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
Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) for non-metastatic bladder cancer (BCa) are limited. The purpose of this study is to describe long-term... Show moreLong-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) for non-metastatic bladder cancer (BCa) are limited. The purpose of this study is to describe long-term oncologic outcomes of patients receiving robotic radical cystectomy at a high-volume European Institution. We analyzed data of 107 patients treated with RARC between 2003 and 2012 at a high-volume robotic center. Clinical, pathologic, and survival data at the latest follow-up were collected. Clinical recurrence (CR)-free survival, cancer-specific mortality (CSM)-free survival, and overall survival (OS) were plotted using Kaplan-Meier survival curves. Cox proportional hazard models investigated predictors of CR and CSM. Competing-risk regressions were utilized to depict cumulative incidences of death from BCa and death from other causes after RARC at long term. Pathologic nonorgan-confined BCa was found in 40% of patients, and 7 (7%) patients had positive soft tissue surgical margins. Median (interquartile range [IQR]) number of nodes removed was 11 (6, 14), and 26% of patients had pN + disease. Median (IQR) follow-up for survivors was 123 (117, 149) months. The 12-year CR-free, CSM-free and overall survival were 55% (95% confidence interval [CI] 44%, 65%), 62% (95% CI 50%, 72%), and 34% (95% CI 24%, 44%), respectively. Nodal involvement on final pathology was associated with poor prognosis on multivariable competing risk analysis. The cumulative incidence of non-cancer death exceeded that of death from BCa after approximately ten years after RARC. We provided relevant data on oncologic outcomes of RARC at a high-volume robotic center, with acceptable rates of clinical recurrence and cancer-specific survival at long-term. In patients treated with RARC, the cumulative incidence of death from causes other than BCa is non-negligible, and should be taken into consideration for post-operative follow-up. Show less
Introduction: The survival benefit of inguinal lymph node dissection (ILND) vs no ILND in patients with squamous cell carcinoma of the penis (SCCP) and the absence of lymph node invasion is unclear... Show moreIntroduction: The survival benefit of inguinal lymph node dissection (ILND) vs no ILND in patients with squamous cell carcinoma of the penis (SCCP) and the absence of lymph node invasion is unclear. We addressed this uncertainty within the Surveillance, Epidemiology and End Results (SEER 2000-2018) database. Material and methods: We identified lymph node negative SCCP patients who either underwent ILND (pN0) or clinical examination only (cN0). We tested for the effect of ILND vs no ILND on cancer-specific mortality (CSM) in Kaplan-Meier plots, univariable and multivariable Cox regression analyses, in a pT stage-specific fashion, before and after 1:3 propensity score matching (PSM). Sensitivity analyses were conducted according to historical and contemporary treatment periods as well as geographic regions. Results: Of 2520 SCCP patients, 369 (15%) underwent ILND (pN0) vs 2151 (85%) did not (cN0). The pN0 vs cN0 distribution according to pT stages was as follows: 80 (7%) vs 1092 (93%) in pT1b, and 289 (21%) vs 1059 (79%) in pT2-3. At 36 months, CSM-free survival in pT2-3 stage was 89% in ILND vs 74% in no ILND patients (multivariable hazard ratio: 0.42, CI 0.30-0.60, p < 0.001). This result was confirmed in sensitivity analyses, and after 1:3 PSM. The same analyses could not be completed in pT1b stage due to insufficient number of observations and events. Conclusions: In pT2-3 stage SCCP, a significantly lower CSM was recorded in lymph node negative patients treated with ILND than in their clinical lymph node negative counterparts who did not undergo ILND. Show less
Background: Extended pelvic nodal dissection (ePLND) represents the gold standard for nodal staging in prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) radioguided surgery (RGS)... Show moreBackground: Extended pelvic nodal dissection (ePLND) represents the gold standard for nodal staging in prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) radioguided surgery (RGS) could identify lymph node invasion (LNI) during robotassisted radical prostatectomy (RARP).Objective: To report the planned interim analyses of a phase 2 prospective study (NCT04832958) aimed at describing PSMA-RGS during RARP.Design, setting, and participants: A phase 2 trial aimed at enrolling 100 patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging with a risk of LNI of >5% was conducted. Overall, 18 patients were enrolled between June 2021 and March 2022. Among them, 12 patients underwent PSMA-RGS and represented the study cohort.Surgical procedure: All patients received Ga-68-PSMA positron emission tomography (PET)/magnetic resonance imaging; Tc-99m-PSMA-I&S was synthesised and administered intravenously the day before surgery, followed by single-photon emission computed tomography/computed tomography. A Drop-In gamma probe was used for in vivo measurements. All positive lesions (count rate >= 2 compared with background) were excised and ePLND was performed.Measurements: Side effects, perioperative outcomes, and performance characteristics of robot-assisted PSMA-RGS for LNI were measured.Results and limitations: Overall, four (33%), six (50%), and two (17%) patients had intermediate-risk, high-risk, and locally advanced PCa. Overall, two (17%) patients had pathologic nodal uptake at PSMA PET. The median operative time, blood loss, and length of stay were 230 min, 100 ml, and 5 d, respectively. No adverse events and intraoperative complications were recorded. One patient experienced a 30-d complication (ClavienDindo 2; 8.3%). Overall, three (25%) patients had LNI at ePLND. At per-region analyses on 96 nodal areas, sensitivity, specificity, positive predictive value, and negative predictive value of PSMA-RGS were 63%, 99%, 83%, and 96%, respectively. On a per-patient level, sensitivity, specificity, positive predictive value, and negative predictive values of PSMA-RGS were 67%, 100%, 100%, and 90%, respectively.Conclusions: Robot-assisted PSMA-RGS in primary staging is a safe and feasible procedure characterised by acceptable specificity but suboptimal sensitivity, missing micrometastatic nodal disease.Patient summary: Prostate-specific membrane antigen radioguided robot-assisted surgery is a safe and feasible procedure for the intraoperative identification of nodal metastases in cN0cM0 prostate cancer patients undergoing robot-assisted radical prostatectomy with extended pelvic lymph node dissection. However, this approach might still miss micrometastatic nodal dissemination. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. Show less
Mazzone, E.; Dell'Oglio, P.; Grivas, N.; Wit, E.; Donswijk, M.; Briganti, A.; ... ; Poel, H. van der 2021
Despite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection ... Show moreDespite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection (ePLND) for prostate cancer is still controversial. For this reason, we aimed to define the added value of SNB (with different tracer modalities) to ePLND in the identification of nodal metastases. Complication rates and oncologic outcomes were also assessed. Methods: From January 2006 to December 2019, prospectively collected data were retrospectively analyzed from a single-institution database regarding prostate cancer patients treated with robot-assisted radical prostatectomy and ePLND with or without additional use of SNB, either with the hybrid tracer indocyanine green (ICG)-Tc-99m-nanocolloid or with free ICG. Multivariable logistic and Cox regression models tested the impact of adding SNB (either with the hybrid tracer or with free ICG) on lymph nodal invasion detection, complications, and oncologic outcomes. Results: Overall, 1,680 patients were included in the final analysis: 1,168 (69.5%) in the non-SNB group, 161 (9.6%) in the ICG-SNB group, and 351 (20.9%) in the hybrid-SNB group. The hybrid-SNB group (odds ratio, 1.61; 95%CI, 1.18-2.20; P = 0.002) was an independent predictor of nodal involvement, whereas the ICG-SNB group did not reach independent predictor status when compared with the non-SNB group (odds ratio, 1.35; 95%CI, 0.89-2.03; P = 0.1). SNB techniques were not associated with higher rates of complications. Lastly, use of hybrid SNB was associated with lower rates of biochemical recurrence (0.79; 95%CI, 0.63-0.98) and of clinical recurrence (hazard ratio, 0.76, P = 0.035) than were seen in the non-SNB group. Conclusion: The implementation of hybrid-SNB technique with ICG-Tc-99m-nanocolloid in prostate cancer improves detection of positive nodes and potentially lowers recurrence rates with subsequent optimization of patient management, without harming patient safety. Show less
Stabile, A.; Dell'Oglio, P.; Soligo, M.; Cobelli, F. de; Gandaglia, G.; Fossati, N.; ... ; Briganti, A. 2021
Background: There is a lack of evidence on the ability of magnetic resonance imaging (MRI) of the prostate to detect clinically significant prostate cancer (csPCa) in young patients.Objective: We... Show moreBackground: There is a lack of evidence on the ability of magnetic resonance imaging (MRI) of the prostate to detect clinically significant prostate cancer (csPCa) in young patients.Objective: We hypothesised that the diagnostic performance of MRI for csPCa varies according to patient's age. To address this, we assessed the variation in the csPCa detection rate of MRI targeted biopsy (MRI-TBx) versus systematic random biopsy (SBx) across different patient ages.Design, setting, and participants: We retrospectively identified 930 patients who underwent prostate MRI and subsequent biopsy at two referral centres between 2013 and 2018. The Prostate Imaging Reporting and Data System (PI-RADS) was used for MRI reporting.Intervention: A lesion with a PI-RADS score of >= 3 detected at MRI received an MRI-TBx in addition to an SBx during the same session.Outcome measurements and statistical analysis: The outcome of our study was the relationship between age and csPCa detection rate at MRI-TBx and SBx, respectively. Clinically significant prostate cancer (PCa) was defined as the presence of PCa with Gleason score >= 3 + 4. Multivariable logistic regression analyses (MVAs) predicting csPCa detection were assessed for both MRI-TBx and SBx. Covariates were age, prostate-specific antigen density, PI-RADS score, previous biopsy status, digital rectal examination, and the number of targeted and systematic cores. The hypothesis that MRI accuracy in detecting csPCa differed by age was finally tested with a nonparametric loess analysis.Results and limitations: The overall rate of csPCa was 54% (n = 506). Overall, 325 (35%) and 461 (50%) patients had csPCa at SBx and MRI-TBx, respectively. The median numbers of SBx and MRI-TBx cores were 12 (interquartile range [IQR]: 10-13) and 5 (IQR: 4-7), respectively. At MVA, age at biopsy was an independent predictor of csPCa at MRI-TBx only (odds ratio: 1.05), after accounting for confounders. In men aged less than roughly 50 yr, SBx had a higher probability of detecting csPCa relative to MRI-TBx (25% vs 16% at 40 yr). Conversely, in patients aged >50 yr, the probability of csPCa was higher in MRI-TBx than in SBx, reaching the highest difference for very elderly patients (48% vs 68% at 80 yr). The main limitations were the retrospective design and the small number of young patients.Conclusions: In this study, we reported the performance of MRI and MRI-TBx in detecting csPCa changes according to patients' age.Patient summary: In young patients, the performance of a systematic random biopsy in detecting clinically significant prostate cancer (csPCa) is higher relative to magnetic resonance imaging targeted biopsy (MRI-TBx), reflecting the lower accuracy of MRI in younger men. Conversely, in older patients, MRI-TBx showed a clinical benefit with a higher csPCa detection rate compared with SBx, suggesting an increase of MRI accuracy with the increase of age. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
BACKGROUND: To examine the predictive value of neutrophil-to-lymphocyte ratio in localized prostate cancer for surgical pathology and recurrence in patients treated by radical prostatectomyMETHODS:... Show moreBACKGROUND: To examine the predictive value of neutrophil-to-lymphocyte ratio in localized prostate cancer for surgical pathology and recurrence in patients treated by radical prostatectomyMETHODS: We evaluated 1258 patients treated by radical prostatectomy at San Raffaele Hospital between 2011 and 2017 and assessed the association between preoperative neutrophil-to-lymphocyte ratio and surgical pathology (advanced stage, grade group >= 4, nodal involvement, grade discordance between biopsy and surgical pathology) and biochemical recurrence.RESULTS: The preoperative neutrophil-to-lymphocyte ratio was not significantly associated with advanced stage (>= T3), International Society of Urological Pathology (ISUP) grade (>= 4) or discordance. At multivariable analysis, patients with higher neutrophil-to-lymphocyte ratio had lower risk of nodal involvement at final pathology (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.64, 0.92; P=0.005). The preoperative level of neutrophil-to-lymphocyte ratio was associated with biochemical recurrence on univariate analysis (OR: 0.81, 95% CI: 0.68, 0.96; P=0.017). Such a relationship was not significant at multivariable analysis adjusting for tumor severity (OR: 0.93, 95% CI: 0.79, 1.09; P=0.4).CONCLUSIONS: Neutrophil-to-lymphocyte ratio does not have clinical utility for the prediction of adverse pathology and biochemical recurrence. Further research should focus on its value for predicting regional lymph node metastasis. Show less
Dell'Oglio, P.; Mazzone, E.; Grivas, N.; Wit, E.; Donswijk, M.; Briganti, A.; ... ; Poel, H. van der 2021
Despite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection ... Show moreDespite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection (ePLND) for prostate cancer is still controversial. For this reason, we aimed to define the added value of SNB (with different tracer modalities) to ePLND in the identification of nodal metastases. Complication rates and oncologic outcomes were also assessed. Methods: From January 2006 to December 2019, prospectively collected data were retrospectively analyzed from a single-institution database regarding prostate cancer patients treated with robot-assisted radical prostatectomy and ePLND with or without additional use of SNB, either with the hybrid tracer indocyanine green (ICG)–99mTc-nanocolloid or with free ICG. Multivariable logistic and Cox regression models tested the impact of adding SNB (either with the hybrid tracer or with free ICG) on lymph nodal invasion detection, complications, and oncologic outcomes. Results: Overall, 1,680 patients were included in the final analysis: 1,168 (69.5%) in the non-SNB group, 161 (9.6%) in the ICG-SNB group, and 351 (20.9%) in the hybrid-SNB group. The hybrid-SNB group (odds ratio, 1.61; 95%CI, 1.18–2.20; P = 0.002) was an independent predictor of nodal involvement, whereas the ICG-SNB group did not reach independent predictor status when compared with the non-SNB group (odds ratio, 1.35; 95%CI, 0.89–2.03; P = 0.1). SNB techniques were not associated with higher rates of complications. Lastly, use of hybrid SNB was associated with lower rates of biochemical recurrence (0.79; 95%CI, 0.63–0.98) and of clinical recurrence (hazard ratio, 0.76, P = 0.035) than were seen in the non-SNB group. Conclusion: The implementation of hybrid-SNB technique with ICG–99mTc-nanocolloid in prostate cancer improves detection of positive nodes and potentially lowers recurrence rates with subsequent optimization of patient management, without harming patient safety. Show less
Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private... Show moreProstate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. In this Perspectives article, the authors introduce the PIONEER project and describe its aims and plans for ultimately improving prostate cancer care through the use of big data. Show less
Witjes, J.A.; Babjuk, M.; Bellmunt, J.; Bruins, H.M.; Reijke, T.M. de; Santis, M. de; ... ; Horwich, A. 2020
Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To... Show moreBackground: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.Setting: Online Delphi survey and consensus conference.Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as >= 70% agreement and <= 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder canceir management until a time when further evidence is available to guide our approach.Patient summary: This report summarises findings from an international, multistake-holder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available. (C) 2019 European Society of Medical Oncology and European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
Maurer, T.; Graefen, M.; Poel, H. van der; Hamdy, F.; Briganti, A.; Eiber, M.; ... ; Leeuwen, F.W.B. van 2020
Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is... Show moreSince its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer. Show less
Horwich, A.; Babjuk, M.; Bellmunt, J.; Bruins, H.M.; Reijke, T.M. de; Santis, M. de; ... ; Witjes, J.A. 2019
Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To... Show moreBackground: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.Setting: Online Delphi survey and consensus conference.Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as >= 70% agreement and <= 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach. Show less
