Prostate cancer screening

Another Prostate Cancer Screening Candidate Outperforms Standard PSA Testing

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A multiparametric blood test for prostate cancer showed potential to avoid more than half of unnecessary biopsies without sacrificing accuracy, a large prospective study showed.

In a comparison against the current PSA testing standard of ≥4 ng/mL, the Stockholm3 biomarker, which incorporates a PSA cutoff of 15 ng/mL with other proteins and genomic information, would have spared 56% of men from biopsies for grade group (GG) 1 or benign disease. The standard PSA cutoff would have avoided 19% of unnecessary biopsies, decreasing to 10% with a cutoff of ≥3 ng/mL.

Sensitivity, specificity, and predictive values with the multicomponent test either approximated or surpassed those achieved with conventional PSA testing, reported Scott Eggener, MD, of the University of Chicago, at the Genitourinary Cancers Symposiumopens in a new tab or window.

“Stockholm3 has the potential to reduce unnecessary harms of prostate cancer screening,” said Eggener. “Stockholm3 has attractive characteristics in this diverse cohort, and [demonstrated] successful recruitment of a large cohort of men from traditionally underrepresented minorities. The Stockholm3 should be available in the early part of 2024.”

During a discussion that followed the presentation, a viewer following online asked how the Stockholm3 compared with other tests, such as the 4Kscoreopens in a new tab or window and the Prostate Health Indexopens in a new tab or window.

“It’s a busy space, the secondary biomarker space, and the question always comes up is how they compare head to head,” said Eggener. “They’re all based on good science. All of them have good studies showing their value. For a variety of reasons that you all probably know, it’s rare for them to go head to head, so we really don’t know.”

In response to another question, Eggener noted that the 16% rate of MRI use in the study was lower than might be expected in a population-based investigation, probably because more than half of the blood specimens were archival from a biobank.

“It would be interesting to see if prospective routine use of MRI would change the operating characteristics,” he said.

A final question related to investigators’ ability to recruit a racially/ethnically diverse population, as Asian, Black, and Hispanic patients accounted for a majority of the blood specimens. Eggener said investigators sought out participating sites that have diverse patient populations.

Stockholm3: The Basics

The Stockholm3 incorporates proteins (total and free PSA plus three cancer-related proteins — GDF15, KLK2, and PSP94), polygenic risk using 101 single-nucleotide polymorphisms, and patient clinical data. The test has a multiplex algorithm that uses the multiparametric data to predict the likelihood of GG ≥2 prostate cancer. A risk score ≥11 is considered indicative of prostate cancer.

An initial studyopens in a new tab or window conducted in Sweden showed use of the test reduced benign biopsies and diagnosis of clinically insignificant prostate cancers. In a subsequent studyopens in a new tab or window, use of the test reduced MRI procedures and referrals for prostate biopsy. Racial and ethnic representation in prostate cancer trials is typically poor, Eggener noted. Investigators in the SEPTA studyopens in a new tab or window sought to address that issue by evaluating Stockholm3 performance metrics in a diverse North American population, involving 17 centers in the U.S. and Canada.

Eligible participants were ages 45-75, had no known prostate cancer but a clinical indication for prostate biopsy, and self-identified as Asian, Black/African American, Hispanic/Latino nonwhite, or white. All participants had blood drawn prior to prostate biopsy.

The primary endpoint was GG ≥2, and the key secondary endpoints were GG 1 prostate cancer or benign disease. A primary objective was to evaluate the relative sensitivity of Stockholm3 (PSA ≥15) and PSA ≥4 for detecting GG ≥2. A second objective was to compare the relative specificity of Stockholm3 and PSA ≥4 for avoiding GG 1 cancer or benign disease.

SEPTA included 912 men recruited from the 17 participating sites plus 1,217 men who had been biopsied and had biobanked blood. Study participants had a median age of 63 and a median PSA of 6.1 ng/mL. A fourth of the patients had an abnormal digital rectal exam, 20% had a family history of prostate cancer, and 20% had a prior negative biopsy. The median Stockholm3 score was 17, and 16% of the patients had undergone MRI-targeted biopsies.

Key Findings

Investigators achieved the ethnic diversity they sought, as 16% of patients were Asian, 24% were Black, 14% were Hispanic, and 46% were white. Biopsy results showed benign disease in 57% of cases, GG 1 prostate cancer in 14%, and GG ≥2 in 29%. Analysis of biopsy findings by ethnicity showed that Asian and Hispanic men had more benign disease (69% and 60%, respectively) and Black men had fewer benign diagnoses (49%). Detection of GG 1 was similar across the groups (11-17%). Black men had more GG ≥2 (37%) and Asians had less (21%).

Biopsy results showed that a PSA ≥3 ng/mL detected 97% of GG ≥2, followed by PSA ≥4 (92%) and Stockholm3 (88%). Use of Stockholm3 avoided almost three times as many unnecessary biopsies as a PSA cutoff of ≥4 ng/mL and almost six times more than a cutoff of ≥3.

As compared with PSA cutoffs of ≥3 or ≥4 ng/mL, the Stockholm3 test achieved the following values:

  • Specificity: 56% vs 10% vs 19%, respectively
  • Negative predictive value (NPV): 92% vs 91% vs 85%
  • Sensitivity: 88% vs 97% vs 92%
  • Positive predictive value (PPV): 44% vs 31% vs 31%

Lowering the Stockholm3 cutoff to ≥11 ng/mL led to slightly better NPV, sensitivity, and PPV, but at the expense of 18% more biopsies for low-risk and benign disease.

Ovarian Cancer: Making the Case for Screening Those at High-Risk

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30-year study suggests transvaginal ultrasound is a viable option for some high-risk women

Results of the 30-year prospective University of Kentucky Ovarian Cancer Screening Trial are adding to a body of evidence suggesting that an annual transvaginal ultrasound can detect early-stage ovarian cancer and improve survival rates for this patient population.

The cohort study by John van Nagell, MD, of the University of Kentucky Markey Cancer Center, and colleagues found that annual ultrasound screening of at-risk asymptomatic women was associated with early detection of lower-stage ovarian cancer and increased disease-free survival for types I and II epithelial ovarian cancer.

The study, published in Obstetrics & Gynecology, enrolled 46,101 women from January 1987 to June 2017 who met the eligibility criteria — women asymptomatic for ovarian cancer ages 50 or older and asymptomatic women ages 25 or older with a documented family history of ovarian cancer in at least one primary or secondary relative. Participants did not get genetic testing, but the women all completed a questionnaire that included medical history, surgical history, menopausal status, hormonal use, and family history of cancer.

The researchers documented a family history of ovarian cancer in 23.2% (20,195) of the participants and a family history of breast cancer in 43.8% (20,195). The women underwent 298,418 scans (mean of 6.5 scans per participant), with 246,275 scans (82.4%) visualizing one or both ovaries. Those women (699 or 1.5%) who had persisting ovarian tumors with transvaginal ultrasound underwent diagnostic surgery. This group was compared with 921 unscreened women with clinically detected epithelial ovarian cancer referred to the cancer center for treatment from 1995 to 2017.

The annual screenings found 71 invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignancy; of those with invasive epithelial ovarian cancer, 30 had stage I disease (42%), 15 had stage II (21%), 26 had stage III (37%), and no one had stage IV. These patients were followed from 9.2 months to 27 years. Looking at 5-, 10-, and 20-year disease-specific survival, the researchers found that the screened group had a significant survival benefit of 30% higher than the unscreened group.

“Sixty-three percent of women whose invasive ovarian cancer was detected by screening had stage I or II disease as opposed to 30% in unscreened women from the same geographic area diagnosed clinically during the same time period,” van Nagell and co-authors wrote. “That there was a substage shift within stage III in the screening group also is important, because there is a 5-year survival advantage of 20% in patients with stage IIIA compared with stage IIIC disease in the era of platinum+ taxane chemotherapy.”

Current Screening Guidelines

Survival for women with ovarian cancer, the leading cause of gynecologic cancer death in the U.S., remains dismally low. The U.S. Preventive Services Task Force (USPSTF) earlier this year reiterated their firm stance that average-risk, asymptomatic women should not be screened for ovarian cancer, citing the harms of screening — false-positive results, leading to unnecessary surgical interventions — and noting that research has not shown a reduction in mortality. The task force does recommend screening with CA-125 and transvaginal ultrasound in women who have genetic mutations and are considered very high-risk.

Asked for her perspective, Veena John, MD, system head of gynecologic cancer at Northwell Health Cancer Institute in New Hyde Park, N.Y., said she is not yet ready to change her clinical practice based on the trial by van Nagell et al., but noted that she follows the USPSTF’s recommendations that yearly screens are only for those women who carry genetic mutations. However, she added, “if the patient has a risk more than the average, it would benefit them to have sonograms.”

Still, she said that the issue of false positives is one of the main reasons for not jumping on the bandwagon of yearly screening considering the anxiety such testing can cause.

The University of Kentucky study acknowledged these concerns, particularly false-positive results from screening. The study authors noted that “in the United Kingdom Collaborative Trial of Ovarian Cancer Screening multimodal screening arm, only 15 of 488 screen-positive women with benign ovarian tumors at surgery (3.1%) experienced a postoperative complication, and 80% of these were minor.” In the Kentucky trial the authors noted that tumor removal via laparoscopy was their standard approach and if benign disease was detected, there was usually no further surgery.

“Surgical complications occurred in only 6.6% of these cases, and 97% of these complications were minor,” the researchers wrote.

Writing in an accompanying editorial, Sharon Robertson MD, MPH, and Jeffrey Peipert, MD, PhD, both of Indiana University School of Medicine in Indianapolis, called the effort of van Nagell and colleagues, “impressive,” but suggested caution interpreting the results for the general population. They pointed out several weaknesses of the study – the higher incidence of ovarian cancer in the study population vs the general population, the lack of genetic testing, and the fact that this was not a randomized controlled study.

Van Nagell, told the Reading Room that he does not dispute these observations and certainly agrees that a randomized controlled study would be warranted, but in a disease where the control group would be women who did not get screened and who would have to wait for clinical diagnosis, he asked, “Who would volunteer to be in that group?” He noted that women understand that ovarian cancer is considered a silent disease with at best, extremely subtle symptoms – for example, a feeling of fullness, abdominal bloating, a change in bowel habits, or urinary problems – and is often not found at its early stages.

Robertson and Peipert wrote that while the study did not reflect the general population they agreed with the authors’ conclusion that ultrasound screening in women at high risk for ovarian cancer may lead to earlier detection of the disease.

Van Nagell said he agreed with the recommendations from the British study for screening women with a lifetime risk of ovarian cancer of 3-10%, which includes women over age 50 or those over 25 with a family history of ovarian cancer.

John said that until there is an established screening guideline, it is important for physicians to understand the extremely subtle symptoms of ovarian cancer: “I tell my colleagues and those who refer patients to me to listen to the patients’ symptoms… please listen to them.” If transvaginal ultrasound screening or even prophylactic salpingo-oophorectomy is the recommended option, physicians and patients will need to discuss all the pros and cons of these options, she noted.

The Question of Mortality

In the Prostate, Lung, Colorectal, and Ovarian Trial conducted by Claire Zhu, PhD, and colleagues, the one trial often pointed to that dismisses routine screening for ovarian cancer, a reduction in mortality was not evident. “However, there was no standard evaluation algorithm for screen-detected ovarian tumors and no uniform treatment protocol for newly diagnosed ovarian cancers in this trial,” van Nagell and co-authors wrote. “As a result there was significant variation in the detection-treatment interval and type of treatment in both the screening and control arms of this trial.”

On the other hand, the U.K. trial did show an association with a reduction in mortality. And, with the University of Kentucky trial the association with reduced mortality was similar to the British study: “The 10-year ovarian cancer mortality was reduced in women receiving screening by 31% and produced 416 life years gained at a cost of $40,851 per life year gained.”

Van Nagell said he doesn’t dispute any of the opinions expressed by the USPSTF, the editorialists, or Veena John, but his ongoing work is erecting some pillars of care that may start to gain the attention of the wider community. While not calling for universal screening of women, establishing algorithms for screening protocols and surgeries certainly would help zero in on a devastating cancer, he said.

“We know if we can detect women with stage I or II cancer of the ovary, we can cure them,” van Nagell said. “We need to be defining a population that benefits from screening. Why on earth aren’t we focusing more on early detection methodology in at-risk women? Why on earth wouldn’t you want to focus on that risk group to try to detect cancer at an earlier and more curable stage?”

Prostate Cancer Screening Rhetoric Amps Up

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In a pair of recently published papers in major cancer journals on prostate cancer screening, advocates and critics are turning to colorful and emphatic language — perhaps in the hope of exerting the power of persuasion and getting their physician audience to look at this much-discussed medical intervention with fresh eyes.

First, in a position statement, titled “Prostate Cancer Screening and the Goldilocks Principle: How Much Is Just Right?”, a group of 10 US urologists conclude that they are “increasingly convinced that a ‘just right’ approach [to screening] on the basis of personalized shared decision making is entirely possible.”

That shared decision-making refers to office visits in which physicians and patients review and discuss the harms and benefits of the prostate-specific antigen (PSA) test.

The team is optimistic that the days of large-scale overtreatment of men, which has been a hallmark of population-based screening for decades, can be a thing of the past.

Going forward, “individualized screening with [shared decision-making] is the foundation on which to build a successful program of diagnosis and treatment,” write the authors, led by Izak Faiena, MD, from the University of California, Los Angeles.

What’s needed is a “balanced approach” to the early detection of prostate cancer, says the team, which includes high-profile urologists, such as David Penson, MD, from Vanderbilt University in Nashville, Tennessee; Matthew Cooperberg, MD, from the University of California, San Francisco; and Maha Hussain, MD, from the University of Michigan in Ann Arbor.

That approach also includes “precision-based strategies, and appropriate risk-based management for men diagnosed with prostate cancer,” they say, referring to, among other things, the use of active surveillance as an initial treatment option in men with low-risk disease.

The new position statement was published online February 5 in the Journal of Clinical Oncology.

Experts interviewed by Medscape Medical News were wary of the position statement, offering comments that ranged from critical to scornful and that featured unprompted metaphors to get their points across.

Comparing prostate cancer screening to Goldilocks, who finally arrives at the “just right” bowl of porridge after trying other problematic bowls, is off the mark at this time, suggested Ruth Etzioni, PhD, a biostatistician at Fred Hutchison Cancer Research Center in Seattle, Washington.

The contention that prostate cancer screening can be substantially improved (ie, “just right”) depends on the idea that it can be personalized, which is “completely hyped,” Etzioni told Medscape Medical News. “There is way too much excitement about an idea that at this point seems very elusive,” she  said.

“It’s the idea of the right shoe for every foot — like Cinderella,” she added.

Early detection of prostate cancer is a “massive endeavor and so many things can go wrong when you are testing a large population,” said Etzioni.

However, she agreed with the position statement authors that, with the increasing use of active surveillance, harms caused by treatment have been reduced.

Like the position statement authors, Etzioni believes that PSA may have considerable value as a single midlife test, which has been found to predict risk for later fatal prostate cancer, as previously reported by Medscape Medical News.  She says the risk-stratification approach needs further validation.

On the other hand, another expert, who is an outspoken critic of PSA testing, had boxing words for the position statement.

“This is a pathetic commentary meant to salvage a costly, unproven, and harmful intervention that is on the ropes of medical opinion,” said Vinay Prasad, MD, from the Knight Cancer Center, Oregon Health and Sciences University in Portland, in an email to Medscape Medical News.

“We have subjected massive numbers of men with disease that was destined to do nothing (the overdiagnosed patients) to treatments that worsened sexual, urinary, or rectal function,” said Prasad.

“There remains no credible evidence that some novel screening strategy saves lives or improves quality of life. The authors want us to think this evidence has magically appeared, but it hasn’t. The USPSTF now gives PSA screening a Grade C recommendation. But make no mistake, that isn’t good,” he contended, referring to the US Preventive Services Task Force’s 2017 upgrade from an earlier Grade D, after tremendous outcry from the urology community and other groups.

The position statement authors point to the management of an elevated PSA at screening as a sign of progress. Lead author, Faiena, explained that now “there are a number of blood-based ancillary tests, as well as imaging modalities, such as MRI, that can help guide the decision to biopsy.” He said tests such as PCA3, PHI, and 4K score “are useful in helping to stratify patients.”

Faiena acknowledged that shared decision-making “has not been evaluated in terms of prostate-specific outcomes” and that “the main benefit lays in patient confidence in the treatment plan proposed.”

Primary Care Docs Can’t Do This

In the second essay, a trio of US physicians call shared decision-making a “mirage” because of the many obstacles that prevent its actualization in primary care settings and the evidence that physicians still unilaterally order most PSA tests.

The obstacle list includes time pressures, competing clinical demands, low health literacy, shifting expert viewpoints, fear of litigation, and language and cultural obstacles, say oncologists Paul Mathew, MD, and Hilal Hachem, MD, from the Tufts Medical Center, Boston, Massachusetts, and internist Paul Han, MD, MPH, from the Maine Medical Center in Portland.

Their essay was published February 22 in JAMA Oncology.

The authors say a shared decision is a mirage because it does not play out in reality. Academics who write position statements and guidelines don’t fully recognize the “practical infeasibility” of shared decision making, they claim.

National surveys of patients show that as many as two thirds of men who have a PSA test cannot recall a conversation about it, the authors also point out.

Doctors also struggle with the complexities of PSA screening. “Many physicians find it difficult to understand and communicate why the harms and benefits associated with PSA testing are close to being equal,” say the essay authors.

The essayists also point out that no payment is involved. “Because there are no incentives for shared decision making, either through quality metrics or reimbursement for time spent, it is difficult to envision a nationwide shift in this fundamental reality of primary care,” they write.

More troubling than a mirage, “quicksand” lies ahead should a PSA test occur and be elevated, say the authors That’s an apt comparison, they believe, because a “cascade of events can follow that, once set in motion, can be difficult or impossible to slow down or reverse.”

The cascade may include antibiotics, false-positive result, secondary assessments that use blood and urine biomarkers, and MRI. In the event of prostate cancer, additional molecular testing may be ordered, along with MRI if not done previously.

Furthermore, should definitive treatment occur, there is a “high” rate of complications.

The math is discouraging, the authors say: “The mortality benefit of 1 life saved per 1000 patients screened for prostate cancer over a 13-year period is set against the earlier physical, emotional, and financial impact of risks and complications.”

The authors summarize with one last metaphor: “Once elevated PSA level is detected, without evidence-based consensus guidelines to shape common practice, physicians and their patients may find themselves in a quicksand of multiple expensive tests of uncertain value. The hope that physicians and patients can together stumble into an oasis where benefit abides and harm is dissipated therefore remains tenuous.”

Men Who Have this Popular PSA Prostate Cancer Screening Have a Staggering 4-Fold Increase in Serious Blood Infections

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Men Who Have this Popular PSA Prostate Cancer Screening Have a Staggering 4-Fold Increase in Serious Blood Infections

Story at-a-glance

  • The benefits of PSA prostate cancer screening has been repeatedly shown to be minimal at best and detrimental at worst. Overall, PSA screening barely has any impact on mortality rates from prostate cancer. As a result, the U.S. Preventive Services Task Force will soon recommend that men not get screened for prostate cancer.
  • According to Stanford University researchers, the PSA test indicates nothing more than the size of your prostate gland. . The false positive rate is high, and the bulk of the harm is a result of subsequent unnecessary treatments.
  • Canadian researchers have raised the alarm over prostate biopsies, citing a four-fold increase in serious blood infections over the past decade from the procedure. Researchers are also questioning the conventional treatments of prostate cancer, which include surgical removal of the prostate gland and radiotherapy, as they may not be necessary for most men.
  • Your diet can greatly impact your prostate health and help prevent enlarged prostate and prostate cancer. Ideally, you’ll want to eat as much organic (preferably raw) food as possible, and limit sugar/fructose and grains from your diet. Highly processed or charcoaled meats, pasteurized dairy products, and trans fats correlate with an increased risk for prostate cancer and should also be avoided. Other specific nutritional therapies are discussed.

Prostate cancer is one of the most common cancers in men, but it is not  as deadly as breast cancer.

According to the latest statistics from the American Cancer Society, an estimated 240,890 men will be diagnosed with prostate cancer this year, and just over 33,700 men may die from it, so only one in seven diagnosed with it will die from it.

Overall, American men have a one in six chance of being diagnosed with prostate cancer at some point in their lives, or one in 42 chance of dying from it..

Most cases of prostate cancer do not occur until after men turn 50, but in recent years there has been a steady rise in the percentage of men in their 30s and 40s with both prostate problems and prostate cancer, primarily as a result of poor diet and increasing environmental pollution.

Unfortunately, investigations over the years have discovered serious flaws with the PSA test used to diagnose prostate cancer.

And the U.S. Preventive Services Task Force—which has also declared women in their 40s don’t need mammograms—may soon recommend that men not get screened for prostate cancer using the PSA test.

Researchers are also questioning the conventional treatments of prostate cancer, which include surgical removal of the prostate gland and radiotherapy, as they may not be necessary for most men.

All in all, I think this really highlights the necessity to employ preventive strategies, which I will discuss at the end of this article.

Moderate to High Certainty PSA Test Does More Harm than Good, Task Force Says

The prostate-specific antigen test (PSA test), analyzes your blood for prostate-specific antigen (PSA), a substance produced by your prostate gland.  When higher-than-normal levels of PSA are detected, it is believed that cancer is present.

However, the PSA test has been criticized as useless for a number of years now. For example, back in 2004, Stanford University News reported:

“The most commonly used screening tool for detecting prostate cancer – the PSA test – is virtually worthless for predicting men’s risk of contracting the disease, medical school researchers have determined. Stanford scientists studied prostate tissues collected in the 20 years since a high PSA test result became the standard for prostate removal. They concluded that as a screen, the test indicates nothing more than the size of the prostate gland.”

The U.S. Preventive Services Task Force is now planning on recommending a “D” rating for PSA testing, meaning that “there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”  A review of studies has shown that the PSA blood test yields “small or no reduction” in prostate cancer deaths.

As reported by CNN:

“The report adds that PSA testing is ‘associated with harms related to subsequent evaluation and treatments.’ … The problem is that many of the cancers that get detected are so small and slow-growing, they’ll never be harmful, and doctors have a difficult time discerning the quick, harmful cancers from the slow, harmless ones.”

The PSA Test for Prostate Cancer is Deceptive

Today, many experts agree that PSA testing is unreliable at best and useless at worst for accurately diagnosing prostate cancer. Many also agree that routine PSA blood tests often lead to over-diagnosis of prostate cancer, resulting in unnecessary treatments. Similar to mammograms, the PSA screen has become little more than an up-sell technique. The false positive rate is high, and the bulk of the harm is a result of subsequent unnecessary treatments.

According to the American Cancer Society: “There can be different reasons for an elevated PSA level, including prostate cancer, benign prostate enlargement, inflammation, infection, age, and race,” all factors that make PSA test results confusing, leading to potential for unnecessary treatment and suffering when tests are elevated.  Getting a PSA test reduces your lifetime risk of dying from prostate cancer from three percent to just 2.4 percent, so the difference is negligible.

Drs. Boyle and Brawley of the International Prevention Research Institute, Lyon, France have said,

“The real impact and tragedy of prostate cancer screening is the doubling of the lifetime risk of a diagnosis of prostate cancer with little if any decrease in the risk of dying from this disease.”

Complications of ill advised prostate cancer treatments include urinary incontinence and erectile dysfunction. Both of these conditions are difficult to reverse and can significantly decrease your quality of life.

Prostate Biopsies Can Result in Dangerous Infections

A positive PSA test will typically lead to a biopsy—which has also come under increasing scrutiny and criticism in recent years. On the one hand, the procedure itself may cause acute or long-term harm, and on the other, the rate of false negatives is high.

There are over one million prostate cancer tissue biopsy procedures performed annually in the U.S. Approximately 25 percent of these tissue biopsies are reported “positive,” indicating the presence of prostate cancer. The remaining 75 percent are reported “negative.” One-third of the men with initial “negative” results for prostate cancer actually do have prostate cancer that was missed by the biopsy.

A prostate biopsy involves inserting fine needles into the prostate gland. But specialists have begun to worry about a recent, significant increase in the risk of complications from the procedure. In particular, they are concerned about hard-to-treat bloodstream infections that can require weeks of treatment. Over the past decade, the rate of hospital admissions in Ontario, Canada, for serious infections caused by prostate biopsy increased four-fold.

Earlier this summer, the NPR reported:

“Doctors all over the world are increasingly concerned about post-biopsy infections. At last week’s annual meeting of the American Urological Association, there were 10 reports on the phenomenon … The underlying problem, many say, is the spread of antibiotic-resistant microbes.”

Prostate biopsies inherently pose a risk for infection because:

  • The needles that collect a tiny piece of prostate tissue can transport bacteria through your rectal wall into the prostate and bloodstream, and/or
  • The needles can spread harmful bacteria present in your gut into your bloodstream

Many Cancer Screenings Don’t Save Lives and May Cause Cancer

A recent article featured on PreventDisease.com brings up yet another problem with the PSA test:

“Perhaps most concerning, the PSA test frequently identifies something that qualifies as cancer under a microscope but acts nothing like cancer in real life. That is to say, the large majority of PSA-discovered “cancers” would never cause any problem whatsoever if they went undetected. Finding something through screening invariably leads to treating it through conventional means which cause cancer themselves.”

An underlying issue that needs to be addressed is that both breast- and prostate cancer screenings (mammography and PSA testing respectively) fail to address prevention. Although they are commonly viewed as “preventive” measures, they’re nothing of the sort.  Furthermore, they both appear to result in increased risk of mortality.

The article on PreventDisease.com also includes the following shocking statistics about breast- and prostate cancer screening:

“In a Swedish study of 60,000 women, 70 percent of the mammographically detected tumors weren’t tumors at all. These “false positives” aren’t just financial and emotional strains, they may also lead to many unnecessary and invasive biopsies. In fact, 70 to 80 percent of all positive mammograms do not, upon biopsy, show any presence of cancer.

When it comes to prostate cancer, a 20-year study from Sweden suggests that screening for prostate cancer does not reduce the risk of death from the disease. In fact, many men receive false-positive results and overtreatment, adding an element of risk to widescale screening, researchers report in the March 31 online issue of the BMJ.

“In the light of our findings, I would say that the benefit from screening is not sufficient to support mass screening,” said study author Dr. Gabriel Sandblom, an associate professor at the Karolinska Institute in Stockholm.”

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Screens and Treatments Involving Radiation Promote Cancer

Cancer screens like mammography and radiation treatment of either breast- or prostate cancer are not benign tests and treatments. It’s important to understand that radiation exposure causes genetic mutations in cells, and is also known to switch off a tumor suppressing gene. According to PreventDisease.com:

“[N]ew research from the Lawrence Berkeley National Laboratory in America (a US Government facility) has shown that radiation both changes the environment around breast cells, and increases the risks of mutation within them; a mutation that can be passed on in cell division. Four to six weeks after exposure to radiation at a level below that of a screening mammogram, breast cells started to prematurely age.

This results in their inability to send certain chemical messages into their immediate environment, which then filled with pre-cancerous mutated cells also from the radiation.

Paul Yaswen, a cell biologist and breast cancer research specialist with Berkeley Lab’s Life Sciences Division says “our work shows that radiation can change the microenvironment of breast cells, and this in turn can allow the growth of abnormal cells with a long-lived phenotype that have a much greater potential to be cancerous.”

Yawsen stated that radiation specialists have been slow in understanding these concepts. “Many in the cancer research community, especially radiobiologists, have been slow to acknowledge and incorporate in their work the idea that cells in human tissues are not independent entities, but are highly communicative with each other and with their microenvironment.”

Despite the Evidence, Many Cling to the PSA Test

Shannon Brownlee, author of Overtreated, recently wrote an insightful article for Time Magazine on this topic as well.  Many men are responding with outrage at the news that the PSA test will no longer be recommended. Many prostate cancer survivors credit the PSA test with saving their lives.

“The trouble is most men who get treated didn’t have a cancer that needed treating,” Brownlee writes. “So while a given man may believe fervently that early treatment saved his life, there’s a better than even chance that he would have been fine even if his cancer had been left well enough alone.

We never hear from the men who died from their prostate cancer treatment or biopsy. And there have been plenty of them. The mortality rate during or shortly after prostate surgery is estimated to be 1 in 200, according to a study published in the Journal of the National Cancer Institute. We also don’t hear much from the men who are suffering from incontinence, impotence, or both, the devastatingly common side effects of treatment.”

This is probably to be expected. If it was you, how willing would you be to tell the world that you’re now incontinent and impotent as a result of opting to get tested for prostate cancer? These are personal details that few men are willing to share.

How to Maintain Optimal Prostate Function and Help Prevent Prostate Cancer

Men over 70 have a 50/50 chance of developing an enlarged prostate, known as benign prostate hyperplasia (BPH). This is not the equivalent of prostate cancer. However, you do need to address this issue, and unfortunately, the conventional route includes drugs. It’s important to know that some of these drugs actually carry a warning label that if you have benign prostate hyperplasia, the drug may increase your cancer risk, and/or may promote a much more aggressive form of cancer.

For more information about this, please review this previous article on prostate health, which includes an informative interview with Dr. Rudi Moerck. Diet is a factor that can greatly impact your prostate health and help prevent enlarged prostate and prostate cancer.

You’ll want to eat as much organic (preferably raw) food as possible, and liberally include fresh herbs and spices, such as ginger. Make sure to limit carbohydrates like sugar/fructose and grains as much as possible to maintain optimal insulin levels, which will help reduce your cancer risk in general. Highly processed or charcoaled meats, pasteurized dairy products, and trans fats correlate with an increased risk for prostate cancer and should also be avoided.

There are also a number of more specific nutritional therapies that are particularly beneficial for avoiding and/or treating prostate cancer.

  • Include prostate-healthy foods in your daily diet: Foods that support prostate health include vegetables and fruits rich in antioxidants, vitamins, cartenoids like astaxanthin, and lycopene. One 2009 study identified tomatoes, cauliflower, broccoli and green tea as being particularly beneficial against prostate cancer
  • Try saw palmetto: The medical literature contains about 100 clinical studies on saw palmetto for prostate health and reduced incidence of prostate cancer. Trying saw palmetto before you resort to a drug is well worth it, considering the stern warnings that accompany some of these drugs. According to Dr. Moerck, saw palmetto in combination with pumpkin seed or lycopene may be an even more potent combination.

    Beware that quality is very important when selecting a saw palmetto supplement. Most brands on the market are ineffectual because they use the inactive form of the plant.

    The highest quality products are the organic supercritical-extracted saw palmetto oils, which are very dark green in color. Only one or two out of every 20 brands will be of this high quality. Dr. Moerck recommends a daily dose of 320 mg of saw palmetto oil (supercritical CO2 extract). Keep in mind that saw palmetto is a fat soluble supplement, so it will not absorb well unless you take it in conjunction with a little bit of fat. I recommend taking it with eggs, which contain phospholipids that enhance absorption of fat soluble nutrients.

  • Optimize your vitamin D levels, ideally by exposing your bare skin to natural sun light on a regular basis. (Your skin also synthesizes vitamin D sulfate, which may account for many of vitamin D’s potent health benefits, so sun exposure is really the ideal way to optimize your levels and get the greatest overall health benefits.) Evidence suggests that vitamin D may be one of the most potent variables associated with a lower risk of prostate cancer.

    There are well over 800 scientific studies confirming the link between vitamin D deficiency and multiple types of cancers, including prostate cancer. For example, according to a 2005 study, men with higher levels of vitamin D in their blood were half as likely to develop aggressive forms of prostate cancer as those with lower amounts. Another study published two years ago found that men with higher levels of vitamin D in their blood were seven times less likely to die from prostate cancer than those with lower amounts.

    Testing your vitamin D levels is done by a simple blood test. Anything below 20 ng/ml is considered a serious deficiency state, which will increase your risk of breast- and prostate cancers.

    The optimal value that you’re looking for is between 50-70 ng/ml. However, research has suggested that maintaining a slightly higher level of 70-100 ng/ml may be optimal for cancer prevention. If you can’t get regular sun exposure, you may want to consider using a safe tanning bed (one that uses electronic rather than magnetic ballasts and has less, not more, UVA than the sun produces). If these are unavaialble you can opt for an oral vitamin D3 supplement. Keep in mind that when using a supplement, regular testing becomes even more important to make sure you’re staying within therapeutic range.

  • Consider a vitamin K2 supplement: Another nutrient that has been found to offer significant protection against prostate cancer is vitamin K2. For more information about that, please refer to this previous article. Although I don’t typically recommend taking a lot of supplements, vitamin K is one you may want to seriously consider because many people don’t get nearly enough of it on a daily basis through the foods they eat.
  • Exercise your body, and your prostate: Having a well-rounded exercise regimen is essential for overall health, and is now becoming more widely accepted as a critical piece of cancer prevention and treatment. Having sex on a regular basis, which exercises your prostate specifically, is also important.
  • Check your testosterone levels: Contrary to popular belief, restoring testosterone levels in aging men does not appear to promote prostate cancer—on the contrary! According to meticulous research by Dr. Abraham Morgentaler, MD, author of Testosterone for Life, men with low testosterone are the ones at greater risk. For an interesting article that contains a lot more information about this, read Dr. Morgentaler’s report Destroying the Myth About Testosterone Replacement and Prostate Cancer.

    It explains how unfortunate assumptions have led to a dogmatic belief that testosterone replacement increases your risk of prostate cancer—a belief that might now be preventing many men from being optimally healthy. If you are low you can consider trans rectal DHEA cream. I personally use about 50 mg twice a day, and it has done wonders to optimize my testosterone levels as DHEA is converted to testosterone in your body.

Ideally, you’ll want to pay close attention to your prostate health early on—avoid waiting until you’re in your 60’s. Incorporating the lifestyle recommendations discussed above can help you prevent prostate problems from developing in the first place.

Source:mercola.com

Prostate Cancer Screening Still Not Recommended for All

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A major European study has shown that blood test screening for prostate cancer saves lives, but doubts remain about whether the benefit is large enough to offset the harms caused by unnecessary biopsies and treatments that can render men incontinent and impotent.

The study, published Wednesday in The Lancet, found that midlife screening with the prostate-specific antigen, or PSA, screening test lowers a man’s risk of dying of the disease by 21 percent. The relative benefit sounds sizable, but it is not particularly meaningful to the average middle-age man, whose risk of dying of prostate cancer without screening is about 3 percent. Based on the benefit shown in the study, routine PSA testing would lower his lifetime cancer risk to about 2.4 percent.

Despite the fact that some men —one out of every 781 men in the screening group — were helped by PSA testing in the European study, the study authors say the finding does not support the use of widespread screening. Instead, cancer experts say, the focus should be on screening men at high risk and working to identify nonaggressive cancers so men will not be unnecessarily treated for the disease.

“We know we are finding a substantial number of cancers, in the range of 30 to 50 percent, that would never do any harm and would not lead to death’’ said the study’s lead author, the urologist Dr. Fritz H. Schröder from Erasmus University Medical Center in the Netherlands. For every 27 cancers detected by PSA screening, only one man’s life would be saved.

“This overdiagnosis is unacceptable because it also leads to treatment,’’ Dr. Schröder said. “That’s why there is consensus worldwide, with very few exceptions, that the time has not come to recommend population-based screening.”

The findings, based on 13 years of data from a continuing randomized study of 162,000 European men, are certain to create confusion about the relative benefits and risks of the PSA test, which uses a blood sample to identify men at risk for prostate cancer. The test often puts men on a path of repeated biopsies and testing, and for some, treatment of a cancer that would have never caused a problem if left alone. In 2011, the United States Preventive Services Task Force concluded that healthy men should not be screened for prostate cancer, a finding that drastically changed the standard of care for middle-age American men who had grown accustomed to annual screenings.

The task force recommendation against PSA testing was based largely on 10 years of data from two major studies: the United States-based Prostate, Lung, Colorectal and Ovarian (P.L.C.O.) cancer screening trial of 77,000 men, and earlier results from the current study, the European Randomized study of Screening for Prostate Cancer. Additional data collected from the European trial since then has shown a slightly larger benefit over time as a result of screening, along with a still sizable risk of overdiagnosis and overtreatment.

“It’s always been a complicated story,’’ said Dr. Ian Thompson,the director of the cancer therapy and research center at the University of Texas Health Science Center at San Antonio, who wrote an accompanying editorial to The Lancet study. Dr. Thompson said that better diagnostic techniques, such as biopsies guided by magnetic resonance imaging tests, along with personalized risk assessment and more informed decision making by men and their doctors were a better way to use the PSA test than to screen every man of a certain age.

“The majority of men who get PSA screening will not benefit from it,’’ Dr. Thompson said. “If you do PSA testing in a more sophisticated, contemporary way, there may be the possibility of achieving the mortality reduction while reducing the morbidity impact.”

Neither the American study nor the European study are viewed as the final word on PSA testing. A flaw in the American study is that many men in the nonscreening group had already received a PSA test before the study began or later sought screening on their own, thus blunting any potential benefit from showing up in the data analysis.

The European study, which recruited men from 50 to 74 in eight countries, also has flaws. One concern is that the increase in survival among men in the screening group may stem from differences in the quality of treatment compared with men in the control group. In addition, there are puzzling differences when comparing the results from individual countries. For instance, men in Sweden showed a benefit while men in Finland, where the incidence and mortality rate of prostate cancer is similar, did not.

“I think this additional follow-up doesn’t change much,’’ said Dr. Gerald L. Andriole, the lead author of the United States-based study and chief of urology at Washington University School of Medicine in St. Louis. “I think there is a benefit to PSA testing, but unfortunately, we’ve been overdoing it, screening the wrong men, overtreating way too many men, and the benefit of screening is being outweighed by the side effects of overtreatment.”

Doctors say that for men who are confused about whether to get a PSA test, there is hope. New M.R.I. tests to guide targeted prostate biopsies may help find the most aggressive cancers that require treatment, thus identifying men who do not need to be treated.

“The trick is to take the complex nature of the information and provide it to men,” Dr. Thompson said. “A man who is fully informed may say I understand and decide against the test, while another man who watched his father die of prostate cancer may want it.”

Urological Group’s Guidelines Recommend Against PSA Screening in Most Men.

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The American Urological Association‘s new guidelines recommend prostate cancer screening only in men aged 55 to 69 and based on shared decision-making and the patient’s preferences. The guidelines put AUA‘s position more in line with other medical organizations.

In the 55-to-69 age group, one prostate-cancer death is prevented for every 1000 men screened over a decade. For men who decide to undergo prostate-specific antigen screening, AUA recommends testing every two years or more, rather than annual testing.

The group now recommends against routine PSA screening for men younger than 55 who are at average risk, those older than 69, and those with less than 10 to 15 years of expected life remaining.

The recommendations come less than a year after the U.S. Preventive Services Task Force recommended against routine PSA screening in all men.

Source:American Urological Association guidelines

Focused PSA Screening Strategy, Based on Empirical Data.

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Three lifetime prostate-specific antigen tests (age: mid 40s, early 50s, and 60) are sufficient for at least half of men.

 

Swedish investigators have reported that 60-year-old men with blood prostate-specific antigen (PSA) levels 1 µg/L have 0.2% risk for prostate cancer within 25 years (JW Gen Med Oct 7 2010). In this study, the same investigators determined the associations between PSA levels at various ages and subsequent risk for metastatic prostate cancer and prostate cancer–related death.

From 1974 to 1984, 21,000 men (age, 52) provided baseline blood samples; 4900 provided additional samples 6 years later. During a median follow-up of 27 years, prostate cancer was diagnosed in 1369 men: Metastatic disease occurred in 241 men, and 163 prostate cancer–related deaths were recorded. Outcomes were as follows:

  • 15-year risk for metastatic prostate cancer was 0.6% for men in the highest PSA decile at age 40 (1.3 µg/L), 1.6% for men in the highest PSA deciles at ages 45 to 49 (1.6 µg/L), and 5.2% for men in the highest deciles at ages 51 to 55 (2.4 µg/L)
  • For men with PSA levels below the median at ages 45 to 49 (0.68 µg/L) and 51 to 55 (0.85 µg/L), 15-year risks for metastatic prostate cancer were only 0.1% and 0.3%, respectively
  • 44% of prostate cancer–related deaths within 30 years occurred in men in the highest PSA deciles at ages 45 to 49 (1.6 µg/L) and 51 to 55 (2.4 µg/L)

Comment: Based on these results, the authors recommend that screening not begin until age 45 and that men with PSA levels 1.0 µg/L undergo one repeat screening in their 50s and one at age 60 (those with PSA levels 1.0 µg/L at age 60 should not undergo further screening). They also suggest that men with PSA levels >1.0 µg/L at any age undergo more frequent screening and that men in the highest PSA deciles at ages 45 to 55 receive “particular focus,” because they contribute close to half of all deaths from prostate cancer before age 75. Although this strategy could be more efficient than the annual screening often conducted in the U.S., whether screening in this manner would prevent prostate cancer–related mortality is unclear.

 

Source:Journal Watch General Medicine

 

Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study.

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Abstract

Objective To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified.

Design Case-control study with 1:3 matching nested within a highly representative population based cohort study.

Setting Malmö Preventive Project, Sweden.

Participants 21 277 Swedish men aged 27-52 (74% of the eligible population) who provided blood at baseline in 1974-84, and 4922 men invited to provide a second sample six years later. Rates of PSA testing remained extremely low during median follow-up of 27 years.

Main outcome measures Metastasis or death from prostate cancer ascertained by review of case notes.

Results Risk of death from prostate cancer was associated with baseline PSA: 44% (95% confidence interval 34% to 53%) of deaths occurred in men with a PSA concentration in the highest 10th of the distribution of concentrations at age 45-49 (≥1.6 µg/L), with a similar proportion for the highest 10th at age 51-55 (≥2.4 µg/L: 44%, 32% to 56%). Although a 25-30 year risk of prostate cancer metastasis could not be ruled out by concentrations below the median at age 45-49 (0.68 µg/L) or 51-55 (0.85 µg/L), the 15 year risk remained low at 0.09% (0.03% to 0.23%) at age 45-49 and 0.28% (0.11% to 0.66%) at age 51-55, suggesting that longer intervals between screening would be appropriate in this group.

Conclusion Measurement of PSA concentration in early midlife can identify a small group of men at increased risk of prostate cancer metastasis several decades later. Careful surveillance is warranted in these men. Given existing data on the risk of death by PSA concentration at age 60, these results suggest that three lifetime PSA tests (mid to late 40s, early 50s, and 60) are probably sufficient for at least half of men.

Discussion

Overview of findings

PSA concentration can be used to predict of long term risk of metastasis or death from prostate cancer. It can identify a small group of men at greatly increased risk compared with a much larger group highly unlikely to develop prostate cancer morbidity if rescreening is delayed for seven or eight years. As PSA screening was extremely rare in this cohort, our findings can be used to design screening programmes by determining the age at which men should start to undergo screening and the interval between screenings. Men at low risk of death from prostate cancer without screening have little to gain from being screened but still risk overdiagnosis and overtreatment; men likely to die from prostate cancer without screening could avoid cancer specific mortality if they choose to be screened.

In an earlier paper, we showed that PSA concentration at age 60 had a strong association with the risk of death from prostate cancer by age 85 (AUC 0.90),7 with extremely low risk (≤0.2%) in men with PSA concentration below the median (≤1.0 µg/L). Taken together with our current data, this suggests a simple algorithm for prostate screening. All men with a reasonable life expectancy could be invited for PSA screening in their mid to late 40s. Men with a PSA concentration <1.0 µg/L would be advised to return for screening in their early 50s and then again at age 60, whereas men with PSA ≥1.0 µg/L would return for more frequent screening, with literature suggesting repeat tests every two or four years.19 The choice of 1.0 µg/L as a tentative threshold might vary according to preference. At age 60, men with PSA at median or lower—that is, ≤1.0 µg/L (or possibly below the highest quarter, ≤2.0 µg/L, depending on preference)—would then be exempted from further screening; men with a higher concentration would continue to undergo screening until around 70.1 Particular focus should be placed on men in the highest 10% of PSA concentrations at age 45-55, who will contribute close to half of all deaths from prostate cancer occurring before the age of 70-75. Some of these men will have concentrations above current thresholds for consideration of biopsy—such as 3 µg/L—and should be referred to a urologist. The remaining men could be told that, although they will probably not die from prostate cancer (with a mean risk of metastasis within 25 years close to 10%), they are at much higher risk than average and that it is especially important that they return for regular, frequent, and possibly more elaborate screening. It is also worth considering whether management of these men should become proactive, with reminder letters and attempts to follow-up non-compliers by telephone. Most importantly, the proposed PSA concentration of 1.0 µg/L to discriminate a low from a higher risk group is not suggested to serve as an indication for biopsy but rather be used to determine the frequency and intensity of subsequent monitoring.

What is known on this topic

  • Prostate specific antigen screening is widely used for the early detection of prostate cancer but remains highly controversial.
  • Focusing on the men at highest risk of prostate cancer metastasis and death could improve the ratio between benefits and harms of screening.
  • It is difficult to justify initiating PSA screening at 40 for men with no other significant risk factor
  • Men with PSA in highest 10th at age 45-49 contribute nearly half of prostate cancer deaths over the next 25-30 years
  • At least half of all men can be identified as being at low risk, and probably need no more than three PSA tests lifetime (mid to late 40s, early 50s, and 60)

What this study adds

Source: BMJ

 

 

 

 

 

 

PSA Screening and Quality of Life.

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Using simulation modeling, researchers estimated potential gains in quality-adjusted life-years from prostate-specific antigen screening.

Prostate-specific antigen (PSA) screening involves a tradeoff between potential mortality benefit and harms of overdiagnosis. In the European Randomized Study of Screening for Prostate Cancer (ERSPC), PSA screening lowered prostate cancer–related mortality at 11 years, but many men underwent surgery or radiation therapy for every death averted. Thus, researchers concluded previously that more analysis was needed “before general [screening] recommendations can be made” (JW Gen Med Mar 14 2012). Now, they present results of simulation modeling in which they integrated (1) ERSPC mortality outcomes, (2) probabilities of adverse diagnosis-related and treatment-related complications (e.g., incontinence, impotence), and (3) estimates of decrements in quality of life resulting from these adverse outcomes.

The model predicted that screening 1000 men (age range, 55–69) annually would extend the lives of 9 men for an average of 8 years each, adding about 73 life-years overall. However, when adverse effects on quality of life (experienced by all screened men who undergo biopsy and treatment) were factored into the model, the benefit of screening dropped from 73 nonadjusted life-years gained to 56 quality-adjusted life-years (QALYs) gained per 1000 men.

The authors then varied their estimates of adverse effects. Under the most favorable estimates, screening would add 97 QALYs per 1000 men; under the least favorable estimates, screening would result in 21 QALYs lost (meaning that screening would be harmful, on average).

Comment: This report reminds us that, at the population level, the value of PSA screening depends substantially on how men weigh the downstream benefits and harms of screening. One puzzling aspect of this theoretical analysis is its conclusion that screening would prevent 9 prostate cancer–related deaths per 1000 men; this benefit is ninefold larger than what actually has been demonstrated thus far in the ERSPC (1 death prevented per 1000 men screened, after mean follow-up of 11 years). Because this model assumes annual screening starting at age 55 and lifetime follow-up (whereas the ERSPC screened only every 4 years and started screening at various ages), the model’s larger mortality benefit is plausible. However, the huge difference between the estimated benefit and actual ERSPC results is surprising. The authors indirectly acknowledge this issue in their cautious conclusion: “Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made.”

Source: Journal Watch General Medicine

Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer.

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Findings of a recent study, the largest and longest of its kind, provide strong evidence supporting a conservative approach to managing prostate cancer in some men. The study was not a randomized clinical trial; rather, it was a long-term analysis of a cohort of men diagnosed with what is called very-low-risk prostate cancer. Instead of immediately undergoing surgery or radiation therapy, the men had opted to undergo a process known as active surveillance at the Johns Hopkins University School of Medicine.

A diagnosis of very-low-risk prostate cancer means that the disease is highly unlikely to become a clinically significant, life-threatening cancer. These men could be safely monitored by active surveillance, the study found, with only a modest percentage eventually requiring some form of treatment and none dying from prostate cancer. The results were published online April 4 in the Journal of Clinical Oncology (JCO).

As is the case with prostate cancer in general in the United States, most of the men in the study were 65 or older. The results provide very strong evidence that active surveillance is the “preferred option” for most men in this age group with very-low-risk disease, said the study’s senior investigator, Dr. H. Ballentine Carter. In fact, he continued, “The overwhelming evidence says that for men over 65 who are diagnosed with low-risk disease, their first question should be whether any therapy is appropriate for them, not which therapy.”

The clinical relevance of the findings is hard to overstate, Dr. Carter stressed. Among the 217,000 men in the United States diagnosed each year with prostate cancer, a substantial proportion has very-low-risk or low-risk disease. The vast majority of these men immediately undergo some form of treatment, including men aged 75 and over, despite the fact that many would be unlikely to experience significant symptoms, let alone die from prostate cancer.

Defining Very-Low-Risk Prostate Cancer

The Johns Hopkins definition of very-low-risk prostate cancer is similar to the NCCN definition. For the study in JCO, very-low-risk was defined as:

  • Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
  • Gleason score of 6 or less
  • PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL or less
  • Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core

Patient Selection, Compliance Are Key

At Hopkins, the active surveillance program involves a semi-annual check-up and an annual biopsy. Patient selection is very important, Dr. Carter explained.

Among the 769 men enrolled in Hopkins’ active surveillance program between 1995 and 2010, approximately 80 percent had very-low-risk disease. Whether a patient has very-low-risk disease is determined based on factors such as the Gleason score (a common measure of tumor aggressiveness) and the extent of cancer in the biopsy samples, or cores, from the prostate gland. (See the sidebar for all of the factors.)

The remaining men had at least one biopsy feature that precluded their disease from being considered very-low-risk, Dr. Carter explained. These men were typically older and had other health problems, he continued, which made active surveillance more attractive than treatment with surgery or radiation, both of which can have significant side effects.

Compliance with the approach has been quite strong, the Hopkins team reported, with nearly 90 percent of participants completing their annual biopsies.

Although no men in the study died of prostate cancer, 255 did undergo some form of treatment, 74 percent of whom did so because their disease was reclassified based on the findings of an annual biopsy.

Overall, 41 percent of men in the study did not require any form of treatment, even after 10 years of follow-up, a “remarkable” finding, said Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis. “This study adds to the accumulating evidence that, in carefully selected patients, active surveillance is safe.”

The results “strongly support” recent revisions to prostate cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN), said the guidelines’ panel chair, Dr. James Mohler from the Roswell Park Cancer Institute. Updated last year, the guidelines recommend that physicians advise men with very-low-risk disease who have a life expectancy of up to 20 years to pursue active surveillance.

Findings like these on active surveillance, combined with related research on the growing problem of overdiagnosis and overtreatment of prostate cancer linked to PSA screening, appear to be reaching down into the community setting, Dr. Mohler believes.

“I think men and their doctors are becoming more educated about the overtreatment issue,” he said.

As evidence, Dr. Mohler pointed to the START trial, a phase III clinical trial being led by NCI-Canada, in collaboration with the U.S. NCI, in which men diagnosed with very-low-risk or low-risk disease are being randomly assigned to active surveillance or immediate treatment. When the trial opened in 2007, most men who declined to enroll did so because they did not want to take the risk of being assigned to the active surveillance arm. “Now most men are declining to participate because they want active surveillance,” Dr. Mohler said.

Having a strong system in place to ensure that men pursuing active surveillance are followed and receive reminders for their check-ups and biopsies is extremely important, Dr. Carter stressed.

At the moment, the Hopkins surveillance program is managed primarily by an administrator using a manual process. But the program is moving to a Web-based approach for monitoring and following patients, he added.

Approaches Can Vary

Although the evidence in favor of active surveillance continues to accumulate, the optimal approach to managing the process is not yet defined, Dr. Mann noted. This is particularly true with respect to how patients’ disease is tracked.

At Hopkins, men are followed via check-ups and annual biopsies. Any reclassification of their disease is typically based on biopsy findings, such as a change in Gleason score, which might then produce a recommendation for treatment. But many other centers, such as Roswell Park, do not require men who choose active surveillance to undergo regular biopsies. Rather, they use some form of what is commonly called PSA kinetics, which are changes in PSA levels over time (for instance, how long it takes for PSA levels to double).

Results from several studies, however, have raised doubts about the value of PSA kinetics in initially identifying or managing prostate cancer. Based on their experience, PSA kinetics is “not reliable for predicting the presence of high-grade cancer on an individual basis,” the Hopkins team wrote in JCO. “Thus, if the goal of surveillance is to identify and treat higher-risk cancers, we believe that annual biopsies may be necessary to ensure patient safety.”

But regular biopsies are by no means without their own risks. A small percentage of men end up in the hospital with antibiotic resistant infections as a result of a prostate biopsy, Dr. Mohler said, and repeat biopsies can lead to inflammation and scar tissue formation that can preclude nerve-sparing surgery to treat the prostate cancer in some men whose disease progresses.

According to Dr. Carter, Hopkins researchers are now studying whether men who have had two consecutive biopsies that show no evidence of disease progression can safely have the interval between routine biopsies extended. In the meantime, the NCCN guidelines are being revised again, Dr. Mohler said, using data from large active surveillance programs at Hopkins, the University of Toronto, and the University of California, San Francisco, to provide recommendations on managing men who choose this conservative approach.

Further clarity on this matter should be forthcoming, Dr. Mann said. In addition to the START trial, which will follow men using both PSA measures and prostate core biopsies, a similar trial is being conducted in the United Kingdom that is using only PSA levels to monitor patients. Also, in December, NCI and CDC are sponsoring an NIH State-of-the-Science Conference to review the role of active surveillance in managing localized prostate cancer and to help guide future research in this area.

Source: NCI.