PURPOSE:To present the outcomes of the York-Mason procedure for managing recto-urethral fistula (RUF) after robot-assisted radical prostatectomy (RARP). METHODS:A single-center retrospective cohort study was conducted at the Antoni van Leeuwenhoek Hospital-Netherlands Cancer Institute. Between January 2011 and May 2024, 12 cases of RUF following RARP, all treated with the York-Mason technique, were identified. Initial treatment involved conservative management with prolonged catheterization. If unsuccessful, surgical intervention followed. The York-Mason procedure is a posterior transsphincteric approach, providing direct access to the fistula through healthy tissue, with precise layer-by-layer closure of the sphincter complex. Successful repair was defined as the absence of anal urinary loss, the absence of fecal material in the catheter bag or pneumaturia, and the absence of leakage on cystogram. RESULTS:Of the 12 cases of RUF, 10 occurred in patients who underwent RARP without radiotherapy (RARP-only), and 8 of these underwent York-Mason procedure as initial surgical treatment, achieving a 100% success rate after a median follow-up of 5.1 years (SD 2.9). The remaining two RARP-only patients initially underwent other surgical interventions, after which one achieved successful closure with subsequent York-Mason repair. The other two patients received both RARP and radiotherapy before fistula detection- one received radiotherapy prior to RARP, and one after. York-Mason was effective when radiotherapy preceded RARP. CONCLUSION:The York-Mason procedure provides promising results for managing RUFs in patients who have undergone RARP without salvage radiotherapy. Its effectiveness is particularly evident when used as the first surgical intervention.

Background and objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is increasingly used for primary staging in prostate cancer. Owing to accurate detection of small metastases on PSMA-PET/CT, patient selection for robot-assisted radical prostatectomy (RARP) has likely changed. This study analyzes oncological outcomes in patients undergoing RARP and extended pelvic lymph node dissection (ePLND) after PSMA-PET/CT staging, compared with those without PSMA-PET/CT. Methods: Patients who underwent staging with PSMA-PET/CT before RARP and ePLND ("PSMA cohort"; 2016-2021) were compared with patients staged without PSMA-PET/ CT ("historical cohort"; 2013-2016). Propensity score matching using preoperative variables was performed to limit confounding. As primary outcome measure of biochemical recurrence (BCR)-free survival (BFS) was analyzed, with BCR defined as a prostate specific antigen value of >= 0.2 ng/ml or start of additional therapy after surgery. Key findings and limitations: After matching, 880 patients were included (440 in each cohort). The median follow-up was 35 mo (interquartile range 21-60) for the entire cohort. In the PSMA cohort, 126/440 patients (29%) experienced BCR versus 205/440 (47%) in the historical cohort (log-rank test p = 0.032). A multivariable Cox regression analysis showed an independent effect of preoperative PSMA-PET/CT staging on BFS (hazard ratio 0.70, 95% confidence interval 0.55-0.89, p = 0.0030). Conclusions and clinical implications: Patients who underwent staging with PSMA-PET/ CT had longer biochemical progression-free survival after RARP and ePLND than those without PSMA-PET/CT. This suggests that PSMA-PET/CT staging alters patient selection for RARP and ePLND, and is associated with improved early oncological outcomes for patients who still undergo surgery. Patient summary: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) at the diagnosis of prostate cancer leads to better visualization of metastases and therefore better selection of prostate cancer patients for surgery. Patients who underwent a PSMA-PET/CT scan at the time of diagnosis showed improved oncological outcomes, including longer progression-free survival and less prostate-specific antigen persistence after surgery. (c) 2024 Published by Elsevier B.V. on behalf of European Association of Urology.

Background:Robot-assisted radical prostatectomy (RARP) has become the standard surgical procedure for localized prostate cancer (PCa). Nerve sparing with neurovascular structure-adjacent frozen-section examination (NeuroSAFE) has been associated with improved functional outcomes while maintaining oncological outcomes. This study investigates the impact of NeuroSAFE on nerve sparing during RARP, using the fascia preservation (FP) score. This score (range 0-6 per side) reflects the extent of preserved fascia at twelve circumferential positions; higher scores indicate greater nerve preservation. Methods:A single-center retrospective cohort study was conducted between January 2022 and December 2024, including 100 PCa patients selected for RARP. A preoperative surgical plan was created, including an estimated FP score using NeuroSAFE. Patients subsequently underwent prostatectomy with NeuroSAFE. The actual FP score was determined perioperatively. Postoperatively, four urologists retrospectively estimated FP scores assuming prostatectomy had been performed without NeuroSAFE. Actual and estimated scores were compared. Interobserver agreement among urologists was assessed using the intraclass correlation coefficient. Results:RARP with NeuroSAFE resulted in statistically significantly higher FP scores on both sides compared to the estimated FP scores without NeuroSAFE (P<0.001). The median FP score was 5 per side (full nerve sparing) with NeuroSAFE versus 4 (partial nerve sparing) without. Interobserver agreement among urologists was moderate for single measurements and high for average measurements. Conclusions:NeuroSAFE enables greater nerve sparing during RARP, as estimated by four expert urologists. Although functional outcomes were not assessed in this cohort, previous randomized evidence has demonstrated an association between greater nerve sparing and improved erectile function.

PurposePatients are increasingly involved in decision making by their clinicians. Yet, there are concerns that involvement in decision making may cause emotional distress in patients. Little research has examined the nature of the burden experienced by patients confronted with a life-changing treatment decision. Therefore, we explored the nature and manifestations of burden experienced by patients with early-stage breast and prostate cancer regarding their involvement in decision making. We further aimed to identify patient-perceived causes and potential solutions for their experienced burden.MethodsWe used semi-structured interviews to explore the perspectives of patients with early-stage breast and prostate cancer. Patients (N = 24) were eligible if they were diagnosed in the past 6 mo and reported some degree of burden regarding their involvement in decision making. Two researchers independently inductively coded the interviews using thematic analysis.ResultsPatients described being burdened by the decision in various ways and at various moments in the decision-making process. Patients attributed their decision-related burden mainly to uncertainty, fear of making the wrong decision, insufficient guidance by their clinician, and feeling an overwhelming sense of responsibility for their treatment decision. Patients indicated various factors that mitigated their burden or facilitated decision making, including having sufficient time, the opportunity to discuss the choice with experts and/or family, and receiving advice or confirmation from family or the clinician.ConclusionThese findings suggest that decision-related burden could be caused by the uncertainty and anxiety patients experience and by a nonpreferred division of roles within the decision-making process.ImplicationsAccordingly, acknowledging patients' feelings by discussing the presence of uncertainty and distress might normalize the burden for patients. Moreover, clinicians could explore and adjust to patients' role preference in decision making and discuss what would facilitate the decision process for patients.HighlightsPatients experience emotional, cognitive, and physical burden from their involvement in decision making.Some of the burden appears to result from the way clinicians involve patients in decision making.In addition to information about options, benefits, and harms, patients require active support in their decision-making process.Clinicians could aim to avoid overfocus on patient autonomy and instead establish authentic, shared decisions, with a role for some clinician control if needed.

Following nerve-sparing (NS) radical prostatectomy (RP), 50% of patients experience persistent erectile dysfunction (ED) 24 months post-RP due to contusion of the neurovascular bundles and the subsequent cavernosal fibrosis. While penile rehabilitation may prevent fibrosis, its long-term effects remain unclear. This study aimed to evaluate the impact of a structured penile rehabilitation (PR) program on erectile function recovery 24 months after NSRP in a large retrospective cohort. We selected PCa patients without pre-operative ED who underwent at least a unilateral NSRP between November 2017 and March 2022 (IRBd19-248), without any adjuvant or salvage treatment. ED was defined as an International Index of Erectile Function-Erectile Function (IIEF-EF) score below 22 or documented inability to achieve or maintain satisfactory erections with or without phosphodiesterase inhibitors (PDE5i). Logistic regression analyses assessed the association between penile rehabilitation and ED 24 months post-NSRP, adjusting for NS, age, cardiovascular disease (CVD), smoking, physical activity, and procedure type (NeuroSAFE). Structured PR was defined as using PDE5i and/or a vacuum device at least five times weekly, with or without additional intracavernosal injections (once weekly) for at least six months. A total of 267 patients (median age 64, IQR 58-69) were retrospectively identified. Of these, 52 (19%) underwent full bilateral NS surgery, and 56 (21%) followed a structured PR program. After 24 months, 3 out of 17 patients (18%) with full bilateral NS and PR reported ED, compared to 24 out of 39 (69%) with unilateral NS and PR. Logistic regression showed PR (OR 0.46, p < 0.001) and degree of NS (OR 0.24 to 0.08, p < 0.05) were linked to lower ED rates at 24 months. Patients over 70 had a higher risk of ED post-NSRP (OR 3.49, p < 0.05). Baseline CVD, smoking, or physical activity did not significantly affect ED risk at 24 months. Structured PR significantly reduces the risk of erectile dysfunction 24 months post-NSRP. Additionally, a higher degree of NS decreases this risk, while age over 70 increases it, aligning with existing literature. We declare no conflicts of interest regarding this retrospective study.

With the heterogeneous use and interpretation of next-generation molecular imaging and approval of new treatment strategies, therapeutic decision-making for de novo metastatic hormone-sensitive prostate cancer (mHSPC) is becoming increasingly challenging. It is conceivable that patients are treated differently in another country, hospital or by another clinician. Here, we aim to provide insights into the clinical practices, challenges, and unmet needs in the management of de novo mHSPC.In this explorative mixed-method study, a survey was sent to urologists and oncologists in 13 Dutch hospitals from the TripleAiM1 network. Additionally, four patient cases were discussed in multi-disciplinary team consultations in four of these hospitals. Results from the survey and patient cases were then discussed in focus group sessions. Three sessions were held with the same expert panel, comprising urologists, medical oncologists, a nuclear medicine physician and radiation oncologist. Major themes were identified and analysed using the Matrix method. Of the 91 surveys distributed, 27 urologists and 19 oncologists responded. Patients with low-volume (LV) disease showed most practice variation; ranging from curative to palliative intent and from single to triplet therapies. Reasons given for this variation include the heterogeneous aspect of LV disease, ambiguous definitions, varying interpretations of study data, lead-time in adoption of novel treatment strategies, and guideline gaps. Adding to this divergence are differences in interpretation of metastatic volume. As the majority of physicians (36/46) use PSMA-PET/CT for staging, while LV and high-volume per CHAARTED criteria are defined on conventional imaging. On a scale of 0-10, metastatic volume (8.5), performance score (8.6), and patient preferences (9.0) were considered the most important factors for selecting treatments. This did not differ significantly between specialties, but showed large dispersion within specialties, suggesting variation at the individual physician level. In conclusion, this study provides insights into clinical practices and challenges in the management of de novo mHSPC. By elucidating the perspectives of Dutch physicians, our findings contribute to a better understanding of the complexities involved in treatment decision-making. Moving forward, there is a need for consensus on definitions, imaging modalities for staging, and treatment selection given the altered diagnostic and therapeutic landscape.

Background and objective: A combined approach of magnetic resonance imaging (MRI) targeted biopsies (TBx) and systematic biopsies (SBx) was recommended previously in patients with unilateral suspicious prostate cancer (PCa) on MRI. Yet, new PCa guidelines suggest that contralateral SBx can be omitted. It is unknown how this guideline modification impacts treatment selection. This study evaluates the value of contralateral SBx in radiation treatment selection in patients with unilateral suspicious lesions (Prostate Imaging Reporting and Data System [PIRADS] >= 3) on MRI. Methods: Case files of 80 patients with a unilateral suspicious lesion on diagnostic MRI who underwent TBx and bilateral SBx were collected. The cases were presented to four radiation oncologists twice: once with diagnostic information of bilateral SBx and TBx, and once with diagnostic information of ipsilateral SBx and TBx pathology results. Based on this information, external beam radiation treatment (EBRT) fractionation scheme, duration of androgen deprivation therapy (ADT), and feasibility of brachytherapy (monotherapy or brachyboost) were considered. Key findings and limitations: After omitting information of contralateral SBx pathology results, selection of EBRT fractionation scheme and ADT duration changed in 14% (95% confidence interval [CI] 9.8-17) and 15% (95% CI 11-19) of cases, respectively. The feasibility of brachytherapy as monotherapy and brachyboost, respectively, changed in 11% (95% CI 7.9-15) and in 21% (95% CI 17-26) of cases, with overall poor interobserver variability for both diagnostic scenarios (Fleiss' kappa 0.15 and 0.16). Conclusions and clinical implications: Our findings indicate that omitting contralateral SBx has an impact on the treatment selection of patients who choose for radiation therapy as their treatment for locally confined PCa. Patient summary: In patients with prostate cancer identified via magnetic resonance imaging on one side of the prostate, exclusion of prostate biopsies from the opposite side affected the selection of radiation treatment. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Background and objective: A survival benefit was demonstrated for patients with low- volume synchronous metastatic hormone-sensitive prostate cancer (mHSPCa) when local radiotherapy to the prostate was added to androgen deprivation therapy. This study aims to determine the incidence of prostate cancer-related events and treatments in those who received and those who did not receive external beam radiotherapy for mHSPCa. Methods: The HORRAD trial is a multicentre randomised controlled trial recruiting originally 432 patients with mHSPCa diagnosed between 2004 and 2014. In a second updated analysis, 328 patients were studied retrospectively for local and nonlocal prostate cancer-related events and treatments. Outcome measurements included the incidence and treatment of local (bladder outlet or ureter obstruction, catheterisation, surgical intervention, ureteric stents, and nephrostomy tubes) and nonlocal (blood transfusions, hospitalisations, and treatment for painful bone metastases) events. Differences between groups were compared using crude and adjusted logistic regression, while time to occurrence of local events was assessed with Kaplan-Meier curves and Cox regression analysis. Key findings and limitations: A significant difference in the incidence of local events was observed: 30 events in the radiotherapy group versus 50 in the nonradiotherapy group (p = 0.04). Time to occurrence of local interventions was significantly longer in the radiotherapy group (hazard ratio 0.61, 95% confidence interval 0.37-0.99, p = 0.04). The study's limitations include its retrospective nature.

Background and objective Image-guided surgical navigation (IGSN) can enhance surgical precision and safety. The expansion of minimally invasive surgery has increased the demand for integration of these navigation systems into robot-assisted surgery. Our objective was to evaluate the integration of electromagnetic tracking with IGSN in robot-assisted sentinel lymph node biopsy (SLNB). Methods We conducted a prospective feasibility study to test the use of IGSN in SLNB. In total, 25 patients scheduled for SLNB at The Netherlands Cancer Institute were included (March 2022 to March 2023). SLNB using IGSN was performed using a standardised technique with a da Vinci robot (Intuitive Surgical, Sunnyvale, CA, USA) in four-arm configuration. Feasibility was determined as the percentage of sentinel nodes (SNs) successfully identified via IGSN. Successful SN resection was defined as SNs correctly localised via navigation and validated ex vivo with a gamma probe. Surgeon feedback on the robot-assisted IGSN workflow was evaluated using the System Usability Scale (SUS). Key findings and limitations In accordance with the protocol, the first five patients were used for workflow optimisation, and the subsequent 20 patients were included in the analysis. IGSN led to successful identification of 91% (50/55) of the SNs. There were no complications associated with navigation. The surgeon feedback (SUS) was 60.9, with lowest scores reported for the user interface and workflow integration. Conclusions IGSN during robot-assisted surgery was feasible and safe. The technique allowed identification and removal of predefined small pelvic lymph nodes. Patient summary We carried out a study on the feasibility of imaging-guided navigation in robot-assisted prostate surgery. Our results show that this technique is feasible, safe, and effective.

Androgen receptor-targeting agents, particularly enzalutamide, show promise in enhancing prostate cancer diagnostic and therapeutic strategies by modulating prostate-specific membrane antigen (PSMA). Methods: A retrospective clinical cohort study investigated 9 men with metastatic castration-resistant prostate cancer on enzalutamide. PSMA PET/CT scans were obtained before and after enzalutamide initiation to assess PSMA expression changes. Lesions and organs at risk were evaluated visually and semiquantitatively. The flare phenomenon was characterized by a significant increase (≥20%) in the SUVmax of existing lesions or the appearance of new PSMA-positive lesions. Results: Exposure to enzalutamide led to a significant PSMA expression increase in 56% of assessed lesions (n = 42), with new lesions detected in 1 patient (11%). PSMA expression in organs at risk remained largely unaffected, indicating a tumor-specific response. Conclusion: Enzalutamide induces PSMA upregulation in metastatic castration-resistant prostate cancer, potentially enhancing diagnostic and therapeutic strategies. Further exploration of the flare phenomenon's clinical implications is warranted.

Background and objective: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) and new treatment modalities have expanded the possibilities for diagnosing and managing metastatic prostate cancer, but have also raised questions about their implementation in daily clinical practice. We sought consensus on definitions, preferred imaging modality for staging, and treatment selection in the era of next-generation imaging. Methods: A modified Delphi method involved two voting rounds and a face-to-face multidisciplinary meeting with 40 Dutch prostate cancer (PCa) experts. Consensus was reached if ≥75% of the panellists chose the same option. Appropriateness was assessed by the RAND Corporation/University of California Los Angeles appropriateness method. Key findings and limitations: There was consensus on performing metastatic screening with PSMA-PET/CT for unfavourable intermediate- or high-risk PCa. PSMA-PET/CT findings were considered feasible for determining treatment in synchronous metastatic hormone-sensitive prostate cancer, but there was no agreement on the validity of the CHAARTED criteria for interpreting the PSMA-PET/CT findings. If the PSMA-PET/CT findings led to upstaging after conventional imaging, 76% of panellists would opt for treatment intensification. In case of downstaging, 71% would choose for deintensification. Panellists would generally treat patients based on metastatic disease volume as per the CHAARTED criteria, except for bulky low-volume disease (LVD) and LVD with multiple (more than ten) bone metastases, all within the axial skeleton. This would be classified as LVD but treated as high-volume disease. Limitations are that the statements are largely consensus based and originate from a national (Dutch) perspective. Conclusions and clinical implications: PSMA-PET/CT was considered the preferred modality for initial PCa staging, which is nowadays the standard of care in The Netherlands. The majority of panellists would incorporate PSMA-PET/CT findings for treatment planning, including intensification and deintensification, but the criteria for interpreting metastatic disease volume on PSMA-PET/CT are still uncertain. Patient summary: A group of Dutch medical specialists discussed on how to diagnose metastatic hormone-sensitive prostate cancer and choose the most appropriate treatment for patients with this condition. It was concluded that imaging based on Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) helps determine appropriate treatment options, with most experts supporting treatment adjustments based on PSMA-PET/computed tomography (CT) results. However, there is still some uncertainty about the criteria for interpreting the extent of metastatic disease with PSMA-PET/CT.

BackgroundVarious risk classification systems (RCSs) are used globally to stratify newly diagnosed patients with prostate cancer (PCa) into prognostic groups.ObjectiveTo compare the predictive value of different prognostic subgroups (low-, intermediate-, and high-risk disease) within the RCSs for detecting metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) for primary staging, and to assess whether further subdivision of subgroups would be beneficial.Design, setting, and participantsPatients with newly diagnosed PCa, in whom PSMA-PET/CT was performed between 2017 and 2022, were studied retrospectively. Patients were stratified into risk groups based on four RCSs: European Association of Urology, National Comprehensive Cancer Network (NCCN), Cambridge Prognostic Group (CPG), and Cancer of the Prostate Risk Assessment.Outcome measurements and statistical analysisThe prevalence of metastatic disease on PSMA-PET/CT was compared among the subgroups within the four RCSs.Results and limitationsIn total, 2630 men with newly diagnosed PCa were studied. Any metastatic disease was observed in 35% (931/2630) of patients. Among patients classified as having intermediate- and high-risk disease, the prevalence of metastases ranged from approximately 12% to 46%. Two RCSs further subdivided these groups. According to the NCCN, metastatic disease was observed in 5.8%, 13%, 22%, and 62% for favorable intermediate-, unfavorable intermediate-, high-, and very-high-risk PCa, respectively. Regarding the CPG, these values were 6.9%, 13%, 21%, and 60% for the corresponding risk groups.ConclusionsThis study underlines the importance of nuanced risk stratification, recommending the further subdivision of intermediate- and high-risk disease given the notable variation in the prevalence of metastatic disease. PSMA-PET/CT for primary staging should be reserved for patients with unfavorable intermediate- or higher-risk disease.Patient summaryThe use of various risk classification systems in patients with prostate cancer helps identify those at a higher risk of having metastatic disease on prostate-specific membrane antigen positron emission tomography/computed tomography for primary staging.

BACKGROUND AND OBJECTIVE:Biochemical recurrence (BCR) of prostate cancer (PCa) after curative radiotherapy (RT) is defined according to the Phoenix criteria, which is a prostate-specific antigen (PSA) rise of ≥2.0 ng/ml above the PSA nadir. Prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) can identify PCa recurrences at very low PSA values. Our aim was to investigate the detection rate and extent of PCa recurrences using PSMA PET/CT after curative RT among patients with a PSA rise of ≥2.0 ng/ml above the nadir (Phoenix positive, Ph+) and patients not reaching this threshold (Phoenix negative, Ph-) and to compare therapeutic management and clinical outcomes in terms of time to androgen deprivation therapy (ADT) and castration-resistance PCa (CRPC), as well as overall survival. METHODS:We conducted a retrospective analysis of the Prostate Cancer Network Amsterdam (2015-2023) cohort of 568 patients who received curative-intent RT for PCa. Data on PSMA PET/CT outcomes, therapeutic management, and clinical follow-up were collected, including (re)initiation of ADT, progression to CRPC, and survival. Results were compared between groups using logistic regression and survival analyses. KEY FINDINGS AND LIMITATIONS:The study cohort comprised 222 patients (39.1%) classified as Ph- and 346 (60.9%) classified as Ph+. PSMA-avid lesions were detected in 170 Ph- patients (76.6%) and 322 (93.1%) Ph+ patients. In these groups, 75.9% of Ph- patients and 45.0% of Ph+ patients were eligible for local salvage therapy (odds ratio [OR 3.84]; p < 0.001). Distant metastases were less frequent in the Ph- group (n = 37, 21.8%) than in the Ph+ group (n = 157, 48.8%; OR 0.29; p < 0.001). Survival analyses revealed longer times to ADT (re)initiation and progression to CRPC, as well as lower overall mortality, in the Ph- group (log-rank p < 0.001). The retrospective study design is the main limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS:For patients with PCa recurrence, PSMA PET/CT can detect this recurrence in the majority of cases not meeting the Phoenix criteria for BCR. Early imaging detects recurrences at a less advanced disease stage, allowing potential salvage treatments. In addition, early PSMA PET/CT is associated with longer times to ADT (re)initiation and progression to CRPC, as well as longer overall survival. These positive clinical implications warrant confirmation of our results in prospective studies to reduce potential leadtime bias. PATIENT SUMMARY:We investigated early use of a special type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) in patients with suspicion of recurrence of their prostate cancer after radiotherapy. Early scans can detect recurrence before the cancer progresses to a more advanced stage.

Samenvatting In de afgelopen jaren wordt de term ‘theranostics’ steeds vaker gebruikt. Een nieuwe, reeds welbekende, theranostic of radioligand -therapie (RLT) is 177 Lu-PSMA, waarmee patiënten met gemetastaseerd castratieresistent prostaatcarcinoom (mCRPC) behandeld worden. Het is een radioactief gelabeld medicijn dat intraveneus wordt toegediend, meestal in 4–6 cycli. De bètastraling veroorzaakt celdood van prostaatkankercellen met PSMA-expressie. Het radioactieve gammaverval kan gebruikt worden voor beeldvorming en dosimetrie. Een internationale gerandomiseerde fase III-studie toonde aan dat eindstadiumprostaatkankerpatiënten die 177 Lu-PSMA-617 krijgen, een overlevingsvoordeel hebben van 4 maanden (15,3 versus 11,3 maanden in de controlearm; p < 0,001). Daarnaast laten diverse onderzoeken zien dat een deel van deze vaak intensief behandelde patiënten beter reageren en een langere overlevingswinst hebben. 177 Lu-PSMA wordt over het algemeen goed door patiënten verdragen en verbetert de kwaliteit van leven. Er treden met name graad I–II-vermoeidheid (~40 %) en xerostomie (~40 %) op, die veelal van voorbijgaande aard zijn. Graad III–IV hematologische toxiciteit (trombocytopenie, leukopenie) wordt gezien bij ~8 % van de patiënten. Vanwege de effectiviteit en het milde bijwerkingenprofiel heeft de Amerikaanse Food and Drug Administration (FDA) en het Europees Medicijn Agentschap (EMA) het medicijn recentelijk goedgekeurd voor klinisch gebruik. Momenteel wordt onderzocht of het zinvol is om 177 Lu-PSMA in een eerder stadium in te zetten, al dan niet als combinatiebehandeling.

In contemporary oncologic diagnostics, molecular imaging modalities are pivotal for precise local and metastatic staging. Recent studies identified fibroblast activation protein as a promising target for molecular imaging across various malignancies. Therefore, we aimed to systematically evaluate the current literature on the utility of fibroblast activation protein inhibitor (FAPI) PET/CT for staging patients with genitourinary malignancies. Methods: A systematic Embase and Medline search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta -Analyses (PRISMA) process, on August 1, 2023. Relevant publications reporting on the diagnostic value of FAPI PET/CT in genitourinary malignancies were identified and included. Studies were critically reviewed using a modified version of a tool for quality appraisal of case reports. Study results were summarized using a narrative approach. Results: We included 22 retrospective studies with a cumulative total of 69 patients, focusing on prostate cancer, urothelial carcinoma of the bladder and of the upper urinary tract, renal cell carcinoma, and testicular cancer. FAPI PET/CT was able to visualize both local and metastatic disease, including challenging cases such as prostate -specific membrane antigen (PSMA)-negative prostate cancer. Compared with radiolabeled 18 F- FDG and PSMA PET/CT, FAPI PET/CT showed heterogeneous performance. In selected cases, FAPI PET/CT demonstrated superior tumor visualization (i.e., better tumor -to -background ratios and visualization of small tumors or metastatic deposits visible in no other way) over 18 F-FDG PET/CT in detecting local or metastatic disease, whereas comparisons with PSMA PET/CT showed both superior and inferior performances. Challenges in FAPI PET/CT arise from physiologic urinary excretion of most FAPI radiotracers, hindering primarylesion visualization in the bladder and upper urinary tract, despite generally providing high tumor -to -background ratios. Conclusion: The current findings suggest that FAPI PET/CT may hold promise as a future tool to aid clinicians in detecting genitourinary malignancies. Given the substantial heterogeneity among the included studies and the limited number of patients, caution in interpreting these findings is warranted. Subsequent prospective and comparative investigations are anticipated to delve more deeply into this innovative imaging modality and elucidate its role in clinical practice.

OBJECTIVE:To investigate whether combination treatment of prostate-specific membrane antigen (PSMA)-based radioguided surgery (RGS) with short-term androgen deprivation therapy (ADT) improves oncological outcomes in men with oligorecurrent prostate cancer (PCa) as compared to treatment with short-term ADT only. METHODS:The TRACE-II study is an investigator-initiated, prospective, randomised controlled clinical trial. Patients (aged >18 years) with hormone-sensitive recurrent PCa after radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy), with involvement of ≤2 lymph nodes or local oligorecurrent disease within the pelvis as determined by PSMA positron emission tomography (PET)/computed tomography (CT) are randomly assigned in a 1:1 ratio between 6-month ADT (Arm A) or 6-month ADT plus RGS (Arm B). The primary objective is to determine clinical progression-free survival (CPFS) at 24 months. After PSMA-RGS, CPFS is defined as the time between the start of treatment and the appearance of a re-recurrence (any N1 or M1) as suggested by PSMA-PET/CT or symptoms related to progressive PCa, or death from any cause. The secondary objectives include metastasis-free survival at 2, 5 and 10 years, biochemical progression-free survival at 2 years, and patient-reported quality of life at 2, 5 and 10 years. A total of 60 patients, 30 per arm, will be included. The trial is powered (80%) to detect at least a 30% absolute difference in CPFS between the two study arms in the period 2 years after randomisation. We expect to enrol the required participants in 3 years. The study has an expected duration of 5 years in total. CONCLUSIONS:Combining RGS with short-term ADT might be oncologically beneficial for patients with oligorecurrent PCa. In this first randomised controlled trial, we are investigating the potential oncological benefits of this combined treatment, while also focusing on maintaining quality of life.