Clinical Health Updates

Informed consent reduces desire for PSA screening

Clinical Question:
Does providing information sufficient for informed consent alter patient interest in screening for prostate cancer with prostate-specific antigen (PSA)?

Bottom Line:
Among primary care patients of predominantly lower socioeconomic status, those who received informed consent were significantly less interested in PSA screening than those who did not. For physicians who offer the PSA as a screening test, this finding highlights the importance of apprising patients of the associated benefits, burdens, and uncertainties and allowing them to participate in the screening decision.

Reference:
Wolf AMD, Nasser JF, Wolf AM, Schorling JB. The impact of informed consent on patient interest in prostate-specific antigen screening. Arch Intern Med 1996;156:1333-36.

Study Design:
Randomized controlled trial (non-blinded)

Synopsis:
Because of the many uncertainties surrounding screening for prostate cancer, authorities recommend that patients be involved in the screening decision. The authors want to determined the impact of informed consent on patient interest in undergoing prostate-specific antigen (PSA) screening. Men 50 years or older with no prior PSA testing and no history of prostate cancer presenting to 1 of 4 university-affiliated primary care practices were eligible for enrollment. Patients were randomized to receive either a scripted informational intervention simulating an informed consent presentation (intervention group, n = 103) or a single sentence about the PSA (control group, n = 102). The main outcome measure was patient interest in undergoing PSA screening measured on a 5-point Likert scale. Patients who received the informational intervention were significantly less interested in undergoing PSA screening than controls (mean difference in interest, 0.8 on 5-point scale, P < .001). Informed patients were much less likely to indicate high interest in screening (odds ratio, 0.34; 95% confidence interval, 0.19-0.60; P < .001). In a multivariate model, family history of prostate cancer was associated with increased interest and advancing age with decreased interest in PSA screening, but the informational intervention remained the strongest predictor of interest.

PSA testing affected by how information is presented

Clinical Question:
Can the decision made by men regarding PSA testing be affected by the manner in which the information about the test is presented?

Bottom Line:
When men are given detailed and balanced information on prostate testing, many will opt not to have the test. The method of presentation probably is a large determinant of the effect of the information. This study found that a video outlining the risks and benefits of PSA testing resulted in 40%-50% of men deciding against testing. Of course, we don’t know what happened when the men went home; other studies of PSA decision making have shown that spouses have a large role in the decision and often overrule the initial decision of the men (Arch Fam Med 1997;6:72-76).

Reference:
Frosch DL, Kaplan RM, Felitti V. Evaluation of two methods to facilitate shared decision making for men considering the prostate-specific antigen test. J Gen Intern Med 2001;16:391-8.

Study Design:
Non-randomized controlled trial

Synopsis:
California law (Grant H. Kenyon Prostate Cancer Detection Act) requires physicians to inform all patients older than aged 50 years who receive a prostate examination about the availability of the prostate-specific antigen (PSA) test. Physicians are not given guidance on how this information should be presented. The investigators sought to evaluate the effects upon PSA screening rates of informing patients about PSA testing by 2 different techniques. Factorial comparison of discussion versus video formats for presenting information about the PSA test. Patients were recruited through the Health Appraisal screening program in the Department for Preventive Medicine, Kaiser Permanente, San Diego, Calif. Male patients undergoing health appraisal screening participated in 1 of 4 groups providing information about PSA screening: usual care ( n=43), discussion about risks and benefits of PSA ( n=45), shared decision-making video ( n=46), or video plus discussion ( n=42). Participants were sequentially assigned to 1 of the 4 groups. No significant differences in demographics or family history was demonstrated between the groups at the time of group assignment. Participants in the intervention groups rated the information as clear, balanced, and fair. There were significant differences in the number of men requesting a PSA test, with the highest rate in the usual care group (97.7%), followed by discussion (82.2%), video (60.0%), and video plus discussion (50.0%).

High rates of PSA use not associated with greater mortality reduction

Clinical Question:
Are higher rates of screening with prostate specific antigen associated with a greater reduction in prostate cancer mortality?

Bottom Line:
These study found no association between the intensity of PSA screening and subsequent decreases in prostate cancer mortality; perhaps the recent reductions in mortality are due to better treatment rather than screening. However, this type of study can only provide indirect, somewhat speculative evidence of the benefit, or lack thereof, of PSA testing. It is by no means the final answer, which will hopefully come in a few years with the publication of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Recruitment for that trial ended in 2001, and we can hope to begin to see results in 2006 or so.

Reference:
Coldman AJ, Phillips N, Pickles TA. Trends in prostate cancer incidence and mortality: an analysis of mortality change by screening intensity. CMAJ 2003; 168:31-5.

Synopsis:
The rate of death from prostate cancer has recently declined in many areas of the world. Over the past 15 years prostate-specific antigen (PSA) screening has increased in popularity, which has resulted in increases in the incidence of prostate cancer. Over the same period there have been changes in the management of the disease and, in particular, the use of androgen ablation. The authors examined the relation between changes in prostate cancer incidence (a surrogate for PSA screening) and subsequent changes in mortality in regions using common treatment recommendations. They used data from prostate cancer cases and deaths reported to the British Columbia Cancer Registry during 1985-1999 to examine trends in incidence and mortality in 88 small health areas (SHAs) among men aged 50-74 years. We conducted 2 analyses. In the first we classified the SHAs by intensity of PSA screening (low, medium or high) according to their ranked age-standardized incidence rate of prostate cancer in 1990-1994 and examined subsequent trends in prostate cancer mortality. In the second analysis we examined the SHA-specific relative change in prostate cancer incidence between 1985-1989 and 1990-1994 and correlated it with the relative change in mortality for cases diagnosed after 1990. Between 1985-1989 and 1990-1994 the incidence of prostate cancer increased by 53.2% and 14.6% among men aged 50-74 and those 75 and over respectively. Between 1985-1989 and 1995-1999 prostate cancer mortality declined by 17.6% and 7.9% in the 2 age groups respectively. Among men aged 50-74 years SHAs with low, middle and high levels of screening had respective increases in prostate cancer incidence of 5.4%, 53.6% and 70.5% between 1985-1989 and 1990-1994. Corresponding decreases in mortality between 1985-1989 and 1995-1999 were 28.9%, 18.0% and 13.5%. Mortality declines were greatest in SHAs with low screening levels (p = 0.032). Before 1990 prostate cancer mortality was similar in the 3 screening groups (p = 0.72). Regions with the smallest increases in incidence had the largest declines in mortality.

Elevated PSA should be confirmed before biopsy

Clinical Question:
How often does an elevated PSA level return to normal?

Bottom Line:
Isolated elevations of serum prostate-specific antigen (PSA) frequently return to normal. Clinicians and their patients with an elevated PSA have 3 choices: (1) immediate referral for biopsy; (2) immediate repeat of the PSA test; or (3) wait 4 to 6 weeks and repeat the test. The repeat testing interval of 4 to 6 weeks is based on studies reporting the time needed for an elevated PSA to return to normal after biopsy or surgery for noncancerous conditions. Studies of prostate cancer progression conclude that a delay of several months from diagnosis to surgery does not affect outcomes. Thus, choice #3 is likely the best one for most patients before proceeding with further testing or referral. (LOE = 2b)

Reference:
Eastham JA, Riedel E, Scardino PT, et al. Variation of serum prostate-specific antigen levels. An evaluation of year-to-year fluctuations. JAMA 2003: 289:2695-700.

Study Design:
Cohort (prospective)

Synopsis:
Serum prostate-specific antigen (PSA) testing is frequently used in early detection programs for prostate cancer. While PSA testing has resulted in an increase in prostate cancer detection, its routine use has been questioned because of a lack of specificity. The authors determined whether year-to-year fluctuations in PSA levels are due to natural variation and render a single PSA test result unreliable. They did a retrospective analysis of an unscreened population of 972 men (median age, 62 years) participating in the Polyp Prevention Trial (1991-1998). Five consecutive blood samples were obtained during a 4-year period and were assessed for total and free PSA levels. Abnormal PSA test result based on a PSA level higher than 4 ng/mL; a PSA level higher than 2.5 ng/mL; a PSA level above the age-specific cutoff; a PSA level in the range of 4 to 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; or a PSA velocity higher than 0.75 ng/mL per year. Prostate biopsy would have been recommended in 207 participants (21%) with a PSA level higher than 4 ng/mL; in 358 (37%) with a level higher than 2.5 ng/mL; in 172 (18%) with a level above the age-specific cutoff; in 190 (20%) with a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; and in 145 (15%) with a velocity higher than 0.75 ng/mL per year. Among men with an abnormal PSA finding, a high proportion had a normal PSA finding at 1 or more subsequent visits during 4-year follow-up: 68 (44%) of 154 participants with a PSA level higher than 4 ng/mL; 116 (40%) of 291 had a level higher than 2.5 ng/mL; 64 (55%) of 117 had an elevated level above the age-specific cutoff; and 76 (53%) of 143 had a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL.

Repair undescended testis before age 13

Clinical Question:
What’s the best time to correct undescended testis?

Bottom Line:
The risk of testicular cancer doubles if you wait until after the patient is 12 years of age to surgically correct undescended testis.

Reference:
Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007;356:1835-1841.

Study Design:
Cohort (prospective)

Synopsis:
Undescended testis, which is a risk factor for testicular cancer, is usually treated surgically, but whether the age at treatment has any effect on the risk is unclear. Investigators studied the relation between the age at treatment for undescended testis and the risk of testicular cancer. They identified men who underwent orchiopexy for undescended testis in Sweden between 1964 and 1999. Cohort subjects were identified in the Swedish Hospital Discharge Register and followed for the occurrence of testicular cancer through the Swedish Cancer Registry. Vital statistics and data on migration status were taken from the Register of Population and Population Changes for the years 1965 through 2000. We estimated the relative risk of testicular cancer using Poisson regression of standardized incidence ratios, comparing the risk in the cohort with that in the general population. They also analyzed the data by means of Cox regression, using internal comparison groups. The cohort consisted of 16,983 men who were surgically treated for undescended testis and followed for a total of 209,984 person-years. We identified 56 cases of testicular cancer during follow-up. The relative risk of testicular cancer among those who underwent orchiopexy before reaching 13 years of age was 2.23 (95% confidence interval [CI], 1.58 to 3.06), as compared with the Swedish general population; for those treated at 13 years of age or older, the relative risk was 5.40 (95% CI, 3.20 to 8.53). The effect of age at orchiopexy on the risk of testicular cancer was similar in comparisons within the cohort.

Tadalafil (Cialis) effective for benign prostatic hypertrophy (BPH)

Clinical Question:
Is tadalafil safe and effective in the treatment of benign prostatic hypertrophy?

Bottom Line:
Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction. It is uncertain, however, how clinically relevant a 3-point change from baseline is on a symptom scale from 4 to 34.

Reference:
McVary KT, Roehrborn CG, Kaminetsky JC, et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urology 2007;177:1401-1407.

Study Design:
Randomized controlled trial (single-blinded)

Synopsis:
The authors assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were “erection increased,” dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment.

Alfuzosin (10 mg) does not affect blood pressure in young healthy men

Clinical Question:
Does Alfuzosin 10mg safe in a normotensive BPH, distal ureteral stones and prostatitis patients?

Bottom Line:
Study shows that alfuzosin 10mg is well tolerated by young healthy subjects and may therefore be safely administered to young normotensive patients affected by distal ureteral stones and prostatitis.

Reference:
Alfuzosin (10 mg) does not affect blood pressure in young healthy men. Mondaini N, Giubilei G, Ungar A, Gontero P, Cai T, Gavazzi A, Bartoletti R, Geppetti P, Carini M. Eur Urol. 2006 Dec;50(6):1292-6; discussion 1297-8

Study Design:
Randomized Controlled Trial (Double Blind)

Synopsis:
Alfuzosin 10mg is a uroselective alpha(1)-adrenoceptor antagonist used to treat lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Recent studies have suggested the potential efficacy of alfuzosin in the treatment of distal ureteral stones and prostatitis syndrome, two conditions frequently encountered in young patients. The authors evaluated the effect of 10mg alfuzosin on blood pressure (BP) and heart rate (HR) in young healthy volunteers. They did a randomized, double-blind, placebo-controlled, crossover study, the effect of alfuzosin 10mg on BP and HR was evaluated in 14 male volunteers (mean age: 28 yr; range: 24-30). BP<135/85>10%) was recorded during each treatment.

Holmium Laser Enucleation versus Transurethral Resection in the treatment of BPH

Clinical Question:
Is holmium laser enucleation of the prostate (HoLEP) effective compare to transurethral resection of the prostate (TURP) for treatment of men with bladder outflow obstruction (BOO) secondary to benign prostatic hyperplasia?

Bottom Line:
HoLEP has less perioperative morbidity and produces superior urodynamic outcomes than TURP, when treating prostates >40 g. At 24 months of follow-up, HoLEP is equivalent to TURP.

Reference:
A randomised trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years.Wilson LC, Gilling PJ, Williams A, Kennett KM, Frampton CM, Westenberg AM, Fraundorfer MR. Eur Urol. 2006 Sep;50(3):569-73. Epub 2006 May 2

Study Design:
Randomized Controlled Trial

Synopsis:
The authors compared holmium laser enucleation of the prostate (HoLEP) with transurethral resection of the prostate (TURP) for treatment of men with bladder outflow obstruction (BOO) secondary to benign prostatic hyperplasia with a minimum of 24-month follow-up. Sixty-one patients were randomised to either HoLEP or TURP. All patients had BOO proven on urodynamic studies pre-operatively (prostate size 40-200 g). One patient died before treatment, which left 30 patients in each group. Perioperative data, as well as symptom scores, Quality of Life (QoL) scores, and maximum urinary flow rates (Qmax) were obtained at one, three, six,12, and 24 months. Post-void residual volumes, transrectal ultrasound (TRUS) volumes, and pressure flow studies were obtained six months post-operatively. Continence and potency data were also recorded. There were no significant differences between the two surgical groups pre-operatively. Mean pre-operative TRUS volume was 77.8+/-5.6 g (42-152) in the HoLEP group and 70.0+/-5.0 g (46-156) in the TURP group. Patients in the HoLEP group had shorter catheter times and hospital stays. More prostate tissue was retrieved in the HoLEP group. At six months, HoLEP was urodynamically superior to TURP in relieving BOO. At 24 months, there was no significant difference between the two surgical groups with respect to American Urology Association scores, QoL scores, or Qmax values; however, two patients in the TURP group required re-operation.

Sildenafil (Viagra) Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction

Clinical Question:
Does sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment?

Bottom Line:
Sildenafil (viagra) nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Reference:
Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial. Sommer F, Klotz T, Engelmann U. Asian J Androl. 2007 Jan;9(1):134-141

Study Design:
Randomized Controlled Trial (prospective open-label trial)

Synopsis:
The authors test the hypothesis that sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment. They did a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of penile cavernous arteries were used to measure the efficacy. After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by 11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (-5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%, 95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most (28/29, 97%) nightly group men who had initially normalized.

Use of cyclooxygenase-2 inhibitor (Celecoxib, Rofecoxib) for prevention of urethral strictures

Clinical Question:
Does cyclooxygenase-2 inhibitor (Celecoxib, Rofecoxib) prevent urethral strictures in post-TURP patients?

Bottom Line:
Postoperative treatment with a COX-2 inhibitor can effectively prevent post-TURP urethral stricture development by specifically interfering with the inflammatory processes that can precede scar formation.

Reference:
Use of cyclooxygenase-2 inhibitor for prevention of urethral strictures secondary to transurethral resection of the prostate.Sciarra A, Salciccia S, Albanesi L, Cardi A, D’Eramo G, Di Silverio F. Urology. 2005 Dec;66(6):1218-22.

Study Design:
Prospective, unblinded, randomized, single-center study

Synopsis:
To analyze whether the addition of a cyclooxygenase (COX)-2 inhibitor after transurethral resection of the prostate (TURP) offers an advantage compared with TURP alone in reducing postoperative urethral strictures. At urethroscopy, stenosis of the urethra with a circumference of less than 19 mm was defined as stricture. This was a prospective, unblinded, randomized, single-center study. Between December 2001 and December 2003, 96 consecutive men with benign prostatic hyperplasia underwent TURP. After TURP, patients were randomly assigned to receive or not receive a COX-2 inhibitor (rofecoxib 25 mg/day). In the group given the COX-2 inhibitor, the therapy was started at catheter removal and continued for 20 days. Follow-up was performed on an outpatient basis after 1 month. A diagnosis of postoperative urethral stricture was assessed during a follow-up of 12 months. At the 1-month visit, the mean and median improvement in the peak urinary flow rate from preoperative values was +6.25 +/- 3.76 mL/s (median 7.30) in the no COX-2 inhibitor group and +9.42 +/- 3.06 mL/s (median 8.75) in the COX-2 inhibitor group. The improvement was significantly (P < 0.0001) greater for the group treated with the COX-2 inhibitor. At 1 year of follow-up, a urethral stricture had been diagnosed in 8.3% of all cases; in particular, in 17% and 0% of cases in the no COX inhibitor group and COX-2 inhibitor group, respectively. Post-TURP COX-2 inhibitor therapy was significantly (P = 0.0039) and inversely (r = -0.2876) associated with urethral stricture development.