Purpose Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore... Show morePurpose Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients.Methods One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey (R). Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method.Results Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of "cannot answer" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions).Conclusions This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines. Show less
The introduction of the tethered DROP-IN gamma probe has enabled targeted robot-assisted radioguided prostate cancer (PCa) resection of pelvic sentinel lymph nodes (SLNs) and prostate-specific... Show moreThe introduction of the tethered DROP-IN gamma probe has enabled targeted robot-assisted radioguided prostate cancer (PCa) resection of pelvic sentinel lymph nodes (SLNs) and prostate-specific membrane antigen (PSMA)-positive lesions. While both procedures use Tc-99m-isotopes, the two vary in signal and background intensity. To understand how the different levels of image guidance impact surgical decision-making, computer-vision algorithms are used to extract the DROP-IN probe kinematic form clinical videos. 44 PCa patients undergo SLN (25) and PSMA-targeted (19) resections. PSMA-PET/CT and SPECT/CT create preoperative roadmaps, and intraoperative probe signal intensities are recorded. Using neural network-based software, probe trajectories are extracted from videos to extract multiparametric kinematics and generate decision-making and dexterity scores. PSMA-targeted resections yield significantly lower nodal signal intensities in preoperative SPECT-CT scans (three-fold; p = 0.01), intraoperative probe readouts (eight-fold; p < 0.001), and signal-to-background ratios (SBR; two-fold; p < 0.001). Kinematics assessment reveal that the challenges encounter during PSMA-targeted procedures converted to longer target identification times and increase in probe pick-ups (both five-fold; p < 0.001). This results in a fourfold reduction in the decision-making score (p < 0.001). Reduced signal intensities and intraoperative SBR values negatively affect the impact that image-guided surgery strategies have on the surgical decision-making process. Show less
Background Targeted real-time imaging during robot-assisted radical prostatectomy provides information on the localisation and extent of prostate cancer. We assessed the safety and feasibility of... Show moreBackground Targeted real-time imaging during robot-assisted radical prostatectomy provides information on the localisation and extent of prostate cancer. We assessed the safety and feasibility of the prostate-specific membrane antigen (PSMA)-targeted fluorescent tracer OTL78 in patients with prostate cancer.Methods In this single-arm, phase 2a, feasibility trial with an adaptive design was carried out in The Netherlands Cancer Institute, Netherlands. Male patients aged 18 years or older, with PSMA PET-avid prostate cancer with an International Society of Urological Pathology (ISUP) grade group of 2 or more, who were scheduled to undergo robot-assisted radical prostatectomy with or without extended pelvic lymph node dissection were eligible. All patients had a robot-assisted radical prostatectomy using OTL78. Based on timing and dose, patients received a single intravenous infusion of OTL78 (0 center dot 06 mg/kg 1-2 h before surgery [dose cohort 1], 0 center dot 03 mg/kg 1-2 h before surgery [dose cohort 2], or 0 center dot 03 mg/kg 24 h before surgery [dose cohort 3]). The primary outcomes, assessed in all enrolled patients, were safety and pharmacokinetics of OTL78. This study is completed and is registered in the European Trial Database, 2019-002393-31, and the International Clinical Trials Registry Platform, NL8552, and is completed.Findings Between lune 29, 2020, and April 1, 2021, 19 patients were screened for eligibility, 18 of whom were enrolled. The median age was 69 years (IQR 64-70) and median prostate-specific antigen concentration was 15 ng/mL (IQR 9 center dot 3-22 center dot 0). In 16 (89%) of 18 patients, robot-assisted radical prostatectomy was accompanied by an extended pelvic lymph node dissection. Three serious adverse events occurred in one (6%) patient: an infected lymphocele, a urosepsis, and an intraperitoneal haemorrhage. These adverse events were considered unrelated to the administration of OTL78 or intraoperative fluorescence imaging. No patient died, required a dose reduction, or required discontinuation due to drug-related toxicity. The dose-normalised maximum serum concentration (Cmax/dose) in patients was 84 center dot 1 ng/mL/mg for the 0 center dot 03 mg/kg dose and 79 center dot 6 ng/mL/mg for the 0 center dot 06 mg/kg dose, the half-life was 5 center dot 1 h for the 0 center dot 03 mg/kg dose and 4 center dot 7 h for the 0 center dot 06 mg/kg dose, the volume of distribution was 22 center dot 9 L for the 0 center dot 03 mg/kg dose and 19 center dot 5 L for the 0 center dot 06 mg/kg dose, and the clearance was 3 center dot 1 L/h for the 0 center dot 03 mg/kg dose and 3 center dot 0 L/h for the 0 center dot 06 mg/kg dose.Interpretation This first-in-patient study showed that OTL78 was well tolerated and had the potential to improve prostate cancer detection. Optimal dosing was 0 center dot 03 mg/kg, 24 h preoperatively. PSMA-directed fluorescence imaging allowed real-time identification of visually occult prostate cancer and might help to achieve complete oncological resections.Funding On Target Laboratories. Show less
Wit, E.M.K.; KleinJan, G.H.; Berrens, A.C.; Vliet, R. van; Leeuwen, P.J. van; Buckle, T.; ... ; Poel, H.G. van der 2023
ObjectiveTo determine the diagnostic accuracy of the hybrid tracer indocyanine green (ICG)-Technetium-99 m(Tc-99m)-nanocolloid compared to sequential tracers of Tc-99m-nanocolloid and free-ICG in... Show moreObjectiveTo determine the diagnostic accuracy of the hybrid tracer indocyanine green (ICG)-Technetium-99 m(Tc-99m)-nanocolloid compared to sequential tracers of Tc-99m-nanocolloid and free-ICG in detecting tumor-positive lymph nodes (LN) during primary surgery in prostate cancer (PCa) patients.IntroductionImage-guided surgery strategies can help visualize individual lymphatic drainage patterns and sentinel lymph nodes (SLNs) in PCa patients. For lymphatic mapping radioactive, fluorescent and hybrid tracers are being clinically exploited. In this prospective randomized phase II trial, we made a head-to-head comparison between ICG-Tc-99m-nanocolloid (hybrid group) and Tc-99m-nanocolloid and subsequent free-ICG injection (sequential group).MethodsPCa patients with a >5% risk of lymphatic involvement according to the 2012 Briganti nomogram and planned for prostatectomy were included and randomized (1:1) between ultrasound-guided intraprostatic tracer administration of ICG-Tc-99m-nanocolloid (n = 69) or Tc-99m-nanocolloid (n = 69) 5 h before surgery. Preoperative lymphoscintigraphy and SPECT/CT were performed to define the locations of the SLNs. Additionally, all participants in the sequential group received an injection of free-ICG at time of surgery. Subsequently, all (S)LNs were dissected using fluorescence guidance followed by an extended pelvic lymph node dissection (ePLND). The primary outcome was the total number of surgically removed (S)LNs and tumor-positive (S)LNs.ResultsThe total number of surgically removed (S)LN packages was 701 and 733 in the hybrid and sequential groups, respectively (p = 0.727). The total number of fluorescent LNs retrieved was 310 and 665 nodes in the hybrid and sequential groups, respectively (p < 0.001). However, no statistically significant difference was observed in the corresponding number of tumor-positive nodes among the groups (44 vs. 33; p = 0.470). Consequently, the rate of tumor-positive fluorescent LNs was higher in the hybrid group (7.4%) compared to the sequential group (2.6%; p = 0.002), indicating an enhanced positive predictive value for the hybrid approach. There was no difference in complications within 90 days after surgery (p = 0.78).ConclusionsThe hybrid tracer ICG-Tc-99m-nanocolloid improved the positive predictive value for tumor-bearing LNs while minimizing the number of fluorescent nodes compared to the sequential tracer approach. Consequently, the hybrid tracer ICG-Tc-99m-nanocolloid enables the most reliable and minimal invasive method for LN staging in PCa patients. Show less
BackgroundLymph node (LN) metastasis is a relevant predictor for survival in patients with a.o. penile cancer (PeCa), malignant melanoma. The sentinel node (SN) procedure comprises targeted... Show moreBackgroundLymph node (LN) metastasis is a relevant predictor for survival in patients with a.o. penile cancer (PeCa), malignant melanoma. The sentinel node (SN) procedure comprises targeted resection of the first tumour-draining SNs. Here, the hybrid tracer indocyanine green (ICG)-Tc-99m-nanocolloid has been used for several years to combine optical and nuclear detection. Recently, the resource of the nanocolloid precursor stopped production and the precursor was replaced by a different but chemically comparable colloid, nanoscan. Our aim was to study the performance of ICG-Tc-99m-nanoscan compared to ICG-Tc-99m-nanocolloid from a nuclear and surgical perspective.MethodsTwenty-four patients with either PeCa or head-and-neck (H&N) melanoma and scheduled for a SN procedure were included. The initial group (n = 11) received ICG-Tc-99m-nanocolloid until no longer available; the second group (n = 13) received ICG-Tc-99m-nanoscan. Tracer uptake was assessed on lymphoscintigraphy and single-photon emission (SPECT). Intraoperatively, SNs were identified using gamma tracing and fluorescence imaging. Ex vivo (back-table) measurements were conducted to quantify the fluorescence emissions. Chemical analysis was performed to compare the ICG assembly on both precursors.ResultsThe mean tracer uptake in the SNs was similar for ICG-Tc-99m-nanocolloid (2.2 +/- 4.3%ID) and ICG-Tc-99m-nanoscan (1.8 +/- 2.6%ID; p = 0.68). 3 SNs (interquartile range (IQR) 3-4) were detected on lymphoscintigraphy in PeCa patients receiving ICG-Tc-99m-nanoscan compared to 2 SNs (IQR 2-3) in PeCa patients receiving ICG-Tc-99m-nanocolloid (p = 0.045), no differences were observed in H&N patients. Back-table measurements of resected SNs revealed a lower total fluorescence intensity in the ICG-Tc-99m-nanoscan group (24*10(9) arbitrary units (A.U) IQR 1.6*10(9)-14*10(9) in the ICG-Tc-99m-nanocolloid group versus 4.6*10(9) A.U. IQR 2.4*10(9)-42*10(9) in the ICG-Tc-99m-nanoscan group, p = 0.0054). This was consistent with a larger degree of "stacked" ICG observed in the nanoscan formulation. No tracer-related adverse events were reported.ConclusionsBased on this retrospective analysis, we can conclude that ICG-Tc-99m-nanoscan has similar capacity for SN identification as ICG-Tc-99m-nanocolloid and can safely be implemented in SN procedures. Show less
Barros, H.A. de; Duin, J.J.; Mulder, D.; Noort, V. van der; Noordzij, M.A.; Wit, E.M.K.; ... ; Poel, H.G. van der 2023
Background: Accurate identification of men who harbor nodal metastases is neces-sary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of... Show moreBackground: Accurate identification of men who harbor nodal metastases is neces-sary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of diagnostic imaging approaches for the detection of nodal micrometastases has led to the exploration of the sentinel lymph node biopsy (SLNB). Objective: To evaluate whether SLNB can be used as a tool to select pathologically node-positive patients who likely benefit from WPRT. Design, setting, and participants: We included 528 clinically node-negative primary prostate cancer (PCa) patients with an estimated nodal risk of >5% treated between 2007 and 2018. Intervention: A total of 267 patients were directly treated with prostate-only radio-therapy (PORT; non-SLNB group), while 261 patients underwent SLNB to remove lymph nodes directly draining from the primary tumor prior to radiotherapy (SLNB group); pN0 patients were treated with PORT, while pN1 patients were offered WPRT. Outcome measurements and statistical analysis: Biochemical recurrence-free survival (BCRFS) and radiological recurrence-free survival (RRFS) were compared using propensity score weighted (PSW) Cox proportional hazard models. Results and limitations: The median follow-up was 71 mo. Occult nodal metastases were found in 97 (37%) SLNB patients (median metastasis size: 2 mm). Adjusted 7-yr BCRFS rates were 81% (95% confidence interval [CI] 77-86%) in the SLNB group and 49% (95% CI 43-56%) in the non-SLNB group. The corresponding adjusted 7-yr RRFS rates were 83% (95% CI 78-87%) and 52% (95% CI 46-59%), respectively. In the PSW multivariable Cox regression analysis, SLNB was associated with improved BCRFS (hazard ratio [HR] 0.38, 95% CI 0.25-0.59, p < 0.001) and RRFS (HR 0.44, 95% CI 0.28-0.69, p < 0.001). Limitations include the bias inherent to the study's Conclusions: SLNB-based selection of pN1 PCa patients for WPRT was associated efit from the addition of pelvis radiotherapy. This strategy results in a longer dura (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. Show less
Berrens, A.C.; Oosterom, M.N. van; Slof, L.J.; Leeuwen, F.W.B. van; Poel, H.G. van der; Buckle, T. 2022
Rationale: In muscle-invasive bladder cancer (MIBC), lymph node invasion has proven to be an independent predictor of disease recurrence and cancer-specific survival. We evaluated the feasibility... Show moreRationale: In muscle-invasive bladder cancer (MIBC), lymph node invasion has proven to be an independent predictor of disease recurrence and cancer-specific survival. We evaluated the feasibility of targeting the sentinel node (SN) for biopsy in MIBC patients using the hybrid tracer indocyanine green (ICG)-Tc-99m-nanocolloid for simultaneous radioguidance and fluorescence guidance. Methods: Twenty histologically confirmed cN0M0 MIBC patients (mean age, 63.3 years; range, 30-82 years), scheduled for radical cystectomy with SN biopsy and extended pelvic lymph node dissection (ePLND), were prospectively included. Twelve patients were operated on following neoadjuvant chemotherapy. The patients received lymphoscintigraphy as well as SPECT/CT after 4 transurethral injections of ICG-Tc-99m-nanocolloid (mean, 208 MBq; range, 172-229 MBq) around the tumor/scar in the detrusor muscle of the bladder on the day before radical cystectomy. Sentinel node resection was performed under radioguidance and fluorescence guidance. Results: Nineteen patients could be analyzed. On preoperative imaging, SNs could be identified in 10 patients (53%; mean, 1.6 SN/patient), which revealed drainage pathways outside the ePLND in 20% of the patients. Interesting to note is that 2 patients (10%) with preoperative nonvisualization displayed fluorescent and radioactive SNs during surgery. Location of the primary tumor near the left lateral side of the bladder seemed to be a factor for nonvisualization. Nodal harvesting with ePLND varied among patients (mean, 23.3). Histopathology confirmed tumor-positive nodes in 4 (21%) of all patients. In the 2 patients where an SN could be identified, the ePLND specimens were tumor-negative. All patients with tumor-positive nodes had advanced disease (stage III). Conclusion: Sentinel node biopsy in bladder cancer using the hybrid tracer ICG-Tc-99m-nanocolloid is feasible, and preoperative imaging is predictive for the ability to perform SN biopsy in 83% of the patients who displayed an SN. In patients with a successful preoperative SN mapping using lymphoscintigraphy and SPECT/CT, the intraoperative SN guidance and detection were effective, even outside the ePLND area. As such, this study underscores the critical role that preoperative imaging plays in challenging image-guided surgery applications. Show less
Azargoshasb, S.; Boekestijn, I.; Roestenberg, M.; KleinJan, G.H.; Hage, J.A. van der; Poel, H.G. van der; ... ; Leeuwen, F.W.B. van 2022
Purpose Surgical fluorescence guidance has gained popularity in various settings, e.g., minimally invasive robot-assisted laparoscopic surgery. In pursuit of novel receptor-targeted tracers, the... Show morePurpose Surgical fluorescence guidance has gained popularity in various settings, e.g., minimally invasive robot-assisted laparoscopic surgery. In pursuit of novel receptor-targeted tracers, the field of fluorescence-guided surgery is currently moving toward increasingly lower signal intensities. This highlights the importance of understanding the impact of low fluorescence intensities on clinical decision making. This study uses kinematics to investigate the impact of signal-to-background ratios (SBR) on surgical performance.Methods Using a custom grid exercise containing hidden fluorescent targets, a da Vinci Xi robot with Firefly fluorescence endoscope and ProGrasp and Maryland forceps instruments, we studied how the participants' (N=16) actions were influenced by the fluorescent SBR. To monitor the surgeon's actions, the surgical instrument tip was tracked using a custom video-based tracking framework. The digitized instrument tracks were then subjected to multi-parametric kinematic analysis, allowing for the isolation of various metrics (e.g., velocity, jerkiness, tortuosity). These were incorporated in scores for dexterity (Dx), decision making (DM), overall performance (PS) and proficiency. All were related to the SBR values.Results Multi-parametric analysis showed that task completion time, time spent in fluorescence-imaging mode and total pathlength are metrics that are directly related to the SBR. Below SBR 1.5, these values substantially increased, and handling errors became more frequent. The difference in Dx and DM between the targets that gave SBR <1.50 and SBR> 1.50, indicates that the latter group generally yields a 2.5-fold higher Dx value and a threefold higher DM value. As these values provide the basis for the PS score, proficiency could only be achieved at SBR> 1.55.Conclusion By tracking the surgical instruments we were able to, for the first time, quantitatively and objectively assess how the instrument positioning is impacted by fluorescent SBR. Our findings suggest that in ideal situations a minimum SBR of 1.5 is required to discriminate fluorescent lesions, a substantially lower value than the SBR 2 often reported in literature. Show less
Background: It has been proven that intraoperative prostate-specific membrane antigen (PSMA)-targeted radioguidance is valuable for the detection of prostate cancer (PCa) lesions during open... Show moreBackground: It has been proven that intraoperative prostate-specific membrane antigen (PSMA)-targeted radioguidance is valuable for the detection of prostate cancer (PCa) lesions during open surgery. Rapid extension of robot-assisted, minimally invasive surgery has increased the need to make PSMA-radioguided surgery (RGS) robot-compliant.Objective: To evaluate whether the miniaturized DROP-IN gamma probe facilitates translation of PSMA-RGS to robotic surgery in men with recurrent PCa.Design, setting, and participants: This prospective feasibility study included 20 patients with up to three pelvic PCa recurrences (nodal or local) on staging PSMA positron emission tomography (PET) after previous curative-intent therapy.Surgical procedure: Robot-assisted PSMA-RGS using the DROP-IN gamma probe was carried out 19-23 h after intravenous injection of (99m)technetium PSMA-Investigation & Surgery (Tc-99m-PSMA-I&S).Measurements: The primary endpoint was the feasibility of robot-assisted PSMA-RGS. Secondary endpoints were a comparison of the radioactive status (positive or negative) of resected specimens and final histopathology results, prostate-specific antigen (PSA) response following PSMA-RGS, and complications according to the Clavien-Dindo classification.Results and limitations: Using the DROP-IN probe, 19/21 (90%) PSMA-avid lesions could be resected robotically. On a per-lesion basis, the sensitivity and specificity of robot-assisted PSMA-RGS was 86% and 100%, respectively. A prostate-specific antigen (PSA) reduction of >50% and a complete biochemical response (PSA <0.2 ng/ml) were seen in 12/18 (67%) and 4/18 (22%) patients, respectively. During follow-up of up to 15 mo,* Corresponding author. Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands. Tel. +31 205126988. E-mail address: h.d.barros@nki.nl (H.A. de Barros) Show less
Given the high risk of systemic relapse following initial therapy for muscle-invasive bladder cancer (MIBC), improved pretreatment staging is needed. We evaluated the incremental value of 18F... Show moreGiven the high risk of systemic relapse following initial therapy for muscle-invasive bladder cancer (MIBC), improved pretreatment staging is needed. We evaluated the incremental value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) after standard conventional staging, in the largest cohort of MIBC patients to date. This is a retrospective analysis of 711 consecutive patients with invasive urothelial bladder cancer who underwent staging contrast-enhanced CT (chest and abdomen) and FDG-PET/CT in a tertiary referral center between 2011 and 2020. We recorded the clinical stage before and after FDG-PET/CT and treatment recommendation based on the stage before and after FDG-PET/CT. Clinical stage changed after FDG-PET/CT in 184/711 (26%) patients. Consequently, the recommended treatment strategy based on imaging changed in 127/711 (18%) patients. In 65/711 (9.1%) patients, potential curative treatment changed to palliative treatment because of the detection of distant metastases by FDG-PET/CT. Fifty (7.0%) patients were selected for neoadjuvant/induction chemotherapy based on FDG-PET/CT. Moreover, FDG-PET/CT detected lesions suspicious for second primary tumors in 15%; a second primary malignancy was confirmed in 28/711 (3.9%), leading to treatment change in ten (1.4%) patients. Contrarily 57/711 (8.1%) had false positive secondary findings. In conclusion, FDG-PET/CT provides important incremental staging information, which potentially influences clinical management in 18% of MIBC patients, but leads to false positive results as well. Show less
Fluorescence imaging is increasingly being implemented in surgery. One of the drawbacks of its application is the need to switch back-and-forth between fluorescence- and white-light-imaging... Show moreFluorescence imaging is increasingly being implemented in surgery. One of the drawbacks of its application is the need to switch back-and-forth between fluorescence- and white-light-imaging settings and not being able to dissect safely under fluorescence guidance. The aim of this study was to engineer 'click-on' fluorescence detectors that transform standard robotic instruments into molecular sensing devices that enable the surgeon to detect near-infrared (NIR) fluorescence in a white-light setting. This NIR-fluorescence detector setup was engineered to be press-fitted onto standard forceps instruments of the da Vinci robot. Following system characterization in a phantom setting (i.e., spectral properties, sensitivity and tissue signal attenuation), the performance with regard to different clinical indocyanine green (ICG) indications (e.g., angiography and lymphatic mapping) was determined via robotic surgery in pigs. To evaluate in-human applicability, the setup was also used for ICG-containing lymph node specimens from robotic prostate cancer surgery. The resulting Click-On device allowed for NIR ICG signal identification down to a concentration of 4.77 x 10(-6) mg/ml. The fully assembled system could be introduced through the trocar and grasping, and movement abilities of the instrument were preserved. During surgery, the system allowed for the identification of blood vessels and assessment of vascularization (i.e., bowel, bladder and kidney), as well as localization of pelvic lymph nodes. During human specimen evaluation, it was able to distinguish sentinel from non-sentinel lymph nodes. With this introduction of a NIR-fluorescence Click-On sensing detector, a next step is made towards using surgical instruments in the characterization of molecular tissue aspects. Show less
Context: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa)... Show moreContext: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa).Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy.Evidence acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed.Evidence synthesis: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, >= 80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy.Conclusions: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement <= 50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified.Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter). (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. Show less
Objective To determine the incidence and types of complications after dynamic sentinel node biopsy (DSNB) in patients with penile cancer (PeCa) and identify risk factors for the occurrence of... Show moreObjective To determine the incidence and types of complications after dynamic sentinel node biopsy (DSNB) in patients with penile cancer (PeCa) and identify risk factors for the occurrence of postoperative complications. Patients and Methods We evaluated 644 patients with PeCa (1284 DSNB procedures) with at least one clinically node negative (cN0) groin who underwent DSNB between 2011 and 2020 at a single high-volume centre. The 30- and 30-90-day postoperative complications were collected according to the modified Clavien-Dindo classification and the standardised methodology proposed by the European Association of Urology panel. Uni- and multivariable generalised linear mixed models were used to identify risk factors for the occurrence of complications per groin. Results A 30-day postoperative complication occurred in 14% of groins (n = 186), of which 94% were mild to moderate. Wound infection and lymphocele formation were most common. A 30-90-day postoperative complication occurred in 3.4% of the groins, all of which were mild or moderate (Grade I-II). The number of removed lymph nodes (LNs) per groin was the main independent predictor for any 30-day complications and Grade >= II complications (odds ratio 1.40; P < 0.001). There was an increase in the probability of postoperative complications with the number of LNs removed after accounting for all confounders. Conclusions Despite being less morbid than (modified) inguinal LN dissection, DSNB is still associated with a considerable risk of postoperative mild-to-moderate complications. This risk increases with increasing number of LNs removed. Further procedural refinement aimed at removing the true sentinel node(s) only, may help further reduce the morbidity of surgical staging in PeCa. Show less
Prostate-specific membrane antigen-targeted positron emission tomography has revolutionized prostate cancer diagnostics and holds the potential to advance metastases-directed therapy through, among... Show moreProstate-specific membrane antigen-targeted positron emission tomography has revolutionized prostate cancer diagnostics and holds the potential to advance metastases-directed therapy through, among other treatments, ablative radiotherapy. Show less
Dell'Oglio, P.; Turri, F.; Larcher, A.; D'Hondt, F.; Sanchez-Salas, R.; Bochner, B.; ... ; YAU Working Grp Robot-Assisted Sur 2022
Robot-assisted radical cystectomy (RARC) continues to expand, and several surgeons start training for this complex procedure. This calls for the development of a structured training program, with... Show moreRobot-assisted radical cystectomy (RARC) continues to expand, and several surgeons start training for this complex procedure. This calls for the development of a structured training program, with the aim to improve patient safety during RARC learning curve. A modified Delphi consensus process was started to develop the curriculum structure. An online survey based on the available evidence was delivered to a panel of 28 experts in the field of RARC, selected according to surgical and research experience, and expertise in running training courses. Consensus was defined as >80% agreement between the responders. Overall, 96.4% experts completed the survey. The structure of the RARC curriculum was defined as follows: (1) theoretical training; (2) preclinical simulation-based training: 5-d simulation-based activity, using models with increasing complexity (ie, virtual reality, and dry-and wet-laboratory exercises), and nontechnical skills training session; (3) clinical training: modular console activity of at least 6 mo at the host center (a RARC case was divided into 11 steps and steps of similar complexity were grouped into five modules); and (4) final evaluation: blind review of a video-recorded RARC case. This structured training pathway will guide a starting surgeon from the first steps of RARC toward independent completion of a full procedure. Clinical implemen-tation is urgently needed. Patient summary: Robot-assisted radical cystectomy (RARC) is a complex procedure. The first structured training program for RARC was developed with the goal of aiding surgeons to overcome the learning curve of this procedure, improving patients' safety at the same time. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could... Show moreIn penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal-epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). Methods: EMI137 tracer performance was initially assessed ex vivo (n = 10) via incubation of freshly excised pSCC in a solution containing EMI137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumor visualization was assessed after intravenous administration of EMI-137 to 5 pSCC patients scheduled for surgical resection using a cyanine-5 fluorescence camera. Fluorescence imaging results were related to standard pathologic tumor evaluation and c-MET immunohistochemistry. Three of the 5 in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green- 99mTc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. Results: No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET-based tumor visualization in all patients. Histopathologic analyses showed that all pSCCs expressed c-MET, with expression levels of at least 70% in 14 of 15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumors, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumor targeting with lymphatic mapping. As such, simultaneous use of cyanine-5 and indocyanine green in the same patient proved to be approach. Show less
Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of... Show moreDevelopments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2'd European Congress on Image-guided surgery. This multidisciplinary survey included questions on the conceptual potential and clinical value of image-guided surgery and was aimed at defining specific areas of research and development in the field in order to stimulate further advances towards precision surgery. Obtained results based on questionnaires filled in by 56 panel experts (clinicians: N=30, researchers: N=20 and industry: N=6) were discussed during a dedicated expert discussion session during the conference. The outcome of this Delphi consensus is indicative of the potential improvements offered by image-guided surgery and of the need for further research in this emerging-field, that can be enriched by the identification of reliable molecular targets. Show less
