The Early Prostate Cancer Trial And Adjuvant Anti-androgen Therapy: Still Defining The Role

The Early Prostate Cancer Trial (EPC) was the largest prostate cancer (CaP) study ever undertaken. It evaluated adjuvant bicalutamide in patients across the world that still had their standard care primary therapy: whether watchful-waiting, radiotherapy or radical prostatectomy.

The original study was published in 2001, and two analyses followed; one in 2004 with 5.4 years follow-up and most recently in 2006 with 7.4 years follow-up. The study design, outcomes and conclusions remain controversial, and thus two substantial commentaries were published in the March 2006 issue of the BJU International.

The first commentary is from Dr. Cora Sternberg, a medical oncologist in Rome Italy. She critiques the fact that the EPC study was actually 3 trials around the world that had different participant mix with regard to CaP stage and distribution of treatments selected.

She notes that there was no improvement in overall survival in patients receiving bicalutamide. As such, she is concerned about the usage of subset analysis to define smaller populations of patients who benefited. For example, bicalutamide plus standard care improved objective progression-free survival (PFS) by 21% compared with standard care alone.

However, this was noted in only two of the three international trials and in her opinion questions the validity of broad interpretation that PFS is improved irrespective of the standard treatment rendered. Also, if patients in the placebo arm were treated with early salvage therapy for a PSA level increase they might have done equally well, but this was not done. Finally, Dr. Sternberg notes that initial reports suggested benefit from bicalutamide for even localized CaP, but now this is presented to benefit only those with locally advanced disease.

In his commentary, the study principal investigator Dr. Peter Iverson, Copenhagen Denmark points out that the EPC was designed to pool the 3 trials. He emphasizes that the sequential data analyses and reporting are a tribute to the integrity of the data set and permit identification of sub-populations of patients that benefit.

Dr. Iverson comments that adjuvant bicalutamide is not for every patient, but has benefit in some and significantly less toxicity than LHRH therapy. He admits that the large scope of the EPC trial and range of patients has damaged its impact, but hypothesizes that had an LHRH agonist been used in the EPC trial, its risks would have outweighed its benefit. This, of course is not known and the EPC continues to spark controversy and reinforce that optimal trial design is paramount to ascertaining data that is universally accepted and applicable.

Study: Experienced surgeons net better prostate cancer results

Study: Experienced surgeons net better prostate cancer results

The more experienced the surgeon, the better the chance a man has staying free of cancer after prostate cancer surgery, says a new study released today.

The findings comes from a large study of nearly 10,000 men who underwent conventional prostate cancer surgery at four U.S. medical centers, in Detroit, New York City, Rochester, MN and Houston, between 1987 and 2003.

It found that a surgeon’s skill was just as important as a tumor’s size and aggressiveness in determining whether prostate cancer recurred in five years. Those whose surgeries were performed by high-volume doctors had a 60% greater chance of being cancer-free at the five-year mark, the study said.

And even among doctors who performed the operation a lot, recurrence rates five years later varied, suggesting that skill varies even among high-volume doctors, said Dr. Fernando Bianco, lead author of the study. He is an urologic oncology fellow at Memorial Sloan-Kettering Cancer Center in New York and former urology resident at the Wayne State University School of Medicine.

The study does not specify how many surgeries are needed to be proficient at it. But a good indication of a top-notch surgeon is one who has performed at least 250 radical prostatectomy procedures, as the operation is called, in a lifetime, Bianco said.

His advice: “Surgeons must have a report card.”

Ask the surgeon about precise rates of cancer recurrence and side effects in his or her patients, Bianco said.

Of 74 surgeons in the study, 36 were classified as high-volume doctors, defined as one performing the procedure at least 40 times.
After that, a surgeon’s skill may be enhanced by doing more of the operations but “the effect isn’t as pronounced,” he said.

At five years, 17% of all patients had a rise in a prostate cancer marker, an indication that a tumor has returned, the study found. It was expected to be presented today in San Francisco at the 2006 Prostate Cancer Symposium, co-sponsored by four organizations in the field.

Prostate cancer is the second leading cause of cancer death in American men. In 2005, an estimated 232,000 men were diagnosed with the disease, more than colon and lung cancer combined, and more than 30,000 died of it, according to the American Cancer Society.

Study: Vitamin supplements don’t prevent prostate cancer

Taking the vitamins E and C or the nutrient beta-carotene doesn’t protect against prostate cancer, says the latest study in the continuing, confusing quest to determine when supplements really help health.

The government research, published Tuesday in the Journal of the National Cancer Institute, is among many large studies examining whether these antioxidants play a role in prostate cancer when taken as pills – instead of when they’re consumed as part of an overall healthy diet.

Previous research has yielded conflicting results, and even this new study of almost 30,000 men doesn’t settle the issue. Indeed, while vitamin E showed no effect on men overall, the study leaves open the possibility that it might help smokers.

The men were enrolled in an NCI study whose primary aim is to test the value of screening tests for prostate cancer. They also were surveyed about their diet and what supplements they took – relying on memory, not nearly as precise as other research now under way that controls supplement doses.

Some 1,338 men were diagnosed with prostate cancer within eight years of entering the study. Supplement users were just as likely to be diagnosed as non-users.

Smokers were 71 per cent less likely to be diagnosed with advanced disease if they had taken high doses of vitamin E for many years. But, perplexingly, the risk of earlier-stage cancer increased among vitamin E-using smokers.

Smoking itself raises the risk of prostate cancer, and even if further research concludes that vitamin E somehow tempers that risk, kicking the habit would be far more protective, Harvard University scientists caution in an accompanying editorial.

• Antioxidants Do Not Prevent Prostate Cancer

Saw Palmetto Not Effective at Relieving Prostate Problems

The herbal remedy saw palmetto is no more effective than a placebo at treating symptoms related to enlargement of the prostate gland, according to a new study in the Feb. 9 issue of the New England Journal of Medicine.

“The results are disappointing, particularly for the estimated 2 million
American men who take saw palmetto,” said Andy Avins, MD, MPH, of the Kaiser Permanente Division of Research in Oakland, Calif., and co-leader of the study.
In Benign Prostatic Hyperplasia (BPH), the prostate gland enlarges,
causing an obstruction that can impair urinary function. Saw palmetto is commonly used as an alternative to prescription medications. The National Institutes of Health says BPH affects more than half of men 60 and older, and more than 90 percent of men 70 and older.

The year-long, double-blind study, by researchers at Kaiser Permanente and UCSF/San Francisco VA Medical Center, followed 225 men diagnosed with BPH. The patients were randomly assigned to take either 160 mg of saw palmetto (the amount used in the vast majority of prior clinical trials) or a placebo twice a day for one year. The researchers say there was no statistically significant difference between the two groups in terms of symptom changes either during the trial, or at the end of the year.

“Obviously this is not encouraging news for men who are considering taking saw palmetto to treat their BPH,” said Avins. “Not only did it show no overall benefit, but it also showed no benefit when we looked at it in subgroups of patients who had different levels of severity of symptoms, or who had different sizes of prostate.”

The study’s findings contradict several previous studies, which suggested the herb was an effective treatment for BPH. The researchers say there are several possible explanations for this. Previous studies were smaller in size and duration. In measuring the severity of BPH, most of those studies did not apply the same method that is commonly used to measure the effectiveness of prescription medications for the problem.

Another potential problem with earlier studies has to do with the nature of saw palmetto itself, according to Stephen Bent, MD, staff physician at the San Francisco VA Medical Center and co-author of the study. “This is a very pungent herb, and it took our research team a long time to create a placebo that convincingly duplicates its strong smell and taste. We suspect that prior trials didn’t adequately address that problem.” Bent said.

He added:  “It’s possible that some of the positive findings in earlier
work may be due to the fact that the blinding wasn’t adequate. Someone who’s taking something that’s smelly and likely to be the plant extract is perhaps more likely to report a benefit than someone who’s taking an odorless and tasteless tablet.”  The researchers say this may not be the final word on the subject. They say it is possible saw palmetto may be effective at higher doses.

Co-authors of the study include:  Christopher Kane, MD, and Katsuto
Shinohara, MD, of the San Francisco VA Medical Center; John Neuhaus, PhD and Esther S. Hudes, PhD, MPH, of UCSF; and Harley Goldberg, DO, of Kaiser Permanente Northern California and UCSF. The study was funded by a grant from the NIH that was administered by the Northern California Institute for Research and Education.

Staging Prostate Cancer Is Improved with MRI

Endorectal magnetic resonance imaging (MRI) and combined endorectal MRI-MR spectroscopic imaging can “contribute significant incremental value” to nomograms and other algorithms designed to stage organ-confined prostate cancer, researchers at Memorial-Sloan Kettering Cancer Center in New York report.

In a study published in the February issue of Radiology, Dr. Peter Scardino and colleagues conducted a study of 299 patients who underwent endorectal MRI and 383 patients who underwent combined endorectal MRI-MR-spect imaging before radical prostatectomy between November 1, 1999 and November 1, 2004. Mean age was 58.

Retrospectively, the investigators assessed the risk of extracapsular extension, seminal vesicle invasion and lymph node metastasis based in imaging studies. Patients were given a score between 1 and 5 for risk of organ-confined prostate cancer.

Staging nomograms were used to calculate the likelihood of organ-confined prostate cancer based on prostate-specific antigen (OPSA), Gleason grade at biopsy and clinical stage. The reference standard was the histological findings.

MR findings “significantly increase the accuracy of identifying which cancers are ‘indolent’ and may not need immediate treatment, whether there is extension through the seminal vesicle invasion as opposed to cancer truly confined to the prostate,” Dr. Scardino told Reuters Health. The addition of imaging was greatest for intermediate- and high-risk patients, the researchers found.

Dr. Scardino noted that “MRI should be done before or at least eight weeks after a needle biopsy of the prostate, but before a treatment decision is made in a patient with presumed organ-confined prostate cancer.  Remember that ‘organ-confined’ is a clinical diagnosis, not a pathological stage.”

“The optimal use [of MRI] is for staging a man already diagnosed with cancer, to determine the probability and location of extension of cancer through the prostate and seminal vesicles,” Dr. Scardino said. “This information can help patients make the best decision about which treatment to select and can help the surgeon plan the operation to be sure all cancer is removed while the critical nerves and the sphincter are removed.”

SOURCE: Radiology 2006;238:597-603.

Prostate Cancer Spurs Rocky Mount Man To Start Special Mission

Black Men Seen As High Risk For Prostate Cancer

Prostate cancer is a global health problem, but the highest incidence and death rate is found in black men in eastern North Carolina. Some people hope to make a change in that statistic.

The message may be spiritual, but the Rev. Thomas Walker also helps his Rocky Mount congregation deal with the physical.

“We deal with a lot of people and we are to be concerned about the whole man,” he said.

Nine years ago, Walker learned he had prostate cancer. He wrote about his treatment and survival. The book sparked a mission to reach people with a prostate health message through television, brochures and even posters in public bathrooms.

“We’re dealing with an epidemic and we have to treat it as such,” he said.

The epidemic is rolling through eastern North Carolina, catching most victims unaware.

One of the challenges in eastern North Carolina about spreading the message of prostate health is that people are spread out. There is limited access to medical care and health education.

Walker helped Marvin Roundtree through his prostate cancer treatment and recovery. The two men helped start a prostate cancer Shepherds group to do the same for others. They shepherd men through the experience after diagnosis and urge others to catch it early when it is most treatable.

“That cancer is not such a dirty word. Go ahead and have yourself checked,” Roundtree said. “There is a possibility of you being cured. You don’t have to die from prostate cancer.”

Doctors recommend most men begin annual prostate exams by age 50. Black men should begin by age 40.

CaP Cure: The Fight Against Prostate Cancer

The next time you’re at your local Safeway store, why not donate to CaP Cure: the fight against prostate cancer.

According to their Web site, CaP Cure was founded in 1993 with an urgent mission: Identify and support prostate cancer research that will rapidly translate into treatments and cures.

Together with survivors, scientists and advocates, CaP CURE has established a system that encourages collaboration, reduces bureaucracy and speeds the process of discovery.

To learn more about CaP Cure and other ways you can help, visit the CaP Cure Web site.

Waistline Protection for the Prostate

Registered dietitian Karen Collins looks at recent studies that have suggested waist size is an effective predictor of prostate cancer.

Since prostate cancer is a common cancer faced by American men, it’s understandable that a lot of media and scientific attention should focus on nutrients and phytochemicals that might help prevent this disease.

But several recent studies suggest that many men may be overlooking a risk factor that is literally right in front of them: a bulging waistline. Moreover, several studies now suggest that being significantly overweight may promote the development of a more aggressive form of prostate cancer.

In one of the new studies that show the risk from excessive body fat, among men treated for prostate cancer, those who had gained more than about three-and-a-half pounds a year between the ages of 25 and 40 were twice as likely to have this cancer recur as men who gained less weight. According to this study, men who were obese when diagnosed with prostate cancer were more likely to have the cancer return than leaner men. The impact on recurrence was even stronger if they were obese by age 40.

Bloods tests for prostate-specific antigens (PSAs) also link obesity with prostate cancer’s return after prostate surgery in studies at the Johns Hopkins School of Medicine. Even after accounting for the stage and type of prostate cancer, increasing amounts of obesity had rising PSA counts and boosted the odds that prostate cancer would return. Researchers say the evidence suggests that obesity creates a more aggressive form of prostate cancer.

Although obesity may worsen the form of prostate cancer and increase the likelihood of its return, an association between excess weight and the risk of getting prostate cancer is not firmly established. Some studies support a link, while others show none. This inconsistency may mean that some men are more vulnerable to the risk from excess weight. This inconsistency could also mean that lifestyle choices are influential, too. A man’s sedentary lifestyle; high fat intake; low consumption of vegetables, fruits, whole grains and beans; or excessive calories could all contribute to his prostate cancer risk.

Excess body fat that is located in and around internal organs and often indicated by more waistline fat may pose particular risks, even if a man is not obese. In a study that used CT (computed tomography) scans, also known as CAT scans, to measure body fat distribution, men with prostate cancer averaged about 50 percent more total abdominal fat than healthy men of the same age. Excess abdominal fat could produce hormone-like substances that promote the development of prostate cancer and other cancers. The elevated levels of insulin and insulin-like growth factors that often accompany excess body fat could also be involved.

Increasing protection against prostate cancer by aiming for and maintaining a healthy weight is by no means incompatible with eating more of the beneficial phytochemicals found in vegetables, fruits, whole grains and beans. On the contrary, tomato, red grapefruit, garlic, onion, broccoli, cauliflower and other cruciferous vegetables can all be incorporated in a personal health plan that reduces the risk of prostate and other cancers.

For the strategy that offers as much cancer-fighting power as possible, men should include a wide variety of fruits and vegetables throughout their daily meals and snacks. Weight control is also easier when you limit foods that are extra-concentrated in calories – such as fat, sugar and alcohol – and take appropriate portions. Lastly, although we don’t know yet whether exercise directly protects men from prostate cancer, exercise should also be a part of your strategy because it’s vital to prevent the creeping weight gain that many adults experience.

Tags: Prostate, Prostate Cancer, Health