American Urological Association

AUA: Low-Carb Diet Quells ADT Effects

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Trial misses insulin-resistance endpoint but may have potential.

A very low-carbohydrate diet failed to prevent insulin resistance in men taking androgen deprivation therapy for prostate cancer, but led to significant weight loss and preserved bone health, a small trial showed.

The dietary intervention led to a significant reduction in homeostatic model assessment (HOMA) of insulin resistance at 3 months, as compared with a control group, but not at 6 months, the primary endpoint. Men on the very low-carbohydrate diet had significant reductions in weight and percent body fat and stable bone mineral content (BMC) versus weight and body fat increases and a reduction in BMC in the control group.

Though the trial missed its primary endpoint, a follow-up study has already begun to test the oncologic benefits of the very low-carbohydrate diet, Stephen Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, reported here at the American Urological Association (AUA) meeting.

“Carbohydrate restriction is a promising tool to prevent androgen deprivation therapy (ADT) -induced metabolic side effects,” said Freedland. “Given that weight loss is generally anticancer, coupled with animal data that this diet slows prostate cancer growth, studies evaluating oncological efficacy and safety are ongoing.”

The diet would pose an adherence challenge for many men, but the challenge has to be weighed against the reality of the disease, said Benjamin Davies, MD, of the University of Pittsburgh.

“These are men who have recurrent cancer,” said Davies, who moderated an AUA press briefing where Freedland discussed the study. “If you tell them that there is preliminary data that this may help them with their physiology and their health, you might be more apt to induce them to follow a proactive approach to change their lifestyle. Whereas if this were just a regular guy without the kind of medical challenge, you can see where there might be some reluctance.”

“Usually, people are more apt to change their lifestyles when their health is at risk,” he added. “I think that gives me some hope that we could actually do that for patients. Obviously, it’s challenging. I don’t know that I could do it … actually, I know that I couldn’t.”

For decades, hormonal therapy, or ADT, has represented standard of care for advanced prostate cancer. Multiple studies have demonstrated survival benefits with ADT. However, recent investigations have documented major side effects, especially metabolic effects (weight gain, insulin resistance, dyslipidemia), in addition to hot flashes, loss of libido, erectile dysfunction, memory loss, and bone mineral loss and osteoporosis.

“Hormonal therapy for prostate cancer increases the risk of diabetes by 40%,” said Freedland. “Diabetes is a problem controlling blood sugar levels. We wondered, what happens if you don’t eat sugar?”

Low-carbohydrate diets have demonstrated the potential to achieve significant weight loss and improve diabetes control, he continued. In animal models, low-carbohydrate diets have been associated with slowing of prostate cancer growth. Such a diet has never been evaluated in a randomized trial involving patients with cancer.

Investigators hypothesized that a very low-carbohydrate diet could prevent insulin resistance and other metabolic side effects in men initiating hormonal therapy for advanced prostate cancer. To test the hypothesis, Freedland and colleagues conducted a prospective, randomized trial, comparing a very low-carbohydrate diet versus usual diet in men initiating ADT.

Men randomized to the intervention arm followed a diet that limited daily carbohydrate consumption to 20 g, similar to the Atkins diet, said Freedland. They also were instructed to exercise 30 minutes a day, 5 days a week. Men assigned to the control arm continued their usual practices regarding diet and exercise.

Investigators randomized 42 patients, and 40 completed the baseline assessment. Subsequently, 14 men in the intervention arm and 20 in the control group completed the 6-month trial. Complete data were available for 11 men in the very low-carbohydrate group and 18 in the control group, and those 29 patients formed the basis for data analysis.

The primary endpoint was change in HOMA at 6 months. The intervention group had a mean change in HOMA of -4 compared with an increase of 36 in the control group (P=0.127). The 3-month values showed a significant difference in favor of the intervention arm (-19 versus +7, P=0.015).

The dietary intervention was not expected to affect PSA values, and the change from baseline (in response to hormonal therapy) ranged from -97% to -99% in both arms at 3 and 6 months. Men in the very low-carbohydrate arm had weight loss that averaged about 15 lbs at 3 months, increasing to 20.5 lbs at 6 months. In the control group, men had gained almost a pound at 3 months and almost 3 lbs at 6 months (P<0.001 versus intervention group at both time points).

Bone mineral content remained unchanged at 6 months in the intervention group as compared with a reduction of 2.3% in the control group (P=0.025). Percent body fat decreased by 16.2 % at 6 months in the intervention group and increased by 11% in the control group (P=0.002).

2014 Top Stories in Urology: Medical Management of Stone Disease.

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In 2014, the American Urological Association (AUA) released a clinical guidelines document focused on the medical management of kidney stone disease.1 This important, but often overlooked, aspect of stone management is an “orphan” field. It requires administration and titration of medications, which is not something that urologists commonly do, but it also entails an understanding of surgical stone management, which is not something that nephrologists commonly do.

The document provides detailed guidelines for the metabolic evaluation and medical management of stone patients, with associated levels of evidence (eg, treatment “standards” based on higher level of evidence vs “expert opinion”) to enable the reader to understand the basis for the recommendations. The detailed literature review combined with professional opinion provides recommendations for initial evaluation, dietary therapies, pharmacologic therapies, and follow-up of newly diagnosed patients and those with recurrent disease.

These guidelines are most welcome, as they demystify and organize the approach to the management of patients with this complex problem. While treating a stone surgically is in the purview of most urologists, employing dietary and pharmacological means to reduce recurrence is a less comfortable task for many. The latter is particularly important given the high recidivism of stone formers, the quality-of-life concerns associated with recurrent symptomatic disease, and the significant financial costs associated with this disease.

The lack of level 1 evidence in the guidelines is apparent and calls for more rigorous, prospective study of the prevention and management of stone disease. The take-away point is that there is good evidence for prevention that is already available and underutilized, and these guidelines should provide a digestible means for practitioners to work on prevention rather than simply treatment.

2014 Top Stories in Urology: Urinary Tract Infections and Inflammation.

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This summer the interstitial cystitis/bladder pain syndrome guideline of the American Urological Association (AUA) was updated. The new guideline and associated treatment algorithm are now on the AUA website. They will be published in the Journal of Urology and presented at the annual meeting of the AUA in New Orleans next year.

Three factors have arisen in the last year that may impact on how urologists use the guideline from a clinical standpoint. In the absence of any major clinical breakthroughs in diagnosis or treatment of urinary infection and inflammation in the last year, I think the guidelines and a couple of clinical reports are worth noting as they may influence treatment of IC/BPS by the front-line provider.

  • In the guideline itself, intradetrusor botulinum toxin A (BTX-A) has been moved from a fifth-line therapy to a fourth-line therapy on par with neuromodulation. The updated literature review retrieved 10 new studies, including 1 randomized controlled trial and 9 prospective observational studies reporting on a total of 378 patients. It should be noted that several studies appear to include overlapping patient groups. As a group, these studies represent a major shift in how BTX-A is employed to treat IC/BPS in several ways, including the combination of BTX-A with hydrodistention, the use of primarily the 100-U dose, the use of repeat treatments with symptom return, and following patients for years rather than months.
  • Elmiron (pentosan polysulfate sodium) remains one of several second-line therapies in the updated guideline, but a recently released paper by Nickel and colleagues details results from a study including a broad population of patients with symptoms consistent with interstitial cystitis.1 There was no treatment effect vs placebo at the standard dose of 100 mg three times daily or 100 mg once daily. In the absence of any dose response at triple the standard label dose reported in an earlier study,2use of the drug might be tempered in the future.
  • Finally, the fifth-line therapy cyclosporine A was shown in a report from Brazil by Jamil Chade and colleagues at the 2014 meeting of the AUA to have little in the way of tachyphylaxis in a group of 45 patients treated with 1.5 mg/kg twice daily for 5 years.3 Results were good, suggesting beneficial effects and clinically significant improvement despite failure of these patients to respond to multiple previous treatments. Further studies are needed.

Taken together, the new guideline update and these new publications may improve the selection of therapies and the results in what can be a very difficult condition to treat successfully.

2014 Top Stories in Urology: Medical Management of Stone Disease

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In 2014, the American Urological Association (AUA) released a clinical guidelines document focused on the medical management of kidney stone disease.1 This important, but often overlooked, aspect of stone management is an “orphan” field. It requires administration and titration of medications, which is not something that urologists commonly do, but it also entails an understanding of surgical stone management, which is not something that nephrologists commonly do.

The document provides detailed guidelines for the metabolic evaluation and medical management of stone patients, with associated levels of evidence (eg, treatment “standards” based on higher level of evidence vs “expert opinion”) to enable the reader to understand the basis for the recommendations. The detailed literature review combined with professional opinion provides recommendations for initial evaluation, dietary therapies, pharmacologic therapies, and follow-up of newly diagnosed patients and those with recurrent disease.

These guidelines are most welcome, as they demystify and organize the approach to the management of patients with this complex problem. While treating a stone surgically is in the purview of most urologists, employing dietary and pharmacological means to reduce recurrence is a less comfortable task for many. The latter is particularly important given the high recidivism of stone formers, the quality-of-life concerns associated with recurrent symptomatic disease, and the significant financial costs associated with this disease.

The lack of level 1 evidence in the guidelines is apparent and calls for more rigorous, prospective study of the prevention and management of stone disease. The take-away point is that there is good evidence for prevention that is already available and underutilized, and these guidelines should provide a digestible means for practitioners to work on prevention rather than simply treatment.

New PSA Screening Guideline from the American Urological Association.

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The target range for “routine” prostate-specific antigen screening has been narrowed to ages 55 to 69.

 

The American Urological Association (AUA) has published a new guideline on prostate-specific antigen (PSA) screening. The guideline has five summary recommendations:

  • No screening for men younger than 40.
  • No “routine” screening for men aged 40 to 54 and at average risk; for those in this age group who are at higher risk (e.g., black men, those with family histories of prostate cancer), individualize screening decisions.
  • For men aged 55 to 69, engage in shared decision making and proceed based on the man’s values and preferences.
  • No “routine” screening for men older than 70 or men with life expectancy shorter than 15 years.
  • When screening, consider biennial instead of annual screening.

Comment: This guideline supplants a 2009 AUA “Best Practice Statement,” which stated that screening “. . . should be offered to healthy, well-informed men 40 years of age or older” (J Urol 2009; 182:2232). The new guideline narrows the age range for “routine” screening to 55 to 69, because that was the core age group in the European screening trial (JW Gen Med Mar 14 2012). Still, the guideline makes for some frustrating reading: Phrases such as “no routine screening” (my italics) are ambiguous, and many clinicians find difficulty in navigating the interplay between a patient’s “values and preferences” and the complexity of potential benefits and harms of screening.

Many media reports publicized the new guideline as evidence that urologists are backing off from aggressive PSA screening. However, some urologists have criticized the AUA for not presenting screening more favorably. And finally, this guideline differs substantially from that of the U.S. Preventive Services Task Force, which recommends against PSA screening for all age groups (JW Gen Med Jun 7 2012).

Source:  Journal Watch General Medicine

 

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

BPH.

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Lower urinary tract symptoms affect more than half of older men. Options for bothersome symptoms include α- adrenergic-receptor blockers, 5α-reductase inhibitors, phosphodiesterase-5 inhibitor therapy, and antimuscarinic therapy. Read the latest Clinical Practice article on this topic. BPH, a histologic diagnosis, is a condition that occurs with aging; the prevalence increases from 25% among men 40 to 49 years of age to more than 80% among men 70 to 79 years of age.

Clinical Pearls

• What are the lower urinary tract symptoms associated with BPH?

The symptoms are classified as obstructive voiding or bladder storage symptoms. Obstructive voiding symptoms include urinary hesitancy, delay in initiating micturition, intermittency, involuntary interruption of voiding, weak urinary stream, straining to void, a sensation of incomplete emptying, and terminal dribbling. Storage symptoms include urinary frequency, nocturia, urgency, incontinence, and bladder pain or dysuria.

• What are the risk factors for developing BPH?

In addition to increased age, additional risk factors include black (vs. white) race, obesity, diabetes, high levels of alcohol consumption, and physical inactivity; mechanisms underlying these associations remain poorly understood. Physiological markers associated with an increased risk of benign prostatic hyperplasia include levels of endogenous testosterone and dihydrotestosterone as well as increased levels of dehydroepiandrosterone and estradiol, insulin-like growth factors, and inflammatory markers (e.g., C-reactive protein).

Morning Report Questions

Q: What office evaluation should be performed when a diagnosis of BPH is being considered?

A: Evaluation includes a complete history to rule out alternative causes of lower urinary tract symptoms, including consideration of excess fluid and caffeine intake and the use of diuretics or medications with antihistaminic effects that may weaken bladder detrusor function. A digital examination of the prostate should be performed and a PSA measurement obtained. A urinalysis should be ordered to screen for urinary tract infection and to look for hematuria, which might indicate urolithiasis or cancer of the kidney, bladder, or prostate. Urinary tract infections should be treated. Evaluation should also include the use of the American Urological Association Symptom Index, a quantitative measure of the severity of lower urinary tract symptoms. If the patient reports a sense of incomplete bladder emptying or has a palpable bladder on abdominal examination, a post-voiding residual urine measurement should be obtained to rule out “silent” urinary retention (normal residual urine volume, <100 ml).

Q: How does one approach the treatment of BPH?

A: A reasonable approach would be to initiate an alpha-blocker (doxazosin), and then to increase the dose based on symptom response. If symptoms are still bothersome, a 5(alpha)-reductase inhibitor can be added as long as the PSA level is higher than 1.5 ng per milliliter (indicating prostatic enlargement). Another option, particularly if the patient also has erectile dysfunction for which he desires treatment, would be to prescribe a phosphodiesterase-5 inhibitor (currently only tadalafil is approved for these symptoms), since this agent could address both problems. In a randomized, placebo-controlled trial comparing doxazosin, a 5(alpha)-reductase inhibitor (finasteride), and the combination of the two, type 15(alpha)-reductase inhibitors (with or without alpha-blocker therapy), but not alpha-blocker therapy alone, significantly reduced rates of secondary outcomes of urinary retention and the need for invasive therapy for BPH.

 

 

Source: NEJM.