USPSTF Says “No” to PSA Screening

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By Dr. Gerald Chodak, M.D.
Medscape Oncology

The update to the PLCO trial was published, showing that we now have up to 13 years of follow-up in over 50% and 10 years of follow-up in 92% of the men in this trial. After that period of time, there is still no evidence for a reduction in mortality from prostate cancer with organized annual screening. Critics of the study have said for some time now that the study is worthless because of the level of contamination, meaning that many of the men assigned to the control group actually were tested. In the end, this is a comparison of opportunistic screening vs intensive systematic screening, with 53% of the men being tested at some point in the control arm compared with 85% in the intervention arm.

Nevertheless, despite this criticism, the findings are still interesting and important. Despite that level of contamination, there was still no difference in mortality, and when the investigators analyzed for level of comorbidity, age, or having had a prostate-specific antigen (PSA) test prior to entering the study, none of these factors affected the overall outcomes. An important fact here is that in the first 4 years, 600 extra cancers were detected in the intervention arm. Many people have looked at changes in mortality in the United States back in 1993, showing that as early as that point in time, with about 3 years of PSA testing, there was a drop in the death rate from prostate cancer. Proponents of screening have always wanted to attribute that to the effect of screening, and yet this study would further drive a hole in that argument because despite the 600 extra cancers detected as early as 3-4 years, there still was no change in mortality.

So where does this leave us? What is our message now? Many people are saying, "Well, it's still too early. We need 15- and 20-year data." That certainly may be true, but what about the large number of men who are being tested and screened with a life expectancy of 10-15 years at best? What message should we be giving to them? Do we tell the American public that despite our best efforts, we still do not have clear proof that screening saves lives? The European trial has been cited as proof that screening saves lives, but that study has many flaws, including differences in the treatment administered to those in the control group compared with those in the intervention group.

Despite years of study and testing and debate, we are left with the fact that we have no strong evidence that screening has a real impact. If anything, we have learned that screening certainly has more harms than people initially realized, with an excess number of cancers being detected and an excess number of men being treated without many of them benefiting from treatment. In this study, it is interesting that more high-grade cancers were detected in the control group, and that still didn't make a difference in mortality.

The bottom line is that after all these years, we need to make sure that people understand what we know and what we don't know about screening. What we know is that if there is a benefit, it's very small and it takes a long time to see it. Most of the men who are getting screened may not benefit and may have a risk of having unnecessary treatment, so better education is clearly important both for the primary care physician who is ordering the PSA test and for the individual man who is considering being tested. Hopefully, more information will be forthcoming, and at least men will get better information about what we know and don't know. Hopefully, we will stop giving a biased message about the overwhelming benefits of screening with PSA when we don't have any data that prove that to be the case.

References: Andriole GL, Crawford ED, Grubb RL, et al; PLCO Project Team. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl. Cancer Inst. 2012 Jan 6.

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Clinical Guidelines

Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement

Virginia A. Moyer, MD, MPH

From the U.S. Preventive Services Task Force, Rockville, Maryland.

Abstract

Description:

Update of the 2008 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for prostate cancer.

Methods:

The USPSTF reviewed new evidence on the benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer, as well as the benefits and harms of treatment of localized prostate cancer.

Recommendation:

The USPSTF recommends against PSA-based screening for prostate cancer (grade D recommendation).

This recommendation applies to men in the general U.S. population, regardless of age. This recommendation does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer; the use of the PSA test for this indication is outside the scope of the USPSTF.

The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.

It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

[url]http://www.annals.org/content/early/2012/05/21/0003-4819-157-2-201207170-00459.full

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The first posting of this information on cancerfocus.org was in October 2011. Yes. That was 7 months ago. And it is what Gary Schwitzer at HealthNewsReview.org has brought up in his blog "Outrageous...an earthquake...an enormous game changer" - but it was there for all to see for 7 months!

News coverage of the Task Force's new recommendation against prostate cancer screening was often hyperbolic and sensational, ignoring the fact that the published recommendation first appeared in draft form in October, fully 7 months ago, and that it was available for public comment for two time periods late last fall.

The news coverage was not surprising, was not unexpected, and the rationale and supporting evidence was posted online for anyone to comment on for 7 full months. Where was all the news coverage of that opportunity for the past seven months?

This reminds me of the anemia drug issue. The FDA first warned about prescribing drugs for anemia in cancer patients in early 2007. It wasn't until 4 years later, the issue seemed to be finally resolved: using pharmaceutical EPO in cancer is harmful, like in increasing mortality in cancer patients.

And it wasn't until this year that it was exposed that dozens of doctors influenced their colleagues to use pharmaceutical EPO for unapproved indications such as cancer-related fatigue (anemia). There have been several nuclear explosions in clinical oncology. Interestingly, it is the highest levels of academia who are most tainted.

But as in the anemia drug issue, the PSA screening issue will probably play out as one more cudgel to beat the more reasonable and gentle practitioners, who either largely avoided such abuse or were led down the path by the path by the scholars, who will themselves skip out unfazed.

[url]http://www.healthnewsreview.org/2012/05/outrageous-an-earthquake-an-enormous-game-changer-but-it-was-there-for-all-to-see-for-7-months/

[url]http://cancerfocus.org/forum/showthread.php?t=294

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(Reuters Health) - The rate of early prostate cancers among older Americans dropped suddenly following a change in screening advice from government-backed experts in 2008, new research shows.

The findings are another sign that the tide could be turning against routine prostate cancer screening, which a growing number of medical groups worry could do more harm than good.

In August, 2008, the U.S. Preventive Services Task Force began discouraging screening in men over 75 given the known risks of screening and lack of clear benefits (The group recently expanded its recommendation to men of all ages).

A survey published earlier this year found no decrease in screening. But that work was based on screening tests reported by patients and could be unreliable, said David H. Howard, a health policy researcher at Emory University in Atlanta, who did the new study.

Using a national cancer registry known as SEER, he found the rate of early-stage prostate tumor diagnoses among men aged 75 and older fell 25 percent from 2007 to 2009 - from 443 to 330 per 100,000 men.

While more-advanced tumors and those in younger men also were on the decline, the drops were not as drastic or sudden as among older men.

That suggests the revised guidelines had an impact on doctors, although insurers still pay for the prostate-specific antigen, or PSA, blood test used to screen for prostate cancer, Howard told Reuters Health.

"Voluntary compliance is better than nothing," he said, "but obviously there is still a long way to go. That may include policy and insurance changes."

According to Howard, about half of elderly men in the U.S. still get screened. Research shows other kinds of cancer screening are also common among seniors, despite doubts about their efficacy in this age group.

More than 2.5 million men in the U.S. are living with a prostate cancer diagnosis today, according to the American Cancer Society, but the vast majority won't die from the disease. That's because many of these cases represent tumors that were picked up by PSA tests without ever having caused any symptoms.

Experts say men with early-stage prostate cancer may choose to wait and see if the disease progresses, which it often doesn't do, instead of getting aggressive treatments such as surgery or radiation right away.

Although it's unclear if such treatments are any more helpful than the wait-and-see approach, side effects such as impotence or incontinence are common.

So far, it's impossible to say whether the drop in the number of early diagnoses will be accompanied by changes in prostate cancer death rates. If there is no uptick in deaths, that will be a sign that the PSA test is being overused.

The Archives of Internal Medicine, which published Howard's results, welcomed the findings in a note entitled "Time to Stop Screening for Prostate Cancer."

"Given that the harms of screening... outweigh the benefits for younger men as well," editor Dr. Mitchell Katz wrote, "we hope to see a similar decrease in early prostate cancer incidence in young men."

Source: Archives of Internal Medicine

A Lancet editorial, “Prostate cancer: Send away the PSA?“

[url]http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961232-X/fulltext

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(Medscape Oncology) In the past, clinicians and the public have heeded the advice of the United States Preventative Services Task Force (USPSTF) about prostate cancer screening, suggests research published online July 23 in the Archives of Internal Medicine.

After the group's 2008 guidance, which recommended against screening men older than 75 years, the incidence of early-stage disease in older men plunged 25% in the United States.

"There was an immediate decline in the incidence of early-stage prostate cancer tumors among men 75 years and older after the USPSTF recommended against screening this group," writes author David Howard, PhD, from the Department of Health Policy and Management at Emory University in Atlanta, Georgia.

The incidence of early-stage disease is an indicator of the amount of prostate-specific antigen (PSA) testing in a population, he explained.

Dr. Howard found that from 2007 to 2009, the adjusted incidence rate for early-stage tumors in men 75 years and older decreased from 443 to 330 per 100,000 (−25.4%; P < .001). The absolute number of cases declined from 8137 to 6162.

Dr. Howard used data from the Surveillance, Epidemiology, and End Results (SEER) 18 registry, which collects information on newly diagnosed cancer cases in catchment areas.

He challenges recent results that indicated that there was no change in PSA screening rates from 2005 to 2010 (JAMA. 2012;307:1692-1694). The data source for that study was the National Health Interview Surveys, in which American residents self-report health behaviors and diseases. "Self-reported PSA testing measures have poor sensitivity and specificity," scolds Dr. Howard.

An immediate question arises from Dr. Howard's analysis: Will it happen again because of the 2012 USPSTF recommendation against routine testing for all healthy men?

The USPSTF's "blanket rejection" of the PSA test is "unlikely to influence practice," according to Sigrid Carlsson, MD, PhD, from the Memorial-Sloan Kettering Cancer Center in New York City and Göteborg University in Sweden, and colleagues. Dr. Carlsson and her fellow experts wrote an essay criticizing the new USPSTF guideline for a number of "very important errors," as reported by Medscape Medical News.

"PSA testing is not likely to go away," wrote Dr. Carlsson and coauthors.

Dr. Howard voiced similar thoughts in an email to Medscape Medical News.

"Physicians are probably more willing to discontinue screening older patients. There might be more resistance to discontinuing screening among younger, healthier men," he said.

But Dr. Howard also said: "I think it will have an impact. There is growing publicity about the problem of 'overdiagnosis', which might make physicians and some patients more receptive to the USPSTF recommendation."

The recently published PIVOT study might also contribute to the way the new guidance is received, noted Dr. Howard. This major randomized controlled trial found that prostatectomy did not improve survival significantly, compared with observation, in men with localized disease. "This research also casts doubt on the benefits of early detection, which may amplify the impact of the USPSTF recommendation," said Dr. Howard about PIVOT.

In addition to finding that the rate of early-stage prostate cancers dropped among older men after the 2008 recommendation, Dr. Howard found that other indicators of PSA testing also dropped.

The incidence of late-stage tumors decreased by 14.3% (P < .001), and the incidence of tumors of unknown stage decreased by 16.8% (P < .001). The incidence of early-stage tumors in men 65 to 74 years decreased by 15.2% (P < .001); in men 30 to 64 years, the incidence decreased by 11% (P < .001).

Overall, Dr. Howard found that 254,184 prostate cancer cases were newly diagnosed during the study period. There were 198,417 early-stage cases, 34,695 late-stage cases, and 21,072 cases of unknown stage. There were 109,053 cases (all stages) in men 30 to 64 years of age, 91,868 cases in men 65 to 74 years, and 53,263 cases in men 75 years and older.

Arch Intern Med. Published online July 23, 2012.

[url]http://archinte.jamanetwork.com/article.aspx?articleid=1221718

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Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement

Ann Intern Med. 17 July 2012;157(2):I-44

Who developed these recommendations?

The U.S. Preventive Services Task Force (USPSTF), which is a group of health experts that makes recommendations about preventive health care.

What is the problem and what is known about it so far?

The prostate is an organ in men that surrounds the tube that empties urine from the bladder. Prostate cancer is the most commonly diagnosed non–skin cancer among men in the United States. The most common prostate cancer symptoms are difficult or frequent urination, but many men have no symptoms.

A blood test that measures prostate-specific antigen (PSA) levels can find prostate cancer before symptoms develop. If the PSA level is high, a prostate biopsy may be needed to see whether cancer is actually present. During biopsy, doctors insert a hollow needle into the prostate to obtain a piece of the prostate to examine under a microscope.

At present, there is no way to tell with certainty which cases of prostate cancer are life-threatening and require treatment, and which cases are not. Most prostate cancer grows very slowly, and many men with prostate cancer die of something other than prostate cancer. However, screening puts men at risk for unnecessary worry and adverse effects of treatment with surgery, hormones, or radiation therapy.

In 2008, the USPSTF recommended that men older than 75 years of age not get PSA-based screening and concluded that there was not enough information to make a recommendation for younger men. It wanted to update that recommendation by reviewing studies that have become available since 2008.

How did the USPSTF develop these recommendations?

The USPSTF reviewed published research to measure the benefits and harms of screening for prostate cancer with PSA testing.

What did the authors find?

Good evidence shows that PSA-based screening prevents only 0 to 1 prostate cancer death for every 1000 men screened. No studies show any benefit in overall death rates.

Good evidence shows that PSA-based screening can cause harms, including pain and complications from prostate biopsy and worry about test results. However, the more worrisome harms are related to treatment of prostate cancer found by screening when most of these cases, if not detected by screening, would never have caused problems for the patient. The side effects of prostate cancer treatments include sexual dysfunction, bowel and bladder incontinence, and even death.

What does the USPSTF recommend that patients and doctors do?

For men of any age, the USPSTF recommends that doctors and patients do not screen for prostate cancer because the potential benefits do not outweigh the harms. However, the USPSTF realizes that some men may continue requesting the PSA test and some physicians may continue offering it. The decision to start or continue screening should be an informed one that reflects an understanding of the possible benefits and harms and should respect an individual man's preferences.

What are the cautions related to these recommendations?

These recommendations apply to men of all ages. They do not include the use of the PSA test for monitoring after a diagnosis of prostate cancer or after treatment of prostate cancer. The recommendations may change as new studies become available.

Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 2012 Jul;157(2):I-44.

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Robert Meier knows what it’s like to have a blind prostate biopsy. It took four times before the 58-year-old high school art teacher was diagnosed with prostate cancer.

“These biopsies can be extremely painful and I was put in the hospital several times so they could be done under general anesthesia,” said Meier, of Visalia, Calif. “It takes about a month to recover.”

But researchers are reporting a new method that could put an end to painful prostate biopsies that miss the tumor. They’ve combined magnetic resonance imaging, or MRI, with ultrasound in a way that can guide a skilled doctor right to a prostate tumor.

Dr. Leonard Marks, a professor of urology at the University of California Los Angeles and colleagues report their method in the Journal of Urology. They say it helped them identify prostate tumors in 53 percent of 171 men who volunteered to try it.

The findings could help solve one of the biggest problems of prostate cancer. There’s a blood analysis called a PSA test that can help doctors guess that a man may be developing prostate cancer. Prostate specifc antigen or PSA is made only by prostate cells — and they produce a lot more of it when they are cancerous.

But the prostate also naturally enlarges as men get older, which can send PSA levels up. And inflammation — caused by an infection or even something as simple as a bicycle ride, can also send levels up.

Because the walnut-sized prostate gland is so hard to reach, doctors have to do a so-called blind biopsy. They take a few chunks of tissue and hope they get a piece of any tumor so they can decide how aggressive the cancer is. But they can completely miss the tumor and get healthy tissue.

That’s what happened to Meier. His PSA started rising in 2008, but repeated biopsies showed no sign of cancer.

“The doctor I was going to did three rounds of biopsies and he never could find it,” Meier said in a telephone interview.

Some men might be comfortable with so-called watchful waiting. But others are anxious when they think they may have cancer but don’t really know — and Meier was one of them. He went to a doctor in Santa Barbara for a second opinion, and got yet another biopsy. It was negative.

“Every time they did a biopsy they couldn’t find anything,” Meier said.

So the second doctor started treating Meier for an enlarged prostate. But the PSA kept going up. “I new in my mind something was wrong,” Meier said.

By 2011 his PSA was nearly 18 — a huge rise from a “normal” reading of 4. Meier was referred to UCLA. He had an MRI in Marks’s lab, and it showed a tumor.

Using standard technology, a urologist would still have to guess where the tumor was to get a sample so a pathologist could determine if it was likely to spread. The new technology that Marks helped develop combines the MRI image of a suspected tumor with ultrasound, so the urologist can guide the biopsy needle right there.

Marks got a piece of Meier’s tumor, and it was an aggressive type.

“It had gone out of the prostate gland a little bit and gone into what’s called the seminal vesicles,” Meier said.

Meier had his prostate surgically removed, as well as two dozen surroudning lymph glands. “As of now it looks pretty good,” he said.

The 171 men in the UCLA study were all being watched for possible prostate cancer, or were under observation for slow-growing tumors. While most prostate tumors grow slowly, some become aggressive and spread quickly, and it's often hard to tell what type a man has.

Men with early state prostate cancer can choose from a range of treatments, including surgery, guided radiation and a treatment using radioactive “seeds” that kill prostate tissue.

Prostate cancer is the biggest cancer killer of U.S. men, after lung cancer. It’s diagnosed in more than 240,000 men a year and kills more than 28,000, according to the American Cancer Society.

Most men with prostate cancer will never develop symptoms, and a biopsy is the only way to take a look at the tumor cells and decide how dangerous the cancer is. Because of the uncertainty, last May the U.S.

Preventive Services Task Force recommended that routine PSA screening be stopped. It said too many men were getting painful biopsies and even surgery and radiation that were not necessary.

Several studies have shown early screening hasn’t lowered the prostate cancer death rate, and one study projected that a million men had been treated needlessly for the disease between 1986 and 2000.

“Because of an elevated PSA level, some men may be diagnosed with a prostate cancer that they would have never even known about at all. It would never have lead to their death, or even caused any symptoms,” the American Cancer Society says.

“Treatments like surgery and radiation can have urinary, bowel, and/or sexual side effects that may seriously affect a man's quality of life.”

Targeting biopsies won’t solve the problems caused by PSA screenings, but they can help doctors and patients decide sooner whether a man really does need treatment for his cancer.

Marks and colleagues said if a tumor looked dangerous on an MRI, the biopsy usually confirmed that it was.

“Biopsy findings correlate with the level of suspicion on MRI. Targeted prostate biopsy has the potential to improve the diagnosis of prostate cancer and may aid in the selection of patients for active surveillance and focal therapy,” Marks’s team wrote.

This article first appeared in Cancer on NBCNEWS.com

The American College of Physicians (ACP) became the latest group to ask doctors to be clear about the limited benefits and “substantial harms” of prostate cancer screening before offering their male patients a prostate-specific antigen (PSA) test.

Source: Annals of Internal Medicine, online April 8, 2013.