Functional Outcomes and Quality of Life in High-risk Prostate Cancer Patients Treated by Robot-assisted Radical Prostatectomy with or Without Adjuvant Treatments.

BACKGROUND: Robot-assisted laparoscopic prostatectomy (RALP) is used frequently to treat prostate cancer; yet, prospective data on the quality of life and functional outcomes are lacking. OBJECTIVE: To assess the quality of life and functional outcomes after radical prostatectomy in different risk groups with or without adjuvant treatments. DESIGN, SETTING, AND PARTICIPANTS: The Be-RALP database is a prospective multicentre database that covers 9235 RALP cases from 2009 until 2016. Of these 9235 patients, 2336 high-risk prostate cancer patients were matched with low/intermediate-risk prostate cancer patients. INTERVENTION: Patients were treated with RALP only or followed by radiotherapy and/or hormone treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a mixed-model analysis to longitudinally analyse quality of life, urinary function, and erectile function between risk groups with or without additional treatments. RESULTS AND LIMITATIONS: Risk group was not significant in predicting quality of life, erectile function, or urinary function after RALP. Postoperative treatment (hormone and/or radiotherapy treatment) was significant in predicting International Index of Erectile Function (IIEF-5), sexual activity, and sexual functioning. CONCLUSIONS: Risk group was not linked with clinically relevant declines in functional outcomes after RALP. The observed functional outcomes and quality of life are in favour of considering RALP for high-risk prostate cancer. Postoperative treatment resulted in lower erectile function measures without clinically relevant changes in quality of life and urinary functions. Hormone therapy seems to have the most prominent negative effects on these outcomes. PATIENT SUMMARY: This study investigated the quality of life, and urinary and erectile function in patients with aggressive and less aggressive prostate cancer after surgery only or in combination with hormones or radiation. We found that quality of life recovers completely, while erectile and urinary function recovers only partially after surgery. Aggressiveness of the disease had a minimal effect on the outcomes; yet, postoperative treatments lowered erectile function further.

"Keep It Short and Simple": Perceptions of patients and healthcare professionals on the use of a mobile health app in the care for patients undergoing radical prostatectomy.

Background: Patients undergoing radical prostatectomy for localised prostate cancer generally have good long-term survival rates. However, late recurrences can occur and require lifelong follow-up. Objective: This research aims to investigate different stakeholders' perceptions on the use of mobile health (mHealth) applications for prostate cancer follow-up after radical prostatectomy. Methods: A cross-sectional qualitative study was conducted to explore stakeholders' perceptions of an mHealth application for follow-up after radical prostatectomy. Urologists, nurses, and patients treated with radical prostatectomy were interviewed, and data were transcribed and analysed using thematic analysis according to Qualitative Analysis Guide of Leuven. Recommended features for an ideal mHealth application were grouped according to the Persuasive Systems Design model. Results and Limitations: A total of 30 stakeholders, consisting of nurse specialists (n = 7), urologists (n = 8), and patients (n = 15), were interviewed. Expected benefits and barriers were mentioned and grouped in five overarching themes: healthcare optimisation, disease management, app compliance, legal and organisational requirements, and patient-mHealth interaction. Stakeholders provided a multitude of suggestions for an ideal mHealth app. Yet, not all types of stakeholders were interviewed, and patient selection limited generalisability of findings. Conclusions: Stakeholders indicate that an mHealth app in the care for post-prostatectomy patients can improve patient care and promote disease management but consider app compliance as a major challenge. Patient Summary: We interviewed patients, nurses, and urologists about using an mHealth application for follow-up after radical prostatectomy. The participants agreed that an mHealth app could improve care optimisation and disease management, but some concerns and barriers were expressed. This resulted in a list of recommended features for an ideal app.

A Multicentre Clinical Trial Evaluating a Drop-in Gamma Probe for Minimally Invasive Sentinel Lymph Node Dissection in Prostate Cancer.

BACKGROUND: This study evaluated the safety and performance of a drop-in gamma probe for prostate cancer (PCa) sentinel lymph node biopsy (SeLNB) in a prospective, open-label, multicentre, single-arm clinical trial. OBJECTIVE: The main objective was to determine the sentinel lymph node (SeLN) detection rate with the drop-in gamma probe system. The secondary objectives were overall performance and safety. DESIGN, SETTING, AND PARTICIPANTS: At three European centres, patients received an ultrasound-guided systemic and tumour-targeted injection of [99mTc]Tc-nanocolloid followed by planar lymphoscintigraphy and/or single-photon emission computerised tomography. The next day, manual laparoscopic or robot-assisted radical prostatectomy was performed, including SeLN dissection (SeLND) and extended pelvic lymph node dissection (ePLND). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: SeLNs were detected with the drop-in probe and a rigid laparoscopic gamma probe (RLGP). The primary endpoint of the study was the SeLND rate defined as the percentage of patients with at least one SeLN detected in vivo by the drop-in probe. The secondary endpoints included diagnostic performance, ease of SeLN detection, number of SeLNs detected, and safety. The first two patients at each site (six in total) were used for familiarisation. RESULTS AND LIMITATIONS: A total of 27 patients were included in the main analysis. SENSEI successfully detected at least one SeLN in all 27 patients, resulting in a detection rate of 100% (95% confidence interval 87.2-100%). The total number of SeLNs identified with SENSEI was 85 (median three SeLNs per patient, range 1-6); of these 85 SeLNs, 12 were located outside of the ePLND template. In the nine patients in whom the RLGP was used, SENSEI detected two SeLNs that could not be detected with the RLGP due to manoeuvrability restrictions. Ten of the 27 patients were pN1; four patients had a false-negative SeLNB. No adverse events or complications were related to the use of the drop-in probe. CONCLUSIONS: The study demonstrated that the drop-in gamma probe meets the performance and safety requirements for SeLNB in PCa. The device provided improved manoeuvrability and SeLN detection compared with the conventional RLGP. PATIENT SUMMARY: A novel device was tested for detecting sentinel lymph nodes during minimally invasive surgery for prostate cancer. In this first evaluation, the performance and safety of the device were evaluated positively.

Double trouble for prostate cancer: synergistic action of AR blockade and PARPi in non-HRR mutated patients.

Prostate cancer (PCa) is the most common cancer in men worldwide. Despite better and more intensive treatment options in earlier disease stages, a large subset of patients still progress to metastatic castration-resistant PCa (mCRPC). Recently, poly-(ADP-ribose)-polymerase (PARP)-inhibitors have been introduced in this setting. The TALAPRO-2 and PROpel trials both showed a marked benefit of PARPi in combination with an androgen receptor signaling inhibitor (ARSI), compared with an ARSI alone in both the homologous recombination repair (HRR)-mutated, as well as in the HRR-non-mutated subgroup. In this review, we present a comprehensive overview of how maximal AR-blockade via an ARSI in combination with a PARPi has a synergistic effect at the molecular level, leading to synthetic lethality in both HRR-mutated and HRR-non-mutated PCa patients. PARP2 is known to be a cofactor of the AR complex, needed for decompacting the chromatin and start of transcription of AR target genes (including HRR genes). The inhibition of PARP thus reinforces the effect of an ARSI. The deep androgen deprivation caused by combining androgen deprivation therapy (ADT) with an ARSI, induces an HRR-like deficient state, often referred to as "BRCA-ness". Further, PARPi will prevent the repair of single-strand DNA breaks, leading to the accumulation of DNA double-strand breaks (DSBs). Due to the induced HRR-deficient state, DSBs cannot be repaired, leading to apoptosis.

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.

Discrimination, Reliability, Sensitivity, and Specificity of Robotic Surgical Proficiency Assessment With Global Evaluative Assessment of Robotic Skills and Binary Scoring Metrics: Results From a Randomized Controlled Trial.

Objective: To compare binary metrics and Global Evaluative Assessment of Robotic Skills (GEARS) evaluations of training outcome assessments for reliability, sensitivity, and specificity. Background: GEARS-Likert-scale skills assessment are a widely accepted tool for robotic surgical training outcome evaluations. Proficiency-based progression (PBP) training is another methodology but uses binary performance metrics for evaluations. Methods: In a prospective, randomized, and blinded study, we compared conventional with PBP training for a robotic suturing, knot-tying anastomosis task. Thirty-six surgical residents from 16 Belgium residency programs were randomized. In the skills laboratory, the PBP group trained until they demonstrated a quantitatively defined proficiency benchmark. The conventional group were yoked to the same training time but without the proficiency requirement. The final trial was video recorded and assessed with binary metrics and GEARS by robotic surgeons blinded to individual, group, and residency program. Sensitivity and specificity of the two assessment methods were evaluated with area under the curve (AUC) and receiver operating characteristics (ROC) curves. Results: The PBP group made 42% fewer objectively assessed performance errors than the conventional group (P < 0.001) and scored 15% better on the GEARS assessment (P = 0.033). The mean interrater reliability for binary metrics and GEARS was 0.87 and 0.38, respectively. Binary total error metrics AUC was 97% and for GEARS 85%. With a sensitivity threshold of 0.8, false positives rates were 3% and 25% for, respectively, the binary and GEARS assessments. Conclusions: Binary metrics for scoring a robotic VUA task demonstrated better psychometric properties than the GEARS assessment.

A Drop-in Gamma Probe for Minimally Invasive Sentinel Lymph Node Dissection in Prostate Cancer: Preclinical Evaluation and Interim Results From a Multicenter Clinical Trial.

PURPOSE: This study evaluated the performance of a drop-in gamma probe for prostate cancer (PCa) sentinel lymph node dissection (SLND) in a pelvic phantom, porcine model, and in PCa patients as part of an ongoing prospective multicenter clinical trial. METHODS: Two design variants of the drop-in gamma probe (SENSEI; Lightpoint Medical Ltd) were assessed in the pelvic phantom, and the preferred design was evaluated in a porcine model with clinically representative volumes and 99mTc activities. In the clinical trial, radical prostatectomy, SLND, and extended pelvic lymph node dissection were performed the day after 99mTc-nanocolloid injection and imaging. Sentinel lymph nodes (SLNs) were detected with the drop-in probe and a rigid laparoscopic gamma probe (RLGP). An interim analysis was performed after 10 patients were recruited. RESULTS: The narrow field of view probe design outperformed the wide field of view design in the pelvic phantom (detection rate, 100% vs 50%). In the porcine model, all activity concentrations could be successfully detected. The drop-in gamma probe successfully detected SLNs in all 10 patients (detection rate, 100%). Two of the SLNs identified by the drop-in gamma probe could not be found with the RLGP. No false-negative cases and no adverse events related to the SLND procedure or the drop-in gamma probe occurred. CONCLUSION: The drop-in gamma probe meets the usability and performance requirements for SLND in PCa and provides performance advantages over the RLGP. The final clinical study results will confirm the performance of the technique across multiple sites.

Inhibition of TRPM8 by the urinary tract analgesic drug phenazopyridine.

BACKGROUND: and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain syndrome (BPS). Whereas the analgesic effect of PAP has been attributed to a local effect on the mucosa of the lower urinary tract (LUT), the molecular targets of PAP remain unknown. We investigated the effect of PAP on pain-related Transient Receptor Potential (TRP) channels expressed in sensory neurons that innervate the bladder wall. EXPERIMENTAL APPROACH: The effects of PAP on the relevant TRP channels (TRPV1, TRPA1, TRPM8, TRPM3) expressed in HEK293 or CHO cells was investigated using Fura-2-based calcium measurements and whole-cell patch-clamp recordings. Activity of PAP on TRPM8 was further analysed using Fura-2-based calcium imaging on sensory neurons isolated from lumbosacral dorsal root ganglia (DRG) of mice. KEY RESULTS: PAP rapidly and reversibly inhibits responses of TRPM8 expressed in HEK293 cells to cold and menthol, with IC50 values between 2 and 10 µM. It acts by shifting the voltage dependence of channel activation towards positive potentials, opposite to the effect of menthol. PAP also inhibits TRPM8-mediated, menthol-evoked calcium responses in lumbosacral DRG neurons. At a concentration of 10 µM, PAP did not significantly affect TRPA1, TRPV1, or TRPM3. CONCLUSION AND IMPLICATIONS: PAP inhibits TRPM8 in a concentration range consistent with PAP levels in the urine of treated patients. Since TRPM8 is expressed in bladder afferent neurons and upregulated in patients with painful bladder disorders, TRPM8 inhibition may underlie the analgesic activity of PAP.

Defining the optimal template of salvage lymph node dissection for unilateral pelvic nodal recurrence of prostate cancer following radical prostatectomy.

OBJECTIVES: Several retrospective studies have shown that salvage bilateral pelvic lymph node dissection (sLND) is a valid treatment option in the setting of oligorecurrent nodal prostate cancer following radical prostatectomy. Little is known about the optimal template of such sLND in patients with strictly unilateral pelvic recurrence on PET-CT imaging. In this study, we investigated whether a unilateral pelvic sLND could be sufficient in such a setting. METHODS: We retrospectively collected data of patients treated with sLND between 2010 and 2019 at the University Hospitals, Leuven. Patients were included if they developed recurrence following radical prostatectomy, characterized by ≤3 unilateral pelvic lymph node metastases on Choline or PSMA PET-CT and received a super-extended bilateral pelvic sLND as first metastasis-directed therapy. As a primary endpoint, we investigated in how many cases a unilateral sLND would have been sufficient. RESULTS: In total, 44 patients with strictly unilateral pelvic recurrence were treated with super-extended bilateral pelvic sLND. In 5 out of 44 (11%) patients, histological examination showed presence of prostate cancer in the contralateral hemi-pelvis. In the group with a single positive node on imaging prior to sLND, only 1 out of 27 (3%) patients had contralateral disease at final pathology. No one (0%) in this group subsequently developed recurrence in the contralateral hemi-pelvis following sLND. CONCLUSIONS: In conclusion, this study suggests that unilateral pelvic sLND could be sufficient in patients with a single unilateral pelvic lymph node recurrence on PET/CT imaging.

ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer.

BACKGROUND: High-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence and metastatic progression following radical prostatectomy (RP). OBJECTIVE: To determine the efficacy of neoadjuvant degarelix plus apalutamide before RP compared with degarelix with a matching placebo. DESIGN, SETTING, AND PARTICIPANTS: ARNEO was a randomized, placebo-controlled, phase II neoadjuvant trial before RP performed between March 2019 and April 2021. Eligible patients had high-risk PCa and were amenable to RP. INTERVENTION: Patients were randomly assigned at a 1:1 ratio to degarelix (240-80-80 mg) + apalutamide (240 mg/d) versus degarelix + matching placebo for 3 mo followed by RP. Prior to and following neoadjuvant treatment, pelvic 18F-PSMA-1007 positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the difference in proportions of patients with minimal residual disease (MRD; = residual cancer burden (RCB) ≤0.25 cm3 at final pathology). Secondary endpoints included differences in prostate-specific antigen responses, pathological staging, and change in TNM stage on prostate-specific membrane antigen (PSMA) PET/MRI following hormonal treatment. Biomarkers (immunohistochemical staining on prostate biopsy [PTEN, ERG, Ki67, P53, GR, and PSMA] and PSMA PET/MRI-derived characteristics) associated with pathological response (MRD and RCB) were explored. RESULTS AND LIMITATIONS: Patients were randomized to neoadjuvant degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 12 wk and underwent RP. Patients in the degarelix + apalutamide arm achieved a significantly higher rate of MRD than those in the control arm (38% vs 9.1%; relative risk [95% confidence interval] = 4.2 [1.5-11], p = 0.002). Patients with PTEN loss in baseline prostate biopsy attained significantly less MRD (11% vs 43%, p = 0.002) and had a higher RCB at final pathology (1.6 vs 0.40 cm3, p < 0.0001) than patients without PTEN loss. Following neoadjuvant hormonal therapy, PSMA PET-estimated tumor volumes (1.2 vs 2.5 ml, p = 0.01) and maximum standardized uptake value (SUVmax; 4.3 vs 5.7, p = 0.007) were lower in patients with MRD than in patients without MRD. PSMA PET-estimated volume and PSMA PET SUVmax following neoadjuvant treatment correlated significantly with RCB at final pathology (both p < 0.001). CONCLUSIONS: In high-risk PCa patients, neoadjuvant degarelix plus apalutamide prior to RP results in a significantly improved pathological response (MRD and RCB) compared with degarelix alone. Our trial results provide a solid hypothesis-generating basis for neoadjuvant phase 3 trials, which are powered to detect differences in long-term oncological outcome following neoadjuvant androgen receptor signaling inhibitor therapy. PATIENT SUMMARY: In this study, we looked at the difference in pathological responses in high-risk prostate cancer patients treated with degarelix plus apalutamide or degarelix plus matching placebo prior to radical prostatectomy. We demonstrated that patients treated with degarelix plus apalutamide achieved a significantly better tumor response than patients treated with degarelix plus matching placebo. Long-term follow-up is required to determine whether improved pathological outcome translates into better oncological outcomes.

The Prevalence of Lower Limb and Genital Lymphedema after Prostate Cancer Treatment: A Systematic Review.

(1) Background: Secondary lymphedema is a chronic, progressive, and debilitating condition with an important impact on quality of life. Lymphedema is a frequently reported complication in oncological surgery but has not been systematically studied in the setting of prostate cancer. (2) Methods: Pubmed/MEDLINE and Embase were systematically searched to identify articles reporting on lower limb or genital lymphedema after primary treatment (surgery of radiation therapy) of the prostate and the pelvic lymph nodes in men with prostate cancer. Primary outcome was the prevalence of lower limb and genital lymphedema. (3) Results: Eighteen articles were eligible for qualitative synthesis. Risk of bias was high in all included studies, with only one study providing a prespecified definition of secondary lymphedema. Eleven studies report the prevalence of lower limb (0-14%) and genital (0-1%) lymphedema after radical prostatectomy with pelvic lymph node dissection (PLND) Seven studies report a low prevalence of lower limb (0-9%) and genital (0-8%) lymphedema after irradiation of the pelvic lymph nodes. However, in the patient subgroups that underwent pelvic irradiation after staging pelvic lymph node dissections, the prevalence of lower limb (18-29%) and genital (2-22%) lymphedema is substantially elevated. (4) Conclusion: Prostate cancer patients undergoing surgery or irradiation of the pelvic lymph nodes are at risk of developing secondary lymphedema in the lower limbs and the genital region. Patients receiving pelvic radiation after pelvic lymph node dissection have the highest prevalence of lymphedema. The lack of a uniform definition and standardized diagnostic criteria for lower limb and genital lymphedema hampers the accurate estimation of their true prevalence. Future clinicals trials are needed to specifically evaluate secondary lymphedema in patients undergoing prostate cancer treatments, to identify potential risk factors and to determine the impact on quality of life.

Machine learning-assisted fluoroscopy of bladder function in awake mice.

Understanding the lower urinary tract (LUT) and development of highly needed novel therapies to treat LUT disorders depends on accurate techniques to monitor LUT (dys)function in preclinical models. We recently developed videocystometry in rodents, which combines intravesical pressure measurements with X-ray-based fluoroscopy of the LUT, allowing the in vivo analysis of the process of urine storage and voiding with unprecedented detail. Videocystometry relies on the precise contrast-based determination of the bladder volume at high temporal resolution, which can readily be achieved in anesthetized or otherwise motion-restricted mice but not in awake and freely moving animals. To overcome this limitation, we developed a machine-learning method, in which we trained a neural network to automatically detect the bladder in fluoroscopic images, allowing the automatic analysis of bladder filling and voiding cycles based on large sets of time-lapse fluoroscopic images (>3 hr at 30 images/s) from behaving mice and in a noninvasive manner. With this approach, we found that urethane, an injectable anesthetic that is commonly used in preclinical urological research, has a profound, dose-dependent effect on urethral relaxation and voiding duration. Moreover, both in awake and in anesthetized mice, the bladder capacity was decreased ~fourfold when cystometry was performed acutely after surgical implantation of a suprapubic catheter. Our findings provide a paradigm for the noninvasive, in vivo monitoring of a hollow organ in behaving animals and pinpoint important limitations of the current gold standard techniques to study the LUT in mice.

Healthy adults empty their bladder many times a day with little thought. This seemingly simple process requires communication between the lower urinary tract and the central nervous system. About one in five adults experience conditions like urinary incontinence, urgency, or bladder pain caused by impairments in their lower urinary tract. Despite the harmful effects these conditions have on people's health and well-being, few good treatments are available. Mice are often used to study lower urinary tract conditions and treatments. One common technique is to fill a mouse's bladder using a catheter and measure changes in pressure as the bladder empties and refills. But these procedures and the anesthesia used during them may affect bladder function and skew results. Here, De Bruyn et al. have developed a new technique that allows scientists to measure bladder function in awake, freely moving mice. The mice's bladders were photographed using a specialized X-ray based fluoroscope that captured 30 images per second over the course of three hours. A machine learning algorithm was then applied which can automatically detect the circumference of the bladder in each captured image (over 30,000 in total) and quantify its volume. This makes it is possible to measure the bladder as it empties and fills even if the mice move between time frames. The new approach showed that 'gold standard' commonly used methods have a profound effect on the bladder. Surgical implantation of a catheter reduced the bladder to a quarter of its capacity. In addition, one of the most widely used anesthetic drugs in urinary tract research was found to affect the bladder's ability to drain. The technique created by De Bruyn et al. provides a new way to study lower urinary tract function and disease in awake, moving animals. This tool would be easy for other academic and pharmaceutical laboratories to implement, and may help scientists discover new therapies for lower urinary tract conditions.

The key role of levator ani thickness for early urinary continence recovery in patients undergoing robot-assisted radical prostatectomy: A multi-institutional study.

BACKGROUND: Urinary continence (UC) recovery dramatically affects quality of life after robot-assisted radical prostatectomy (RARP). Membranous urethral length (MUL) has been the most studied anatomical variable associated with UC recovery. OBJECTIVE: To investigate whether levator ani thickness (LAT), assessed with multi-parametric magnetic resonance imaging (mpMRI), correlates with UC recovery after RARP. DESIGN, SETTING, AND PARTICIPANTS: The study included 209 patients treated with RARP by expert surgeons with extensive robotic experience from 2017 to 2019. All patients had complete, clinical, mpMRI, pathological, and postoperative data including pelvic floor muscle training (PFMT) protocols. INTERVENTION: After a radiologist-specific training, two urologists independently examined the files, blinded to clinical and pathological findings as well as to postoperative continence status. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: On mpMRI, LAT, bladder neck (BN) shape, MUL, and apex overlapping (AO) were measured. UC recovery was defined as use of 0 or 1 safety pad at follow-up. Multivariable models were used to assess the association between variables and UC recovery. RESULTS AND LIMITATIONS: Overall, 173 (82.8%) patients were continent after a median follow-up of 23 months (interquartile range [IQR]: 17-28). Of these, 98 (46.9%) recovered within 3 months after surgery, 42 (20.1%) from 3 to 6 months, and 33 (15.8%) from 6 months onwards. A significant higher rate of patients with LAT > 10 mm (88.1 vs.75.8%; p = 0.03) experienced UC recovery, compared to those with LAT < 10 mm. This difference was observed in the first 3 months after surgery. At multivariable analysis, LAT (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 1.02-1.37; p = 0.02), Preoperative ICIQ score (OR: 0.91, 95% CI: 0.82-0.98, p = 0.03) and PFMT (OR: 1.98, 95% CI: 1.01-3.93; p = 0.04) independently predict higher UC recovery within 3 months, after accounting for age, BMI, preoperative PSA, D'Amico risk group, MUL, BN shape and AO. CONCLUSIONS: LAT greater than 1 cm was associated with greater UC recovery. Specifically, LAT greater than 1 cm seems to be associated with higher UC rate at 3 months after RARP, compared to those with LAT < 1 cm. PATIENT SUMMARY: Magnetic resonance features can help in predicting the risk of incontinence after robot-assisted radical prostatectomy and should be taken into account when counseling patients before surgery.

Radium-223 in patients with prostate specific antigen (PSA) progression and without clinical metastases following maximal local therapy: A pilot study.

BACKGROUND: Despite the curative intent of radical prostatectomy (RP) (+/- radiotherapy (RT)), 30% of the clinically localized prostate cancer (CaP) patients will develop rising PSA (prostate specific antigen). In absence of clinical recurrence, there is a lack of effective treatment strategies in order to control the disease at its earliest (micro)metastatic stage. The aim of this study was to assess safety, tolerability, and biochemical response of off-label Radium-223 (Xofigo) treatment in CaP patients with PSA relapse following maximal local therapy. METHODS: We conducted a prospective, single arm, single center open-label, pilot study with Radium-223 in CaP patients with rising PSA (>0.2 ng/ml) following RP + adjuvant/salvage RT. Negative staging with 68Ga-PSMA-11 PET/CT and whole-body MRI was mandatory at time of inclusion. Patients were eligible if they exhibited adverse clinico-pathological features predictive of significant recurrence. Safety, tolerability, biochemical progression (defined as PSA increase >50% from PSA nadir) and clinical recurrence were assessed. RESULTS: In total, 23 patients were screened of whom 8 patients were included is the study. Radium-223 treatment was safe with no serious treatment related adverse events. One patient developed grade 3 lymphopenia. All patients rapidly developed PSA progression (median PSA progression-free survival: 5.5 months). Eventually all patients experienced clinical recurrence (median clinical recurrence-free survival 11.0 months) of whom only 2 patients developed skeletal recurrence. CONCLUSIONS: Radium-223 in patients with PSA relapse following maximal local treatment without clinical metastases is safe. However, the clinical benefit of Ra-223 in this setting is doubtful as significant oncological benefit is lacking.

Supportive care needs and utilization of bladder cancer patients undergoing radical cystectomy: A longitudinal study.

OBJECTIVES: Investigating supportive care (SC) needs and utilization/willingness to use SC services from diagnosis to one year after radical cystectomy in bladder cancer (BC) patients. MATERIALS & METHODS: A longitudinal cohort study was conducted in 90 BC patients at Ghent/Leuven University Hospitals between April 2017 and December 2020. The Supportive Care Needs Survey-short form (SCNS-SF34) was used before radical cystectomy, one, three, six and 12 months after radical cystectomy. Additional questions assessed utilization/willingness to use SC services. Linear mixed models were performed. RESULTS: The majority of BC patients report at least one moderate or high SC need at diagnosis (82%), month 1 (84%), month 3 (86%), month 6 (64%), and month 12 (60%). Significant decreases over time were seen for all domains (p < 0.001), except for sexuality (p = 0.275). From baseline to month 1, physical needs first significantly increased (p = 0.001) after which they decreased. Psychological (e.g. fears about the future) and informational (e.g. information on how to get better) needs were most common at baseline whereas physical (e.g. lack of energy) and informational needs were more common in the early postoperative phases. The majority of patients (ranging from 81% (month 1) to 91% (month 12)) did not make use of SC services and the majority of the patients (ranging from 81% (month 1) to 88% (month 12)) did not wish to talk about their problems to someone. Those willing to talk to someone preferred their physician. CONCLUSIONS: A clear gap exists between the large proportion of SC needs experienced by BC patients undergoing radical cystectomy and the low use of SC services.

Prospective comparison of simultaneous [68Ga]Ga-PSMA-11 PET/MR versus PET/CT in patients with biochemically recurrent prostate cancer.

OBJECTIVES: PSMA-PET has become the PET technique of choice to localise the site of biochemically recurrent prostate cancer (PCa). With hybrid PET/MRI, the advantages of MRI are added to molecular characteristic of PET. The aim of this study was to investigate the incremental value of PET/MR versus PET/CT in patients with biochemically recurrent PCa by head-to-head comparison. METHODS: Thirty-four patients with biochemically recurrent PCa were prospectively included. They underwent [68Ga]Ga-PSMA-11 PET/CT, followed by simultaneous PET/MR. All PET (PETCT, PETMR), CT and MR images were evaluated for number of lesions and location. The number of lesions at specific sites was compared using Wilcoxon-sign-rank test. For PET, the maximum and mean standardised uptake values (SUVs) were calculated for each lesion compared using a two-sided paired t test. RESULTS: PETCT and PETMR scans were positive in 19 and 20 patients, detecting 73 and 79 lesions respectively. All lesions detected on PETCT were also detected on PETMR. CT and MRI only were positive in 14 and 17 patients, detecting 38 and 50 lesions, respectively, which was significantly lower than PETCT and PETMR respectively. Combined interpretation showed more lesions on PET/MR than on PET/CT (88 vs 81). No significant difference in detection of presence of local recurrence nor distant metastases was found. SUVmean and SUVmax values were significantly higher on PETMR than on PETCT in local recurrence and lymph node metastases. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/MR was able to detect biochemically recurrent PCa at least as accurately as PET/CT for local recurrence, lymph node metastasis and distant metastasis. KEY POINTS: • PSMA PET/MRI detects the location of biochemical recurrence at least as accurately as PET/CT. • Substitution of PET/CT by PET/MRI adds sensitivity in PSMA lesion detection also in the setting of distant recurrence due to both the MR and TOF PET components.

Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.

Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens. However, despite results from these studies demonstrating a reduction in positive surgical margins and tumour volume, no benefit has been observed in hard oncological end points, such as cancer-related death. The introduction of potent androgen receptor signalling inhibitors (ARSIs), such as abiraterone, apalutamide, enzalutamide and darolutamide, has led to a renewed interest in using neoadjuvant hormonal treatment in high-risk prostate cancer. The addition of ARSIs to androgen deprivation therapy has demonstrated substantial survival benefits in the metastatic castration-resistant, non-metastatic castration-resistant and metastatic hormone-sensitive settings. Intuitively, a similar survival effect can be expected when applying ARSIs as a neoadjuvant strategy in high-risk prostate cancer. Most studies on neoadjuvant ARSIs use a pathological end point as a surrogate for long-term oncological outcome. However, no consensus yet exists regarding the ideal definition of pathological response following neoadjuvant hormonal therapy and pathologists might encounter difficulties in determining pathological response in hormonally treated prostate specimens. The neoadjuvant setting also provides opportunities to gain insight into resistance mechanisms against neoadjuvant hormonal therapy and, consequently, to guide personalized therapy.

X-ray videocystometry for high-speed monitoring of urinary tract function in mice.

Lower urinary tract dysfunction (LUTd) represents a major health care problem with a high, unmet medical need. Design of additional therapies for LUTd requires precise tools to study bladder storage and voiding (dys)function in animal models. We developed videocystometry in mice, combining intravesical pressure measurements with high-speed fluoroscopy of the urinary tract. Videocystometry substantially outperforms current state-of-the-art methods to monitor the urine storage and voiding process, by enabling quantitative analysis of voiding efficiency, urethral flow, vesicoureteral reflux, and the relation between intravesical pressure and flow, in both anesthetized and awake, nonrestrained mice. Using videocystometry, we identified localized bladder wall micromotions correlated with different states of the filling/voiding cycle, revealed an acute effect of TRPV1 channel activation on voiding efficiency, and pinpointed the effects of urethane anesthesia on urine storage and urethral flow. Videocystometry has broad applications, ranging from the elucidation of molecular mechanisms of bladder control to drug development for LUTd.

Longitudinal Follow-Up of Urinary Tract Infections and Their Treatment in Mice using Bioluminescence Imaging.

Urinary tract infections (UTI) rank among the most common bacterial infections in humans and are routinely treated with empirical antibiotics. However, due to increasing microbial resistance, the efficacy of the most used antibiotics has declined. To find alternative treatment options, there is a great need for a better understanding of the UTI pathogenesis and the mechanisms that determine UTI susceptibility. In order to investigate this in an animal model, a reproducible, non-invasive assay to study the course of UTI is indispensable. For years, the gold standard for the enumeration of bacterial load has been the determination of Colony Forming Units (CFU) for a particular sample volume. This technique requires post-mortem organ homogenates and serial dilutions, limiting data output and reproducibility. As an alternative, bioluminescence imaging (BLI) is gaining popularity to determine the bacterial load. Labeling pathogens with a lux operon allow for the sensitive detection and quantification in a non-invasive manner, thereby enabling longitudinal follow-up. So far, the adoption of BLI in UTI research remains limited. This manuscript describes the practical implementation of BLI in a mouse urinary tract infection model. Here, a step-by-step guide for culturing bacteria, intravesical instillation and imaging is provided. The in vivo correlation with CFU is examined and a proof-of-concept is provided by comparing the bacterial load of untreated infected animals with antibiotic-treated animals. Furthermore, the advantages, limitations, and considerations specific to the implementation of BLI in an in vivo UTI model are discussed. The implementation of BLI in the UTI research field will greatly facilitate research on the pathogenesis of UTI and the discovery of new ways to prevent and treat UTI.