Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance

BACKGROUND: We aimed to validate Decipher to predict adverse pathology (AP) at radical prostatectomy (RP) in men with National Comprehensive Cancer Network (NCCN) favorable-intermediate risk (F-IR) prostate cancer (PCa), and to better select F-IR candidates for active surveillance (AS). METHODS: In all, 647 patients diagnosed with NCCN very low/low risk (VL/LR) or F-IR prostate cancer were identified from a multi-institutional PCa biopsy database; all underwent RP with complete postoperative clinicopathological information and Decipher genomic risk scores. The performance of all risk assessment tools was evaluated using logistic regression model for the endpoint of AP, defined as grade group 3-5, pT3b or higher, or lymph node invasion. RESULTS: The median age was 61 years (interquartile range 56-66) for 220 patients with NCCN F-IR disease, 53% classified as low-risk by Cancer of the Prostate Risk Assessment (CAPRA 0-2) and 47% as intermediate-risk (CAPRA 3-5). Decipher classified 79%, 13% and 8% of men as low-, intermediate- and high-risk with 13%, 10%, and 41% rate of AP, respectively. Decipher was an independent predictor of AP with an odds ratio of 1.34 per 0.1 unit increased (p value = 0.002) and remained significant when adjusting by CAPRA. Notably, F-IR with Decipher low or intermediate score did not associate with significantly higher odds of AP compared to VL/LR. CONCLUSIONS: NCCN risk groups, including F-IR, are highly heterogeneous and should be replaced with multivariable risk-stratification. In particular, incorporating Decipher may be useful for safely expanding the use of AS in this patient population

RAS-NOTECHS: validity and reliability of a tool for measuring non-technical skills in robotic-assisted surgery settings

BACKGROUND Non-technical skills (NTS) are essential for safe surgical practice as they impact workflow and patient outcomes. Observational tools to measure operating room (OR) teams' NTS have been introduced. However, there are none that account for the specific teamwork challenges introduced by robotic-assisted surgery (RAS). We set out to develop and content-validate a tool to assess multidisciplinary NTS in RAS. METHODOLOGY Stepwise, multi-method procedure. Observations in different surgical departments and a scoping literature review were first used to compile a set of RAS-specific teamwork behaviours. This list was refined and expert validated using a Delphi consensus approach consisting of qualitative interviews and a quantitative survey. Then, RAS-specific behaviours were merged with a well-established assessment tool on OR teamwork (NOTECHS II). Finally, the new tool-RAS-NOTECHS-was applied in standardized observations of real-world procedures to test its reliability (inter-rater agreement via intra-class correlations). RESULTS Our scoping review revealed 5242 articles, of which 21 were included based on pre-established inclusion criteria. We elicited 16 RAS-specific behaviours from the literature base. These were synthesized with further 18 behavioural markers (obtained from 12 OR-observations) into a list of 26 behavioural markers. This list was reviewed by seven RAS experts and condensed to 15 expert-validated RAS-specific behavioural markers which were then merged into NOTECHS II. For five observations of urologic RAS procedures (duration: 13~h and 41~min), inter-rater agreement for identification of behavioural markers was strong. Agreement of RAS-NOTECHS scores indicated moderate to strong agreement. CONCLUSIONS RAS-NOTECHS is the first observational tool for multidisciplinary NTS in RAS. In preliminary application, it has been shown to be reliable. Since RAS is rapidly increasing and challenges for effective and safe teamwork remain at the forefront of quality and safety of surgical care, RAS-NOTECHS may contribute to training and improvement efforts in technology-facilitated surgeries

Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766

Introduction: Lower urinary tract symptoms (LUTS) due to overactive bladder (OAB) are caused by spontaneous detrusor contractions. Medical treatment with muscarinic receptor antagonists or β3-adrenoceptor agonists aims to inhibit detrusor contractions, but overall results are unsatisfactory. Consequently, improved understanding of bladder smooth muscle contraction and identification of novel compounds for its inhibition are needed to develop alternative options. A role of the GTPase Rac1 for smooth muscle contraction has been reported from the prostate, but is unknown in the human detrusor. Here, we examined effects of the Rac inhibitors NSC23766, which may also antagonize muscarinic receptors, and EHT1864 on contraction of human detrusor tissues. Methods: Female and male human detrusor tissues were obtained from radical cystectomy. Effects of NSC23766 (100 µM) and EHT1864 (100 µM) on detrusor contractions were studied in an organ bath. Results: Electric field stimulation induced frequency-dependent contractions of detrusor tissues, which were inhibited by NSC23766 and EHT1864. Carbachol induced concentration-dependent contractions. Concentration response curves for carbachol were shifted to the right by NSC23766, reflected by increased EC50 values, but unchanged Emax values. EHT1864 reduced carbachol-induced contractions, resulting in reduced Emax values for carbachol. The thromboxane analog U46619 induced concentration-dependent contractions, which remained unchanged by NSC23766, but were reduced by EHT1864. Conclusions: NSC23766 and EHT1864 inhibit female and male human detrusor contractions. NSC23766, but not EHT1864 competitively antagonizes muscarinic receptors. In addition to neurogenic and cholinergic contractions, EHT1864 inhibits thromboxane A2-induced detrusor contractions. The latter may be promising, as the origin of spontaneous detrusor contractions in OAB is noncholinergic. In vivo, both compounds may improve OAB-related LUTS

Ghrelin Aggravates Prostate Enlargement in Rats with Testosterone-Induced Benign Prostatic Hyperplasia, Stromal Cell Proliferation, and Smooth Muscle Contraction in Human Prostate Tissues

Epidemiologic studies revealed a context between lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and metabolic syndrome. However, molecular mechanisms underlying this relationship are largely unknown. Prostate enlargement and increased prostate smooth muscle tone are important factors in the pathophysiology of LUTS suggestive of BPH. In the present study, we studied effects of the metabolic hormone ghrelin on prostate enlargement in rats with experimentally induced BPH, growth of cultured stromal cells from human prostate (WPMY-1), and smooth muscle contraction of human prostate tissues. Ghrelin (20 nmol/kg daily, p.o., 2 weeks) increased prostate size in rats with testosterone-induced BPH. Microarray identified 114 ghrelin-upregulated genes (2-fold or more) in these prostates, with possible roles in growth, smooth muscle contraction, or metabolism. 12 genes were selected for further analyses. In human prostate tissues, mRNA levels of 11 of them correlated positively with ghrelin receptor (GHSR) expression, but only two with the degree of BPH. Accordingly, no correlation was evident between GHSR expression level and BPH in human prostate tissues. In WPMY-1 cells, the GHRS agonist MK0677 upregulated 11 of the selected genes. MK0677 induced proliferation of WPMY-1 cells, shown by EdU assay, colony formation, proliferation markers, flow cytometry, and viability. In myographic measurements, GHSR agonists enhanced contractions of human prostate strips. Together, ghrelin may aggravate prostate enlargement, stromal cell growth, and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH

Technical outcome, clinical success, and complications of low-milliampere computed tomography fluoroscopy-guided drainage of lymphoceles following radical prostatectomy with pelvic lymph node dissection

To evaluate the technical outcome, clinical success, and safety of low-milliampere CT fluoroscopy (CTF)-guided percutaneous drain (PD) placement in patients with lymphoceles following radical prostatectomy (RP) with pelvic lymph node dissection (LND). This retrospective analysis comprised 65 patients with PD placement in lymphoceles following RP under low-milliampere CTF guidance. Technical and clinical success were evaluated. Complications within a 30-day time interval associated with CTF-guided PD placement were classified according to SIR. Patient radiation exposure was quantified using dose-length products (DLP) of the pre-interventional planning CT scan (DLPpre), of the sum of intra-interventional CT fluoroscopic acquisitions (DLPintra) and of the post-interventional control CT scan (DLPpost). Eighty-nine lymphoceles were detected. Seventy-seven CT-guided interventions were performed, with a total of 92 inserted drains. CTF-guided lymphocele drainage was technically successful in 100% of cases. For all symptomatic patients, improvement in symptoms was reported within 48 h after intervention. Time course of C-reactive protein and Leucocytes within 30 days revealed a statistically significant (p < 0.0001) decrease. Median DLPpre, DLPintra and DLPpost were 431 mGy*cm, 45 mGy*cm and 303 mGy*cm, respectively. Only one minor complication (self-resolving haematoma over the bladder dome; SIR Grade 2) was observed. Low-milliampere CTF-guided drainage is a safe treatment option in patients with lymphoceles following RP with pelvic LND characterized by high technical and good clinical success rates, which provides rapid symptom relief and serves as definite treatment or as a bridging therapy prior to laparoscopic marsupialisation.peer-reviewe

Feasibility of Different Tumor Delineation Approaches for 18F-PSMA-1007 PET/CT Imaging in Prostate Cancer Patients

Background: Delineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68Ga-labeled ligands; nonetheless, 18F-labeled PET ligands are gaining increasing importance due to advantages over 68Ga-labeled compounds. However, standardized tumor delineation methods for 18F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18F-PSMA-1007 PET. Methods: Fifty patients with metastatic prostate cancer, 18F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to III) liver (SUVliver), IV) parotis (SUVparotis) and V) spleen (SUVspleen). Results: A fixed SUV of 4.0 (r=0.807, r2 = 0.651, p0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUVmax, 42% SUVmax and 20% SUVmax) revealed inferior association for LNM delineation. Conclusions: A threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated

Radium-223 for primary bone metastases in patients with hormone-sensitive prostate cancer after radical prostatectomy

Radium-223 dichloride (Ra-223) is the first bone-targeting agent showing improvement in overall survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases. We aimed to assess feasibility of Ra-223 treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ten patients with primary bone metastases received Ra-223 following radical prostatectomy (RP). Changes in alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were recorded, while pain intensity was evaluated using the self-reporting Brief Pain Inventory (BPI) questionnaire. Bone scintigraphy (BS) was performed to assess treatment response. Seven patients completed six cycles of Ra-223. Discontinuation was due to leuko-and lymphopenia, progressive lymph node metastasis or newly diagnosed liver metastasis. Treatment-related adverse events occurred in three patients and included leuko-and lymphopenia, fatigue, abdominal discomfort and nausea. Overall, a median decrease of 28% in ALP and a median decrease of 83% in PSA were noted at follow-up. However, PSA progressed in five patients at follow-up. Improvement of pain was observed in all patients (median decrease of 36% after 3 cycles and of 40% at the end of therapy). On BS, three patients showed remission, four had stable disease, and one showed progressive disease at follow-up. Our results suggest that Ra-223 for primary bone metastases in patients with mHSPC after RP is feasible and alleviates pain. ALP, rather than PSA, may be a good marker for assessing treatment response. Ra-223 could therefore be taken into consideration as part of a multimodal approach for carefully selected patients with advanced prostate cancer