Aiding patients' decisions on PSA screening

Routine prostate-specific antigen (PSA) screening of all men over a certain age began about 20 years ago, but the certainty about whether that was or is wise medical practice is long gone.

Routine prostate-specific antigen (PSA) screening of all men over a certain age began about 20 years ago, but the certainty about whether that was or is wise medical practice is long gone. Today, with internists often advising patients about routine screening, more is known about the side effects of prostate cancer treatment, guidelines are conflicting, and trial data are inconclusive.

“Patients need to understand that this is controversial, there is a lot of uncertainty, and there are tradeoffs between preventing prostate cancer deaths and overdiagnosis and overtreatment,” said Richard M. Hoffman, FACP, professor of medicine at the University of New Mexico School of Medicine and staff physician at the Raymond G. Murphy VA Medical Center in Albuquerque. “There is a lot of information to cover, and it needs to be covered objectively and consistently.”

The informed consent process is complex with prostate cancer
The informed consent process is complex with prostate cancer.

Thomas W. Flaig, MD, assistant professor in the division of medical oncology at the University of Colorado Denver and the University of Colorado Health Sciences Center, said that the issue at the heart of the controversy is whether PSA screening is a wise choice at all for many men who may subsequently be treated for cancer that would never cause problems or shorten their lives.

“I see a lot of prostate cancer patients as a medical oncologist and see all the side effects induced by the primary therapy, whether it be radiation or surgery, including urinary incontinence, loss of sexual function and, occasionally, severe perioperative side effects,” he said. “I know that the side effects were caused by what we have done, that they are medicine's imprint on the life of this patient. What we don't know is what would have happened if we had not done anything or whether the treatment was necessary, especially in older and low-risk patients.”

Substantial side effects

The American Cancer Society updated its guideline on early detection of prostate cancer last year, detailing the potential side effects of treatment. Rates of perioperative transfusion can be as high as 20% in men who undergo radical prostatectomy, and the long-term effects can include anastomotic stricture in 5% to 14% of men, total or stress urinary incontinence in 12% to 16%, and sexual dysfunction in 19% to 27%, the guideline said. For those treated with radiation therapy, acute toxicities and erectile dysfunction can develop in up to 50%.

But other experts, such as Dr. Hoffman, stated that the Scandinavian Prostate Cancer Group Study 4 found 90% erectile dysfunction at four years after radical prostatectomy and observational data that ranged widely, with an upper estimate of 90%.

Len Lichtenfeld, MACP, deputy chief medical officer of the American Cancer Society, said that when he was a primary care physician in the 1980s, he recommended prostate cancer screening for all men who came to his office because physicians assumed that it saved lives.

“Today I wonder how many people I helped and how many I hurt by following the rationale that finding every cancer at the earliest possible moment has to be a good thing when there is no solid proof that that is a good thing,” he said. “I find myself years later in the middle of this discussion and feeling somewhat disappointed and disillusioned about our lack of progress with being able to answer the question with high-quality evidence.”

Associated with aging

A look at statistics about prostate cancer shows that it is prevalent in men as they grow older, but is often slow to develop and may never cause a problem. According to the American Urological Association, autopsy studies have found that 1 in 3 men over age 50 have prostate cancer, but up to 80% of the tumors are limited in size and grade and are therefore clinically insignificant. The lifetime risk of prostate cancer death is about 3%, according to the American Urological Association.

The American Cancer Society estimates that 23% to 42% of screen-detected cancers would never have been detected if screening had not been done.

“This degree of potential overdiagnosis and the associated overtreatment of invasive disease appear to be greater than that for any other cancer for which routine screening currently occurs,” the 2010 guideline update stated. Moreover, as mentioned, the adverse effects from treatment of prostate cancer are serious and potentially life-altering.

Conflicting guidelines

Guidelines on the issue don't agree and aren't based on level one evidence, leaving internists with the task of sorting through them, and helping their patients do so as well.

But review of the current guidelines is a good starting point for decision making about screening. The U.S. Preventive Services Task Force recommendation clearly states that men age 75 and over should not be screened. The task force makes no recommendation for men younger than 75 years. Even though prostate cancer is more common in black men and men with a family history of prostate cancer, the task force states that the same uncertainties about the effects of screening apply to these groups, which may be at higher risk.

According to Dr. Hoffman, the U.S. Preventive Services Task Force, which is “considered to offer the most evidence-based recommendations,” has not yet updated its statement on PSA screening since the publication of the most recent randomized trials.

The American Urological Association recommends PSA screening for “well-informed” men who decide to pursue early diagnosis. Men are well-informed, according to the statement, if they are given information about the risks and benefits of testing, the risks of overdetection and overtreatment, and evidence from a randomized trial that showed a mortality decrease associated with PSA screening. The association's 2009 update to its best practice statement on PSA testing states that baseline PSA should be obtained at age 40 for men expected to live another 10 years or longer; decisions about future screenings can be based on that number. However, Dr. Hoffman said, “There is really no convincing evidence for starting screening at age 40 for either high- or average-risk men.”

The American Urological Association recommendations advise that men who choose to be screened should be given a digital rectal exam (DRE) along with the PSA. Physicians should also consider several factors when determining which patients are appropriate candidates for screening: patient age and comorbidities, patient preferences, family history, race, PSA history, and prior biopsy.

The American Cancer Society's 2010 updated guideline, the one cited most favorably by the experts contacted for this article, recommends that black men and men with a first-degree relative with prostate cancer be informed about the uncertainties, risks and potential benefits of prostate cancer screening beginning at age 45.

For men with multiple first-degree relatives diagnosed with prostate cancer before age 65, the guideline states, the discussion should take place at age 40. Men at average risk should receive this information at age 50. Asymptomatic men with at least a 10-year life expectancy should be given the chance to make an informed decision with their doctor. Men with an expected lifespan of 10 years or less should not be screened.

“These guidelines are very reasonable,” Dr. Flaig said. “It's a short, reasonable recommendation to start the discussion at age 50 or earlier in those with risk factors. I think that's a simple and reasonable way to approach it.”

Dr. Lichtenfeld cautioned that the American Cancer Society “does not say that prostate cancer screening does not save lives, but what we are saying is that we are not certain that it does. As a result of that, the decision by each man should be based on an informed and shared decision-making process.”

And Marc B. Garnick, FACP, clinical professor in the department of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, added that these recommendations were made without any level one evidence to support their use. “In fact, the level one evidence would argue against anything other than encouraging a discussion about whether to be tested at all for an average-risk patient.”

In 2009, 10-year data were released from two major trials that many had hoped would clear up the confusion about screening efficacy. Unfortunately, the results were contradictory.

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial found no cancer-specific survival advantage with screening. Men randomized to the screening arm in the PLCO trial had a PSA test every year for the first 6 years and digital rectal exam for 4 years; follow-up was between 9 and 11 years. The incidence of death per 10,000 person years was 2.0 in the group that was screened versus 1.7 in the control group (N Engl J Med. 2009;360:1310-9).

The European Randomized Study of Screening for Prostate Cancer (ERSPC) found a cancer-specific survival benefit by year 7 to 8 in the group that was screened. In ERSPC, men in the screening arm had an average of 2.1 PSA tests over the course of the study; the screening interval ranged from 2 to 7 years. At year 7 to 8, the mortality rates began to diverge between the two arms of the study. The trial results (N Engl J Med. 2009;360:1320-8) indicate that 1,410 men would need to be screened and 48 additional prostate cancer cases would need to be treated to prevent one death from prostate cancer.

Longer-term follow-up is expected from both trials over the next 5 to 10 years. In the meantime, Dr. Hoffman cautioned in ACP Journal Club that, based upon evidence from the Göteborg study (Lancet Oncol. 2010:11:725-32), screening seems to confer only a small survival benefit that is offset by substantially increased risks for prostate cancer diagnosis and adverse events from treatments.

Talking to the patient

Discussions between doctors and patients should cover some of this background information so that patients are better able to make an informed decision.

“The most important point for an average-risk, 55-year-old man to understand is that we don't have clear evidence that everyone agrees to that shows that prostate cancer screening does in fact save lives,” said Dr. Lichtenfeld. “If he is inclined to pursue screening, he needs to understand that there are a lot of uncertainties about what the results of the test mean. A high PSA does not necessarily mean that a man has prostate cancer, and a low PSA does not necessarily mean that a man does not have cancer.”

Dr. Flaig agreed. “The question in prostate cancer is whether a PSA is a valid test that will make men's lives better, considering the risks and benefits, and there is no evidence to clearly answer that question. Everyone needs to recognize that this issue is hard on providers and it's hard on patients. Although it's difficult to have that conversation, I don't know of a fairer or clearer way of making a decision about initiating prostate cancer screening.”

Helping an average-risk patient decide whether to have PSA screening should be done directly and honestly, according to Dr. Garnick. He recommends that internists discuss the following points with their patients:

  1. 1. There is a blood test that can help detect prostate cancer when there would be no reason to suspect the presence of prostate cancer.
  2. 2. If the results are abnormal, we would likely refer you to a urologist, who would likely do a prostate biopsy to determine if cancer was present.
  3. 3. If we do a biopsy and it shows cancer, we would probably recommend treatment, either surgery or radiation therapy.
  4. 4. Treatment can be associated with incontinence, impotence or rectal bleeding.
  5. 5. Even if we treat, there is no good evidence that you will live any longer or that treatment will even decrease the likelihood of your dying of prostate cancer. If it does decrease the likelihood of dying of prostate cancer, the effect is small.
  6. 6. How would you like to proceed?

Dr. Garnick, editor-in-chief of Harvard Medical School's Annual Report on Prostate Diseases and its website, and author of the PIER module for prostate cancer screening guidelines, also recommends that the date of the conversation and the patient's decision be documented in that patient's file.

Beyond the discussion about the pros and cons of screening, the patient also needs to think about his own values and preferences, according to the American Cancer Society. Values and preferences can be approached by talking about the following:

  1. 1. Is the patient very worried about dying of prostate cancer, and would he be willing to accept the risks of treatment to get rid of the cancer?
  2. 2. Is the patient more concerned about overdiagnosis, urinary incontinence, and sexual dysfunction, or other side effects of treatment?
  3. 3. Is the patient the type of person who would want to do something about the cancer, even if there are serious side effects?
  4. 4. Would he be comfortable adopting a watchful waiting or active surveillance approach if cancer is detected?

Giving a decision aid to patients in advance can help them sort through their own preferences about screening, according to the experts.

“Primary care providers really don't have the time in a routine clinic visit to address all of these issues. By giving a decision aid in advance of an appointment, it allows the patient time to review it, discuss with family and friends, and then have a much more focused discussion when meeting with the physician,” said Dr. Hoffman, who edits the PSA screening decision aid produced by the Foundation for Informed Medical Decision Making.

Some patients, however, want the physician to decide for them. Then, the American Cancer Society recommends that the physician do so after considering the patient's general health preferences.

“There are going to be men who understand the risks of treatment but want everything done possible to locate every abnormal cancer or disease in their body and therefore want to be screened,” Dr. Lichtenfeld said. “And there will be men who are going to take their chances and will say that if you can't tell them definitely that a treatment will work, they don't want to be screened. There are clearly two ends of the spectrum and also a large number of men in the middle who do look to their physician for guidance.”