Common prostate cancer treatment associated with decreased survival in older men

A common prostate cancer therapy should not be used in men whose cancer has not spread beyond the prostate, according to a new study led by researchers at Henry Ford Hospital.

The findings are particularly important for men with longer life expectancies because the therapy exposes them to more adverse side effects, and it is associated with increased risk of death and deprives men of the opportunity for a cure by other methods.

The research study has been published online in European Urology.

The focus of the new study is androgen deprivation therapy (ADT), in which an injectable or implanted medication is used to disrupt the body's ability to make testosterone. ADT is known to have significant side effects such as heart disease, diabetes, increased weight gain and impotence; however a growing body of evidence suggests ADT may in fact lead to earlier death.

Since the 1940s, the therapy has been a mainstay of treatment for prostate cancer that has metastasized, or spread beyond the prostate gland. Still other studies support the use of ADT when it is used as an adjuvant, or in addition to, radiation therapy for higher risk prostate cancer. No evidence exists to support the exclusive use of ADT for low risk or localized prostate cancer.

"The use of ADT as the primary treatment for localized and low risk prostate cancer increased over time, despite known harmful side effects and a lack of data to support such use," says Jesse D. Sammon, D.O., a researcher at Henry Ford Hospital's Vattikuti Urology Institute and lead author of the new study. "In the 1990's it became exceedingly common to use ADT in place of radical prostatectomy or radiation therapy."
Concerns over the possible misuse of ADT alone in the treatment of prostate cancer, as well as a growing awareness of its potential damage, led to changes in Medicare reimbursement policies for ADT in 2004.

This resulted in a 40 percent drop in reimbursement, and a reduction in inappropriate use of ADT from 38.7 percent to 25.7 percent for newly diagnosed localized prostate cancers.

"At the same time, there was a growing awareness of ADT's many possible adverse effects, including decreased libido, anemia and fatigue, and a higher risk of metabolic and cardiovascular disease," Dr. Sammon says.

"In designing our study, we hypothesized that the adverse effects of ADT might be more pronounced in men with longer life expectancies since they would likely be treated with ADT for a longer period- and be exposed to more treatment-related side effects."

Drawing on data from nations largest cancer registry (SEER) (Surveillance, Epidemiology, and End Results) the researchers then linked to records from Medicare and identified 46,376 men diagnosed with localized prostate cancer who did not undergo radical prostatectomy or radiation therapy for prostate cancer, diagnosed between 1992-2009. Among them, 38.5 percent were treated with ADT.

Further statistical analysis confirmed the study's hypothesis, notes Dr. Sammon.

"No evidence supports the use of ADT in men with low risk, localized prostate cancer, while use of this therapy is decreasing over time it is still very common," he says

"We found that primary ADT is associated with decreased survival in men with localized prostate cancer relative to men who receive no active treatment, particularly in men with longer life expectancies. So we concluded that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate or men with moderate to high risk disease undergoing radiation therapy."

PSA-testing and early treatment decreases risk of prostate cancer death

The study is based on data from nation-wide, population-based registers in Sweden including the Cancer Register, The Cause of Death Register and the National Prostate Cancer Register (NPCR) of Sweden.
“Our results show that prostate cancer mortality was 20 procent lower in counties with the highest incidence of prostate cancer, indicating an early and rapid uptake of PSA testing, compared with counties with a slow and late increase in PSA testing,” says Pär Stattin, lead investigator of the study.
“Since the difference in the number of men diagnosed with prostate cancer is related to how many men undergo PSA testing, we think our data shows that PSA testing and early treatment is related to a modest decrease in risk of prostate cancer death,” says Håkan Jonsson statistician and senior author of the study.
“In contrast to screening in randomized studies our data is based on unorganized, real life PSA testing. We therefore used a statistical method that excludes men that were diagnosed prior to the introduction of PSA testing since these men could not benefit from the effect of PSA testing,” continues Håkan Jonsson.
“The results in our study are very similar to those obtained in a large European randomized clinical study (ERSPC) thus confirming the effect of PSA testing on the risk of prostate cancer death. However, we have to bear in mind that the decrease in mortality is offset by overtreatment and side effects from early treatment. PSA testing sharply increases the risk of overtreatment, i.e. early treatment of cancers that would never have surfaced clinically. We also know that after surgery for prostate cancer most men have decreased erectile function and that a small group of men suffer from urinary incontinence. Our data pinpoints the need for refined methods for PSA testing and improved prostate cancer treatment strategies,” concludes dr Stattin.

Surgery may trump a "watch-and-wait" approach when it comes to treating prostate cancer, especially in younger patients

Surgery may trump a "watch-and-wait" approach when it comes to treating prostate cancer, especially in younger patients, according to a new study.

Death and the spread of cancer were less likely for men who underwent a radical prostatectomy to remove the prostate gland compared to those who didn't -- regardless of age, said study co-author Jennifer Rider, an assistant professor in the department of epidemiology at the Harvard School of Public Health.

"And when we looked at subgroups of age, we found the benefit really appeared to be limited to men with the longest life expectancy," she said.

For years, experts have debated how best to treat the disease -- either using a watch-and-wait approach or removing the gland to help reduce the cancer's spread and extend life.

Dr. Jim Hu, director of robotic and minimally invasive surgery in the urology department of the University of California, Los Angeles, said: "There has been considerable controversy in the United States about PSA [prostate specific antigen] screening for prostate cancer and treatment of prostate cancer."

Experts opposed to surgery say many tumors won't become life-threatening and can be monitored with tests from time to time.

The prostate is a small, walnut-shaped gland that sits below a man's bladder. It produces the fluid that nourishes and transports sperm. According to the American Cancer Association, about 233,000 men in the United States will be diagnosed this year with prostate cancer, which can be detected by a PSA test and by a physical exam.

The Harvard researchers, along with colleagues from Uppsala University Hospital in Sweden, used data from a large Scandinavian prostate cancer study to evaluate about 700 men with early prostate cancer to learn more about life expectancy with the disease.

The men were randomly assigned to either surgery or a watchful-waiting group that received no initial treatment. All were under age 75 and had a life expectancy of 10 or more years. The scientists followed them for up to 23 years, through 2012.

The researchers reported in the March 6 issue of the Journal of the American Medical Association that about 58 percent of the men in the surgery group and 71 percent of the men in the watchful-waiting group died during the study. Prostate cancer was the cause of 18 percent of deaths in the surgery group and about 28 percent in the watchful-waiting group.

Rider said it's important to note that the men in the study had not had their prostate cancer detected using a PSA test and that the data was collected between 1989 and 1999, when the primary form of detection involved a manual exam by the doctor.

"We know PSA screening advances a man's diagnosis by about five to 10 years," Rider said. "So a man today would have the disease diagnosed earlier in his life than in our study."

Hu said it's also key to keep in mind that prostate cancer is typically a slow-growing tumor.

"A lot of the benefit in treating prostate cancer isn't seen for years," Hu said. This study demonstrates that with a median follow-up of 13.4 years, eight men needed to undergo radical prostatectomy to save one from prostate cancer. That's when they saw the survival benefits for surgery versus watchful waiting. This number will continue to go down with longer follow-up."

Rider also said men over 65 who had surgery were less likely to have their cancer spread. "But we don't know if that translates to a mortality benefit," she said.

It was a nice study design, Hu said. "It shows there is a benefit to treating men with prostate cancer," he said.

But he said the findings differ from another recent study by the U.S. Veteran's Administration hospitals that demonstrated that radical prostatectomy did not appear to have a benefit compared to watchful waiting. He said those results, however, could be because the study involved older participants who had other chronic health problems.

Rider said the study results aren't definitive, but she thinks the findings add important information to the debate.

 

Reliable pretreatment information assists prostate cancer patients in decision-making

Men who have been diagnosed with prostate cancer need to assimilate information rapidly in order to weigh the treatment options and make informed decisions. Although patients consult a variety of information sources, outcome information that is specific to the treating physician leads to greater patient satisfaction following treatment, according to a new study published in The Journal of Urology®.

The benefits of patient information are broad. For many people confronted with a cancer diagnosis, information translates to greater involvement in management decisions, improved ability to cope, reduced anxiety and distress, better communication with family members, and increased satisfaction with treatment choices.

"The availability and quality of information are particularly relevant in prostate cancer, which affects a large number of men and is associated with significant treatment-related side effects. Despite its high prevalence, though, we know relatively little about the use and helpfulness of patient information materials among prostate cancer patients," says lead investigator John T. Wei, MD, MS, of the Department of Urology, University of Michigan Health System, Ann Arbor.

Researchers conducted a prospective, multicenter study on the use of information and satisfaction among a sample of men recently diagnosed with early stage prostate cancer undergoing definitive therapy. Over 1,200 men were enrolled in the PROST-QA (Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment) study. Study participants completed several questionnaires before treatment and during follow-up through computer-assisted telephone interviews.

Although nearly 90% of the participants were Caucasian, 135 subjects of minority race also participated. Primary treatment included radical prostatectomy, external beam radiation therapy, or brachytherapy, with or without androgen deprivation therapy.

Researchers found that information sources used by patients varied significantly according to race, education, and study site. The most commonly used source of information was physician description (93.2%), followed by print sources such as pamphlets and brochures (82.5%). The majority of men also used other sources, including websites (68%), family and friends (63.7%), and books on prostate cancer (59.1%). Other sources, such as video media, access to other men treated for prostate cancer, and summaries of physician-specific outcomes were used less often.

The use and helpfulness of different information sources varied by factors such as age, race, education level, income, and marital status. Differences in the use of sources were apparent among men of different backgrounds. In general, younger, non-black, married men with college educations and higher incomes used more sources of information. This was most apparent in the use of Internet-based sources, where there were significant differences among men of different socioeconomic and educational backgrounds. Significant differences were also seen in the use of books, family and friends, and access to other men with previous experience with prostate cancer treatments.

"These differences may be related to knowledge of and access to greater resources, although variation in information seeking behaviors and coping mechanisms among men of different demographic backgrounds cannot be discounted," observes Wei.

"For prostate cancer patients, the impact of treatment on health-related quality of life is an important consideration. Reliable pretreatment information may allow patients to set expectations regarding treatment outcomes and make informed decisions in selecting therapy. Our results indicate that outcome information specific to the treating physician is associated with greater patient satisfaction following treatment, and that this type of information may assist patients in the decision making process," he concludes.

Pain drugs used in prostate gland removal linked to cancer outcome

The methods used to anesthetize prostate cancer patients and control pain when their prostate glands are surgically removed for adenocarcinoma may affect their long-term cancer outcomes, a study led by Mayo Clinic has found. Opioids, painkillers commonly given during and after surgery, may suppress the immune system's ability to fight cancer cells. The research suggests that supplementing general anesthesia with a spinal or epidural painkiller before a radical prostatectomy reduces a patient's need for opioids after surgery, and this finding was associated with a lower risk of cancer recurrence. The findings are published online in the British Journal of Anaesthesia.

The immune system's strength is especially important in cancer surgery because surgical manipulation of a tumor may spread cancer cells. The immune system can be impaired by general anesthesia, the overall stress surgery places on the body and by post-surgical systemic opioid use. The study found better outcomes in radical prostatectomy patients who had general anesthesia supplemented with spinal or epidural delivery of a long-acting opioid such as morphine, than in those who received general anesthesia only.

"We found a significant association between this opioid-sparing technique, reduced progression of the prostate tumor and overall mortality," says senior author Juraj Sprung, M.D., Ph.D., a Mayo Clinic anesthesiologist.

Researchers used Mayo Clinic's prostatectomy registry, anesthesia database and electronic medical records to identify patients who had prostate gland surgery for adenocarcinoma from January 1991 through December 2005. Reports of recurrence of cancer, cancer spread and death were confirmed with patients' physicians.

While promising, the findings must be tested in randomized trials, Dr. Sprung says: "Provided future studies confirm what we've found in this study, maybe down the line this would be a standard of care for pain management in patients undergoing cancer surgery."

New Procedure May Shrink Enlarged Prostate Without Surgery

Men who need treatment for an enlarged prostate may soon have a new nonsurgical option, a small, early study suggests.

Called prostatic artery embolization (PAE), the technique uses a catheter threaded into an artery in the leg. The catheter is guided to the artery that supplies blood to the prostate. Then, tiny beads are injected into the artery, which temporarily block the blood supply to the prostate.

The temporary loss of blood supply causes the prostate to shrink, relieving symptoms, according to study lead author Dr. Sandeep Bagla. What's more, the new treatment doesn't appear to have the same risk of serious complications, such as incontinence and impotence, that often accompany enlarged prostate treatment.

"This is fantastic news for the average man with benign prostatic hyperplasia. Many men decline current treatments because of the risks. But, for the average man, PAE is a no-brainer," said Bagla, an interventional radiologist at Inova Alexandria Hospital, in Virginia.

The procedure has only been available as part of Bagla's trial until recently, but he said some interventional radiologists have started doing prostatic artery embolization, and he expects the procedure will become more widely available by the end of the year.

Benign prostatic hyperplasia is the medical term for an enlarged prostate. An enlarged prostate is very common as men get older. As many as half of all men in their 60s will have an enlarged prostate, according to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). By the time men are in their 70s and 80s, up to 90 percent have benign prostatic hyperplasia, according to the NIDDK.

Some men experience no symptoms, while others may feel the need to urinate frequently, but they have a weak urinary stream, the NIDDK says. There are a number of treatments available for benign prostatic hyperplasia, including medications and surgery.

Bagla said that interventional radiologists in Europe and South America have been using prostatic artery embolization, and that the current study is the first in the United States to test the procedure.

He and his colleagues hope to treat a total of 30 patients, but they're reporting on the results from the first 18 patients on Monday at the annual meeting of Society of Interventional Radiology, in New Orleans. The data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.

For the study, the average age of the patients who underwent prostatic artery embolization was 67 years. None of the men had to be admitted to the hospital after the procedure.

Ninety-four percent of the men (17 of 18) had a significant decrease in their symptoms one month after surgery. And, none reported any major complications following the surgery.

Bagla said the exact cost of the new procedure is difficult to estimate right now, but prostatic artery embolization will be cheaper than most of the currently used procedures, he said, because there's no need for an operating room and overnight hospital stays. In addition, he said, because the new procedure doesn't appear to cause complications, that will save health care dollars as well.

"This may become part of the armamentarium of treatments that can be offered for [benign prostatic hyperplasia]," said Dr. Art Rastinehad, director of interventional urologic oncology at North Shore-LIJ Health System in New Hyde Park, N.Y. He was not involved with the new study.

"This was a small series and a limited study to draw significant conclusions from. But, it's very exciting to see it evaluated and moving forward," he said.

New Study Questions Prostate Cancer Screening for Older Men

Only one-third of men over age 65 who receive an abnormal result from their PSA test actually undergo prostate biopsy to look for disease, a new study finds.

Prostate-specific antigen (PSA) screening is a common test that measures the level of a key marker for prostate cancer in the blood. In general, the higher the level of this protein, the more likely it is that a man has prostate cancer, according to the U.S. National Cancer Institute.

The value of the PSA test has recently come into question, however, with several studies suggesting it causes men more harm than good -- spotting too many slow-growing tumors that, especially in older patients, may never lead to serious illness or death.

The new study focused on this issue once again, tracking outcomes for nearly 300,000 men, aged 65 and older, who underwent PSA screening in the U.S. Veterans Affairs health care system in 2003. The men's health was followed for up to five years.

There were more than 25,000 men with clinically abnormal PSA levels. According to the study authors, during the five-year follow-up period, only 33 percent of those men underwent at least one prostate biopsy to check for evidence of cancer. About 63 percent of those who did have a biopsy were diagnosed with prostate cancer, of whom 82 percent were treated for their cancer.

The older the man, the less likely he was to have a prostate biopsy after having an abnormal PSA screening test result. Men with other health problems were also less likely to undergo a prostate biopsy, the investigators reported.

The study was published online April 15 in the journal JAMA Internal Medicine.

Among men with biopsy-detected prostate cancer, the risk of death from causes other than prostate cancer increased with age and with the presence of other health problems, Dr. Louise Walter, of San Francisco Veterans Affairs Medical Center, and colleagues pointed out in a journal news release.

Two experts not connected to the study said the findings weren't surprising, given the patients' ages.

"PSA screening has been controversial as it has a relatively low yield for finding clinically significant cancer as well as potential complications and expense related to diagnosis and treatment," said Dr. Louis Kavoussi, chairman of urology at North Shore-LIJ's Arthur Institute for Urology in New Hyde Park, N.Y.

In the new study, "as age and other chronic illnesses of aging increased, the less likely biopsy was performed," he said. "This makes sense as the authors report that older individuals and those with [other illnesses] are more likely to die of a non-prostate cancer-related cause."

Therefore, the decision to test for PSA levels in older men must take into account their relatively low risk of dying of prostate cancer, Kavoussi said. "Overall, it is known that about 10 percent of individuals diagnosed with prostate cancer succumb to the disease," he said. "In this older patient population study it was 2.2 percent -- much lower, but not zero."

Another expert agreed, saying that younger men may benefit most from regular PSA screening.

"For screening to be effective, we need to focus on men with a long life expectancy," said Dr. Stacy Loeb, assistant professor in the department of population health at NYU Langone Medical Center, New York City. "Screening allows us to diagnose the life-threatening cancers in time for cure [but] diagnosis does not mandate treatment," she explained.

"Once a diagnosis is made, many patients with low risk disease can be safely monitored conservatively," Loeb said. "Men should be actively involved in all of these choices, with a discussion about risks and benefits."

What's really needed, according to Kavoussi, is a screen that can tell a patient whether his prostate cancer is aggressive or not.

There's a "need for better ways of detecting clinically significant disease in this older population, both to avoid overtreatment and to minimize the risk of missing significant disease," Kavoussi said.

More information

The U.S. National Cancer Institute has more about prostate cancer screening.