Prostate-specific antigen (PSA) is a well-known clinical biomarker in prostate cancer (PCa) diagnosis, but a better test is still needed, as the serum-level-based PSA quantification exhibits... Show moreProstate-specific antigen (PSA) is a well-known clinical biomarker in prostate cancer (PCa) diagnosis, but a better test is still needed, as the serum-level-based PSA quantification exhibits limited specificity and comes with poor predictive value. Prior to PSA, prostatic acid phosphatase (PAP) was used, but it was replaced by PSA because PSA improved the early detection of PCa. Upon revisiting PAP and its glycosylation specifically, it appears to be a promising new biomarker candidate. Namely, previous studies have indicated that PAP glycoforms differ between PCa and non-PCa individuals. However, an in-depth characterization of PAP glycosylation is still lacking. In this study, we established an in-depth glycoproteomic assay for urinary PAP by characterizing both the micro- and macroheterogeneity of the PAP glycoprofile. For this purpose, PAP samples were analyzed by capillary electrophoresis coupled to mass spectrometry after affinity purification from urine and proteolytic digestion. The developed urinary PAP assay was applied on a pooled DRE (digital rectal examination) urine sample from nine individuals. Three glycosylation sites were characterized, namely N-94, N-220, and N-333, via N-glycopeptide analysis. Taking sialic acid linkage isomers into account, a total of 63, 27, and 4 N-glycan structures were identified, respectively. The presented PAP glycoproteomic assay will enable the determination of potential glycomic biomarkers for the early detection and prognosis of PCa in cohort studies. Show less
Berrens, A.C.; Scheltema, M.; Maurer, T.; Hermann, K.; Hamdy, F.C.; Knipper, S.; ... ; Leeuwen, F.W.B. van 2023
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
Schepens, M.H.J.; Hooff, M.L. van; Galien, O. van der; Plantes, C.M.P.Z. des; Somford, D.M.; Leeuwen, P.J. van; ... ; Limbeek, J. van 2023
BackgroundOn the basis of previous analyses of the incidence of urinary incontinence (UI) after radical prostatectomy (RP), the hospital RP volume threshold in the Netherlands was gradually... Show moreBackgroundOn the basis of previous analyses of the incidence of urinary incontinence (UI) after radical prostatectomy (RP), the hospital RP volume threshold in the Netherlands was gradually increased from 20 per year in 2017, to 50 in 2018 and 100 from 2019 onwards.ObjectiveTo evaluate the impact of hospital RP volumes on the incidence and risk of UI after RP (RP-UI).Design, setting, and participantsPatients who underwent RP during 2016–2020 were identified in the claims database of the largest health insurance company in the Netherlands. Incontinence was defined as an insurance claim for ≥1 pads/d.Outcome measurements and statistical analysisThe relationship between hospital RP volume (HV) and RP-UI was assessed via multivariable analysis adjusted for age, comorbidity, postoperative radiotherapy, and lymph node dissection.Results and limitationsRP-UI incidence nationwide and by RP volume category did not decrease significantly during the study period, and 5-yr RP-UI rates varied greatly among hospitals (19–85%). However, low-volume hospitals (≤120 RPs/yr) had a higher percentage of patients with RP-UI and higher variation in comparison to high-volume hospitals (>120 RPs/yr). In comparison to hospitals with low RP volumes throughout the study period, the risk of RP-UI was 29% lower in hospitals shifting from the low-volume to the high-volume category (>120 RPs/yr) and 52% lower in hospitals with a high RP volume throughout the study period (>120 RPs/yr for 5 yr).ConclusionsA focus on increasing hospital RP volumes alone does not seem to be sufficient to reduce the incidence of RP-UI, at least in the short term. Measurement of outcomes, preferably per surgeon, and the introduction of quality assurance programs are recommended.Patient summaryIn the Netherlands, centralization of surgery to remove the prostate (RP) because of cancer has not yet improved the occurrence of urinary incontinence (UI) after surgery. Hospitals performing more than 120 RP operations per year had better UI outcomes. However, there was a big difference in UI outcomes between hospitals. Show less
Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to... Show moreKetodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans. Show less
Dassen, M.G.; Janssen, T.; Kusters, M.; Pos, F.; Kerkmeijer, L.G.W.; Heide, U.A. van der; Bijl, E. van der 2023
PurposeTo quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate... Show morePurposeTo quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV).Materials and methodsClinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0–5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions.ResultsThe PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm.ConclusionATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations. Show less
Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely... Show moreNon-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center. Receiver operating characteristic curves were used to assess the positive (PPV) and negative (NPV) predictive values of QUS T-scores of 0, -1.0, and - 1.8 in identifying DXAdiagnosed osteoporosis (T-scores < - 2.5 and < -2) at lumbar spine and/or femoral neck. Complete sets of data were available in 256 patients, median age 70.9 (53.6-89.5) years; 93.0 % had received local treatment, 84.4 % with additional ADT. Prevalence of osteoporosis and osteopenia was respectively 10.5 % and 53 %. Mean QUS Tscore was -0.54 +/- 1.58. Whereas PPV at any QUS T-score was <25 %, precluding the use of QUS as surrogate for DXA in screening for osteoporosis, QUS T-scores of -1.0 to 0.0 had a NPV of >= 94.5 % for DXA T-scores < 2.5 and < -2 at any site, confidently identifying patients least likely to have osteoporosis, thereby significantly reducing the number of patients requiring DXA screening for diagnosing osteoporosis by up to two-third. Osteoporosis screening is a significant unmet need in non-metastatic prostate cancer patients treated with ADT, and QUS may represent a valuable alternative pre-screening strategy to overcome logistics, time demands, and economic barriers encountered with current strategies for osteoporosis screening in these patients. Summary: Osteoporosis and associated increased fracture risk are common in non-metastatic prostate carcinoma, mainly due to androgen deprivation therapy, but these often remain underdiagnosed and untreated. We demonstrate that QUS is a safe, less costly pre-screen tool that reduces by up to two-third the number of patients requiring referral for DXA for osteoporosis screening. 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
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
Mehra, N.; Kloots, I.; Vlaming, M.; Aluwini, S.; Dewulf, E.; Oprea-Lager, D.E.; ... ; Ausems, M. 2023
Background: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are... Show moreBackground: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined.Objective: To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa.Design, setting, and participants: The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting.Outcome measurements and statistical analysis: Consensus was reached if >75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method.Results and limitations: Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hered-itary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveil-lance was considered appropriate, except in case of the patient being a BRCA2 germ -line pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as fol-lows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline.Conclusions: The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa.Patient summary: A group of Dutch specialists discussed the use of germline and tumour genetic testing in prostate cancer (PCa) patients, indication of these tests (which patients and when), and impact of these tests on the management and treatment of PCa.(c) 2022 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. org/licenses/by/4.0/). Show less
Wit, E.M.K.; Beurden, F. van; Kleinjan, G.H.; Grivas, N.; Korne, C.M. de; Buckle, T.; ... ; Poel, H.G. van der 2021
Introduction Previous studies indicated that location and amount of detected sentinel lymph nodes (SLNs) in prostate cancer (PCa) are influenced where SLN-tracer is deposited within the prostate.... Show moreIntroduction Previous studies indicated that location and amount of detected sentinel lymph nodes (SLNs) in prostate cancer (PCa) are influenced where SLN-tracer is deposited within the prostate. To validate whether intratumoral (IT) tracer injection helps to increase identification of tumor-positive lymph nodes (LNs) better than intraprostatic (IP) tracer injection, a prospective randomized phase II trial was performed.Methods PCa patients with a > 5% risk of lymphatic involvement were randomized between ultrasound-guided transrectal injection of indocyanine green-[Tc-99m]Tc-nanocolloid in 2 depots of 1 mL in the tumor (n = 55, IT-group) or in 4 depots of 0.5 mL in the peripheral zone of the prostate (n = 58, IP-group). Preoperative lymphoscintigraphy and SPECT/CT were used to define the location of the SLNs. SLNs were dissected using combination of radio- and fluorescence-guidance, followed by extended pelvic LN dissection and robot-assisted radical prostatectomy. Outcome measurements were number of tumor-bearing SNs, tumor-bearing LNs, removed nodes, number of patients with nodal metastases, and metastasis-free survival (MFS) of 4-7-year follow-up data.Results IT-injection did not result in significant difference of removed SLNs (5.0 vs 6.0, p = 0.317) and histologically positive SLNs (28 vs 22, p = 0.571). However, in IT-group, the SLN-positive nodes were 73.7% of total positive nodes compared to 37.3% in IP-group (p = 0.015). Moreover, significantly more node-positive patients were found in IT-group (42% vs 24%, p = 0.045), which did not result in worse MFS. In two patients (3.6%) from whom the IT-tracer injection only partly covered intraprostatic tumor spread, nodal metastases in ePLND without tumor-positive SNs were yielded.Conclusions The percentage-positive SLNs found after IT-injection were significantly higher compared to IP-injection. Significantly more node-positive patients were found using IT-injection, which did not affect MFS. IT-injection failed to detect nodal metastases from non-index satellite lesions. Therefore, we suggest to combine IT- and IP-tracer injections in men with visible tumor on imaging. Show less
The relation between prostate-specific antigen (PSA) and other relevant prebiopsy information is often combined in a risk calculator (RC). If the setting for RC use differs from that in which it... Show moreThe relation between prostate-specific antigen (PSA) and other relevant prebiopsy information is often combined in a risk calculator (RC). If the setting for RC use differs from that in which it was developed, there is a risk of making clinical decisions based on incorrect estimates of the absolute risk. The ERSPC-MRI RC predicts clinically significant prostate cancer (csPC; Gleason >= 3 + 4) on targeted and systematic biopsy using information on PSA, digital rectal examination, prostate volume, age, previous negative biopsy, and Prostate Imaging-Recording and Data System score. This calculator was developed on a clinical cohort of 961 men (2012-2017) with a csPC prevalence of 36%. Discrimination was good (area under the receiver operating characteristic curve 0.84). With the increasing use of multiparametric magnetic resonance imaging, we foresee that this RC will also be used for men with a lower a priori likelihood of PC. We investigated the effect of such a scenario on individual risk predictions. A small update of the intercept for the calculator can restore the accuracy to support decision-making with locally valid risk estimates.Patient summary: Decisions on who to refer for a prostate biopsy with its risk of sepsis and overdiagnosis require more than a prostate-specific antigen test. A prediction tool may take other relevant prebiopsy information into account, but may need to be updated to contemporary center-specific settings to provide accurate estimates of the risk of having prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology. Show less
Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum... Show moreEarly detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum concentrations of prostate-specific antigen (PSA) as an indicator of risk. However, this test has been widely criticized as it shows poor specificity and sensitivity. In order to improve early detection and diagnosis, several studies have investigated whether different PSA proteoforms are correlated to prostate cancer. Until now, studies and methodologies for the comprehensive characterization of PSA proteoforms from biofluids are scarce. For this purpose, we developed an intact protein assay to analyze PSA by capillary electrophoresis-electrospray ionization-mass spectrometry after affinity purification from patients? urine. Here, we determined six proteolytic cleavage variants. In regard to glycosylation, tri-, di-, mono- and non-sialylated complex-type N-glycans were found on non-cleaved PSA, as well as the non-glycosylated variant. The performance of the intact protein assay was assessed using a pooled sample, obtaining an inter-day variability of 15%. Furthermore, urinary patient samples were analyzed by intact protein analysis and a bottom-up approach (glycopeptide analysis). This combined approach revealed complimentary information on both levels, demonstrating the benefit of using two orthogonal techniques to provide a thorough profile of urinary PSA.Significance: The detection of clinically relevant prostate cancer requires a more specific and sensitive biomarker and, in this case, several PSA proteoforms may be able to aid or improve the current PSA test. However, a comprehensive analysis of the intact PSA proteoform profile is still lacking. This study investigated the PSA proteoforms present in urine and, in particular, determined the relative contribution of cleaved PSA and noncleaved PSA forms to the total glycosylation profile. Importantly, intact protein analysis did not require further sample treatment before being measured by CE-ESI-MS. Furthermore, its glycosylation was also assessed in a bottom-up approach to provide complementary information. Overall, these results represent an important basis for future characterization and biomarker studies. Show less
Background: Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be... Show moreBackground: Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be delineated accurately.Objective: To describe and evaluate surgical technique, biochemical response, and therapy-free survival (TFS) after salvage surgery in patients with local recurrence in the seminal vesicle bed.Design, setting, and participants: We retrospectively assessed 40 patients treated with open salvage surgery in two centres (11/2014-02/2020). All patients presented with biochemical recurrence (BCR) after RP with a singular local recurrence at PSMA PET imaging. Thirty-three (82.5%) patients received previous salvage radiation therapy.Surgical procedure: Open salvage surgery with PSMA radioguidance.Measurements: Prostate-specific antigen (PSA) nadir and percentage of patients with complete biochemical response (cBR) without further treatment (PSA < 0.2 ng/ml) after 6-16 wk were assessed. BCR-free survival and TFS were calculated using Kaplan-Meier estimates. Clavien-Dindo complications were evaluated.Results and limitations: Prior to salvage surgery, median PSA was 0.9 ng/ml (interquartile range [IQR]: 0.5-1.7 ng/ml). Postoperatively, median PSA nadir was 0.1 ng/ml (IQR: 0-0.4 ng/ml). In 31 (77.5%) patients, cBR was observed. During the median follow-up of 24.4 months, 22 (55.0%) patients experienced BCR and 12 (30.0%) received further therapy. At 1 yr of follow-up, BCR-free survival rate was 62.2% and TFS rate was 88.3%. Three (7.5%) Clavien-Dindo grade III complications were observed. The main limitations are the retrospective design, short follow-up, and lack of a control group.Conclusions: Salvage surgery of local recurrence within the seminal vesicle bed is feasible. It may present an opportunity in selected, locally recurrent patients to prolong BCR-free survival and increase TFS. Further studies are needed to confirm our findings.Patient summary: We looked at the outcomes from prostate cancer patients with locally recurrent disease after radical prostatectomy and radiotherapy. We found that surgery in well-selected patients may be an opportunity to prolong treatment-free survival. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
Albers, L.F.; Tillier, C.N.; Muilekom, E. van; Werkhoven, E. van; Elzevier, H.W.; Rhijn, B.W.G. van; ... ; Hendricksen, K. 2021
Background: Preservation of erectile function is an important postoperative quality of life concern for patients after robot-assisted radical prostatectomy (RARP) for prostate cancer. Although... Show moreBackground: Preservation of erectile function is an important postoperative quality of life concern for patients after robot-assisted radical prostatectomy (RARP) for prostate cancer. Although erectile function may recover, many men continue to suffer from erectile dysfunction (ED).Aim: This study aims to determine whether satisfaction with sexual life improves in patients with ED after RARP and which factors are associated with satisfaction during follow-up.Methods: A review was carried out of a prospectively maintained database of patients with prostate cancer who underwent a RARP between 2006 and 2019. The 'International Index of Erectile Function' questionnaire was used to describe ED (range 5-25), overall satisfaction with sexual life and sexual desire (range for both: 2-10). Patients with ED due to RARP were compared with those without ED after RARP. Mixed effect model was used to test differences in satisfaction over time. Mann-Whitney U tests and multiple logistic regression were used to assess factors associated with being satisfied at 24 and 36 months.Outcomes: The main outcomes of this study are the overall satisfaction with sexual life score over time and factors which influence sexual satisfaction.Results: Data of 2808 patients were reviewed. Patients whose erectile function was not known (n = 643) or who had ED at the baseline (n = 1281) were excluded. About 884 patients were included for analysis. They had an overall satisfaction score of 8.4. Patients with ED due to RARP had mean overall satisfaction scores of 4.8, 4.8, 4.9, and 4.6 at 6 mo, 12 mo, 24 mo, and 36 mo. These scores were significantly lower than those of patients without ED at every time point. In multiple regression analysis, higher overall satisfaction score at the baseline and higher sexual desire at 24 and 36 months' follow-up were associated with satisfaction with sexual life at 24 and 36 months? follow-up. No association was found for erectile function.Clinical implications: Interventions focusing on adjustment to the changes in sexual functioning might improve sexual satisfaction; especially for those men who continue to suffer from ED.Strengths & Limitations: Strengths of this study are the large number of patients, time of follow-up, and use of multiple validated questionnaires. Our results must be interpreted within the limits of retrospectively collected, observational data.Conclusion: Satisfaction with sexual life in men with ED due to RARP may take a long time to improve. One could counsel patients that sexual satisfaction is based on individual baseline sexual satisfaction and the return of sexual desire after RARP. Copyright (C) 2020, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine. Show less
Background: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the... Show moreBackground: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.Objective: To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.Design, setting, and participants: Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.Surgical procedure: After intraprostatic injection of indocyanine green (ICG)-Tc-99m-nanocolloid (n = 12) or Tc-99m-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.Measurements: Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).Results and limitations: Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.Conclusions: Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.Patient summary: Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. Show less
Collamati, F.; Oosterom, M.N. van; Simoni, M. de; Faccini, R.; Fischetti, M.; Terracciano, C.M.; ... ; Morganti, S. 2020
Background Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve... Show moreBackground Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-IN beta) detector. Methods Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of similar to 70 MBq(68)Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-IN(beta)probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments. Results After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-IN(beta)probe prototype was tested in a robotic setting. In the ex vivo setting, the probe-positioned by the robot-was able to identify(68)Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located < 1 mm below the specimen surface.Ga-68-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-IN(beta)probe (S/B > 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing. Conclusions This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-IN(beta)detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes. Show less
Grivas, N.; Bergh, R.C.N. van den; Brouwer, O.R.; Kleinjan, G.H.; Ramirez-Backhaus, M.; Wilthagen, E.A.; Poel, H.G. van der 2020
Purpose To systematically review the relevant literature that evaluates the LN topographical distribution and propose a uniform template. Methods A bibliographic search of PubMed/Medline, Embase... Show morePurpose To systematically review the relevant literature that evaluates the LN topographical distribution and propose a uniform template. Methods A bibliographic search of PubMed/Medline, Embase and SCOPUS was performed for studies reporting data of LN imaging and/or nodal resection. Results 101 and 26 articles met the inclusion criteria for PCa and BCa, respectively. In PCa, the most common locations of positive LNs for surgical and imaging studies were external iliac (both 38 studies), followed by obturator (38 and 37, respectively). Similarly, in BCa, the most common location of positive nodes for surgical and imaging studies were external iliac (19 and 4, respectively), followed by obturator (15 and 3 studies, respectively). In PCa, median percentages of positive external iliac nodes/patient were 12.2% and 11.6% for surgical and imaging studies, respectively while corresponding rates for BCa were 3.9% and 17.6%. There were high risks of bias across studies as well as high heterogeneity in the definition of the anatomic boundaries of lymphadenectomy templates. ConclusionsThis review highlights the lack of detailed information on exact LN templates and metastases location, which in turn hinders generation of high-quality evidence on optimal lymphadenectomy templates. Our proposed template is applicable for both imaging and surgical description and could facilitate the translation of anatomical location from imaging to surgical resection. Show less
Page, E.C.; Bancroft, E.K.; Brook, M.N.; Assel, M.; Battat, M.H. al; Thomas, S.; ... ; IMPACT Study Collaborators 2019
Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in... Show moreBackground: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.Design, setting, and participants: Men aged 40-69 yr with a germline pathogenic BRCA1/ 2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA> 3.0 ng/ml, men were offered prostate biopsy.Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p= 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. (C) 2019 The Authors. Published by Elsevier B.V. Show less
Korne, C.M. de; Wit, E.M.; Jong, J. de; Olmos, R.A.V.; Buckle, T.; Leeuwen, F.W.B. van; Poel, H.G. van der 2019
