A Comparison of Globally Applied Prognostic Risk Groups and the Prevalence of Metastatic Disease on Prostate-specific Membrane Antigen Positron Emission Tomography in Patients with Newly Diagnosed Prostate Cancer.

BACKGROUND: Various risk classification systems (RCSs) are used globally to stratify newly diagnosed patients with prostate cancer (PCa) into prognostic groups. OBJECTIVE: To 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 PARTICIPANTS: Patients 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 ANALYSIS: The prevalence of metastatic disease on PSMA-PET/CT was compared among the subgroups within the four RCSs. RESULTS AND LIMITATIONS: In 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. CONCLUSIONS: This 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 SUMMARY: The 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.

The Impact of Omitting Contralateral Systematic Biopsy on the Surgical Planning of Patients with a Unilateral Suspicious Lesion on Magnetic Resonance Imaging Undergoing Robot-assisted Radical Prostatectomy for Prostate Cancer.

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

A Systematic Review on the Impact of Quality Assurance Programs on Outcomes after Radical Prostatectomy.

BACKGROUND AND OBJECTIVE: The implementation of quality assurance programs (QAPs) within urological practice has gained prominence; yet, their impact on outcomes after radical prostatectomy (RP) remains uncertain. This paper aims to systematically review the current literature regarding the implementation of QAPs and their impact on outcomes after robot-assisted RP, laparoscopic RP, and open prostatectomy, collectively referred to as RP. METHODS: A systematic Embase, Medline (OvidSP), and Scopus search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) process, on January 12, 2024. Studies were identified and included if these covered implementation of QAPs and their impact on outcomes after RP. QAPs were defined as any intervention seeking quality improvement through critically reviewing, analyzing, and discussing outcomes. Included studies were assessed critically using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool, with results summarized narratively. KEY FINDINGS AND LIMITATIONS: Ten included studies revealed two methodological strategies: periodic performance feedback and surgical video assessments. Despite conceptual variability, QAPs improved outcomes consistently (ie, surgical margins, urine continence, erectile function, and hospital readmissions). Of the two strategies, video assessments better identified suboptimal surgical practice and technical errors. Although the extent of quality improvements did not appear to correlate with the frequency of QAPs, there was an apparent correlation with whether or not outcomes were evaluated collectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Current findings suggest that QAPs have a positive impact on outcomes after RP. Caution in interpretation due to limited data is advised. More extensive research is required to explore how conceptual differences impact the extent of quality improvements. PATIENT SUMMARY: In this paper, we review the available scientific literature regarding the implementation of quality assurance programs and their impact on outcomes after radical prostatectomy. The included studies offered substantial support for the implementation of quality assurance programs as an incentive to improve the quality of care continuously.

A Systematic Review on the Diagnostic Value of Fibroblast Activation Protein Inhibitor PET/CT in Genitourinary Cancers.

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 18F-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 18F-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 primary-lesion 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.

Development and Internal Validation of a Novel Nomogram Predicting the Outcome of Salvage Radiation Therapy for Biochemical Recurrence after Radical Prostatectomy in Patients without Metastases on Restaging Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

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

The Probability of Metastases Within Different Prostate-specific Antigen Ranges Using Prostate-specific Membrane Antigen Positron Emission Tomography in Patients with Newly Diagnosed Prostate Cancer.

Background and objectives: The association between prostate-specific antigen (PSA) level and probability of metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has not yet been established in patients with newly diagnosed prostate cancer (PCa). Our objective was to assess the probability of metastatic disease within different PSA ranges using PSMA PET/CT for initial staging of PCa, and to identify both the anatomical distribution and the predictors of metastases on PSMA PET/CT. Methods: In total, 2193 patients with newly diagnosed PCa were retrospectively studied. PSMA PET/CT was performed for staging purposes between January 2017 and May 2022. The proportion of patients with PSMA-avid metastases, stratified by PSA level, was studied. A vast majority of patients in whom at least one high-risk prognostic factor was present underwent PSMA PET/CT. A multivariable logistic regression analysis was performed to identify the predictors of metastases on PSMA PET/CT using clinical, biochemical, radiological, and pathological variables. Key findings and limitations: The median PSA level at PSMA PET/CT was 14.1 ng/ml. Any metastatic disease (miN1-M1a-c) was observed in 34.7% (763/2193) of all patients and distant metastases (miM1a-c) in 25.4% (557/2193) of patients. The presence of any metastatic disease increased with PSA levels, being 15.4% in men with PSA levels <10 ng/ml and 87.5% in men with PSA levels >100 ng/ml. The multivariable logistic regression analysis found significant associations between the presence of any metastatic disease and PSA subgroups, clinical tumor stage ≥T2, grade group >3, and radiological tumor stage ≥T3b. Conclusions and clinical implications: This is the first large epidemiological study in patients with PCa demonstrating the association between PSA subgroups and metastatic disease on modern imaging PSMA PET/CT. Data from this study can be used to counsel patients on the probability of metastatic disease at the time of PSA screening and to provide guidance on existing guidelines. Patient summary: The prostate-specific antigen level could be used to assess the risk of metastases on prostate-specific membrane antigen positron (PSMA) emission tomography/computed tomography (PET/CT). This knowledge is valuable for selecting patients who will benefit most from metastatic screening with PSMA PET/CT.

99m TcPSMA-radioguided surgery in oligorecurrent prostate cancer: the randomised TRACE-II trial.

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.

The accuracy and intra- and interobserver variability of PSMA PET/CT for the local staging of primary prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) is recognized as the most accurate imaging modality for detection of metastatic high-risk prostate cancer (PCa). Its role in the local staging of disease is yet unclear. We assessed the intra- and interobserver variability, as well as the diagnostic accuracy of the PSMA PET/CT based molecular imaging local tumour stage (miT-stage) for the local tumour stage assessment in a large, multicentre cohort of patients with intermediate and high-risk primary PCa, with the radical prostatectomy specimen (pT-stage) serving as the reference standard. METHODS: A total of 600 patients who underwent staging PSMA PET/CT before robot-assisted radical prostatectomy was studied. In 579 PSMA positive primary prostate tumours a comparison was made between miT-stage as assessed by four nuclear physicians and the pT-stage according to ISUP protocol. Sensitivity, specificity and diagnostic accuracy were determined. In a representative subset of 100 patients, the intra-and interobserver variability were assessed using Kappa-estimates. RESULTS: The sensitivity and specificity of the PSMA PET/CT based miT-stage were 58% and 59% for pT3a-stage, 30% and 97% for ≥ pT3b-stage, and 68% and 61% for overall ≥ pT3-stage, respectively. No statistically significant differences in diagnostic accuracy were found between tracers. We found a substantial intra-observer agreement for PSMA PET/CT assessment of ≥ T3-stage (k 0.70) and ≥ T3b-stage (k 0.75), whereas the interobserver agreement for the assessment of ≥ T3-stage (k 0.47) and ≥ T3b-stage (k 0.41) were moderate. CONCLUSION: In a large, multicentre study evaluating 600 patients with newly diagnosed intermediate and high-risk PCa, we showed that PSMA PET/CT may have a value in local tumour staging when pathological tumour stage in the radical prostatectomy specimen was used as the reference standard. The intra-observer and interobserver variability of assessment of tumour extent on PSMA PET/CT was moderate to substantial.

Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy.

OBJECTIVE: To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT). PATIENTS AND METHODS: We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥2, extracapsular extension >0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA-PET for csPCa (separate and combined) was calculated within a four-quadrant prostate model by receiver-operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi-ablative FT. RESULTS: In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA-PET to 0.84, 87%, 80%, 81% and 86%, respectively (P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi-ablative FT. Addition of PSMA-PET correctly identified 26/46 (57%) non-suitable patients and resulted in 4/138 (3%) false-positive exclusions. CONCLUSIONS: Addition of PSMA-PET to the conventional work-up by mpMRI and systematic biopsies could improve selection for hemi-ablative FT and guide exclusion of patients for whom whole-gland treatments might be a more suitable treatment option.

Optimization and validation of 18F-DCFPyL PET radiomics-based machine learning models in intermediate- to high-risk primary prostate cancer.

INTRODUCTION: Radiomics extracted from prostate-specific membrane antigen (PSMA)-PET modeled with machine learning (ML) may be used for prediction of disease risk. However, validation of previously proposed approaches is lacking. We aimed to optimize and validate ML models based on 18F-DCFPyL-PET radiomics for the prediction of lymph-node involvement (LNI), extracapsular extension (ECE), and postoperative Gleason score (GS) in primary prostate cancer (PCa) patients. METHODS: Patients with intermediate- to high-risk PCa who underwent 18F-DCFPyL-PET/CT before radical prostatectomy with pelvic lymph-node dissection were evaluated. The training dataset included 72 patients, the internal validation dataset 24 patients, and the external validation dataset 27 patients. PSMA-avid intra-prostatic lesions were delineated semi-automatically on PET and 480 radiomics features were extracted. Conventional PET-metrics were derived for comparative analysis. Segmentation, preprocessing, and ML methods were optimized in repeated 5-fold cross-validation (CV) on the training dataset. The trained models were tested on the combined validation dataset. Combat harmonization was applied to external radiomics data. Model performance was assessed using the receiver-operating-characteristics curve (AUC). RESULTS: The CV-AUCs in the training dataset were 0.88, 0.79 and 0.84 for LNI, ECE, and GS, respectively. In the combined validation dataset, the ML models could significantly predict GS with an AUC of 0.78 (p<0.05). However, validation AUCs for LNI and ECE prediction were not significant (0.57 and 0.63, respectively). Conventional PET metrics-based models had comparable AUCs for LNI (0.59, p>0.05) and ECE (0.66, p>0.05), but a lower AUC for GS (0.73, p<0.05). In general, Combat harmonization improved external validation AUCs (-0.03 to +0.18). CONCLUSION: In internal and external validation, 18F-DCFPyL-PET radiomics-based ML models predicted high postoperative GS but not LNI or ECE in intermediate- to high-risk PCa. Therefore, the clinical benefit seems to be limited. These results underline the need for external and/or multicenter validation of PET radiomics-based ML model analyses to assess their generalizability.

Using prostate-specific membrane antigen positron-emission tomography to guide prostate biopsies and stage men at high-risk of prostate cancer.

OBJECTIVE: To assess whether a diagnostic pathway in which prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is used as a single imaging modality is feasible to guide targeted biopsy and to detect clinically significant prostate cancer (csPCa) in biopsy-naïve men at high-risk of disease. PATIENTS AND METHODS: A total of 60 men with a prostate-specific antigen (PSA) level of 20-50 ng/mL underwent 18 F-PSMA(DCFPyL)-PET/CT prior to prostate biopsies in this prospective, non-randomised cohort study. Magnetic resonance imaging (MRI) was not performed. Using a 12-segment mapping model of the prostate, PSMA-guided targeted biopsy was performed along with systematic biopsies. The detection rate of PCa and csPCa was assessed for combined systematic and targeted biopsy, and for targeted biopsy only. csPCa was defined as a prostate biopsy with an International Society of Uropathology (ISUP) Grade Group ≥2. RESULTS: Lesions suspicious for PCa in the prostate gland were observed on all PSMA-PET/CTs. A total of 27/60 men (45%) already had metastatic disease on staging 18 F-PSMA(DCFPyL)-PET/CT. Combined PSMA-guided targeted and systematic biopsies detected PCa in 56/60 (93.3%) patients, with 52 of them (92.9%) having csPCa. PSMA-guided targeted biopsy, if performed as a single biopsy modality, identified PCa in 52/60 men (86.7%) and in 27/27 men (100%) men with metastases. CONCLUSIONS: Using the PSMA-driven single imaging modality pathway in biopsy-naïve men at high-risk of PCa, a substantial number of diagnostic MRI scans could be avoided while at the same time obtaining adequate targeting, staging, and detection of csPCa.

TripleAiM1: a nationwide registry of de novo metastatic hormone-sensitive prostate cancer with prospective quality-of-life assessment.

INTRODUCTION: The treatment landscape for de novo metastatic hormone sensitive prostate cancer (mHSPC) is rapidly evolving. With an abundance of available treatment strategies, selecting the optimal strategy for an individual patient is becoming increasingly challenging. TripleAiM1 aims to evaluate the impact of mHSPC treatments on health-related quality of life (HRQoL) and to provide real-world data insights on diagnostics, treatment strategies, patient subgroups and related healthcare expenditure for mHSPC. The aspirational target of TripleAiM1 is that in the near future, a more tailored therapy can be offered based on the individual patient's wishes and needs in accordance with the overarching principle of value-based healthcare. METHODS AND ANALYSIS: We describe the TripleAiM1 study design; a nationwide registry comprising a retrospective and prospective cohort of patients with de novo mHSPC. Starting in May 2020, eligible patients are identified, selected and recruited in 14 participating hospitals in the Netherlands. Our hypothesis is that, in a real-world setting, differences in clinically meaningful HRQoL deterioration will be observed for treatment strategies over time. HRQoL data, assessed with patient-reported outcome measures, costs and clinical data will be collected for 24 months.For the retrospective cohort, all patients diagnosed with de novo mHSPC from January 2017 onwards are eligible for inclusion. Patient and tumour characteristics, imaging modalities and treatment patterns will be analysed descriptively to provide a real-world overview.Time-to-event endpoints will be assessed using the Kaplan-Meier method and regression models will be employed to analyse baseline characteristics associated with an increased likelihood of death, progression and HRQoL deterioration. Longitudinal mixed-effects models will be employed to assess change of patient-reported outcome scores from baseline until the end of follow-up. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Research Ethics Committee, Twente. Study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NL9719.

Higher Preoperative Maximum Standardised Uptake Values (SUVmax) Are Associated with Higher Biochemical Recurrence Rates after Robot-Assisted Radical Prostatectomy for [68Ga]Ga-PSMA-11 and [18F]DCFPyL Positron Emission Tomography/Computed Tomography.

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.

Treating Primary Node-Positive Prostate Cancer: A Scoping Review of Available Treatment Options.

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.

The Diagnostic Value of PSMA PET/CT in Men with Newly Diagnosed Unfavorable Intermediate-Risk Prostate Cancer.

Our objective was to determine the diagnostic value of prostate-specific membrane antigen (PSMA) PET/CT in staging men with newly diagnosed unfavorable intermediate-risk prostate cancer (PCa). Methods: Patients with newly diagnosed unfavorable intermediate-risk PCa, in whom PSMA PET/CT was performed as a primary staging modality, were retrospectively studied. PSMA PET/CT was performed at several diagnostic centers and reported by expert nuclear medicine physicians within 2 high-volume PCa centers. A multivariate logistic regression analysis, taking into account clinical, biochemical, pathologic, and radiologic variables, was performed to identify potential independent predictors for metastatic disease on PSMA PET/CT. Results: In total, 396 men with newly diagnosed unfavorable intermediate-risk PCa were studied. Metastatic disease was observed in 37 (9.3%) men, of whom 29 (7.3%) had molecular imaging locoregional lymph node metastases (miN1) and 16 (4.0%) had distant metastases (miM1). A radiologic tumor stage of at least T3 on MRI (odds ratio, 2.72 [95% CI, 1.27-5.83]; P = 0.01) and more than 50% positive prostate biopsies (odds ratio, 3.87 [95% CI, 1.74-8.62]; P = 0.001) were found to be independently associated with metastatic disease on PSMA PET/CT. Conclusion: Given that metastatic disease was observed in nearly 1 in 10 men with newly diagnosed unfavorable intermediate-risk PCa, PSMA PET/CT is considered to be of diagnostic value within this population. Further stratification using the radiologic tumor stage and the percentage of positive prostate biopsies could aid in identifying those patients at risk of having metastatic disease on PSMA PET/CT.

Staging fluorodeoxyglucose positron emission tomography/computed tomography for muscle-invasive bladder cancer: a nationwide population-based study.

OBJECTIVE: To provide insight into the use and staging information on lymph-node involvement added by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with muscle-invasive bladder cancer (MIBC), based on a nationwide population-based cohort study. PATIENTS AND METHODS: We analysed a nationwide cohort of patients with MIBC without signs of distant metastases, newly diagnosed in the Netherlands between November 2017 and October 2019. From this cohort, we selected patients who underwent pre-treatment staging with CT only or CT and FDG-PET/CT. The distribution of patients, disease characteristics, imaging findings, nodal status (clinical nodal stage cN0 vs cN+) and treatment were described for each imaging modality group (CT only vs CT and FDG-PET/CT). RESULTS: We identified 2731 patients with MIBC: 1888 (69.1%) underwent CT only; 606 (22.2%) underwent CT and FDG-PET/CT, 237 (8.6%) underwent no CT. Of the patients who underwent CT only, 200/1888 (10.6%) were staged as cN+, vs 217/606 (35.8%) who underwent CT and FDG-PET/CT. Stratified analysis showed that this difference was found in patients with clinical tumour stage (cT)2 as well as cT3/4 MIBC. Of patients who underwent both imaging modalities and were staged with CT as cN0, 109/498 (21.9%) were upstaged to cN+ based on FDG-PET/CT. Radical cystectomy (RC) was the most common treatment within both imaging groups. Preoperative chemotherapy was more frequently applied in cN+ disease and in FDG-PET/CT-staged patients. Concordance of pathological N stage after upfront RC was higher among patients staged as cN+ with CT and FDG-PET/CT (50.0% pN+) than those staged as cN+ with only CT (39.3%). CONCLUSION: Patients with MIBC who underwent pre-treatment staging with FDG-PET/CT were more often staged as lymph node positive, regardless of cT stage. In patients with MIBC who underwent CT and FDG-PET/CT, FDG-PET/CT led to clinical nodal upstaging in approximately one-fifth. Additional imaging findings may influence subsequent treatment strategies.

Development and External Validation of a Novel Nomogram to Predict the Probability of Pelvic Lymph-node Metastases in Prostate Cancer Patients Using Magnetic Resonance Imaging and Molecular Imaging with Prostate-specific Membrane Antigen Positron Emission Tomography.

BACKGROUND: Preoperative assessment of the probability of pelvic lymph-node metastatic disease (pN1) is required to identify patients with prostate cancer (PCa) who are candidates for extended pelvic lymph-node dissection (ePLND). OBJECTIVE: To develop a novel intuitive prognostic nomogram for predicting pathological lymph-node (pN) status in contemporary patients with primary diagnosed localized PCa, using preoperative clinical and histopathological parameters, magnetic resonance imaging (MRI), and prostate-specific membrane antigen (PSMA) positron emission tomography (PET). DESIGN, SETTING, AND PARTICIPANTS: In total, 700 eligible patients who underwent robot-assisted radical prostatectomy and ePLND were included in the model-building cohort. The external validation cohort consisted of 305 surgically treated patients. Logistic regression with backward elimination was used to select variables for the Amsterdam-Brisbane-Sydney nomogram. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance of the final model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analyses. Models were subsequently validated in an external population. RESULTS AND LIMITATIONS: The Amsterdam-Brisbane-Sydney nomogram included initial prostate-specific antigen value, MRI T stage, highest biopsy grade group (GG), biopsy technique, percentage of systematic cores with clinically significant PCa (GG ≥2), and lymph-node status on PSMA-PET. The AUC for predicting pN status was 0.81 (95% confidence interval [CI] 0.78-0.85) for the final model. On external validation, the Amsterdam-Brisbane-Sydney nomogram showed superior discriminative ability to the Briganti-2017 and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms (AUC 0.75 [95% CI 0.69-0.81] vs 0.67 [95% CI 0.61-0.74] and 0.65 [95% CI 0.58-0.72], respectively; p < 0.05), and similar discriminative ability to the Briganti-2019 nomogram (AUC 0.78 [95% CI 0.71-0.86] vs 0.80 [95% CI 0.73-0.86]; p = 0.76). The Amsterdam-Brisbane-Sydney nomogram showed excellent calibration on external validation, with an increased net benefit at a threshold probability of ≥4%. CONCLUSIONS: The validated Amsterdam-Brisbane-Sydney nomogram performs superior to the Briganti-2017 and MSKCC nomograms, and similar to the Briganti-2019 nomogram. Furthermore, it is applicable in all patients with newly diagnosed unfavorable intermediate- and high-risk PCa. PATIENT SUMMARY: We developed and validated the Amsterdam-Brisbane-Sydney nomogram for the prediction of prostate cancer spread to lymph nodes before surgery. This nomogram performs similar or superior to all presently available nomograms.

Genetic Aspects and Molecular Testing in Prostate Cancer: A Report from a Dutch Multidisciplinary Consensus Meeting.

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.

Identifying Patients in Whom the Follow-Up Scheme after Robot-Assisted Radical Prostatectomy Could Be Optimized in the First Year after Surgery: Reducing Healthcare Burden.

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 <1 year of PSA follow-up. Postoperative PSA values were collected. Biochemical persistence (BCP) was defined as PSA level >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.

Added Clinical Value of 18F-FDG-PET/CT to Stage Patients With High-Risk Non-Muscle Invasive Bladder Cancer Before Radical Cystectomy.

INTRODUCTION AND OBJECTIVES: 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET/CT) is increasingly used in the preoperative staging of patients with muscle-invasive bladder cancer. The clinical added value of FDG-PET/CT in high-risk non-muscle invasive bladder cancer (NMIBC) is unknown. In this study, the value of FDG-PET/CT in addition to contrast enhanced (CE)-CT was evaluated in high-risk NMIBC before radical cystectomy (RC). MATERIALS AND METHODS: This is a retrospective analysis of consecutive patients with high risk and very-high risk urothelial NMIBC scheduled for RC in a tertiary referral center between 2011 and 2020. Patients underwent staging with CE-CT (chest and abdomen/pelvis) and FDG-PET/CT. We assessed the clinical disease stage before and after FDG-PET/CT and the treatment recommendation based on the stage before and after FDG-PET/CT. The accuracy of CT and FDG-PET/CT for identifying metastatic disease was defined by the receiver-operating curve using a reference-standard including histopathology/cytology (if available), imaging and follow-up. RESULTS: A total of 92 patients were identified (median age: 71 years). In 14/92 (15%) patients, FDG-PET/CT detected metastasis (12 suspicious lymph nodes and 4 distant metastases). The disease stage changed in 11/92 (12%) patients based on additional FDG-PET/CT findings. FDG-PET/CT led to a different treatment in 9/92 (10%) patients. According to the reference standard, 25/92 (27%) patients had metastases. The sensitivity, specificity and accuracy of FDG-PET/CT was 36%, 93% and 77% respectively, versus 12%, 97% and 74% of CE-CT only. The area under the ROC curve was 0.643 for FDG-PET/CT and 0.545 for CT, P = .036. CONCLUSION: The addition of FDG-PET/CT to CE-CT imaging changed the treatment in 10% of patients and proved to be a valuable diagnostic tool in a selected subgroup of NMIBC patients scheduled for RC.