AUA: AMERICAN UROLOGICAL ASSOCIATION MEETING
May 17-22, 2008 in Orlando, Florida, USA
Posted on 22 May, 2008
Study Link Cholesterol to Prostate Cancer Recurrence
Controlling serum cholesterol may help reduce the risk of prostate cancer as well as heart disease, two studies reported at the 2008 AUA Meeting suggest.
Men with the highest cholesterol levels had more than a two-fold greater risk of biochemical relapse after radical prostatectomy compared with men who had the lowest cholesterol levels, according to Lionel L. Banez, M.D. & colleagues, of DukeUniversity. HDL was not associated with recurrence risk.
"These findings suggest that cholesterol may play a role in prostate cancer progression," said Dr. Banez. "Cholesterol-lowering drugs, such as statins, should be investigated for a possible role in the treatment of prostate cancer."
How cholesterol might influence prostate cancer risk is unclear, said Dr. Banez. However, he pointed out that cholesterol is a precursor to testosterone, which fuels prostate growth and function.
Another mechanistic explanation posits that cholesterol interferes with signal transduction associated with normal cell growth, he said.
A second study, presented by Robert J. Hamilton, M.D., of the University of Toronto, showed a correlation between higher cholesterol levels and higher PSA values.
Those findings support previous evidence that men treated with statin drugs to lower their cholesterol levels also had reductions in PSA levels, Dr. Hamilton said.
New Therapies Show Promise for BPH
Two new therapeutic strategies for benign prostatic hyperplasia (BPH) -- one oral, one injectable -- showed promise in clinical trials, investigators report at the AUA 2008 Meeting.
The vitamin D agonist elocalcitol significantly slowed prostate growth and improved urinary flow in a placebo-controlled dose-finding study. Elocaocitol demonstrated anti-inflammatory and antiproliferative activity in preclinical studies. It arrests prostate growth and improves bladder function.
A second study found that a single intraprostatic injection of a PSA-activated protoxin PRX302 (a modified bacterial protoxin)significantly reduced prostate symptoms and volume in a small phase 1 clinical evaluation. The researchers hypothesized that the reduction in prostate mass reduces the pressure on the urethra, leading to a reduction in prostate symptoms. The protoxin was well tolerated.
Autologous Cell Transplant Show Promise for Stress Urinary Incontinence
For stress urinary incontinence, the use of transplanted autologous muscle-derived cells has led to significant and durable symptom improvement, investigators report.
Of 177 patients followed for up to two years, fewer than 10% of women and 30% of men required absorbent pads, Hannes Strasser, M.D., of the Medical University of Innsbruck in Austria, said at the American Urological Association meeting.
"The procedure is safe and minimally invasive," said Dr. Strasser. "Ultrasonography-guided injection of autologous cells has been very effective and also very precise, which is of utmost importance."
Since April 2004, Dr. Strasser and colleagues have used cell transplantation to treat 65 men and 112 women, starting with removal of a small amount of muscle from the patient's upper arm. Myoblasts and fibroblasts are grown in culture for six to eight weeks. The fibroblasts are mixed with a small amount of collagen, which serves as a carrier and prevents cell migration.
Guided by transurethral ultrasound, the fibroblasts are injected into the urethral submucosa to treat atrophy, and the myoblasts are injected into the rhabdosphincter to effect reconstruction.
Follow-up examinations revealed thickening of the urethra and rhabdosphincter and increased contractility of the rhabdosphincter. There were no severe treatment side effects or complications.
Longer follow-up is needed to confirm the safety and efficacy of the procedure, Dr. Strasser said, and a multicenter trial is needed to demonstrate replicability.
"This is not a wonder therapy that works in every incontinent patient," Dr. Strasser cautioned. "It cannot be used in patients with hypermobility or in patients with prolapse. It works very well in patients with intrinsic sphincter insufficiency."
PSA Testing Might Not Be Necessary for Older Men
At age 75, men who have PSA levels less than 3 ng/mL can safely discontinue routine prostate cancer screening because they have a low risk of developing aggressive disease, data from a large prospective cohort study suggest.
In fact, the probability of prostate cancer death and high-risk disease declined steadily in those men, Anna E. Kettermann, of Johns Hopkins, reported at the American Urological Association meeting.
In contrast, a PSA level of 3 ng/mL or greater was associated with an increased probability of developing high-risk prostate cancer.
"Men who have a PSA level below 3 ng/mL at age 75 to 80 are unlikely to develop aggressive prostate cancer during their remaining life, and for these men, PSA testing might be safely discontinued," said Kettermann.
The findings came from an analysis of data on 849 participants in the Baltimore Longitudinal Study on Aging.
Bariatric Surgery Imoroves Sexual Function for Obese Men
Morbidly obese men frequently have severe sexual dysfunction that improves dramatically after bariatric surgery, investigators reported at the AUA 2008 Meeting.
Surgery helped the men rid themselves of more than 80% of their excess body weight, which was associated with normalization of sexual function, found Jason A. Smith, M.D., of the Albert Einstein Healthcare Network in Philadelphia.
"Obesity clearly causes sexual dysfunction in men in a dose-dependent fashion, and substantial weight loss normalizes sexual function in morbidly obese men," said Dr. Smith. "Sexual dysfunction should be considered one of the numerous potentially reversible complications of obesity.Every domain of sexual functioning that was assessed improved significantly after surgery.”
Weight loss had the greatest impact on sexual drive, erection, and ejaculation. It also had a favorable effect on comorbid conditions, particularly diabetes and hypertension.
Urinary Symptoms in Older Men Linked to Increased Fall Risk
Lower urinary tract symptoms significantly increase the risk of falls in older men, a large prospective cohort study suggested.
Both moderate and severe symptoms independently influenced the risk of falls, J. Kellogg Parsons, M.D., of the University of California San Diego, reported at the American Urological Association meeting here. Falls were most closely associated with urgency, straining to start urination, and nocturia.
"These results may justify routine assessment of urinary symptoms in primary care," Dr. Parsons concluded.
Lower urinary tract symptoms affect 15% to 60% of men age 40 and older, and the prevalence increases with age. Falls also become more prevalent with age, and 25% of men older than 65 have one or more falls each year, Dr. Parsons noted.
Gene Transfer Shows Promise as Therapy for Erectile Dysfunction
The next generation of therapy for erectile dysfunction could include semiannual intracavernosal injections of a gene that improves smooth muscle function, preliminary clinical results suggest.
A single injection of hMaxi-K led to restoration of normal erectile function that lasted for six months in two men treated with the highest dose, Arnold Melman, M.D., of Albert Einstein College of Medicine in New York, reported here at the American Urological Association meeting.
"The results were exactly as we had predicted from our animal studies," said Dr. Melman. "If these findings hold up in further clinical investigations, we think men will require two injections a year to maintain normal sexual function."
The therapy evolved from recognition that abnormal smooth muscle function plays a major role in erectile dysfunction. It has potential application in a variety of conditions involving smooth muscle dysfunction such as overactive bladder.
Low Testosterone Linked to Balanitis Xerotica Obliterans
Patients with balanitis xerotica obliterans had near-complete resolution of the genitalia-focused inflammatory condition when treated with systemic and topical testosterone, according to a small clinical series.
Seven of eight patients who completed surgical and medical treatment have had successful outcomes, Charles L. Secrest, M.D., of the University of Mississippi in Jackson, said at the American Urological Association meeting here. In each case, inflammation-associated tissue destruction almost disappeared.
"We feel that low testosterone plays a significant role in the progression or recurrence of this terrible condition," said Dr. Secrest. "Overall, these data show dramatic improvement after the start of aggressive testosterone replacement therapy. Even in the most advanced cases, we observed a near-normal appearance in the glans, meatus, and prepuce of the penis."
He added, "Use of two-stage reconstruction technique allows us to apply topical testosterone cream directly on the affected areas, and we think this plays a role in the results we have seen."
Balanitis xerotica obliterans, also called penile lichen sclerosus, is a rare, chronic inflammatory condition with an undetermined etiology. Some evidence suggests the condition occurs more often in uncircumcised boys and men. Severe tissue destruction can occur in the prepuce and glans, and often causes meatal stenosus and urethral strictures.
No consensus exists about the optimal approach to treatment for balanitis xerotica obliterans. Surgery (including skin grafting), a variety of pharmacologic therapies, and laser treatment have been used with varying degrees of success.
While reviewing patient records, Dr. Secrest and colleagues found that many of the men had low testosterone levels. As a result, they began to treat patients with a combination of subcutaneous testosterone pellets and 2% testosterone cream, which they applied directly to affected areas between the first and second stages of surgery. They found that surgical results improved dramatically after adding testosterone replacement to the protocol.
"After treatment with testosterone cream, the skin becomes remarkably supple, even at the interface to the urethral plate and surrounding skin," said Dr. Secrest.
Active Surveillance Still Viable for Some Prostate Cancer Patients
For men with low-risk, localized prostate cancer, active surveillance remains a viable option, but not without a "small but very real" risk, new data suggest.
During 30 months of follow-up, the need for intervention could be predicted by characteristics of the first and second biopsy, Scott E. Eggener, M.D., of the University of Chicago, said at the American Urological Association meeting.
Specifically, the number of positive cores in the first and second biopsies and the presence of cancer in the second biopsy identified men with an increased likelihood of stopping active surveillance in favor of treatment, Dr. Eggener said.
"Every single day patients come to doctors' offices wondering whether they need treatment, whether they should be subjected to the side effects of treatment, which can be with them for decades," Dr. Eggener said in an interview. "This is just another piece of data to use when counseling them."
"For highly select patients, active surveillance seems to be a safe, reasonable, feasible option, but doctors need to know there is a low but real risk of dangerous progression," he added.
The advent of routine screening for prostate cancer with PSA testing has led to "an element of overdetection of cancer," Dr. Eggener noted. An estimated 30% to 50% of men who undergo radical prostatectomy have cancer with pathologic features associated with a low risk of biochemical recurrence.
Increased recognition of the large percentage of patients with low-risk prostate cancer has fueled use of active surveillance. However, the practice has evolved largely in the absence of data to guide patient selection and long-term follow-up, Dr. Eggener continued.
To better define the clinical environment of active surveillance, investigators at three academic medical centers in the U.S. and one in Canada retrospectively reviewed prospectively collected data.
Analysis of factors associated with primary treatment revealed only two predictive factors: a greater number of positive cores on the first and second biopsy combined and cancer in the second biopsy.
Age at diagnosis, PSA value at diagnosis, clinical stage, prostate volume, number of positive cores at initial diagnosis, and total number of biopsy cores did not correlate with outcome.
Prostate Vaccine Linked to Improved Survival in Small Trial
More than half of men with metastatic, hormone-refractory prostate cancer had longer-than-estimated survival after treatment with an adenovirus/PSA vaccine, showed a phase I study.
About half the patients had increased PSA doubling time and about 70% had anti-PSA T-cell responses associated with tumor destruction, reported David Lubaroff, Ph.D., of the University of Iowa in Iowa City. No patient had a vaccine-related adverse event.
"We've evaluated the vaccine in only a small number of patients, but at this point, we are very encouraged," said Dr. Lubaroff at the American Urological Association meeting here.
Dr. Lubaroff reported that 55% of the 32 patients in the study outlived nomogram-predicted survival. The increase in survival after a single vaccine dose ranged from two months to 47 months.
A phase 2 trial of the vaccine has already begun and will focus on efficacy in men with advanced prostate cancer.
|
