Search

Background and objective: A positive surgical margin (PSM) occurs in up to 32% of patients undergoing robot-assisted radical prostatectomy (RARP). Diffuse reflectance spectroscopy (DRS), which measures tissue composition according to its optical properties, can potentially be used for real-time PSM detection during RARP. Our objective was to assess the feasibility of DRS in distinguishing prostate cancer from benign tissue in RARP specimens. Methods: In a single-center prospective study, DRS measurements were taken ex vivo for RARP specimens from 59 patients with biopsy-proven prostate carcinoma. Discriminating features from the DRS spectra were used to create a machine learning–based classification algorithm. The data were split patient-wise into training (70%) and testing (30%) sets, with ten iterations to ensure algorithm robustness. The average sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) from ten classification iterations were calculated. Key findings and limitations: We collected 542 DRS measurements, of which 53% were tumor and 47% were healthy-tissue measurements. Twenty discriminating features from the DRS spectra were used as the input for a support vector machine model. This model achieved average sensitivity of 89%, specificity of 82%, accuracy of 85%, and AUC of 0.91 for the test set. Limitations include the binary label input for classification. Conclusions and clinical implications: DRS can potentially discriminate prostate cancer from benign tissue. Before implementing the technique in clinical practice, further research is needed to assess its performance on heterogeneous tissue volumes and measurements from the prostate surface. Patient summary: We looked at the ability of a technique called diffuse reflectance spectroscopy to guide surgeons in discriminating prostate cancer tissue from benign prostate tissue in real time during prostate cancer surgery. Our study showed promising results in an experimental setting. Future research will focus on bringing this technique to clinical practice.

Background and objective: A combined approach of magnetic resonance imaging (MRI)-targeted biopsy (TBx) and bilateral systematic biopsy (SBx) is advised in patients who have an increased risk of prostate cancer (PCa). The diagnostic gain of SBx in detecting PCa for treatment planning of patients undergoing robot-assisted radical prostatectomy (RARP) is unknown. This study aims to determine the impact of omitting contralateral SBx on the surgical planning of patients undergoing RARP in terms of nerve-sparing surgery (NSS) and extended pelvic lymph node dissection (ePLND). Methods: Case files from 80 men with biopsy-proven PCa were studied. All men had a unilateral suspicious lesion on MRI, and underwent TBx and bilateral SBx. Case files were presented to five urologists for the surgical planning of RARP. Each case file was presented randomly using two different sets of information: (1) results of TBx + bilateral SBx, and (2) results of TBx + ipsilateral SBx. The urologists assessed whether they would perform NSS and/or ePLND. Key findings and limitations: A change in the surgical plan concerning NSS on the contralateral side was observed in 9.0% (95% confidence interval [CI] 6.4-12.2) of cases. Additionally, the indication for ePLND changed in 5.3% (95% CI 3.3-7.9) of cases. Interobserver agreement based on Fleiss’ kappa changed from 0.44 to 0.15 for the indication of NSS and from 0.84 to 0.83 for the indication of ePLND. Conclusions and clinical implications: In our series, the diagnostic information obtained from contralateral SBx has limited impact on the surgical planning of patients with a unilateral suspicious lesion on MRI scheduled to undergo RARP. Patient summary: In patients with one-sided prostate cancer on magnetic resonance imaging, omitting biopsies on the other side rarely changed the surgical plan with respect to nerve-sparing surgery and the indication to perform extended lymph node dissection.

Summary: Background: Metastatic retroperitoneal lymph node dissection (LND) for nodal recurrence is applied for a variety of cancers, such as urological, gynaecological and rectal cancer. Precise localisation and resection of these lymph nodes (LNs) during surgery can be challenging, especially after previous radiotherapy or surgery. The objective of this study was to assess the added value of surgical navigation for targeted LND in the retroperitoneum. Methods: We performed an open-label randomised, controlled, phase 3 trial at the Netherlands Cancer Institute, Amsterdam. Eligible participants were over 18 years of age, scheduled for targeted retroperitoneal LND by laparotomy, with removal of one or more suspected (targeted) LN(s) as assessed by diagnostic imaging. Patients were randomised (1:1) between conventional LND and LND using surgical navigation, by means of a minimisation method stratified for tumour origin (urological, colorectal and other). For the surgical navigation, a digital 3D model of the patients' anatomy was created from diagnostic CT scans, including delineation of the targeted LN(s). The 3D model was linked to the patients’ position in the operation room. Using an electromagnetic tracking system, with a sterile tracked pointer, the actual position of the pointer was shown in the 3D model, enabling the surgeon to localize the targeted LN(s). The primary outcome of the study was the percentage of successful procedures. Success was defined as no residual target LN(s) visible on postoperative CT imaging. This study was registered with ClinicalTrials.gov, NCT05867095. Findings: From January 2017 to December 2020, 69 participants were included in the study, 35 (51%) in the conventional arm and 34 (49%) in the navigation arm. Four patients were not evaluable and excluded from further analysis; three in the conventional arm (patients withdraw from study participation), one in the navigation arm (discontinued surgery, misclassified diagnosis). According to intention-to-treat analysis, 50% (16/32) of the surgical procedures was successful in the conventional arm, versus 85% (28/33) in the surgical navigation arm (one-tailed p = 0.0028, 90% CI: 14%–56%). Using the Clavien-Dindo classification, the overall complication rate was comparable between the conventional arm and the navigation arm. Surgeons judged the surgical navigation setup as valuable, the median preference score to use surgical navigation was 3.7 (3.3–4.0) (scale 1–5), and the median system usability score was 75 (70–85) (scale 0–100). Interpretation: Surgical navigation allows for significantly better localisation and removal of target LN(s) in the retroperitoneum. Funding: This research was supported by the KWF-Alpe d'HuZes (NKI 2014-6596) and by an institutional grant of The Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport.

Background and objective: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease. Methods: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT. Key findings and limitations: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64–0.79). Using our nomogram, patients with a predicted risk of >20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT. Conclusions: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment. Patient summary: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.

Background and objective: The possible negative impact of radical surgery on patients’ health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes. Methods: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds. Key findings and limitations: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning. Conclusions and clinical implications: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery. Patient summary: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery.

Background and objectives: The association between prostate-specific antigen (PSA) level and probability of metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has not yet been established in patients with newly diagnosed prostate cancer (PCa). Our objective was to assess the probability of metastatic disease within different PSA ranges using PSMA PET/CT for initial staging of PCa, and to identify both the anatomical distribution and the predictors of metastases on PSMA PET/CT. Methods: In total, 2193 patients with newly diagnosed PCa were retrospectively studied. PSMA PET/CT was performed for staging purposes between January 2017 and May 2022. The proportion of patients with PSMA-avid metastases, stratified by PSA level, was studied. A vast majority of patients in whom at least one high-risk prognostic factor was present underwent PSMA PET/CT. A multivariable logistic regression analysis was performed to identify the predictors of metastases on PSMA PET/CT using clinical, biochemical, radiological, and pathological variables. Key findings and limitations: The median PSA level at PSMA PET/CT was 14.1 ng/ml. Any metastatic disease (miN1-M1a-c) was observed in 34.7% (763/2193) of all patients and distant metastases (miM1a-c) in 25.4% (557/2193) of patients. The presence of any metastatic disease increased with PSA levels, being 15.4% in men with PSA levels 100 ng/ml. The multivariable logistic regression analysis found significant associations between the presence of any metastatic disease and PSA subgroups, clinical tumor stage ≥T2, grade group >3, and radiological tumor stage ≥T3b. Conclusions and clinical implications: This is the first large epidemiological study in patients with PCa demonstrating the association between PSA subgroups and metastatic disease on modern imaging PSMA PET/CT. Data from this study can be used to counsel patients on the probability of metastatic disease at the time of PSA screening and to provide guidance on existing guidelines. Patient summary: The prostate-specific antigen level could be used to assess the risk of metastases on prostate-specific membrane antigen positron (PSMA) emission tomography/computed tomography (PET/CT). This knowledge is valuable for selecting patients who will benefit most from metastatic screening with PSMA PET/CT.

Background: On 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. Objective: To evaluate the impact of hospital RP volumes on the incidence and risk of UI after RP (RP-UI). Design, setting, and participants: Patients 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 analysis: The 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 limitations: RP-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). Conclusions: A 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 summary: In 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.

Background: Transperineal focal laser ablation (TPLA) treatment for prostate cancer (PCa) is an experimental focal ablative therapy modality with low morbidity. However, a dosimetry model for TPLA is lacking. Objective: To determine (1) the three-dimensional (3D) histologically defined ablation zone of single- and multifiber TPLA treatment for PCa correlated with magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) and (2) a reliable imaging modality of ablation zone volumetry. Design, setting, and participants: This was a prospective, multicenter, and interventional phase I/II pilot study with an ablate-and-resect design. TPLA was performed in 12 patients with localized prostate cancer divided over four treatment regimens to evaluate potential variation in outcomes. Intervention: TPLA was performed approximately 4 wk prior to robot-assisted radical prostatectomy (RARP) in a daycare setting using local anesthesia. Outcome measurements and statistical analysis: Four weeks after TPLA, ablation zone volumetry was determined on prostate MRI and CEUS by delineation and segmentation into 3D models and correlated with whole-mount RARP histology using the Pearson correlation index. Results and limitations: Twelve office-based TPLA procedures were performed successfully under continuous transrectal ultrasound guidance using local perineal anesthesia. No serious adverse events occurred. A qualitative analysis showed a clear demarcation of the ablation zone on T2-weighted MRI, dynamic contrast-enhanced MRI, and CEUS. On pathological evaluation, no remnant cancer was observed within the ablation zone. Ablation zone volumetry on CEUS and T2-weighted MRI compared with histology had a Pearson correlation index of r = 0.94 (95% confidence interval [CI] 0.74–0.99, p

Context: Identifying malignant tissue and leaving adjacent structures undisturbed constitute an ongoing challenge in prostate cancer (PCa) surgery. Image and radioguided surgical technologies targeting the prostate-specific membrane antigen (PSMA) receptor may facilitate identification and removal of diseased tissue. Objective: To perform a systematic review of the clinical studies on PSMA-targeted surgery. Evidence acquisition: The MEDLINE (OvidSP), Embase.com, and Cochrane Library databases were searched. Identified reports were critically appraised according to the Idea, Development, Exploration, Assessment, Long-term framework criteria. The risk of bias (RoB) was assessed as per the Risk Of Bias In Non-randomized Studies—of Interventions tool. The strengths and limitations of the techniques and corresponding oncological outcomes were extracted as areas of interest. Data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Evidence synthesis: In total, 29 reports were selected, including eight prospective studies, 12 retrospective analyses, and nine case reports, all with a high or an unclear RoB. In 72.4% of studies, PSMA targeting was achieved via radioguided surgery (RGS), predominantly using 99mTc-PSMA-I&S (66.7%). Hybrid approaches that complement RGS with optical guidance are emerging. The majority of studies retrieved were pilot studies with a short follow-up. In 13 reports, salvage lymph node surgery was discussed (44.8%). In 12 more recent reports (41.4%), PSMA targeting was studied in primary PCa surgery (50.0% lymph nodes and 50.0% surgical margins), and four studied both primary and salvage surgery (13.8%). Overall, specificity was higher than sensitivity (median 98.9% and 84.8%, respectively). Oncological outcomes were discussed only in reports on the use of 99mTc-PSMA-I&S in salvage surgery (median follow-up of 17.2 mo). A decline in prostate-specific antigen level of >90% ranged from 22.0% to 100.0%, and biochemical recurrence ranged from 50.0% to 61.8% of patients. Conclusions: In PSMA-targeted surgery, most studies address salvage PSMA-RGS using 99mTc-PSMA-I&S. Available evidence suggests that the specificity of intraoperative PSMA targeting is higher than the sensitivity. The studies that included follow-up did not yet objectify a clear oncological benefit. Lacking solid outcome data, PSMA-targeted surgery remains investigational. Patient summary: In this paper, we review recent advances in prostate–specific membrane antigen (PSMA)-targeted surgery, which is used to help identify and remove prostate cancer. We found good evidence to suggest that PSMA targeting helps identify prostate cancer during surgery. The oncological benefits have yet to be investigated further.

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 membrane antigen (PSMA)‐positive lesions. While both procedures use 99mTc‐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

Abstract Background Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29–47%. [177Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [177Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields. Methods The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [177Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [177Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [177Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [177Lu]Lu-PSMA-617. Discussion This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments. Trial registration ClinicalTrials, NCT05162573 . Registered 7 October 2021.

Background: Accurate identification of men who harbor nodal metastases is necessary 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 radiotherapy (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 retrospective nature. Conclusions: SLNB-based selection of pN1 PCa patients for WPRT was associated with significantly improved BCRFS and RRFS compared with (conventional) imaging-based PORT. Patient summary: Sentinel node biopsy can be used to select patients who will benefit from the addition of pelvis radiotherapy. This strategy results in a longer duration of prostate-specific antigen control and a lower risk of radiological recurrence.

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 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 hereditary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveillance was considered appropriate, except in case of the patient being a BRCA2 germline 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 follows: (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.

Background: Considering that most men benefit diagnostically from increased sampling of index lesions, limiting systematic biopsy (SBx) to the region around the index lesion could potentially minimize overdetection while maintaining the detection of clinically significant prostate cancer (csPCa). Objective: To evaluate the diagnostic performance of a hypothetical magnetic resonance imaging (MRI)-directed targeted-plus-perilesional biopsy approach. Design, setting, and participants: This single-center, retrospective analysis of prospectively generated data included all biopsy-naïve men with unilateral MRI-positive lesions (Prostate Imaging Reporting and Data System category ≥3), undergoing both MRI-directed targeted biopsies and SBx. Grade group 2–5 cancers were considered csPCa. Outcome measurements and statistical analysis: The diagnostic performance of a targeted-plus-perilesional biopsy approach was compared with that of a targeted-plus-systematic biopsy approach. The primary outcome was the detection of csPCa. Secondary outcomes included the detection of clinically insignificant prostate cancer (ciPCa) and the number of total biopsy cores. Results and limitations: A total of 235 men were included in the analysis; csPCa and ciPCa were detected, respectively, in 95 (40.4%) and 86 (36.6%) of these 235 men. A targeted-plus-perilesional biopsy approach would have detected 92/95 (96.8%; 95% confidence interval [CI] 91.0–99.3%) csPCa cases. At the same time, detection of systematically found ciPCa would be reduced by 11/86 (12.8%; 95% CI 6.6–21.7%). If a targeted-plus-perilesional biopsy approach would have been performed, the number of biopsy cores per patient would have been reduced significantly (a mean difference of 5.2; 95% CI 4.9–5.6, p

Abstract Background High urinary activity in urinary bladder and ureters may hamper interpretation of prostate cancer and regional nodal metastases in prostate-specific membrane antigen (PSMA) PET/CT. The goal of this study was to assess effects of furosemide and choice of tracer on urinary activity in the bladder and ureters, as well as on occurrence of peri-bladder artefacts in PET/CT. Methods Four cohorts with a total of 202 men staged with PSMA PET/CT for prostate cancer received either 68Ga-PSMA-11 as tracer, with (cohort G+) or without 10mg intravenous furosemide (G−) concurrent with tracer, or 18F-DCFPyL with (F+) or without furosemide (F−). SUVmax of bladder and ureters, presence, type, and severity of peri-bladder artefacts were compared between cohorts. The influence of furosemide and choice of tracer was determined while taking differences in biodistribution time into account. Results Median SUVmax bladder was 43,5; 14,8; 61,7 and 22,8 in cohorts G−, G+, F− and F+, respectively, resulting in significant overall (p

The use of healthcare insurance claims data for urinary incontinence (UI) pads has the potential to serve as an objective measure for assessing post-radical prostatectomy UI rates, but its validity for this purpose has not been established. The aim of this study is to correlate claims data with Patient Reported Outcome Measures (PROMs) for UI pad use. Patients who underwent RP in the Netherlands between September 2019 and February 2020 were included. Incontinence was defined as the daily use of ≥1 pad(s). Claims data for UI pads at 12–15 months after RP were extracted from a nationwide healthcare insurance database in the Netherlands. Participating hospitals provided PROMS data. In total, 1624 patients underwent RP. Corresponding data of 845 patients was provided by nine participating hospitals, of which 416 patients were matched with complete PROMs data. Claims data and PROMs showed 31% and 45% post-RP UI (≥1 pads). UI according to claims data compared with PROMs had a sensitivity of 62%, specificity of 96%, PPV of 92%, NPV of 75% and accuracy of 81%. The agreement between both methods was moderate (κ = 0.60). Claims data for pads moderately align with PROMs in assessing post-prostatectomy urinary incontinence and could be considered as a conservative quality indicator.

Context: Systematic biopsies are additionally recommended to maximize the diagnostic performance of the magnetic resonance imaging (MRI) diagnostic pathway for men with suspected prostate cancer (PCa) and positive scans. To reduce unnecessary systematic biopsies (SBx), MRI-directed approaches comprising targeted plus regional biopsy (TBx + RBx) are being investigated. Objective: To systematically evaluate the diagnostic performance of MRI-directed TBx + RBx approaches in comparison to MRI-directed TBx alone and TBx + SBx approaches. Evidence acquisition: The MEDLINE and Embase databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. Detection of grade group (GG) ≥2 PCa was the endpoint of interest. Fixed-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Only MRI-positive men were included. Evidence synthesis: A total of eight studies were included for analysis. Among a cumulative total of 2603 men with suspected PCa, the GG ≥2 PCa detection rate did not significantly differ between MRI-directed TBx + RBx and TBx + SBx approaches (risk ratio [RR] 0.95, 95% confidence interval [CI] 0.90–1.01; p = 0.09). The TBx + RBx results were obtained using significantly fewer biopsy cores and avoiding contralateral SBx altogether. By contrast, there was significant difference in GG ≥2 PCa detection between MRI-directed TBx + RBx and TBx approaches (RR 1.18, 95% CI 1.10–1.25; p

Background: Soractelite™ transperineal focal laser ablation (TPLA) for the treatment of localized prostate cancer (PCa) using the Echolaser® system is a novel minimally invasive technique that has the potential to induce tissue ablation, while reducing treatment-related morbidity, when compared with robot-assisted radical prostatectomy (RARP) and radiotherapy. Objective: To determine the short-term safety and feasibility of single or multifiber TPLA, its functional outcomes, and quality of life (QoL). Design, setting, and participants: TPLA was performed in 12 patients, consecutively assigned to four treatment regimens, with localized PCa who were scheduled for RARP (“ablate and resect design”). The treatment regimens were as follows: (1) a single fiber at 3 W, (2) two fibers at 5 mm distance at 3 W, (3) two fibers at 10 mm distance at 3 W, and (4) a single fiber at 5 W. TPLA was scheduled 4 wk prior to RARP. Intervention: TPLA using the Echolaser® system under local anesthesia at the outpatient clinic. Outcome measurements and statistical analysis: Safety and feasibility were determined by the assessment of device-related peri- and postoperative adverse events (AEs), and length of hospital stay. Functional outcomes and QoL were measured using validated questionnaires. Feasibility of RARP was assessed by a questionnaire for the urologist. Results and limitations: Patients were dismissed after a median (interquartile range) hospital admission of 3.25 (1.25) h. No device-related AEs occurred. AEs that occurred were mostly related to lower urinary tract symptoms and were mild (grade 1–2). Most AEs resolved within 1 wk. A QoL analysis showed no significant differences for all treatment regimens. Functional outcomes remained unchanged, except for erectile function after 1 wk, which returned to baseline after 4 wk. TPLA treatment did not compromise RARP, based on the questionnaires. Conclusions: TPLA for the treatment of PCa at the outpatient clinic appears to be safe and feasible with good short-term QoL and functional outcomes; oncological results are awaited. Patient summary: Focal treatment of localized prostate cancer can safely be performed in a daycare setting using a new technique, based on laser ablation, without compromising quality of life.

This study aimed to investigate the association between the 68Ga- or 18F-radiolabeled prostate-specific membrane antigen (PSMA) tracer expression, represented by the maximum standardised uptake value (SUVmax) of the dominant intraprostatic lesion, and biochemical recurrence (BCR) in primary prostate cancer (PCa) patients prior to robot-assisted radical prostatectomy (RARP). This was a retrospective, multi-centre cohort study of 446 patients who underwent [68Ga]Ga-PSMA-11 (n = 238) or [18F]DCFPyL (n = 206) Positron Emission Tomography/Computed Tomography (PET/CT) imaging prior to RARP. SUVmax was measured in the dominant intraprostatic PCa lesions. [18F]DCFPyL patients were scanned 60 ([18F]DCFPyL-60; n = 106) or 120 ([18F]DCFPyL-120; n = 120) minutes post-injection of a radiotracer and were analysed separately. To normalise the data, SUVmax was log transformed for further analyses. During a median follow-up of 24 months, 141 (30.4%) patients experienced BCR. Log2SUVmax was a significant predictor for BCR (p < 0.001). In the multivariable analysis accounting for these preoperative variables: initial prostate-specific antigen (PSA), radiologic tumour stage (mT), the biopsy International Society of Urological Pathology grade group (bISUP) and the prostate imaging and reporting data system (PI-RADS), Log2SUVmax was found to be an independent predictor for BCR in [68Ga]Ga-PSMA-11 (HR 1.32, p = 0.04) and [18F]DCFPyL-120 PET/CT scans (HR 1.55, p = 0.04), but not in [18F]DCFPyL-60 ones (HR 0.92, p = 0.72). The PSMA expression of the dominant intraprostatic lesion proved to be an independent predictor for BCR in patients with primary PCa who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL-120 PET/CT scans, but not in those who underwent [18F]DCFPyL-60 PET/CT scans.

There is currently no consensus on the optimal treatment for patients with a primary diagnosis of clinically and pathologically node-positive (cN1M0 and pN1M0) hormone-sensitive prostate cancer (PCa). The treatment paradigm has shifted as research has shown that these patients could benefit from intensified treatment and are potentially curable. This scoping review provides an overview of available treatments for men with primary-diagnosed cN1M0 and pN1M0 PCa. A search was conducted on Medline for studies published between 2002 and 2022 that reported on treatment and outcomes among patients with cN1M0 and pN1M0 PCa. In total, twenty-seven eligible articles were included in this analysis: six randomised controlled trials, one systematic review, and twenty retrospective/observational studies. For cN1M0 PCa patients, the best-established treatment option is a combination of androgen deprivation therapy (ADT) and external beam radiotherapy (EBRT) applied to both the prostate and lymph nodes. Based on most recent studies, treatment intensification can be beneficial, but more randomised studies are needed. For pN1M0 PCa patients, adjuvant or early salvage treatments based on risk stratification determined by factors such as Gleason score, tumour stage, number of positive lymph nodes, and surgical margins appear to be the best-established treatment options. These treatments include close monitoring and adjuvant treatment with ADT and/or EBRT.

Occult lymph node (LN)-metastases are frequently found after upfront radical cystectomy (uRC) for bladder cancer (BC). We evaluated whether the implementation of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) influenced nodal staging at uRC. All consecutive BC patients who underwent uRC with bilateral pelvic lymph node dissection (PLND) were identified and divided into two cohorts: cohort A consisted of patients staged with FDG PET/CT and contrast-enhanced CT (CE-CT) (2016–2021); cohort B consisted of patients staged with CE-CT only (2006–2011). The diagnostic performance of FDG PET/CT was assessed and compared with that of CE-CT. Thereafter, we calculated the occult LN metastases proportions for both cohorts. In total, 523 patients were identified (cohort A n = 237, and cohort B n = 286). Sensitivity, specificity, PPV and NPV of FDG PET/CT for detecting LN metastases were 23%, 92%, 42%, and 83%, respectively, versus 15%, 93%, 33%, 81%, respectively, for CE-CT. Occult LN metastases were found in 17% of cohort A (95% confidence interval (CI) 12.2–22.8) and 22% of cohort B (95% CI 16.9–27.1). The median size of LN metastases was 4 mm in cohort A versus 13 mm in cohort B. After introduction of FDG PET/CT, fewer and smaller occult LN metastases were present after uRC. Nevertheless, up to one-fifth of occult (micro-)metastases were still missed.

Two nomograms have been developed to predict the outcome of positron emission tomography (PET)/computed tomography (CT) imaging with68Ga-labeled ligands for prostate-specific membrane antigen (68Ga-PSMA) for patients with rising prostate-specific antigen after radical prostatectomy (RP). These nomograms quantify the ability of PSMA PET/CT to detect prostate cancer recurrences, and therefore provide critical information in determining the optimal timing for PSMA PET/CT in guiding salvage therapies. We validated the ability of these nomograms to accurately predict PET/CT outcome using another ligand tracer, 18F-DCFPyL. The external validation cohort consisted of 157 men from the Prostate Cancer Network Netherlands who underwent 18F-DCFPyL PET/CT to guide salvage therapies after RP. The nomogram of Rauscher et al (predicting a positive scan) showed accurate prediction of 50–80% (discrimination 0.68, 95% confidence interval [CI] 0.59–0.76). The nomogram of Luiting et al (predicting recurrence outside the prostatic fossa) showed accurate prediction for predicted probability values between 15% and 65%, with a small degree of overestimation for predicted probability values between 30% and 50% (discrimination 0.74, 95% CI 0.28–1.24). According to calibration curves, discrimination results, and decision curve analysis, we conclude that clinicians can use these 68Ga-PSMA–based nomograms to predict 18F-DCFPyL PET/CT outcome. These nomograms improve shared decision-making in determining the optimal time to initiate PSMA PET/CT–guided salvage therapies. Patient summary: Prediction tools developed for prostate scans (positron emission tomography, PET) using one type of radioactive tracer (chemicals labeled with gallium-68) are also accurate in predicting scan findings with another tracer (a chemical labeled with fluorine-18). Our study confirms that these tools can be used to guide decisions on the timing of treatments for prostate cancer recurrence.

Prostate MRI has an important role in prostate cancer diagnosis and treatment, including detection, the targeting of prostate biopsies, staging and guiding radiotherapy and active surveillance. However, there are other ‘’less well-known’’ applications which are being studied and frequently used in our highly specialized medical center. In this review, we focus on two research topics that lie within the expertise of this study group: (1) anatomical parameters predicting the risk of urinary incontinence after radical prostatectomy, allowing more personalized shared decision-making, with special emphasis on the membranous urethral length (MUL); (2) the use of three-dimensional models to help the surgical planning. These models may be used for training, patient counselling, personalized estimation of nerve sparing and extracapsular extension and may help to achieve negative surgical margins and undetectable postoperative PSA values.

Background: The currently advised follow-up scheme of PSA testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. Methods: All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network in the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had 0.10 ng/mL at 0–4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA level >0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time points after surgery. Results: Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥ 0.2 ng/mL. BCR further developed in 51 (4.7%) and 37 (3.4%) patients at 5–8 and 9–12 months after RARP, respectively. In 12 patients, BCR was found at 5–8 months after RARP in the absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA level at 0–4 months after RARP also had an unmeasurable PSA level 5–8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Conclusions: Patients with an unmeasurable PSA level at 3–4 months after RARP may not need to be retested until 12 months of follow-up, as almost 100% of patients will not have the biochemically recurrent disease at 5–8 months of follow-up. This will reduce PSA testing substantially at the cost of hardly any missed patients with recurrent disease.

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 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-INβ) detector. Methods Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq 68Ga-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-INβ 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-INβ probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located 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-INβ 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.

Abstract Background To evaluate the impact of Gallium-68 [68Ga] labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on staging and clinical management of men evaluated for primary prostate cancer (PCa). Methods Men with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent [68Ga]PSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board. Results Sixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status. Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted. High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence. Conclusions PSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa.

Introduction. To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC). Materials and Methods. Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA

Objective. To compare the performance of multiparametric resonance imaging/ultrasound fusion targeted biopsy (MRI/US-TBx) to a combined biopsy strategy (MRI/US-TBx plus 24-core transperineal template saturation mapping biopsy (TTMB)). Methods. Between May 2012 and October 2015, all patients undergoing MRI/US-TBx at our institution were included for analysis. Patients underwent MRI/US-TBx of suspicious lesions detected on multiparametric MRI +/- simultaneous TTMB. Subgroup analysis was performed on patients undergoing simultaneous MRI/US-TBx + TTMB. Primary outcome was PCa detection. Significant PCa was defined as ≥Gleason score (GS) 3+4=7 PCa. McNemar’s test was used to compare detection rates between MRI/US-TBx and the combined biopsy strategy. Results. 148 patients underwent MRI/US-TBx and 80 patients underwent MRI/US-TBx + TTMB. In the MRI/US-TBx versus combined biopsy strategy subgroup analysis (n=80), there were 55 PCa and 38 significant PCa. The detection rate for the combined biopsy strategy versus MRI/US-TBx for significant PCa was 49% versus 40% (p=0.02) and for insignificant PCa was 20% versus 10% (p=0.04), respectively. Eleven cases (14%) of significant PCa were detected exclusively on MRI/US-TBx and 7 cases (8.7%) of significant PCa were detected exclusively on TTMB. Conclusions. A combined biopsy approach (MRI/US-TBx + TTMB) detects more significant PCa than MRI/US-TBx alone; however, it will double the detection rate of insignificant PCa.