Skip to main content

Without PSA Testing, What Would Happen?


July 30, 2012 — Routine screening for prostate cancer with the prostate-specific antigen (PSA) test has come under fire in recent months, but what would happen if there was no such screening?
Three times as many men would have advanced prostate cancer on diagnosis, according to a new analysis, published online July 30 inCancer. The researchers suggest that PSA testing in the United States prevents about 17,000 men each year from having advanced metastatic prostate cancer at diagnosis.
"Our findings are very important in the light of the recent controversy over PSA testing," said lead researcher Edward Messing, MD, from the University of Rochester Medical Center in New York.
The controversy erupted after the US Preventive Services Task Force recently recommended against routine useof the PSA test for screening asymptomatic men for prostate cancer, concluding that the potential harms from doing so outweigh the potential benefits. The test can identify cases of prostate cancer that are indolent and would probably never interfere with quality of life, yet once they are found, these cases are often treated aggressively, and each treatment has adverse effects.
Dr. Messing and colleagues focus on the other side of this coin. They home in on prostate cancer at the other end of the scale, where the prostate cancer is already metastatic at diagnosis. For their analysis, they used a mathematical model to determine what might happen if PSA testing was abandoned.
"Our data clearly indicate that not doing the PSA test will result in many more men presenting with far advanced prostate cancer," Dr. Messing said in a statement. "Almost all men with clinically apparent metastases at initial diagnosis will die from prostate cancer," he added.
In an interview with Medscape Medical News, Dr. Messing elaborated: "The PSA test does what it is supposed to do — it detects prostate cancer. In a sense, maybe it's too good, because it is picking up disease that you don't need to know about, but it is catching the bad disease early."
Comparing Data Before and After
For their analysis, the researchers used data from the National Cancer Registry and the Surveillance Epidemiology, and End Results (SEER) database.
The team compared data collected from 1983 to 1985, which was immediately before routine PSA testing was introduced, with data collected from 2006 to 2008, when PSA testing was widespread.
The researchers collected incidence rates on metastatic prostate cancer reported in several geographic regions, and then extrapolated the findings to the entire United States.
The actual data (presented in the paper in tabular form) give details of the incidence rates for metastatic prostate cancer by age group and race (black and white). The largest differences in the incidence of metastatic prostate cancer are seen in older men. For example, in white men 75 to 79 years of age, the incidence of metastatic prostate cancer was 156 per 100,00 men from 1983 to 1985, and was 41 per 100,000 men in 2006 to 2008 (incidence difference, 115).
The difference between the 2 time periods was even greater in older black men. In black men 75 to 79 years of age, the incidence of metastatic prostate cancer was 331 per 100,000 men from 1983 to 1985, and was 54 per 100,000 men from 2006 to 2008 (Incidence difference, 277).
The researchers do not provide overall figures for the incidence of metastatic prostate cancer in all men in the 2 time periods. However, they do give one overall figure — they estimate that there were 8000 cases of metastatic prostate cancer diagnosed in the United States in 2008. Using the data from the earlier time period, they estimate that if this testing had not been in place in 2008, the incidence would actually be 3 times greater, and there would have been 25,000 cases of metastatic prostate cancer.
Dr. Messing and colleagues caution that it is important to keep 2 significant issues in mind when interpreting these findings: the possibility of residual confounding, and lead-time effects resulting from screening.
Residual confounding covers factors other than PSA testing that can influence the incidence of prostate cancer. One example is obesity, which has increased in the United States over the 2 decades that the study spans, and has been reported to increase the risk for metastatic prostate cancer.
Lead-time effects relate to the possibility that screening has no impact on overall survival, despite finding the cancer at an earlier stage of presentation.
Rapid Reduction in Metastatic Presentation
Dr. Messing and colleagues report that their data show that the introduction of PSA testing resulted in a rapid reduction in the incidence of men presenting with metastatic prostate cancer in the early and middle 1990s.
Again, these data are presented for specific age groups (this time as graphs). The largest decrease in the annual incidence rates of men presenting with metastatic prostate cancer was seen in black men 70 years and older — there is a sharp drop from around 350 cases per 100,000 men in 1990 to around 150 per 100,000 men in 1995.
The argument that PSA screening leads to earlier detection of prostate cancer, and thus reduces the number of men presenting with advanced prostate cancer, has been put forward by several expert groups, including the American Urological Association (AUA), as a reason to continue to screen with PSA.
This is also the clinical experience of older physicians who have been treating prostate cancer over several decades, as reported previously by Medscape Medical News.
"It was as if people were drowning all around us," said Ian Thompson, MD, director of the Cancer Therapy & Research Center at the University of Texas Health Science Center at San Antonio, and chair of the AUA prostate cancer guideline panel. When the PSA test came along in the 1980s, urologists saw it as a life preserver that could save patients' lives by detecting prostate cancer at an earlier stage, he said earlier this year at the AUA annual meeting.
Doesn't Address Main Controversy
Dr. Messing acknowledged to Medscape Medical News that the paper does not touch on the main controversy surrounding PSA screening — that it leads to overdiagnosis and overtreatment.
But he noted that there is now enough evidence to support observation and active surveillance instead of treatment, and that diagnostic criteria and methodology have evolved. For example, he said, "Gleason 6 used to be considered a real disease, but now its an indolent tumor."
In the continuum from PSA testing to treatment for prostate cancer, there are now many places that the process can be stopped. "Even when the train is moving, you can still stop it," he said.
Dr. Messing is not advocating wholesale PSA screening for all men: "I am not sure this is the right thing to do." But there is a place for the test in older men. One of the benefits of testing — as shown in this paper — is that you can catch "bad disease earlier on," he explained.
However, 2 outspoken critics of using the PSA test to screen for prostate cancer, Richard Ablin, PhD, from the Department of Pathology at the University of Arizona College of Medicine in Tucson, and Mark Haythorn, from the Robert Benjamin Ablin Foundation for Cancer Research in Tucson, are not convinced, and told Medscape Medical News that the paper is based on calculated estimates.
"The authors' conclusion of 'possibly' preventing 17,000 men annually from having advanced disease at diagnosis is based on one assumption after another," they explain in an email to Medscape Medical News.
The 2 researchers coauthored an essay last year detailing the limitation of the PSA test (Biomarker Med. 2011;5:515-526), in which they conclude that "continuing with the current thinking, 'PSA testing is the best thing we have,' and misusing and overusing a test that cannot do what it is purported to do is not in keeping with the dictum...'first do no harm'."
Now, although Dr. Messing and colleagues make some "interesting calculations...it does not change our mind," they note.
"The fact remains that the manner in which the PSA test has been used is flawed," they explain.

Comments

  1. Unknown17 April 2013 at 04:53

    I do believe that after a certain age PSA tests should be required. The test has it's benefits and anyone who can't see that is not trying to. All you have to do is read super beta prostate supplement reviews or something like them to see how many men have benefitted from the PSA test. It's use needs to be moderated but you can't do away with it altogether.

    ReplyDelete

Post a Comment

Popular posts from this blog

Missing Data Lead FDA Panel to Vote Against Rivaroxaban for ACS May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting, the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel, or ticlopidine. Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the risk of bleeding and intracranial hemorrhage, but the studies were hindered by early patient withdrawals and missing data. We Don't Know What We're Missing Based on the ATLAS ACS 2 results, FDA reviewer Dr Karen Hicks recommended approval of rivaroxaban for the requested indications except all-cause mortality. However, another FDA reviewer, Dr Thomas Marciniak, was adamant that the trial results are not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. A total of 1294 subjects discontinued the trial prematurely, and the company was only able to contact 183, of which 177 were confirmed to be alive. Because of the patient dropouts, the company adopted a "modified intention-to-treat analysis," whereby patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as the FDA originally suggested. Marciniak criticized the sponsor's efforts to follow the patients and said that three patient deaths not counted in the modified intention-to-treat analysis may just be the "tip of the iceberg." Because the percentage of patients whose ultimate vital status remains unknown is much greater than the reported differences in mortality rates, the claimed mortality benefits are not reliable. The majority of the panel sided with Marciniak. For example, Dr Sanjay Kaul (University of California, Los Angeles) voted "no" because "there was enough uncertainty in the quality and robustness of the data that dissuaded me from voting yes. . . . The 'missingness' of the data doesn't invalidate it, but it certainly makes it hard to infer [the conclusion]." Dr Steven Nissen (Cleveland Clinic, OH) said that the decision to use the modified intention-to-treat analysis had a "profound impact" on the interpretability of the data. "It's saying we don't care what happens after 30 days, [and] that colored the trial in ways we couldn't recover from." Given the risk of major bleeding, "I want to see better evidence that this strategy of adding an Xa inhibitor or a direct thrombin inhibitor or something else to a good antiplatelet agent is robustly better for the patient," Nissen said. He recommends that the companies run a new trial of the 2.5 twice-daily dose of rivaroxaban using a strict intention-to-treat approach, but, he said, "I don't expect the death benefit to be too robust." Several panelists said they were concerned that the patients who dropped out of the trial were disproportionately likely to have a bleeding event, which led them to quit the trial, or a "protopathic" event, as statistician Dr Scott Emerson (University of Washington, Seattle) put it. "We're worried that an impending event is what is changing their behavior. We see that all the time in clinical trials--that regularly measured end points do not pick up [all of] the events," he said. He said that since the company was only able to contact 183 of the over 1200 patients who dropped out, it is possible that the dropouts skew the outcomes comparison of the trial. "Differential event rates after dropout are the number-one thing we're afraid of, so you have to explore it" in a statistical sensitivity analysis of the potential impact of these unknown outcomes. "It would not surprise me if, at the end of the day, these data did not hold up under a proper sensitivity analysis," he said. "What I want to know is, among the people who had events, how differential was the follow-up, but I can tell you by just looking at it, there was a very slightly different amount of follow-up of the people in the treatment arm. But I don't know whether everyone in the treatment arm was cured and they were trekking in the Himalayas and everyone in the placebo arm went home to die. I don't know that that's not the case." Dr Maury Krantz (University of Colorado, Denver) voted in favor of approval but said he does not know how rivaroxaban would perform in general clinical practice, especially when used with aspirin and clopidogrel. "I felt very much torn by this. This isn't a simple paradigm shift. It means going to triple therapy, which is really a three-headed monster in many ways. I think that what you're going to see in practice, if this is not done carefully with the proper labeling and secondary studies, is really dramatic magnification of bleeding and perhaps minimization of the efficacy benefit."

May 23, 2012   (Updated May 24, 2012)  (Silver Spring, Maryland)  —  The missing data issues plaguing the  ATLAS ACS 2 TIMI 51   trial of the factor Xa inhibitor  rivaroxaban  (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the  FDA  Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting , the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus  clopidogrel , or  ticlopidine . Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the  ATLAS ACS TIMI 46   phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the ri...
Post a Comment
Read more

Antidepressants Linked to Higher Diabetes Risk in Kids

Pediatric patients who use antidepressants may have an elevated risk for type 2 diabetes, the authors of a new study report. In a retrospective cohort study of more than 119,000 youths 5 to 20 years of age, the risk for incident type 2 diabetes was nearly twice as high among current users of certain types of antidepressants as among former users, Mehmet Burcu, PhD, and colleagues report in an article  published online October 16 in  JAMA Pediatrics . The risk intensified with increasing duration of use, greater cumulative doses, and higher daily doses of these antidepressants. The findings point to a growing need for closer monitoring of these products, including greater balancing of risks and benefits, in the pediatric population, the authors caution. They undertook the study because, despite growing evidence of an association between antidepressant use and an increased risk for type 2 diabetes in adults, similar research in pediatric patients was scarce. "To our know...
Post a Comment
Read more

Contact Precautions May Have Unintended Consequences

Contact precautions, including gloves, gowns, and isolated rooms, have helped stem the transmission of hospital pathogens but have also had some negative consequences, according to findings from a new study. Healthcare worker (HCWs) visited patients on contact precautions less frequently than other patients and spent less time with those patients when they did visit, report Daniel J. Morgan, MD, from the University of Maryland School of Medicine and the Veterans Affairs (VA) Maryland Health Care System, Baltimore, and colleagues. Moreover, patients on contact precautions also received fewer outside visitors. "Less contact with HCWs suggests that other unintended consequences of contact precautions still exist," Dr. Morgan and coauthors write. "The resulting decrease in HCW contact may lead to increased adverse events and a lower quality of patient care due to less consistent patient monitoring and poorer adherence to standard adverse event prevention methods (such...
Post a Comment
Read more