Direct MRI-guided In-Bore Targeted Biopsy of the Prostate: A Step-by-Step How To and Lessons Learned.

Multiparametric MRI-the most accurate imaging technique for detection of prostate cancer-has transformed the landscape of prostate cancer diagnosis by enabling targeted biopsies. In a targeted biopsy, tissue samples are obtained from suspicious regions identified at prebiopsy diagnostic MRI. The authors briefly compare the different strategies available for targeting an MRI-visible suspicious lesion, followed by a step-by-step description of the direct MRI-guided in-bore approach and an illustrated review of its application in challenging clinical scenarios. In this technique, direct visualization of the needle, needle guide, and needle trajectory during the procedure provides a precise and versatile strategy to accurately sample suspicious lesions, improving detection of clinically significant cancers. Published under a CC BY 4.0 license Test Your Knowledge questions for this article are available in the supplemental material.

Sensitivity of multiparametric MRI and targeted biopsy for detection of adverse pathologies (Cribriform gleason pattern 4 and intraductal carcinoma): Correlation of detected and missed prostate cancer foci with whole mount histopathology.

PURPOSE: Accurate preoperative detection of prostate cancer (PCa) exhibiting "cribriform" morphology (intraductal carcinoma [IDC-P] or cribriform Gleason pattern 4 [CrP4]) is important as it is independently associated with a variety of adverse clinical outcomes. The sensitivity of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa exhibiting "cribriform" morphology remains controversial. MATERIALS AND METHODS: A total of 117 eligible men with prospectively reported mpMRI who underwent in-bore MRI targeted biopsy followed by whole-mount radical prostatectomy (RP) were analyzed for lesion-level imaging-pathology correlation. RESULTS: Of the 206 PCa foci at RP (117 index and 89 non-index), 74% (152/206) were detected by mpMRI. Of the 54 tumors missed by mpMRI, most were non-index (98%, 53/54), grade group (GG) 1 (68%, 37/54) or GG 2 (26%, 14/54), with a median size of 1.0 cm (range, 0.7-1.5 cm), and non-cribriform morphology (96%, 52/54). Cribriform morphology was detected in 26% (53/206) of all tumors, and although targeted biopsies identified 96% (51/53) of these cancers, the cribriform component was depicted in only 45% (24/53). Of these, mpMRI detected all (100%, 44/44) index and 78% (7/9) of the non-index tumors. At univariable analysis, tumor size greater than 5 mm, % pattern 4 > 5%, cribriform morphology, zone (transition versus peripheral zone), and region (apex versus mid/base) were significantly associated with tumor visibility at mpMRI. At multivariable analysis, only tumor size, presence of any pattern 4, and peripheral zone remained significant predictors for visibility by mpMRI. CONCLUSION: At a lesion level, mpMRI offers high sensitivity for the detection of cribriform morphologies, however, the cribriform component is frequently missed by targeted biopsies. The MRI visibility is significantly associated with larger tumor size, presence of Gleason pattern 4, and peripheral zone location.

Gleason Grade Group Concordance between Preoperative Targeted Biopsy and Radical Prostatectomy Histopathologic Analysis: A Comparison Between In-Bore MRI-guided and MRI-Transrectal US Fusion Prostate Biopsies.

Purpose: To determine and compare rates of grade group (GG) discrepancies between different targeted biopsy techniques (in-bore vs fusion) after propensity score weighting using whole-mount radical prostatectomy (RP) histopathologic analysis as the reference standard. Materials and Methods: This retrospective study evaluated men who underwent targeted (fusion or in-bore) biopsy between April 2017 and January 2019 followed by prostatectomy. The primary endpoint of the study was a change in GG from biopsy to RP at a patient level. For downgrade and upgrade analysis, men with biopsy GG1 (downgrade not possible) and GG5 (upgrade not possible) were excluded, respectively. GG upgrade, downgrade, and concordance rates of each targeting approach were compared using propensity score weighting and logistic regression with inverse probability of treatment weighting. Significance level was set at .05. Index lesion GG on RP specimen served as the reference standard. Results: A total of 191 men (90 in the in-bore [mean age, 63 years ± 7 (standard deviation)] and 101 in the fusion biopsy group [mean age, 65 years ± 7]) were eligible and included. Fewer GG upgrades were noted in the in-bore biopsy group (14%; 12 of 85) compared with the fusion plus systematic biopsy group (30%; 28 of 93) (P = .012). The incidence of GG downgrade in the in-bore group (25%; 21 of 84) was higher than in the fusion group (17%; 16 of 93); however, the difference was not statistically significant (P = .2). Of the 77 men misclassified by both biopsy techniques, the majority (56%, n = 43) had a change in GG of 2 to 3 or 3 to 2. Conclusion: Superior sampling accuracy with MRI-guided in-bore biopsies offers a lower incidence of GG upgrades compared with MRI-transrectal US fusion biopsies upon RP.Keywords: Biopsy/Needle Aspiration, MR-Imaging, Oncology, Pathology, Prostate Supplemental material is available for this article.© RSNA, 2021.

Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.

Impact of the Number of Cores on the Prostate Cancer Detection Rate in Men Undergoing in-Bore Magnetic Resonance Imaging-Guided Targeted Biopsies.

OBJECTIVE: To determine the incremental detection rate of clinically significant prostate cancer (csPCa) provided by sequential cores during in-bore magnetic resonance imaging (MRI)-guided prostate biopsies. METHODS: Single-center, retrospective interpretation of prospectively acquired data in men without previous diagnosis of csPCa who underwent in-bore MRI-guided prostate biopsy between May 2017 and December 2019. Endpoints included detection of csPCa (grade group [GG] ≥ 2) and rate of GG upgrade provided by additional cores. Descriptive statistics presented as mean and standard deviation for the continuous variables, and frequency and percentage for the categorical variables. RESULTS: Four hundred and forty-three men with 747 lesions met eligibility criteria. Clinically significant prostate cancer was detected in 43.1% (322/747) of the biopsied lesions and GG 2 PCa or greater was identified by the first core in 78.3% (252/322) of them. On a per-core basis, cores 2, 3, 4, and 5 found new csPCa in 6% (42/744), 4% (26/719), 1% (2/137), and 0% (0/11) of the cases. Core biopsy 2, 3, 4, and 5 resulted in GG upgrade in 12% (91/744), 7% (49/719), 7% (9/137), and 0% (0/11) of the lesions, respectively. Each additional core was associated with a mean increase of 5 minutes in the duration of the biopsy. CONCLUSIONS: In men undergoing in-bore MRI-guided prostate biopsies, 3 targeted cores per lesion provide an optimal trade-off between detection of clinically significant tumors and biopsy duration.

Prospective evaluation of fexapotide triflutate injection treatment of Grade Group 1 prostate cancer: 4-year results.

PURPOSE: This study was undertaken to determine the safety and efficacy of fexapotide triflutate (FT) 2.5 mg and 15 mg for the treatment of Grade Group 1 prostate cancer. METHODS: Prospective randomized transrectal intraprostatic single injection FT 2.5 mg (n = 49), FT 15 mg (n = 48) and control active surveillance (AS) (n = 49) groups were compared in 146 patients at 28 U.S. sites, with elective AS crossover (n = 18) to FT after first follow-up biopsy at 45 days. Patients were followed for 5 years including biopsies (baseline, 45 days, and 18, 36, and 54 months thereafter), and urological evaluations with PSA every 6 months. Patients with Gleason grade increase or who elected surgical or radiotherapeutic intervention exited the study and were cumulatively included in the data analysis. Percentage of normal biopsies in baseline focus quadrant, tumor grades, and volumes; and outcomes including Gleason grade in entire prostate as well as treated prostate lobe, interventions associated with Gleason grade increase and total incidence of interventions were assessed. RESULTS: Significantly improved long-term clinical outcomes were found after 4-year follow-up, with percentages of patients progressing to interventions with and without Gleason grade increase significantly reduced by FT single treatment. Results in the FT 15-mg group were superior to the FT 2.5-mg dose group. There were no drug-related serious adverse events (SAEs). CONCLUSIONS: FT showed statistically significant long-term efficacy in the treatment of Grade Group 1 patients regarding clinical and pathological progression. FT 15 mg showed superior results to FT 2.5 mg. There were no drug-related SAEs; FT injection was well tolerated.

Convective Radio Frequency Thermal Therapy for Treatment of Benign Prostatic Hyperplasia: Single Office Experience with 255 Patients over 4 Years.

INTRODUCTION: Convective radio frequency thermal therapy with the Rezum® system is a relatively new treatment for benign prostatic hyperplasia with proven short-term durability. We report an update of previously published data from a single center showing durability through 4 years. METHODS: A retrospective review of 255 patients who underwent the Rezum procedure from a single surgeon was performed, including 25 patients from the Rezum II study, from March 2014 to April 2018. Maximum urinary flow rate, I-PSS (International Prostate Symptom Score), I-PSS-QOL (quality of life), post-void residual, medication use and adverse events were monitored. Data were analyzed at baseline, and 3, 6, 12, 24, 36 and 48 months after treatment. RESULTS: Statistically significant improvement in maximum urinary flow rate (57.2%), I-PSS (54.7%) and I-PSS-QOL (59.2%) appear to be durable through 48 months, with improvement greater than 50% at most recent followup. We report a similarly low reoperation rate compared to the most recent data from the Rezum II study (3.1% vs 4.4%), but with higher rates of urinary tract infection (18.8% vs 3.7%) and urinary retention (15.7% vs 3.7%). Overall satisfaction with the procedure experience (93.9%) and the outcome (90.9%) was high, with 97% of men interviewed recommending the procedure to a friend. In addition, 80% of men were able to stop all medication. CONCLUSIONS: Our experience provides the largest published cohort of patients undergoing this procedure and shows durable improvements in maximum urinary flow rate, I-PSS and I-PSS-QOL through 4 years. Patients outside of the inclusion criteria of Rezum II appear to benefit from the procedure.

Magnetic Resonance Imaging-guided In-bore and Magnetic Resonance Imaging-transrectal Ultrasound Fusion Targeted Prostate Biopsies: An Adjusted Comparison of Clinically Significant Prostate Cancer Detection Rate.

BACKGROUND: With the increasing adoption of targeted prostate biopsies, it becomes important to understand the strengths and shortcomings of the techniques available for targeting suspicious lesions. OBJECTIVE: To compare clinically significant prostate cancer (csPCa) detection rate with magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion versus in-bore biopsy in men with abnormal multiparametric MRI (mpMRI). DESIGN, SETTING, AND PARTICIPANTS: This single-center, retrospective analysis of prospectively generated data included all men with abnormal mpMRI and fusion or in-bore biopsy between May 2017 and April 2018. Grade group (GG) 2-5 cancers were considered csPCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Detection of csPCa was adjusted according to patient- and lesion-related characteristics using propensity score weighting. Secondary endpoints included the detection of clinically insignificant tumors and the rate of GG upgrade from biopsy to prostatectomy specimen. Analyses were performed at patient and lesion levels. RESULTS AND LIMITATIONS: A total of 103 and 300 men were included in the in-bore and fusion cohorts, respectively. On a per-patient basis, in-bore biopsies detected a higher proportion of csPCa (61%, 63/103) than fusion plus systematic biopsies (47%, 141/300; adjusted odds ratio [OR]: 2.1, 95% confidence interval [CI]: 1.6-2.8, p<0.0001). In-bore biopsies also detected fewer (11%, 11/103) clinically insignificant cancers than fusion biopsies (18%, 53/300; OR: 0.5, 95% CI: 0.3-0.8, p=0.001). Of those who had radical prostatectomy, GG upgrade after surgery was seen in 17% (4/24) of the men in the in-bore cohort and in 27% (22/82) of the men in the fusion cohort (p=0.55). CONCLUSIONS: MRI-guided in-bore biopsies detected more clinically significant and fewer insignificant prostate cancers than MRI-TRUS fusion targeted biopsies. Further cost-utility and patient outcome analyses are needed. PATIENT SUMMARY: In-bore biopsies (where the patient is on the magnetic resonance imaging [MRI] scanner itself) detected more aggressive cancers and fewer indolent cancers than fusion (where software blends MRI and ultrasound images) biopsies. These findings may help patients and physicians choose the best biopsy approach.

Optimal sampling scheme in men with abnormal multiparametric MRI undergoing MRI-TRUS fusion prostate biopsy.

OBJECTIVES: To determine the implications of different prostate sampling schemes on the diagnosis of clinically significant prostate cancer (csPCA, ISUP group 2-5) and clinically insignificant prostate cancer (ciPCA, ISUP group 1) in men with abnormal multiparametric magnetic resonance imaging (mpMRI) undergoing MRI-transrectal ulrasound fusion targeted biopsies. MATERIALS AND METHODS: This is a retrospective analysis of a cohort including all men who had a single lesion on mpMRI of the prostate performed between January 2016 and June 2017. All men underwent an MRI-transrectal ulrasound fusion biopsy and systematic (SBx) sampling of the prostate, which combined and were considered the standard of reference. The hypothetical 3 biopsy sampling schemes were defined as follows: Targeted biopsy only (TBx), TBx + ipsilateral SBx (ipsi-SBx) and TBx + contralateral SBx (contra-SBx) and were evaluated for the detection of csPCA and ciPCA. Sensitivity and 95% intervals were calculated, McNemar test was used to compare sensitivities between the various sampling schemes. RESULTS: TBx + SBx detected csPCa in 47% (55 of 116) of the 116 men who met eligibility criteria. Sensitivity and 95% confidence intervals for csPCa detection was 85.5% (73.3%-93.5%), 96.4% (87.5%-99.6%), and 92.7 (82.4%-98%) for TBx alone, TBx + ipsi-SBx and TBx + contra-SBx, respectively. csPCa detection rates were higher for both TBx + ipsi-SBx and TBx + contra-SBx compared to TBx alone. Clinically insignificant cancers alone were detected in 7.7% (9 of 116), 10.3% (12 of 116), and 14.6% (17 of 116) of the cohort by TBx only and TBx + ipsi-SBx, and TBx + contra-SBx, respectively. CONCLUSIONS: TBx + ipsi-SBx may increase the detection of csPCa while limiting overdiagnosis of indolent cancers.

Prospective Inclusion of Apparent Diffusion Coefficients in Multiparametric Prostate MRI Structured Reports: Discrimination of Clinically Insignificant and Significant Cancers.

OBJECTIVE: The purpose of this study was to assess the diagnostic performance of prospectively assigned mean apparent diffusion coefficient (ADC) values in multiparametric MRI (mpMRI) structured reports for discriminating clinically insignificant (International Society of Urological Pathology [ISUP] group 1) from clinically significant (ISUP groups 2-5) prostate cancer. MATERIALS AND METHODS: This single-center study included men with abnormal 3-T mpMRI findings (Prostate Imaging Reporting and Data System version 2 score, ≥ 3) who subsequently underwent radical prostatectomy or targeted biopsy with positive results. One of nine radiologists prospectively reported the mean ADC for each lesion during clinical interpretation. Lesions with ADC ≤ 0.700 mm2/s × 10-3 were flagged as concerning for clinically significant prostate cancer. The index lesion at MRI correlated with the site-concordant lesion at targeted biopsy or whole-mount histopathologic analysis. Logistic regression was used to evaluate the utility of mean ADC values for discriminating ISUP grade group 1 from groups 2-5. Diagnostic performance was assessed by ROC AUC. RESULTS: Among the 218 eligible men, those with ISUP group 2-5 lesions had lower mean ADC values than those with ISUP 1 lesions; overall, 0.598 vs 0.803 mm/s2 × 10-3 (p < 0.0001); peripheral zone (PZ), 0.597 vs 0.855 mm/s2 × 10-3 (p < 0.0001); transition zone (TZ), 0.600 vs 0.660 mm/s2 × 10-3 (p = 0.035). The AUC for the PZ was 0.91 and for the TZ was 0.70. The optimal ADC cutoff values were 0.682 mm/s2 × 10-3 for PZ lesions and 0.638 mm2/s × 10-3 for TZ lesions, resulting in sensitivity and specificity of 78% and 94% for the PZ and 72% and 67% for the TZ. CONCLUSION: ADC values estimated prospectively in a clinical setting can help differentiate clinically insignificant from clinically significant prostate cancer, facilitating prebiopsy and pretreatment risk stratification.

Fexapotide triflutate: results of long-term safety and efficacy trials of a novel injectable therapy for symptomatic prostate enlargement.

PURPOSE: These studies were undertaken to determine if fexapotide triflutate 2.5 mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy for the treatment of benign prostatic hyperplasia (BPH). METHODS: Two placebo controlled double-blind randomized parallel group trials with 995 BPH patients at 72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years, median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were evaluated. 12 months post-treatment patients elected no further treatment, approved oral medications, FT, or interventional treatment. Primary endpoint variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co-endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients versus patients crossed over to oral BPH medications and (2) surgery or acute urinary retention in FT-treated CO placebo patients versus placebo patients crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical and symptomatic outcomes in FT reinjected patients versus conventional BPH medication CO and control subgroups at 2 and 3 years. RESULTS: FT injection had no significant safety differences from placebo. LF IPSS change from baseline was higher in FT treated patients compared to placebo (median FT group improvement - 5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients. LF incidence of intervention for BPH was reduced in the FT group versus oral BPH medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of intervention or AUR in placebo CO group with FT versus placebo CO group with oral medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28 secondary efficacy endpoints were reached in LF CO re-injection studies. CONCLUSIONS: FT 2.5 mg is a safe and effective transrectal injectable for LT treatment of BPH. FT treated patients also had reduced need for BPH intervention, and reduced incidence of PCa and AUR.

Convective radiofrequency water vapor thermal therapy for benign prostatic hyperplasia: a single office experience.

BACKGROUND: Convective radiofrequency water vapor thermal therapy with the Rezum system is a relatively new treatment for benign prostatic hyperplasia (BPH). We present results from a single surgeon in an office setting. METHODS: A retrospective review of 129 patients from a single surgeon who underwent the Rezum procedure was performed. All patients were at least 4 months out from treatment. International prostate symptom scores (IPSS), maximum flow rates (Qmax), residual urine volumes, medication usage, and adverse events were monitored. Data were analyzed at baseline, 15-45 days, 46-90 days, and 91-180 days after treatment. A scripted patient questionnaire was attempted over the phone to all patients. It was administered by a resident and medical student who do not work in the provider's office. RESULTS: Maximal effects were noted at the 91-180 day interval. IPSS improved from a baseline of 18.3 to 6.9 and Qmax from 10.5 to 16.8 mL/s. Improvements were independent of starting symptom score, median lobe treatment, and prostate size. There was a 17% prostate volume reduction based on TRUS and 14% based on PSA. The most common adverse events were urinary tract infections (17%) and transient urinary retention (14%). In total 90% of patients were able to come off their BPH medications and 86% of patients would recommend the procedure to a friend. CONCLUSIONS: Rezum radiofrequency water vapor thermal therapy offers a minimally invasive option for BPH management with moderate improvement in symptoms and flow rate. The results appear to be independent of prostate size or presence of a median lobe, and have now been replicated in a single office setting.

Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.

PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezum® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

Erectile and Ejaculatory Function Preserved With Convective Water Vapor Energy Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Randomized Controlled Study.

INTRODUCTION: Most surgical treatments for male lower urinary tract symptoms and benign prostatic hyperplasia affect erectile and ejaculatory functions negatively, leading to patient dissatisfaction. AIM: To determine whether water vapor thermal therapy, when conducted in a randomized controlled trial, would significantly improve lower urinary tract symptoms secondary to benign prostatic hyperplasia and urinary flow rate while preserving erectile and ejaculatory functions. METHODS: Men at least 50 years old with International Prostate Symptom Scores of at least 13, a peak flow rate of at least 5 to no higher than 15 mL/s, and prostate volume of 30 to 80 cm(3) were randomized 2:1 between Rezum System thermal therapy and control. Thermal water vapor (103°C) was injected into lateral and median lobes as required for treatment of benign prostatic hyperplasia. The control procedure entailed rigid cystoscopy with simulated active treatment sounds. MAIN OUTCOME MEASURES: Blinded group (active = 136, control = 61) comparison occurred at 3 months and the active arm was followed to 12 months for International Prostate Symptom Score, peak flow rate, and sexual function using the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. The minimal clinically important difference in erectile function perceived by subjects as beneficial was determined for each erectile function severity category. Subjects not sexually active were censored from sexual function analysis. RESULTS: No treatment- or device-related de novo erectile dysfunction occurred after thermal therapy. International Index of Erectile Function and Male Sexual Health Questionnaire for Ejaculatory Function scores were not different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved 31% over baseline (P = .0011). Also, 32% of subjects achieved minimal clinically important differences in erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile dysfunction. International Prostate Symptom Score and peak flow rate were significantly superior to controls at 3 months and throughout 1 year (P < .0001). CONCLUSION: Convective water vapor thermal therapy provides sustainable improvements for 12 months to lower urinary tract symptoms and urinary flow while preserving erectile and ejaculatory functions.

Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezum® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. RESULTS: There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. CONCLUSIONS: Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe.

Is PSA related to serum cholesterol and does the relationship differ between black and white men?

BACKGROUND: Previously, in prostate cancer-free men, we found that statin initiation resulted in a 4.1% decline in PSA. This decline in PSA was proportional to the decline in cholesterol, suggesting a link between cholesterol and PSA levels. Whether these associations vary by race has not been explored and therefore we examined the association between pre-statin serum cholesterol and PSA in black and white prostate cancer-free men. METHODS: We conducted a retrospective, cross-sectional analysis of 1,163 men (709 white and 454 black) without prostate cancer who initiated a statin between 1994 and 2006. Linear regression was used to test the association between pre-statin serum cholesterol and PSA levels, adjusting for potential confounders and stratifying by race. RESULTS: Black men were younger, had higher low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels (both P < 0.05) and a trend toward higher total cholesterol (P = 0.063). There was no difference in PSA or year of statin prescription by race (P = 0.900 and P = 0.217, respectively). On multivariable analysis, we found a positive correlation between serum PSA and total cholesterol (P = 0.005) and LDL (P = 0.003) in white men, but no association among black men. HDL was not significantly related to PSA levels in black or white men (both P > 0.5). CONCLUSIONS: Among prostate cancer-free men about to begin a statin, pre-statin total cholesterol and LDL were correlated with PSA levels in white, but not black men. If confirmed in future studies, these findings suggest that serum cholesterol may be related to prostate biology, and that this effect may vary by race.

A novel approach to evaluate the pharmacokinetic biocomparability of a monoclonal antibody derived from two different cell lines using simultaneous crossover design.

A parallel study design with a large number of subjects has been a typical path for pharmacokinetic (PK) biocomparability assessment of biotherapeutics with long half-lives and immunogenic propensity, for example, monoclonal antibodies (mAb). A recently published innovative bioanalytical method that can quantify mAb produced from two different cell lines in the same sample opened an avenue to exploring a simultaneous crossover study design for PK biocomparability assessment of biotherapeutics. Siltuximab, a chimeric IgG1 mAb-targeting interleukin-6, was studied as an example. The pharmacokinetic biocomparability of siltuximab derived from mouse myeloma (Sp2/0) cells and Chinese hamster ovary cells was previously assessed and demonstrated in a clinical PK biocomparability study that enrolled more than 140 healthy subjects using a parallel trial design. The biocomparability was successfully shown in six cynomolgus monkeys in a preclinical proof-of-concept study using the new crossover study design supported by the analytical method. The impact of antidrug antibodies on the assessment of biocomparability was minimal. This novel approach opened up a new arena for the evaluation of PK biocomparability of biotherapeutics with unique molecular signatures such as a mAb derived from different cell lines.

Correlations between pharmacokinetics of IgG antibodies in primates vs. FcRn-transgenic mice reveal a rodent model with predictive capabilities.

Transgenic mice expressing human neonatal Fc receptor (FcRn) instead of mouse FcRn are available for IgG antibody pharmacokinetic (PK) studies. Given the interest in a rodent model that offers reliable predictions of antibody PK in monkeys and humans, we set out to test whether the PK of IgG antibodies in such mice correlated with the PK of the same antibodies in primates. We began by using a single research antibody to study the influence of: (1) different transgenic mouse lines that differ in FcRn transgene expression; (2) homozygous vs. hemizygous FcRn transgenic mice; (3) the presence vs. absence of coinjected high-dose human intravenous immunoglobulin (IVIG), and (4) the presence vs. absence of coinjected high-dose human serum albumin (HSA). Results of those studies suggested that use of hemizygous Tg32 mice (Tg32 hemi) not treated with IVIG or HSA offered potential as a predictive model for PK in humans. Mouse PK studies were then done under those conditions with a panel of test antibodies whose PK in mice and primates is not significantly affected by target binding, and for which monkey or human PK data were readily available. Results from the studies revealed significant correlations between terminal half-life or clearance values observed in the mice and the corresponding values reported in humans. A significant relationship in clearance values between mice and monkeys was also observed. These correlations suggest that the Tg32 hemi mouse model, which is both convenient and cost-effective, can offer value in predicting antibody half-life and clearance in primates.