Lars M. Eri

A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy.

BACKGROUND Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). OBJECTIVE To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. DESIGN, SETTING, AND PARTICIPANTS This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. INTERVENTION In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB. RESULTS AND LIMITATIONS Detection rates for any cancer (MRI group 51/86, 59%; control group 48/89, 54%; p=0.4) and csPCa (38/86, 44% vs 44/89, 49%; p=0.5) did not significantly differ between the groups. Detection of csPCa was comparable between two-core MRI/TRUS-TB (33/86, 38%) and 12-core RB in the control group (44/89, 49%; p=0.2). In a subset analysis of patients with normal DRE, csPCa detection was similar between two-core MRI/TRUS-TB (14/66, 21%) and 12-core RB in the control group (15/60, 25%; p=0.7). Among biopsy-proven csPCas in MRI group, 87% (33/38) were detected by MRI/TRUS-TB. The definition of csPCa was only based on biopsy outcomes. CONCLUSION Overall csPCa detection was similar between the MRI and control groups. Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection. PATIENT SUMMARY Our randomized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) and 12-core random biopsy. The traditional 12-core random biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinically significant prostate cancer.

EFFECTS OF THE LUTEINIZING HORMONE-RELEASING HORMONE AGONIST LEUPROLIDE ON LIPOPROTEINS, FIBRINOGEN AND PLASMINOGEN ACTIVATOR INHIBITOR IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

The impact of chronic administration of the luteinizing hormone-releasing hormone agonist leuprolide depot on cardiovascular risk factors was investigated in a controlled double-blind study comprising 50 evaluable patients with benign prostatic hyperplasia. In the 26 patients receiving leuprolide the mean total cholesterol level increased by 10.6%, high density lipoprotein cholesterol by 8.2% and triglycerides by 26.9% (p = 0.003, 0.052 and 0.050, respectively). Low density lipoprotein cholesterol levels were unchanged. Apolipoprotein A1 increased by 13.2% (p = 0.001), while apolipoprotein B, fibrinogen, thrombocytes and plasminogen activator inhibitor were unchanged. Hemoglobin decreased by 1.2 gm./100 ml. without a concomitant decrease in serum erythropoietin concentration. These changes act in different directions with regard to cardiovascular risk and the overall effect is difficult to assess.

Alpha-Blockade in the Treatment of Symptomatic Benign Prostatic Hyperplasia

PURPOSE The clinical and urodynamic effects of oral alpha 1-selective adrenoceptor blockers in the treatment of symptomatic benign prostatic hyperplasia were quantified, and side effects and patient tolerance were assessed. MATERIALS AND METHODS A total of 29 original reports of placebo controlled clinical trials of alpha-blockers in which results were adequately presented was identified and reviewed, along with additional pertinent literature. We assumed that the efficacy of the different alpha-blockers was basically the same and the weighted average treatment effect was calculated in comparison with placebo. RESULTS The average improvement in maximum urine flow rate was 1.5 ml. per second but this rate would probably approach 1.8 to 1.9 ml. per second if all dosages had been titrated up to the highest level tolerated. Overall symptom score decreased by 14% and residual urine volume decreased by 29%. A slight decrease in detrusor pressure during voiding was suggested. CONCLUSIONS alpha-Blockers were beneficial in the treatment of benign prostatic hyperplasia. Tolerance to treatment appeared to develop in a large proportion of patients after 6 months of therapy. However, for patients who benefit from long-term use of alpha-blockers effective treatment might be maintained for years.

Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone

To examine the performance of T2‐weighted (T2W) and diffusion‐weighted (DW) magnetic resonance imaging (MRI) for detecting the index tumour in patients with prostate cancer and to examine the agreement between MRI and histology when assessing tumour volume (TV) and overall tumour burden.

A prospective, placebo-controlled study of the luteinizing hormone-releasing hormone agonist leuprolide as treatment for patients with benign prostatic hyperplasia

Several physicians have used luteinizing hormone-releasing hormone agonists for small, selected groups of patients with benign prostatic hyperplasia but their clinical role in this indication is still not well defined. We investigated the effect of the luteinizing hormone-releasing hormone agonist leuprolide given as an injection every 28 days for 24 weeks in a double-blind, placebo-controlled trial with 50 evaluable patients along an extensive protocol with the main emphasis on objective parameters for outcome assessment. Prostate volume decreased by 34.5% (2.6% in the placebo group). Maximum flow rate at spontaneous micturition and after instillation of saline improved by 2.0 ml. per second (32%) and 3.0 ml. per second (54%) more than with placebo. Detrusor pressure during micturition decreased by approximately 24% for patients who received leuprolide compared to placebo and was accompanied by a 25% increase in flow rate, which indicated decreased bladder outlet resistance. Improvement in urodynamic parameters generally was of statistical significance. Symptom scores improved significantly for both groups throughout the study when compared to those before treatment. At between group comparison, the improvement for irritative symptoms in favor of leuprolide reached statistical significance at week 48. With few exceptions, leuprolide patients tolerated the treatment well even if they had side effects, such as flushing and decreased sexual function.

A Prospective, Placebo-Controlled Study of the Antiandrogen Casodex as Treatment for Patients with Benign Prostatic Hyperplasia

Casodex, a new nonsteroidal antiandrogen, is presently being investigated in phase III studies as a new hormonal treatment for advanced prostatic cancer. The safety and efficacy of Casodex at a dosage of 50 mg. daily for 24 weeks in patients with benign prostatic hypertrophy were investigated in this double-blind placebo-controlled trial, initially planned for 60 patients. Inclusion was discontinued at 30 patients after report of liver toxicity when Casodex was given long-term at high doses to mice. Prostate volume was decreased by 26.4% at the end of therapy (3.7% in the placebo group). The differences between Casodex and placebo therapy for the changes in values from baseline to 24 weeks of treatment in maximum urinary flow rate at spontaneous micturition and after instillation of saline were 0.8 and 1.4 ml. per second (not statistically significant). Pressure-flow examinations and frequency-volume charts did not show any treatment effect. Casodex patients tended to obtain more improvement in symptom scores than placebo patients, reaching statistical significance for irritative symptoms at week 24. Even if all patients had side effects, mostly mild, Casodex was well tolerated and patient compliance was excellent.

Can sexual bother after radical prostatectomy be predicted preoperatively? Findings from a prospective national study of the relation between sexual function, activity and bother

Whats known on the subject? and What does the study add?

Safety, Side Effects and Patient Acceptance of the Luteinizing Hormone Releasing Hormone Agonist Leuprolide in Treatment of Benign Prostatic Hyperplasia

The luteinizing hormone releasing hormone agonist leuprolide was investigated in a double-blind, randomized, placebo-controlled study comprising 50 evaluable patients with moderate to severe symptoms resulting from benign prostatic hyperplasia. Patients received 3.75 mg. leuprolide depot or placebo as an injection every 28 days for 24 weeks. Hemoglobin level decreased by 0.8 gm/100 ml. (p = 0.0052) for patients receiving leuprolide. Mean testicular volume decreased by 28.9% (p < 0.001) compared to placebo. Of 26 patients receiving leuprolide 5 had a weight gain of more than 3 kg. Almost all patients receiving leuprolide experienced hot flushes. Breast changes, and loss of energy and vigor were not more pronounced than for patients receiving placebo. Erectile function and sexual activity were lost during treatment. Libido also decreased but was still partially retained. Despite this, patients receiving leuprolide were generally contented with their sexual life during treatment. Side effects were bothersome for some patients but were reversible. Of the patients in our study 73% expressed that they could repeat or continue treatment if that had been possible. The high cost of these drugs will limit their use for a benign condition, such as benign prostatic hyperplasia.

A prospective study of transition from laparoscopic to robot-assisted radical prostatectomy: Quality of life outcomes after 36-month follow-up

OBJECTIVE To compare quality of life (QOL) outcomes after conversion from laparoscopic radical prostatectomy (LRP) to robot-assisted radical prostatectomy (RALP) as the routine procedure for surgical treatment of localized cancer of the prostate (CaP). METHODS In November 2007, we changed the routine operative technique for localized CaP from LRP to RALP. The last 210 consecutive patients operated with LRP were compared with the first 210 consecutive patients operated with RALP. The patients were mailed University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and Short Form Health Survey (SF)-12 questionnaires at baseline and at 3, 12, and 36-month follow-up. RESULTS In the LRP group, 89.0%, 93.8%, 93.8%, and 88.1% of patients answered questionnaires at baseline and at 3, 12, and 36-month follow-up. The corresponding numbers in the RALP group were 92.4%, 94.3%, 85.7%, and 76.4%. At 36-month follow-up, 87.9% and 82.6% of LRP and RALP patients, respectively, had regained baseline urinary function score (ns). At 36-month follow-up, 57.3% and 61.3% of LRP and RALP patients, respectively, had regained baseline sexual function score (ns). Nerve-sparing surgical procedures mitigated the adverse effects on sexual function in both groups. Surgical method was not associated with urinary function and sexual function at 36 months. Better urinary function was associated with better general mental health. CONCLUSION Introduction of RALP did not result in improvement of functional outcome. There was no difference regarding urologic function/bother score or sexual function/bother score at 36-month follow-up in patients treated with LRP or RALP.

Does Preoperative Magnetic Resonance Imaging Reduce the Rate of Positive Surgical Margins at Radical Prostatectomy in a Randomised Clinical Trial

BACKGROUND Magnetic resonance imaging (MRI) has the potential to help the surgeon tailor radical prostatectomy (RP) more accurately according to the location and extent of the tumour and thereby reduce the rate of positive surgical margins (PSMs). OBJECTIVE To evaluate the benefit of performing MRI prior to RP. DESIGN, SETTING, AND PARTICIPANTS This single-institution randomised trial included 438 patients between December 2009 and June 2012 who were scheduled for robot-assisted laparoscopic prostatectomy. The study was registered (ClinicalTrials.gov identifier NCT01347320). INTERVENTION Patients were preoperatively randomly assigned to non-MRI or MRI groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was the difference in the PSM rates between the two groups. Secondary end points were the rates of PSMs in clinical subgroups. Summary statistics were extracted from descriptive analyses, chi-square, or Fisher exact test, and logistic regression was used to analyse the data according to the intention-to-treat principle. RESULTS AND LIMITATIONS A total of 216 patients were randomised to non-MRI; 222 were randomised to MRI. There were 49 cases (23%) of PSMs in the non-MRI group and 43 cases (19%) in the MRI group (p=0.4). The relative and absolute risk reduction was 15% and 4%, respectively. Patients with cT1 constituted 55% of the cohort, in which the rate of PSMs was 27% in the non-MRI group and 16% in the MRI group (p=0.035). The relative and absolute risk reduction was 41% and 11%, respectively. A limitation was suboptimal communication between the radiologist and urologist. CONCLUSIONS MRI prior to RP did not reduce the overall risk for PSMs in this patient cohort. However, at subgroup analysis we observed a possible benefit of MRI in patients with cT1. PATIENT SUMMARY This study could not demonstrate a definite benefit of performing magnetic resonance imaging before surgery for all patients. However, there was a possible improved result in patients in which physical examination could not detect the cancer.