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
Groen, V.H.; Schie, M. van; Zuithoff, N.P.A.; Monninkhof, E.M.; Kunze-Busch, M.; Boer, J.C.J. de; ... ; Kerkmeijer, L.G.W. 2022
Purpose or objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical... Show morePurpose or objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade >= 2 in the entire cohort.Material and methods: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade >= 2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade >= 1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated.Results: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm(3) and urethra D0.1 cm(3), with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p < 0.0001) and 1.12 (95% CI 1.11-1.14, p < 0.0001), respectively. Additionally, associations between the dose to the urethra and bladder and the subdomains urinary frequency, urinary retention and urinary incontinence were observed.Conclusion: Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to the urethra and other organs at risk should be a focus for future research, as we have shown that a focal boost is beneficial in the treatment of prostate cancer. (C) 2021 The Author(s). Published by Elsevier B.V. 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
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
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
Background: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) can visualize metastatic lesions in recurrent prostate cancer (PC). However, reliable... Show moreBackground: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) can visualize metastatic lesions in recurrent prostate cancer (PC). However, reliable identification of small and/or atypically localized lesions during salvage surgery procedures is challenging.Objective: To describe the technique, feasibility, and short-term outcomes of (99m)Technetium (Tc-99m)-based PSMA-radioguided surgery (Tc-99m-PSMA-RGS) for removal of recurrent PC lesions.Design, setting, and participants: Thirty-one consecutive patients with evidence of recurrent PC on Ga-68-PSMA N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'-diacetic acid (Ga-68-PSMA-11) PET after radical prostatectomy undergoing Tc-99m-PSMA-RGS were retrospectively analyzed.Surgical procedure: Salvage surgery with intraoperative radioguidance using a gamma probe was performed after intravenous application of Tc-99m-PSMA investigation and surgery (mean activity 571 MBq, mean time to surgery 19.7 h).Measurements: Radioactive rating (positive vs negative) of resected tissue was compared with the findings of postoperative histopathological analysis. Best prostate-specific antigen (PSA) response without additional treatment was determined after 8-16 wk postoperatively. Biochemical recurrence- and treatment-free survival was evaluated.Results and limitations: In total,132 tissue specimens were removed, of which 58 showed metastatic involvement on histological analysis. On a specimen basis, radioactive rating yielded a sensitivity of 83.6% (confidence interval [CI]: 70.9-91.5%), a specificity of 100%, and an accuracy of 93.0% (CI: 85.5-96.7%). With Tc-99m-PSMA-RGS, all lesions visualized on preoperative Ga-68-PSMA-11 PET could be removed. Moreover, Tc-99m-PSMA-RGS detected additional metastases as small as 3 mm in two patients. Thirteen patients suffered from complications related to surgery (Clavien-Dindo grade 1: 12 patients; grade 3a: one patient). A PSA reduction below 0.2 ng/ml was observed in 20 patients. Thirteen patients remained biochemical recurrence free after a median follow-up of 13.8 (range: 4.6-18.3) mo. Twenty patients continued to be treatment free after a median follow-up of 12.2 (range: 5.5-18.3) mo.Conclusions: As a new technique for surgical guidance, Tc-99m-PSMA-RGS is feasible, and has been proved to be of high value for successful intraoperative detection and removal of metastatic lesions in PC patients scheduled for salvage surgery. Its long-term impact on outcome has to be evaluated.Patient summary: In this report, we evaluated a novel technique to identify metastatic lesions intraoperatively in patients with recurrent prostate cancer to facilitate surgical removal. After intravenous injection of radioactive molecules that specifically bind to prostate cancer cells that show increased expression of the prostate-specific membrane antigen, we were able to detect and remove these metastatic lesions during surgery. Following salvage surgery, 41.9% of patients remained biochemical recurrence free (median follow-up of 13.8 mo) and 64.5% continued to be treatment free (median follow-up of 12.2 mo). (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
