has saved a few men, is the trade off worth it? Upon reflection I glad that I'm not one to panic nor trust everything said to me. Along with being very fortunate to learn of a the local university Urologic Oncology department who way back in 2007 was of the belief PCa was being massively over treated. That was a very radical opinion back then but has become prevalent with many other doctors now. If I was diagnosed today I'd likely choose AS. But if nothing else my skepticism and not panicking over the "C" word has resulted in my being one of the two most successfully (TFT) treated men here. My only side effect being a 60% loss of ejaculant. My worse treatment experience was 5 days with a catheter. See what's possible if one takes their time learning all options and weighing possible side effects along with quality of life issues. Don't be one of those who jump up on the OR table asap after dx... you may well regret that the rest of your life... Only accept treatment of whatever means when you are comfortable with it and your doctor.