Comparison of 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT in Patients with Localized Prostate Cancer Who Are Candidates for Radical Prostatectomy: A Prospective, Single-Arm, Single-Center, Phase II Study.

Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with 68Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and 68Ga-RM2 (68Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm3), 68Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and 68Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered 68Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of 68Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for 68Ga-RM2. Median 68Ga-RM2 SUVmax was significantly higher than median 68Ga-PSMA-617 SUVmax in the ISUP-2 subgroup (P = 0.01). Conclusion: 68Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and 68Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.

Evolution of Day-Case Holmium Laser Enucleation of the Prostate Success Rate Over Time.

Objectives: To describe the evolution of day-case success rate over the years and to identify predictive factors for prolonged hospitalization or readmissions. Methods: Retrospective review of all consecutive day-case holmium laser enucleation of the prostate (HoLEP) performed by a single surgeon between January 2013 and February 2019 using a prospective database. Day-case success was defined as discharge within less than 12 hours from admission without any readmission within 48 hours after discharge. Protocol for day-case treatment included systematic bladder catheter insertion with continuous irrigation for ∼2 hours and catheter removal on postoperative day 1. Patients were reached by phone on postoperative day 1 to ensure voiding. For the descriptive statistics, an analysis of variance was performed. Univariate and multivariate analyses were used to identify risk factors. Results: A total of 266 patients were retrieved and dispatched as follows: group 1 (n = 88) from January 2013 to July 2015, group 2 (n = 89) from August 2015 to June 2017, and group 3 (n = 89) from July 2017 to February 2019. The overall success rate was 80.5% (214/266) over the study period. It significantly improved over time from 70% in group 1 to 84% in group 2 and 87% in group 3 (p = 0.014). In the meantime, the operating time and the total energy delivered to the tissue decreased from 77 minutes in the first group to 60.4 minutes in the second group and 55.4 minutes in the third group (p < 0.001), and from 95.2 kJ in the first group to 84 kJ in the second group and 77.9 kJ in the third group (p = 0.041). On multivariate analysis, the only risk factor significantly associated with day-case failure was prostate volume greater than 90 cc (odds ratio = 2.041, p = 0.047). Conclusion: Day-case HoLEP is a reliable and safe procedure with a high success rate. The surgeon's experience seems to be crucial to improve perioperative outcomes, but prostate volume greater than 90 cc remains associated with higher failure rates.

Benign Prostatic Hyperplasia Endoscopic Surgical Procedures in Kidney Transplant Recipients: A Comparison Between Holmium Laser Enucleation of the Prostate, GreenLight Photoselective Vaporization of the Prostate, and Transurethral Resection of the Prostate.

Purpose: The main objective of this multicentric retrospective pilot study was to evaluate the 1-year follow-up safety (i.e., minor [Clavien-Dindo I-II] and major [Clavien-Dindo ≥III] complications) of holmium laser enucleation of the prostate (HoLEP), GreenLight photoselective vaporization of the prostate (GL PVP), and transurethral resection of the prostate (TURP) performed after kidney transplantation (KT). The secondary objectives were to evaluate the efficacy and to assess the impact of these procedures on graft function. Materials and Methods: We retrospectively included all KT recipients who underwent a HoLEP or GL PVP or TURP for benign prostatic hyperplasia (BPH) in three French university centers. Results: From January 2013 to April 2018, 60 BPH endoscopic surgical procedures in KT recipients were performed: 17 HoLEP (HoLEP group), 9 GL PVP (GL PVP group), and 34 TURP (TURP group). Age, body mass index, preoperative serum creatinine, preoperative International Prostatic Symptom Score, preoperative Qmax, preoperative prostate-specific antigen, medical history of acute urinary retention (AUR), urinary tract infection (UTI), and indwelling urethral catheter were similar in all study groups. Mean preoperative prostate volume was higher in HoLEP group. The rate of overall postoperative complications was statistically higher in the HoLEP group (11/17 [64.7%] vs 1/9 [11.1%] vs 12/34 [35.3%] in HoLEP group, GL PVP group, and TURP group, respectively, p = 0.02), with higher rate of long-term UTI and AUR. Qmax improved in all groups after operation. Delta postoperative month 12-preoperative serum creatinine was similar in the all groups. Conclusions: Although our study is underpowered, the rate of postoperative complications is higher with HoLEP procedure, in comparison with GL PVP, for the treatment of BPH after KT. One-year efficacy is similar in HoLEP, GL PVP, and TURP groups. Further prospective randomized controlled trials are needed to confirm our results.

Do patients have to choose between ejaculation and miction? A systematic review about ejaculation preservation technics for benign prostatic obstruction surgical treatment.

PURPOSE: Ejaculatory dysfunction is the most common side effect related to surgical treatment of benign prostatic obstruction (BPO). Nowadays, modified surgical techniques and non-ablative techniques have emerged with the aim of preserving antegrade ejaculation. Our objective was to conduce a systematic review of the literature regarding efficacy on ejaculatory preservation of modified endoscopic surgical techniques, and mini-invasive non-ablatives techniques for BPO management. METHODS: A systematic review of the literature was carried out on the PubMed database using the following MESH terms: "Prostatic Hyperplasia/surgery" and "Ejaculation", in combination with the following keywords: "ejaculation preservation", "photoselective vaporization of the prostate", "photoselective vapo-enucleation of the prostate", "holmium laser enucleation of the prostate", "thulium laser", "prostatic artery embolization", "urolift", "rezum", and "aquablation". RESULTS: The ejaculation preservation rate of modified-TURP ranged from 66 to 91%. The ejaculation preservation rate of modified-prostate photo-vaporization ranged from 87 to 96%. The only high level of evidence studies available compared prostatic urethral lift (PUL) and aquablation versus regular TURP in prospective randomized-controlled trials. The ejaculation preservation rate of either PUL or aquablation compared to regular TURP was 100 and 90 versus 34%, respectively. CONCLUSIONS: Non-ablative therapies and modified endoscopic surgical techniques seemed to be reasonable options for patients eager to preserve their ejaculatory functions.

Learning curves and perioperative outcomes after endoscopic enucleation of the prostate: a comparison between GreenLight 532-nm and holmium lasers.

PURPOSE: To compare the learning curves, perioperative and early functional outcomes after HoLEP and GreenLEP. METHODS: Data from the first 100 consecutive cases treated by GreenLEP and HoLEP by two surgeons were prospectively collected from dedicated databases and analysed retrospectively. En-bloc GreenLEP and two-lobar HoLEP enucleations were conducted using the GreenLight HPS™ 2090 laser and Lumenis™ holmium laser. Patients' characteristics, perioperative outcomes and functional outcomes after 1, 3 and 6 months were compared between groups. RESULTS: Total energy delivered and operative times were significantly shorter for GreenLEP (58 vs. 110 kJ, p < 0.0001; 60 vs. 90 min, p < 0.0001). Operative time reached a plateau after 30 procedures in each group. Length of catheterization and hospital stay were significantly shorter in the HoLEP group (2 vs. 1 day, p < 0.0001; 2 vs. 1 day, p < 0.0001). Postoperative complications were comparable between GreenLEP and HoLEP (19 vs. 25 %; p = 0.13). There was a greater increase of Q max at 3 months and a greater IPSS decrease at 1 month for GreenLEP, whereas decreases in IPSS and IPSS-Q8 at 6 months were greater for HoLEP. Transient stress urinary incontinence was comparable between both groups (6 vs. 9 % at 3 months; p = 0.42). Pentafecta was achieved in four consecutive patients after the 18th and the 40th procedure in the GreenLEP and HoLEP group, respectively. Learning curves ranged from 14 to 30 cases for GreenLEP and 22 to 40 cases for HoLEP. CONCLUSION: Learning curves of GreenLEP and HoLEP provided roughly similar peri-operative and short-term functional outcomes.

Multicentre prospective evaluation of the learning curve of holmium laser enucleation of the prostate (HoLEP).

OBJECTIVES: To describe the step-by-step learning curve of the holmium laser enucleation of the prostate (HoLEP) surgical technique. SUBJECTS/PATIENTS AND METHODS: A prospective, multicentre observational study was conducted, involving surgeons experienced in transurethral resection of the prostate and open prostatectomy but never having performed HoLEP. The main judgment criterion was the ability of the surgeon to perform four consecutive successful procedures, defined by the following: complete enucleation and morcellation within <90 min, without any conversion to standard transurethral resection of the prostate (TURP), with acceptable stress, and with acceptable difficulty (evaluated by Likert scales). Each surgeon included 20 consecutive cases. RESULTS: Of nine centres, three abandoned HoLEP before the end of the study due to complications, and one was excluded for treating patients off protocol. Only one centre achieved the main judgment criterion of four consecutive successful HoLEP procedures. Overall, the procedures were successfully performed in 43.6% of cases. Reasons for unsuccessful procedures were mainly operative time >90 min (n = 51), followed by conversion to TURP (n = 14), incomplete morcellation (n = 8), significant stress (n = 9), or difficulty (n = 14) during HoLEP. Ignoring operating time, 64% of procedures were successful and four out of five centres did four consecutive successful cases. Of the five centres that completed the study, four chose to continue HoLEP. CONCLUSION: Even in a prospective training structure, HoLEP has a steep learning curve exceeding 20 cases, with almost half of our centres choosing to abandon or not to continue with the technique. Operating time and difficulty of the enucleation seem the most important problems for a beginner. A more intensely mentored and structured mentorship programme might allow safer adoption of the procedure.

Effects of hexanic extract of Serenoa repens (Permixon® 160 mg) on inflammation biomarkers in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia.

BACKGROUND: Chronic prostatic inflammation (CPI) could be a cause of symptomatic or complicated benign prostatic hyperplasia (BPH). In previous in vitro and in vivo studies, Hexanic Extract of Serenoa repens (HESr) namely Permixon(®) has demonstrated potent anti-inflammatory properties. With the aim to provide new insight onto HESr anti-inflammatory properties in human we explore its effect on CPI biomarkers in men with lower urinary tract symptoms (LUTS) related to BPH using a non-invasive method and investigate links between biomarkers and clinical symptoms. METHODS: An international, randomized, double-blind, parallel-group, tamsulosin-controlled study was carried out in 206 men with BPH-related LUTS. Patients received oral daily HESr 320mg or tamsulosin 0.4 mg during 3 months. The first urine stream after digital rectal examination (DRE) was collected at Day 1 and Day 90 and mRNA was extracted from prostatic epithelial cells desquaming in the lumen of the glands and seminal plasma fluid after DRE. mRNA quantification of the 29 most significant published inflammation markers in BPH and protein detection in urine was performed. RESULTS: At D90, a decrease in mean gene expression was observed for 65.4% of the markers detected in the HESr group versus 46.2% in the tamsulosin group. In the 15 most frequently expressed genes, this difference was higher (80% vs. 33% respectively). Three proteins (MCP-1/CCL2, IP-10/CXCL10, and MIF) were detected. At D90, a decrease in the number of patients who expressed MCP-1/CCL2 and IP-10/CXCL10 was observed only in the HESr group. Moreover, MIF expression was significantly reduced by HESr compared with tamsulosin (P = 0.007). Finally, in contrast to tamsulosin, the subgroup of patients treated by HESr and who over expressed MIF at baseline, had a higher response to the International Prostate Symptom Score (I-PSS) than those who did not over express this protein (mean I-PSS change: -6.4 vs. -4.5 respectively). As the study is exploratory, results should be confirmed in a powered clinical study. CONCLUSIONS: These results showed for the first time at clinical level the anti-inflammatory properties of HESr, already indicated in BPH-related LUTS. Thus, HESr could be of interest to prevent unfavourable evolution in patients with CPI.

Lipidosterolic extract of serenoa repens modulates the expression of inflammation related-genes in benign prostatic hyperplasia epithelial and stromal cells.

Despite the high prevalence of histological Benign Prostatic Hypeplasia (BPH) in elderly men, little is known regarding the molecular mechanisms and networks underlying the development and progression of the disease. Here, we explored the effects of a phytotherapeutic agent, Lipidosterolic extract of the dwarf palm plant Serenoa repens (LSESr), on the mRNA gene expression profiles of two representative models of BPH, BPH1 cell line and primary stromal cells derived from BPH. Treatment of these cells with LSESr significantly altered gene expression patterns as assessed by comparative gene expression profiling on gene chip arrays. The expression changes were manifested three hours following in vitro administration of LSESr, suggesting a rapid action for this compound. Among the genes most consistently affected by LSESr treatment, we found numerous genes that were categorized as part of proliferative, apoptotic, and inflammatory pathways. Validation studies using quantitative real-time PCR confirmed the deregulation of genes known to exhibit key roles in these biological processes including IL1B, IL1A, CXCL6, IL1R1, PTGS2, ALOX5, GAS1, PHLDA1, IL6, IL8, NFkBIZ, NFKB1, TFRC, JUN, CDKN1B, and ERBB3. Subsequent analyses also indicated that LSESr treatment can impede the stimulatory effects of certain proinflammatory cytokines such as IL6, IL17, and IL15 in these cells. These results suggest that LSESr may be useful to treat BPH that manifest inflammation characteristics. This also supports a role for inflammation in BPH presumably by mediating the balance between apoptosis and proliferation.

Transurethral plasma vaporization of the prostate: 3-month functional outcome and complications.

UNLABELLED: Study Type - Therapy (multi-centre cohort). Level of Evidence 2b. OBJECTIVE: To evaluate the early functional outcomes of transurethral plasma vaporization of the prostate (TUVis) in a multicentre study. PATIENTS AND METHODS: A prospective multicentre observational study was conducted in eight urology departments. The inclusion criterion was benign prostatic hyperplasia (BPH) requiring surgical treatment. Patients on anti-coagulant therapy were not excluded. The TUVis procedure was performed according to a classic transurethral resection of the prostate (TURP) scheme following the manufacturer's recommendations. We evaluated subjective functional outcome using self-questionnaires (International Prostate Symptom Score [IPSS] and five-item International Index of Erectile Function [IIEF-5]) and objective criteria (prostate volume, prostate-specific antigen [PSA], uroflowmetry, post residual volume) at baseline and at 1- and 3-month follow-ups. All types of complications were systematically recorded. RESULTS: Despite 52% of patients receiving anticoagulant therapy before surgery, we reported only 3% with haemorrhagic complications, no blood transfusion, a mean catheterization time of 44 h and a mean postoperative stay of 2.9 nights. No significant change in irrigation time, catheter time or hospital stay was observed in patients with or without anticoagulant therapy. The IPSS and bother scores significantly decreased after the 3-month follow-up (57% and 59%, respectively), but the average remaining prostate volume was 29 cc and the tissue ablation rate was only 0.5 cc/min. Three major complications occurred, consisting of two urinary fistulas and one partial bladder coagulation. CONCLUSIONS: The TUVis procedure has a proven fast postoperative recovery time, good short-term functional outcome and good haemostatic efficiency. However, the tissue ablation rate was lower than expected and we encountered three major complications, the mechanisms of which remain unclear. Considering the high energy level required to create the plasma effect, the generator, cable and resectoscope must be carefully checked before each procedure.

Surgical management of BPH in patients on oral anticoagulation: transurethral bipolar plasma vaporization in saline versus transurethral monopolar resection of the prostate.

INTRODUCTION: To compare postoperative outcomes of patients on oral anticoagulation (OA) treated with transurethral plasma vaporization of the prostate in saline water (TUVis) and transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Between January and December 2009, 111 patients on OA therapy were treated with either TURP or TUVis in eight centers. Types of OA and perioperative management were collected. Postoperative outcomes were statistically compared between the two groups. RESULTS: A total of 57 (51%) and 54 (49%) patients were treated with TURP and TUVis, respectively. Types of OA were not significantly different between the two groups, but bladder catheterization prior to surgery was more frequently observed in the TUVis group. Before surgery, 28 patients were treated with warfarin alone, 74 with a platelet aggregation inhibitor (PAI) alone, and 9 with a combination of both. PAI was withdrawn preoperatively in 50 patients. All treatments with warfarin were switched for heparin. Comparison of the two groups showed significantly less hemorrhagic complications after TUVis. Patients treated with TUVis experienced less bladder washouts (2% versus 18%, p = 0.008), less late hematuria (4% versus 19%, p = 0.02), and lower decrease of serum hemoglobin (mean decrease of 0.66 versus 1.47 g/dL, p = 0.02). Postoperative bladder catheterization and hospital stay were significantly shorter, whereas the rate of urinary retention was significantly higher. Three months after surgery, functional results were not significantly different between the two groups. CONCLUSIONS: In patients on OA, TUVis led to significantly less bleeding, as well as shorter bladder catheterization and hospital stay than TURP.

Transforming growth factor ß-receptor II protein expression in benign prostatic hyperplasia is associated with prostate volume and inflammation.

OBJECTIVE: To assess transforming growth factor ß-receptor II (TGFBRII) protein expression in benign prostatic hyperplasia (BPH) using immunohistochemistry analysis, and to compare the analysis with phenotypic properties. METHODS: TGFBRII protein expression was profiled using three clinical outcome tissue microarrays (TMAs), sampled from 231 patients who underwent surgery for BPH. Using these TMAs, five inflammatory cell markers were also assessed, including CD3, CD4, CD8, CD20, and CD163. The surgical procedure was open prostatectomy in 95 patients and transurethral resection of the prostate in 136 patients. RESULTS: TGFBRII protein expression was found in BPH epithelium cells for both basal and secretory cells, as well as in fibromuscular stromal cells. TGFBRII staining was also strong in most of the lymphocytes infiltrating the prostate. TGFBRII stromal staining was found to be significantly associated with prostate volume (P = 0.04), whereas TGFBRII epithelial staining was found to be significantly associated with 5-α-reductase-inhibitor medical therapy received by patients before surgery (P = 0.004). Both stromal and epithelial TGFBRII staining were found to be associated with CD4 T-lymphocyte infiltrate, independently of prostate volume (P < 0.001 and P = 0.002). CONCLUSIONS: TGFBRII protein expression in BPH is associated with prostate gland volume and with CD4 T-lymphocyte prostatitis. TGFBRII might be a promising therapeutic target to prevent prostate enlargement or even to decrease prostate volume.

Impact of oral anticoagulation on morbidity of transurethral resection of the prostate.

AIM: To assess the impact of oral anticoagulation (OA) on morbidity of transurethral resection of the prostate (TURP). OA included warfarin and platelet aggregation inhibitors (PAI). PATIENTS AND METHOD: Multicenter analysis of patients operated for symptomatic benign prostatic hyperplasia (BPH) by TURP. Patients under OA were compared to those with no OA. RESULTS: Out of 612 patients included in the analysis, 206 (33%) were on OA prior surgery (55 warfarin, 142 PAI, and 9 warfarin and PAI). No patient continued warfarin and clopidogrel during the operating period. Patients under OA were significantly older (75 vs. 71 yo, P < 0.001), had larger prostate volume (56 vs. 49 ml, P = 0.05), and had higher rate of bladder catheter prior surgery (26 vs. 17%, P = 0.02). At 3 months follow-up, patients in the OA group had a higher weight of resected tissue (24 vs. 21.7 g, P < 0.001), a longer duration of hospitalization (6.4 vs. 4.7 days P < 0.001), a higher rate of bladder clots (13 vs. 4.7%, P < 0.001), red cell transfusion (1.9 vs. 1.0%, P = 0.026), late hematuria (15.0 vs. 8.4%, P = 0.004), and thromboembolic events (2.4 vs. 0.7, P = 0.02). In multivariable analysis, OA status was the sole independent parameter associated with bladder clots (P = 0.004) and with late hematuria (P = 0.03). CONCLUSION: OA had a significant and independent impact on TURP outcome in terms of bleeding complications. This data could be used for treatment decision and for patient's information prior BPH surgery.

Blood loss during transurethral resection of the prostate as measured by the chromium-51 method.

PURPOSE: To evaluate blood loss during transurethral resection of the prostate (TURP), and its predictive factors, using the chromium 51 (51Cr) labeling method. PATIENTS AND METHODS: From January to June 2008, 41 patients who underwent TURP for symptomatic benign prostatic hyperplasia (BPH) at four French urology centers were included in the analysis. Red cells volume was measured by the 51Cr method 1 day before TURP, and on postoperative day 3. Overall blood loss was estimated by multiplication of red cells volume loss and preoperative venous hematocrit value. RESULTS: Mean preoperative red cells volume was 1997 mL. Mean loss of red cells volume was 209 ml, which corresponds to an estimated blood loss of 507 mL. Mean delta of hematocrit and hemoglobin were 1.4% and 0.71 g/dL, respectively. In univariate analysis, prostate volume, weight of resected tissue, preoperative red cells volume, and resection time were significantly and directly associated with loss of red cells volume (P = 0.038, P = 0.004, P = 0.002, and P = 0.039, respectively). Bipolar and monopolar TURP did not lead to significant difference of red cells loss. In multivariate analysis, both preoperative red cells volume and weight of resected tissue were independent predictors of red cells loss (P = 0.017 and P = 0.048 respectively). CONCLUSION: We present the first study to measure blood loss secondary to TURP using the 51Cr method. This technique allowed evaluating blood loss not only during the surgical procedure but also during the postoperative period. We learned from this study that, on average, blood loss from the procedure until postoperative day 3 was more than 500 mL, which is larger than previously reported amounts as measured by other methods. Because significant blood loss might occur during the postoperative period, the 51Cr method should be used to measure blood loss when evaluating new emerging techniques to manage BPH.