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CONTEXT: It remains unclear whether men with hormone-sensitive prostate cancer (PCa) metastasized to nonregional lymph nodes (M1a) benefit from prostate-directed therapy (PDT) and/or metastasis-directed therapy (MDT). OBJECTIVE: To systematically summarize the literature regarding oncological outcomes of de novo and recurrent M1a PCa patients treated with PDT and/or MDT. EVIDENCE ACQUISITION: We searched Medline (Ovid), Embase, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reports on oncological outcomes of de novo or recurrent hormone-sensitive M1a PCa patients treated with PDT (radical prostatectomy or radiotherapy) and/or MDT (nodal radiotherapy or salvage lymph node dissection) with or without androgen deprivation therapy. A descriptive data synthesis and a methodological quality assessment were performed to evaluate the impact of PDT and/or MDT on survival in M1a PCa patients. EVIDENCE SYNTHESIS: A total of 6136 articles were screened and 24 studies were included in this systematic review. In de novo M1a PCa patients, PDT was associated with improved oncological outcomes compared with no PDT. In recurrent M1a PCa, MDT could delay the need for systemic treatment in a selection of patients, but high-level evidence from prospective phase III randomized controlled trials is still awaited. CONCLUSIONS: This systematic review summarized the limited literature data on the management of M1a PCa. Subgroup analyses suggest a role for PDT plus systemic therapy in de novo M1a PCa. MDT to distant nodal metastases delayed the need for systemic therapy in recurrent disease, but robust data are lacking. The predominantly retrospective nature of the included studies and significant heterogeneity in study designs limit the strength of evidence. PATIENT SUMMARY: We reviewed the treatment of patients with prostate cancer that has spread to lymph nodes outside the pelvis without metastases in other organ systems. There is evidence that treatment of the primary prostate tumor improves outcomes in well-selected patients and that treatment targeting distant lymph node metastases can delay the start of systemic treatment.

SamenvattingIn dit prospectieve, in vivo haalbaarheidsonderzoek met 20 patiënten met recidiverend prostaatkanker is onderzocht of een geminiaturiseerde DROP-IN-gammaprobe mogelijkheden biedt voor robotgeassisteerde op PSMA gebaseerde radiogeleide chirurgie (RGC) (NCT03857113). Patiënten met ≤ 3 prostaatkankerrecidieven in het kleine bekken (lokaal of lymfeklier) op een PSMA PET-CT-scan na primaire behandeling werden geïncludeerd. Na intraveneuze toediening van een 99mTechnetium-gelabeld PSMA-ligand (99mTc-PSMA-I&S) vond met de DROP-IN-gammaprobe robotgeassisteerde PSMA-RGC plaats. Primair werd de haalbaarheid van robotgeassisteerde PSMA-RGC onderzocht. Met behulp van de DROP-IN-probe konden 19 van de 21 (90%) preoperatief geïdentificeerde laesies gereseceerd worden. Op laesieniveau bedroeg de ex-vivosensitiviteit van PSMA-RGC 86% en de specificiteit 100%. Bij één patiënt trad een Clavien-Dindo-graad V‑complicatie op. Wij concluderen dat de DROP-IN-gammaprobe robotgeassisteerde PSMA-RGC mogelijk maakt. Met deze procedure is de intraoperatieve detectie en resectie van zowel nodale als lokale prostaatkankerrecidieven mogelijk.

SamenvattingDoel van deze studie was de klinische toepasbaarheid van 3D-modellen onderzoeken in de preoperatieve planning van robotgeassisteerde radicale laparoscopische prostatectomie (RALP). Er werden 20 virtuele 3D-modellen en 3D-prints gemaakt, waarna 7 urologen op basis hiervan de mate van zijdespecifieke zenuwsparing bepaalden. Vervolgens werden de mate van zenuwsparing per zijde per modaliteit en de absolute overeenkomst in de geplande zenuwsparing tussen urologen geanalyseerd, waaruit bleek dat er tussen de urologen een klinisch-relevant verschil was in de mate van preoperatieve zijdespecifieke zenuwsparing tussen MRI en de virtuele modellen en MRI en de 3D-prints in 25 en 26% van de gevallen met een intraclasscorrelatiecoëfficient van 0,40 (95%-BI 0,28–0,55) voor MRI, van 0,52 (0,39–0,66) voor virtuele 3D-modellen en van 0,58 (0,45–0,71) voor 3D-prints. De conclusie is dat de 3D-modellen een klinisch-relevante impact hebben op de preoperatieve planning van zenuwsparing bij RALP.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p

PURPOSE: This study aimed to assess the medium-term oncologic outcomes of an active surveillance protocol, replacing confirmatory biopsy with serial multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A total of 172 men were enrolled in this single-arm prospective trial. Men with prostate cancer (Gleason 3+3=6 or Gleason 3+4=7 with ≤10% Gleason pattern 4 overall and 0.2 ng/ml/cc). RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric magnetic resonance imaging to detect progression to clinically significant prostate cancer were 57% (95% CI 39%-74%), 82% (95% CI 74%-89%), 50% (95% CI 38%-62%), and 86% (95% CI 81%-90%), respectively. Both multiparametric magnetic resonance imaging and prostate specific antigen density were significant predictors for progression (multiparametric magnetic resonance imaging OR 6.20, 95% CI 2.72-14.16, P < .001; prostate specific antigen density OR 6.19, 95% CI 2.14-17.92, P = .001). Only 2.3% (4/172) of patients had false-negative multiparametric magnetic resonance imaging and high-risk pathological features (pT3 or high-volume International Society of Urological Pathology >2). After a median 69 months (Q1-Q3 56-79) follow-up of all patients in the cohort, freedom from biochemical recurrence, metastasis, and prostate cancer-related death were 99.3%, 100%, and 100%, respectively. CONCLUSIONS: Final analysis of the Magnetic Resonance Imaging in Active Surveillance trial indicates that there is minimal risk to omitting 1-year confirmatory biopsy during active surveillance if baseline magnetic resonance-targeted + saturation template biopsy was performed; however, standardized 3-year systematic biopsy should be performed due to occasional magnetic resonance imaging-invisible tumors.

The objective of this study was to evaluate the safety and feasibility of (99m)Tc-based prostate-specific membrane antigen (PSMA) robot-assisted–radioguided surgery to aid or improve the intraoperative detection of lymph node metastases during primary robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Methods: Men with primary high-risk PCa (≥ cT3a, International Society of Urological Pathology (ISUP) grade group ≥ 3 or prostate-specific antigen of ≥ 15 ng/mL) with potential lymph node metastasis (Briganti nomogram risk > 10% or on preoperative imaging) were enrolled in the study. Patients underwent staging (68)Ga-PSMA PET/CT scanning. Preoperatively, a (99m)Tc-labeled PSMA ligand ((99m)Tc PSMA I&S; 500 MBq) was administered followed by SPECT/CT. A RARP including extended pelvic lymph node dissection was performed, with intraoperative tracing of PSMA-avid tissues using a prototype DROP-IN γ-probe. Resected specimens were also measured ex vivo. Histopathologic concordance with probe findings was evaluated. A radiotracer count of ≥ 1.5 times the background reference (in vivo), and ≥ 10 (absolute count) in the ex vivo setting, was considered positive. Results: Twelve patients were included (median age, 68 y, and prostate-specific antigen, 9.15 ng/mL). Most of the patients harbored ISUP 5 PCa (75%) and had avid lymph nodes on preoperative PSMA PET (64%). The DROP-IN probe aided resection of PSMA-avid (out-of-template) lymph nodes and residual disease at the prostate bed. Eleven metastatic lymph nodes were identified by the probe that were not observed on preoperative (68)Ga-PSMA PET/CT. Of the 74 extraprostatic tissue specimens that were resected, 22 (29.7%) contained PCa. The sensitivity, specificity, positive predictive value, and negative predictive value of inpatient use of the γ-probe were 76% (95% CI, 53%–92%), 69% (95% CI, 55%–81%), 50%, and 88%, respectively. Ex vivo, the diagnostic accuracy was superior: 76% (95% CI, 53%–92%), 96% (95% CI, 87%–99%), 89%, and 91%, respectively, for sensitivity, specificity, positive predictive value, and negative predictive value. Of the missed lymph nodes in vivo (n = 5) and ex vivo (n = 5), 90% were micrometastasis (≤3 mm). No complications greater than Clavien–Dindo Grade I occurred. Conclusion: Robot-assisted (99m)Tc-based PSMA-radioguided surgery is feasible and safe in the primary setting, optimizing the detection of nodal metastases at the time of RARP and extended pelvic lymph node dissection. Further improvement of the detector technology may optimize the capabilities of robot-assisted (99m)Tc-based PSMA-radioguided surgery.

Objective: To assess the predictive value of biopsy-identified cribriform carcinoma and/or intraductal carcinoma (CR/IDC) within the Briganti and MSKCC nomograms predicting lymph node metastasis (LNM) in patients with primary prostate cancer (PCa). Methods: We retrospectively included 393 PCa patients who underwent radical prostatectomy with extended pelvic lymph node dissection at 3 tertiary referral centers. We externally validated 2 prediction tools: the Briganti 2012 nomogram and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Both nomograms were augmented with CR/IDC. The original model was compared with the CR/IDC-updated model using the likelihood ratio test. The performance of the prediction tools was assessed using calibration, discrimination, and clinical utility. Results: Overall, 109 (28%) men were diagnosed with LNM. Calibration plots of the Briganti and MSKCC nomograms demonstrated an underestimation of the LNM risk across clinically relevant thresholds (≤15%). The addition of CR/IDC to the Briganti nomogram increased the fit of the data (χ 2(1) = 4.30, P = .04), but did not improve the area under the curve (AUC) (0.69, 95% CI 0.63-0.75 vs 0.69, 95% CI 0.64-0.75). Incorporation of CR/IDC in the MSKCC nomogram resulted in an increased fit on the data (χ 2(1) = 10.04, P

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 < 0.001). Conclusions: An MRI-directed targeted-plus-perilesional biopsy approach detected almost all csPCa cases, while limiting overdiagnosis and reducing the number of biopsy cores. Prospective clinical trials are needed to substantiate the withholding of nonperilesional SBx in men with unilateral lesion(s) on MRI. Patient summary: Limiting systematic biopsies to the proximity of the suspicious area on magnetic resonance imaging helps detect an equivalent number of aggressive cancers and fewer indolent cancers. These findings may help patients and physicians choose the best biopsy approach.

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.

BACKGROUND: Radiolabeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has shown superior diagnostic accuracy to conventional imaging for the detection of prostate cancer deposits . Consequently, clinical management changes have been reported in patients with biochemical recurrence (BCR) of disease after robot-assisted radical prostatectomy (RARP). We hypothesized that, due to the exclusion of patients with metastatic disease on PSMA-PET/CT, those who underwent local salvage radiation therapy (SRT) after restaging PSMA-PET/CT for BCR may have better oncological outcomes than patients who underwent "blind" SRT.OBJECTIVE: To compare the oncological outcome of a patient cohort that underwent PSMA-PET imaging prior to SRT with that of a patient cohort that did not have PSMA-PET imaging before SRT.DESIGN, SETTING, AND PARTICIPANTS: We included 610 patients who underwent SRT, of whom 298 underwent PSMA-PET/CT prior to SRT and 312 did not. No additional hormonal therapy was prescribed.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To compare both cohorts, case-control matching was performed, using the prostate-specific antigen (PSA) value at the initiation of SRT, pathological grade group, pathological T stage, surgical margin status, and biochemical persistence after RARP as matching variables. The outcome variable was biochemical progression at 1 yr after SRT, defined as either a rise of PSA ≥0.2 ng/ml above the nadir after SRT or the start of additional treatment.RESULTS AND LIMITATIONS: After case-control matching, 216 patients were matched in both cohorts (108 patients per cohort). In the patient cohort without PSMA-PET/CT prior to SRT, of 108 patients, 23 (21%) had biochemical progression of disease at 1 yr after SRT, compared with nine (8%) who underwent restaging PSMA-PET/CT prior to SRT (p = 0.007).CONCLUSIONS: PSMA-PET/CT is found to be associated with an improved oncological outcome in patients who undergo SRT for BCR after RARP.PATIENT SUMMARY: Performing prostate-specific membrane antigen positron emission tomography/computed tomography imaging in patients with biochemical recurrence of disease after robot-assisted radical prostatectomy, before initiating salvage radiation therapy, resulted in improved short-term oncological outcomes.

SamenvattingHet positieve effect van de Rotterdam Prostate Cancer Risk Calculator (RPCRC)-3/4 en RPCRC-MRI is reeds bevestigd. Toch worden de prestaties en de toepasbaarheid ervan in de klinische praktijk in twijfel getrokken. Deze studie verricht een externe validatie van de RPCRC-3/4 en -MRI binnen een Nederlands klinisch hoogrisicocohort. Mannen (n = 1.575) die tussen 2018 en 2021 prostaatbiopten ondergingen in verband met een klinische verdenking op prostaatkanker (PCa) werden retrospectief geïncludeerd. Bij 996/1.575 (63,2 %) en 656/1.575 (41,7 %) mannen werd respectievelijk PCa en klinisch significant PCa (csPCa) gediagnosticeerd. Uit analyse bleek de RPCRC-3/4 het risico op csPCa te onderschatten: al zou RPCRC-3/4 37,3 % van alle MRI’s voorkomen, dan nog zou 18,3 % van de csPCa-diagnoses worden gemist. Herkalibratie en aanpassing van risicodrempels was om die reden dan ook geïndiceerd. De RPCRC-MRI presteerde daarentegen adequaat en herkalibratie was niet noodzakelijk.

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.

Contains fulltext : 291602.pdf (Publisher’s version ) (Open Access) 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.

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.

CONTEXT: Robot-assisted radical prostatectomy (RARP) has become the standard surgical procedure for localized prostate-cancer (PCa). Nerve-sparing surgery (NSS) during RARP has been associated with improved erectile function and continence rates after surgery. However, it remains unclear what are the most appropriate indications for NSS.OBJECTIVE: The objective of this study is to systematically review the available parameters for selection of patients for NSS. The weight of different clinical variables, multiparametric magnetic-resonance-imaging (mpMRI) findings, and the impact of multiparametric-nomograms in the decision-making process on (side-specific) NSS were assessed.EVIDENCE ACQUISITION: This systematic review searched relevant databases and included studies performed from January 2000 until December 2020 and recruited a total of 15 840 PCa patients. Studies were assessed that defined criteria for (side-specific) NSS and associated them with oncological safety and/or functional outcomes. Risk of bias assessment was performed.EVIDENCE SYNTHESIS: Nineteen articles were eligible for full-text review. NSS is primarily recommended in men with adequate erectile function, and with low-risk of extracapsular extension (ECE) on the side-of NSS. Separate clinical and radiological variables have low accuracy for predicting ECE, whereas nomograms optimize the risk-stratification and decision-making process to perform or to refrain from NSS when oncological safety (organ-confined disease, PSM rates) and functional outcomes (erectile function and continence rates) were assessed.CONCLUSIONS: Consensus exists that patients who are at high risk of ECE should refrain from NSS. Several multiparametric preoperative nomograms were developed to predict ECE with increased accuracy compared with single clinical, pathological, or radiological variables, but controversy exists on risk thresholds and decision rules on a conservative versus a less-conservative surgical approach. An individual clinical judgment on the possibilities of NSS set against the risks of ECE is warranted.PATIENT SUMMARY: NSS is aimed at sparing the nerves responsible for erection. NSS may lead to unfavorable tumor control if the risk of capsule penetration is high. Nomograms predicting extraprostatic tumor-growth are probably most helpful.

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.

Biochemical recurrence of prostate cancer (PCa) after curative radiotherapy is defined as a prostate-specific antigen (PSA) rise of ≥2 ng/ml above the nadir ("Phoenix criteria", 2005). With the introduction of prostate-specific membrane antigen positron emission tomography (PSMA-PET), the ability to localise PCa recurrences has increased markedly. Here, we reviewed 315 patients scanned with PSMA-PET after curative radiotherapy in the Prostate Cancer Network Amsterdam (2015-2018). Sixty-three patients (20.3%) were scanned below the Phoenix threshold (PSA rise

To investigate whether patients with suspected pelvic lymph node metastases (molecular imaging [mi] N1) on staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) had a different oncological outcome compared to those in whom the PSMA PET/CT did not reveal any pelvic lymph node metastases (miN0).All patients with pelvic lymph node metastatic (pN1) disease after robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) between January 2017 and December 2020 were included. To assess predictors of biochemical progression of disease after RARP, a multivariable Cox regression analysis was performed, including number of tumour-positive lymph nodes, diameter of the largest nodal metastasis, and extranodal extension.In total, 145 patients were diagnosed with pN1 disease after ePLND. The median biochemical progression-free survival in patients with miN0 on PSMA PET/CT was 13.7 months, compared to 7.9 months in patients with miN1 disease (P = 0.006). On multivariable Cox regression analysis, both number of tumour-positive lymph nodes (2 vs 1-2: hazard ratio [HR] 1.97; P = 0.005) and diameter of the largest nodal metastasis (HR 1.12; P 0.001) were significant independent predictors of biochemical progression of disease.Patients in whom pelvic lymph node metastases were suspected on preoperative PSMA imaging (miN1), patients diagnosed with2 tumour-positive lymph nodes, and patients with a larger diameter of the largest nodal metastasis had a significantly increased risk of biochemical disease progression after surgery.

The membranous urethral length (MUL), defined as the length between the apex and penile base as measured on preoperative prostate magnetic resonance imaging (MRI), is an important predictor for urinary incontinence after radical prostatectomy. Literature on inter- and intra - observer agreement of MUL measurement is limited. We studied the inter- and intra-observer agreement between radiologists using a well-defined method to measure the MUL on the prostate MRI.Prostate cancer patients underwent a preoperative MRI and robot-assisted radical prostatectomy (RARP) at one high-volume RARP center. MUL measurement was based on well-defined landmarks on sagittal T2-weighted (anatomical) images. Three radiologists independently performed MUL measurements retrospectively in 106 patients blinded to themselves, to each other, and to clinical outcomes. The inter- and intra-observer agreement of MUL measurement between the radiologists were calculated, expressed as intra-class correlation coefficient (ICC).The initial inter-observer agreement was ICC 0.63; 95% confidence interval (CI) 0.28-0.81. Radiologist 3 measured the MUL mean 3.9 mm (SD 3.3) longer than the other readers, interpreting the caudal point of the MUL (penile base) differently. After discussion on the correct anatomical definition, radiologist 3 re-assessed all scans, which resulted in a high inter-observer agreement (ICC 0.84; 95% CI 0.66-0.91). After a subsequent reading by radiologists 1 and 2, the intra-observer agreements were ICC 0.93; 95% CI 0.89-0.96, and ICC 0.98; 95% CI 0.97-0.98, respectively. Limitation is the monocenter design.The MUL can be measured reliably with high agreement among radiologists.• After discussion on the correct anatomical definition, the inter- and intra - observer agreements of membranous urethral length (MUL) measurement on magnetic resonance imaging (MRI) were high. • A reproducible method to measure the MUL can improve the clinical usefulness of prediction models for urinary continence after RARP which may benefit patient counselling.

The aim of this study was to estimate and subsequently measure the occupational radiation exposure for all personnel involved in producing, administering, or performing imaging or surgery with [99mTc]Tc-PSMA-I&S, which has been introduced for identification of tumor-positive lymph nodes during salvage prostate cancer surgery. Methods: The effective dose was estimated and subsequently measured with electronic personal dosimeters for the following procedures and personnel: labeling and quality control by the radiopharmacy technologist, syringe preparation by the nuclear medicine laboratory technologist, patient administration by the nuclear medicine physician, patient imaging by the nuclear medicine imaging technologist, and robot-assisted laparoscopic salvage lymph node dissection attended by an anesthesiology technologist, scrub nurse, surgical nurse, and surgeon. The dose rate of the patient was measured immediately after administration of [99mTc]Tc-PSMA-I&S, after imaging, and after surgery. Results: The estimated dose per procedure ranged from 1.59 × 10-10 μSv (imaging technologist) to 9.74 μSv (scrub nurse). The measured effective dose ranged from 0 to 5 μSv for all personnel during a single procedure with [99mTc]Tc-PSMA-I&S. The highest effective dose was received by the scrub nurse (3.2 ± 1.3 μSv), whereas the lowest dose was measured for the surgical nurse (0.2 ± 0.5 μSv). If a single scrub nurse were to perform as many as 100 procedures with [99mTc]Tc-PSMA-I&S in a year, the total effective dose would be 320 μSv/y. Immediately after administration, the dose rate at 50 cm from the patient was 18.5 ± 1.6 μSv/h, which dropped to 1.8 ± 0.3 μSv/h after imaging the following day, reducing even further to 0.56 ± 0.33 μSv/h after surgery. Conclusion: The effective dose for personnel involved in handling [99mTc]Tc-PSMA-I&S is comparable to that of other 99mTc-radiopharmaceuticals and therefore safe for imaging and radioguided surgery.

SamenvattingHet doel van deze studie was te onderzoeken of de bevindingen op een 18F‑DCFPyL PET/CT-scan leiden tot een verandering van het behandeladvies voor patiënten met een biochemisch recidief (BCR) prostaatkanker. 253 patiënten met BCR-prostaatkanker bij wie een 18F‑DCFPyL PET/CT-scan werd gemaakt ter herstadiëring, werden geïncludeerd. Twee urologen formuleerden een voorgestelde behandeling voor elke patiënt voor- en nadat zij kennis hadden genomen van de uitslagen van de 18F‑DCFPyL PET/CT-scan. Bij 103/253 patiënten (40,7%) werd een verandering van het behandeladvies beschreven. Een positieve 18F‑DCFPyL PET/CT-scan (p p = 0,024) waren significante voorspellers van een voorgenomen beleidswijziging, terwijl een positieve chirurgische marge (p = 0,022) negatief geassocieerd was met een voorgenomen beleidswijziging. De conclusie luidt dat bevindingen op een 18F‑DCFPyL PET/CT-scan een significante impact hebben op het voorgestelde beleid bij patiënten met BCR-prostaatkanker.

SamenvattingHet doel van deze studie was om de rol van PSMA-PET/CT vast te stellen bij patiënten met biochemische persistentie (BCP) van prostaatkanker na robotgeassisteerde laparoscopische radicale prostatectomie (RALP). Geïncludeerd werden 150 patiënten met BCP na RALP, bij wie een PSMA-PET/CT-scan werd gemaakt. Een multivariabele logistische regressieanalyse werd uitgevoerd ter identificatie van voorspellers voor de detectie van metastasen buiten de prostaatloge (≥miN1) op PSMA-PET/CT. Bij 89/150 patiënten waren er aanwijzingen voor prostaatkanker buiten de prostaatloge (≥miN1). Een hogere PSA-waarde na RALP (p = 0,004) en een positieve pathologische lymfeklierstatus (p = 0,006) waren voorspellers voor PSMA-avide laesies buiten de prostaatloge. Het bleek dat bij een groot deel van de patiënten op de PSMA-PET/CT-scan met BCP na een RALP vanwege gelokaliseerd prostaatkanker, metastasen buiten de prostaatloge werden gezien. Hogere PSA-waarden en een positieve pathologische lymfeklierstatus waren significant geassocieerd met metastasen buiten de prostaatloge. De conclusie luidt dat bij patiënten met BCP een PSMA-PET/CT-scan is geïndiceerd om tot salvagebehandelbeslissingen te komen.

PURPOSE: Catheter-related bladder discomfort occurs in up to 63% of patients following robot-assisted radical prostatectomy. The optimal intraoperative anesthesia regime to prevent patients from catheter-related bladder discomfort is unknown.MATERIALS AND METHODS: A prospective cohort analysis was conducted. Patients with biopsy-proven prostate cancer selected for robot-assisted radical prostatectomy were included between January 2017 and April 2020 from a high volume prostate cancer center. Eight different treatment regimens were compared, ie a combination of general anesthesia and a transversus abdominis plane block with either an additional dose of clonidine or an additional dose of ketamine, or perivesical infiltrations (with 20 ml ropivacaine), or periurethral infiltrations (with ropivacaine); or a dorsal penile nerve block (with 20 ml ropivacaine). Multiple logistic regression and linear mixed models were used to analyze differences in catheter-related bladder discomfort and pain (0-10) at the postoperative recovery unit between the treatment protocols.RESULTS: Of the 391 patients included, those with a combination transversus abdominis plane block, perivesical and periurethral block with ropivacaine had the lowest incidence of catheter-related bladder discomfort, clinically relevant and statistically significantly lower compared to our baseline protocol (transversus abdominis plane block only), ie 36% vs 70%, p=0.001. Overall, patients who were treated with periurethral and/or perivesical infiltrations reported a statistically significantly lower incidence of catheter-related bladder discomfort compared to patients who did not receive this local infiltration (46.5% vs 60.7%, p=0.001).CONCLUSIONS: Perivesical and periurethral injections with ropivacaine have the potential to reduce the incidence of early postoperative catheter-related bladder discomfort by up to 49%. Further randomized studies are necessary to determine the optimal treatment regime to prevent early postoperative catheter-related bladder discomfort.

PURPOSE: We sought to identify a subset of patients in whom an extended pelvic lymph node dissection during robot-assisted laparoscopic radical prostatectomy for localized prostate cancer could be omitted when preoperative prostate specific membrane antigen positron emission tomography showed no lymph node metastatic prostate cancer. MATERIALS AND METHODS: A total of 434 patients who underwent prostate specific membrane antigen positron emission tomography prior to robot-assisted laparoscopic radical prostatectomy and extended pelvic lymph node dissection were retrospectively analyzed. Patients were excluded from analysis when the prostate specific membrane antigen positron emission tomography showed evidence of distant metastases. The primary outcome was whether a negative for metastases prostate specific membrane antigen positron emission tomography was able to correctly rule out pelvic lymp node metastases after extended pelvic lymph node dissection, ie its negative predictive value. RESULTS: Overall sensitivity, specificity, positive predictive value and negative predictive value of prostate specific membrane antigen positron emission tomography for the detection of pelvic lymp node metastases were 37.9%, 94.1%, 64.3% and 84.4%, respectively. The negative predictive value of prostate specific membrane antigen positron emission tomography in patients with intermediate risk prostate cancer was 91.6% (95% CI 86-97), compared to 81.4% (95% CI 77-86) in patients with high risk prostate cancer. When only assessing patients with

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.

Introduction: Cerenkov luminescence imaging (CLI) is a novel imaging technology that might have the ability to assess surgical margins intra-operatively during prostatectomy using Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11). This study evaluates the accuracy of CLI compared to histopathology and as exploratory objective investigates the characteristics of the identified chemiluminescence signal. Materials and Methods: After intravenous injection of a mean 68Ga-PSMA-11 activity of 69MBq intraoperatively, all excised specimens were imaged with CLI. Areas of increased signal were marked for histopathological comparison and scored for likelihood of being a positive surgical margin (PSM) using a 5-point Likert scale. In addition, the chemiluminescence signal was investigated in three radioactive and three non-radioactive specimens using CLI. Results: In 15 patients, the agreement between CLI and histopathology was 60%; this improved to 83% when including close surgical margins (≤1mm). In six hotspots, CLI correctly identified PSMs on histopathology, located at the apex and mid-prostate. In all 15 patients an increased signal at the prostate base was observed, without the presence of the primary tumor in this area in eight patients. This chemiluminescence signal was also observed in non-radioactive prostate specimens, with a half-life of 48±11min. The chemiluminescence hampered the visual interpretation of four PSMs at the base. Conclusion: CLI is able to correctly identify margin status, including close margins, in 83% of the cases. The presence of a diathermy-induced chemiluminescent signal hampered image interpretation, especially at the base of the prostate. In the current form, CLI is most applicable to detect PSMs and close margins in the apex and mid-prostate.

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.

Purpose The aim of this study was to investigate whether an early, accurate identification of disease using 18F-DCFPyL PET/CT imaging resulted in a change of decision on treatment management, for individual patients with biochemically recurrent (BCR), hormone-sensitive prostate cancer. Methods In this retrospective study, a total of 253 patients with BCR who underwent restaging 18F-DCFPyL PET/CT were assessed. Two urologists specialized in uro-oncology were asked to formulate a preferred treatment for each patient before and after knowing the results of the 18F-DCFPyL PET/CT. Results Out of 253 patients, 191 (75%) underwent robot-assisted radical prostatectomy (RARP) as primary therapy, and 62 (25%) external beam radiation therapy (EBRT). In 103/253 cases (40.7%), a preferred treatment change based on the 18F-DCFPyL PET/CT findings was reported. In patients post-RARP, a positive 18F-DCFPyL PET/CT (OR 6.21; 95%CI 2.78–13.8; p p = 0.024) were significant predictors for an intended change of management, whereas a positive surgical margin (OR 0.42; 95%CI 0.20–0.88; p = 0.022) was inversely associated with an intended change of management. Conclusion In this study, we found a significant impact of 18F-DCFPyL PET/CT on the intended management of patients with biochemically recurrent hormone-sensitive prostate cancer. A positive 18F-DCFPyL PET/CT scan, positive pathological lymph node status, and a negative surgical margin status were significantly associated with increased odds of having a change of management based on 18F-DCFPyL PET/CT findings.

This study aims to externally validate the Rotterdam Prostate Cancer Risk Calculator (RPCRC)-3/4 and RPCRC-MRI within a Dutch clinical cohort.Men subjected to prostate biopsies, between 2018 and 2021, due to a clinical suspicion of prostate cancer (PCa) were retrospectively included. The performance of the RPCRC-3/4 and RPCRC-MRI was analyzed in terms of discrimination, calibration and net benefit. In addition, the need for recalibration and adjustment of risk thresholds for referral was investigated. Clinically significant (cs) PCa was defined as Gleason score ≥ 3 + 4.A total of 1575 men were included in the analysis. PCa was diagnosed in 63.2% (996/1575) of men and csPCa in 41.7% (656/1575) of men. Use of the RPCRC-3/4 could have prevented 37.3% (587/1575) of all MRIs within this cohort, thereby missing 18.3% (120/656) of csPCa diagnoses. After recalibration and adjustment of risk thresholds to 20% for PCa and 10% for csPCa, use of the recalibrated RPCRC-3/4 could have prevented 15.1% (238/1575) of all MRIs, resulting in 5.3% (35/656) of csPCa diagnoses being missed. The performance of the RPCRC-MRI was good; use of this risk calculator could have prevented 10.7% (169/1575) of all biopsies, resulting in 1.2% (8/656) of csPCa diagnoses being missed.The RPCRC-3/4 underestimates the probability of having csPCa within this Dutch clinical cohort, resulting in significant numbers of csPCa diagnoses being missed. For optimal performance of a risk calculator in a specific cohort, evaluation of its performance within the population under study is essential.

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 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 99mtechnetium PSMA-Investigation & Surgery (99mTc-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 III complication. Conclusions: The DROP-IN probe helps in realizing robot-assisted PSMA-RGS. The procedure is technically feasible for intraoperative detection of nodal or local PSMA-avid PCa recurrences. Patient summary: A device called the DROP-IN probe facilitates minimally invasive, robot-assisted surgery guided by radioactive tracers in patients with recurrent prostate cancer. This procedure holds promise for improving the intraoperative identification and removal of prostate cancer lesions.

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 p adjusted p p p p = 0.001) and of furosemide on SUVmax ureter (p p = 0.001 resp. p p = 0.033). Conclusions Increased urinary activity and higher incidence of peri-bladder artefacts were found in 18F-DCFPyL compared to 68Ga-PSMA-11 PET/CT. Effective reduction of urinary activity may be reached through forced diuresis using 10mg intravenous furosemide, which is especially advantageous in 18F-DCFPyL PET/CT.

SamenvattingWe presenteren hier een model dat de kans op het detecteren van een prostaatkankerrecidief buiten de prostaatfossa op de prostaatspecifiek membraanantigeen (PSMA) positronemissietomografie/computertomografie (PET/CT)-scan voorspelt bij patiënten met een biochemisch recidief (BCR) na radicale prostatectomie (RP). 419 patiënten met een BCR prostaatspecifiek antigeen (PSA) 68Ga-PSMA PET/CT-scan ondergingen, werden geïncludeerd. Met multivariabele logistische regressieanalyse werden voorspellers voor de detectie van prostaatkankerrecidief buiten de prostaatfossa geïdentificeerd. Bij een mediane PSA-waarde van 0,40 ng/ml (interkwartielafstand 0,30–0,70) werd met PSMA PET/CT bij 174 (42%) patiënten een prostaatkankerrecidief buiten de prostaatfossa gedetecteerd. Significante voorspellers voor het detecteren van prostaatkankerrecidief buiten de prostaatfossa waren de PSA-waarde ten tijde van de PSMA PET/CT-scan en de Gleason-score, het lymfeklierstadium en het snijrandstadium van het RP-preparaat. De PSA-waarde ten tijde van de PSMA PET/CT en de Gleason-score, het lymfeklierstadium en het snijrandstadium van het RP-preparaat waren belangrijke voorspellers voor het vinden van prostaatkankerrecidief buiten de prostaatfossa met de PSMA PET/CT. Het dashboard (https://psma.prostatecancer-riskcalculator.com/) kan gebruikt worden om het klinisch meest relevante moment voor het verrichten van een PSMA PET/CT-scan te bepalen.

SamenvattingReal-time intraoperatieve begeleiding tijdens prostaatkankerchirurgie kan helpen bij de realisatie van een volledige en veilige resectie van de primaire tumor en/of de lymfekliermetastasen. Radio- en fluorescentiegeleide chirurgie zijn veelbelovend voor chirurgen die complexe chirurgische interventies uitvoeren. Dit soort begeleiding kan gerealiseerd worden met behulp van receptorgebonden tracers. De introductie van positronemissietomografie (PET) radiofarmaca die zijn gericht op het prostaatspecifieke membraanantigeen (PSMA) heeft geleid tot verbeterde stadiëring, vooral bij mannen met een recidief prostaatkanker en relatief lage PSA-waarden. Deze PSMA-receptor kan ook als target dienen voor het betrouwbaar peroperatief identificeren van kleine en/of atypisch gelokaliseerde laesies en/of tumorresiduen na primaire resectie. In dit overzicht bespreken we de huidige inzichten van op PSMA gebaseerde radio- en fluorescentiegeleide chirurgie.

Background: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. Objective: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. Design, setting, and participants: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. Outcome measurements and statistical analysis: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. Results and limitations: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. Conclusions: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. Patient summary: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation. A multidisciplinary panel reached consensus that oligometastatic prostate cancer (OMPC) is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should provide insight into the biology and clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC.

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 < 0.001). Conclusions: MRI-directed TBx + RBx approaches showed a nonsignificant difference in detection of GG ≥2 PCa compared to the recommended practice of MRI-directed TBx + SBx. However, owing to the extensive heterogeneity among the studies included, future prospective clinical studies are needed to further investigate, optimize, and standardize this promising biopsy approach. Patient summary: We reviewed the scientific literature on prostate biopsy approaches using magnetic resonance imaging (MRI)-directed targeted biopsy plus regional biopsy of the prostate. The studies we identified found arguments to potentially embrace such a combined biopsy approach for future diagnostics in prostate cancer.

The aim of this study was to evaluate the effect of salvage radiation therapy (sRT) on survival, functional outcomes, and quality of life in men with persistent prostate-specific antigen (PSA0.1 ng/mL) after a robot-assisted radical prostatectomy (RARP) and reveal subgroups that benefit more from sRT.Data of 3409 patients who underwent RARP was retrieved from a high-volume institute database, and 313 patients with persistent PSA were included in further analyses. Patients who received sRT and those who did not were compared after propensity score matching. Progression-free survival (PFS), metastasis-free survival (MFS), androgen deprivation therapy (ADT)-free, cancer-specific survival, and overall survival, as well as patient-reported outcomes were the endpoints. Multivariable Cox regression models were developed to reveal treatment effect sizes for the subgroups.The overall persistent PSA rate was 9.2%, and the median follow-up time after RARP was 4.5 years (interquartile range, 2.7-7.9 years). The sRT was associated with improved PFS (hazard ratio [HR]: 0.29; P.001), ADT-free survival (HR: 0.34; P.001), MFS (HR: 0.39; P = .001), cancer-specific survival (HR: 0.34; P = .03), and overall survival (HR: 0.24; P = .001). Positive surgical margins (HR: 0.26; P.001 for ADT-free survival), advanced pathological T stage (HR: 0.24; P.001 for PFS) and positive lymph nodes (HR: 0.15; P = .001 for MFS), and lower Gleason score (HR: 0.15; P = .001 for PFS) were associated with marked survival benefits of sRT. Bowel symptoms were observed more frequently in patients who had sRT with or without ADT compared with patients with persistent PSA but no sRT (34.3% vs 19.2%; P = .01). Early sRT (6 months after surgery) was associated with bothering incontinence (P.001) and bowel symptoms (P = .03).Persistent PSA after a radical prostatectomy is still a common challenge in the robotic surgery era. sRT provides clear survival benefits for all endpoints, especially with unfavorable locoregional factors but a low Gleason score.