Biochemical Response of <0.1 ng/ml Predicts Therapy-free Survival of Prostate Cancer Patients following Prostate-specific Membrane Antigen-targeted Salvage Surgery.

BACKGROUND: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. OBJECTIVE: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022). INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. RESULTS AND LIMITATIONS: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. PATIENT SUMMARY: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Location-Based Oncological Outcomes of Sentinel Node Dissection in Radical Prostatectomy.

PURPOSE: To assess the oncological outcomes of sentinel-node dissection during radical prostatectomy according to nodal location in comparison to extended pelvic lymph node dissection. MATERIALS AND METHODS: Prospectively collected data of clinically node negative patients that underwent prostatectomy and extended lymph node dissection with or without sentinel-node from 2013 to January 2023 was retrospectively analyzed. The primary endpoint was to assess oncological outcomes on the whole population. Kaplan-Meier curves were used to depict biochemical and clinical recurrence free survival. Multivariable Cox regression models assessed the impact of nodal location on SPECT on oncological outcomes. Adjustment for case mix included: pathological T stage, ISUP grade group, initial PSA, nodal burden, age at surgery and surgical margin status. Secondarily, a propensity score match was performed according to age at surgery, PSA, biopsy ISUP, clinical T stage and Briganti risk of nodal invasion. Survival and regression analyses were than performed also in the matched population. RESULTS: 55.8% patients had at least one sentinel node outside of lymph node dissection template at SPECT/CT. Log-rank test showed comparable 36-months biochemical (P = .3) and clinical recurrence-free survival (P = .6) among patients with sentinel-node inside template, outside template or ePLND alone. At Cox regression, sentinel-node location outside template was associated with lower hazard of metastases (HR 0.62; P = .04) in the overall cohort, while in the matched cohort benefits were observed only for biochemical recurrence (HR 0.57; P = .001). CONCLUSIONS: Wider nodal resection boundaries outside "classic" template, driven by sentinel node procedure, have a positive impact on oncological outcomes in selected patient.

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.

Estimating Surgical Urethral Length on Intraoperative Robot-Assisted Prostatectomy Images using Artificial Intelligence Anatomy Recognition.

Objective To construct a Convolutional Neural Network (CNN) model that can recognize and delineate anatomic structures on intraoperative video frames of robot-assisted radical prostatectomy (RARP) and to use these annotations to predict the surgical urethral length (SUL). Background Urethral dissection during RARP impacts patient urinary incontinence (UI) outcomes, and requires extensive training. Large differences exist between incontinence outcomes of different urologists and hospitals. Also, surgeon experience and education are critical towards optimal outcomes. Therefore new approaches are warranted. SUL is associated with UI. Artificial intelligence (AI) surgical image segmentation using a CNN could automate SUL estimation and contribute towards future AI-assisted RARP and surgeon guidance. Methods Eighty-eight intraoperative RARP videos between June 2009 and September 2014 were collected from a single center. 264 frames were annotated according to: prostate, urethra, ligated plexus and catheter. Thirty annotated images from different RARP videos were used as a test dataset. The Dice coefficient (DSC) and 95th percentile Hausdorff distance (Hd95) were used to determine model performance. SUL was calculated using the catheter as a reference. Results The DSC of the best performing model were 0.735 and 0.755 for the catheter and urethra classes respectively, with a Hd95 of 29.27 and 72.62 respectively. The model performed moderately on the ligated plexus and prostate. The predicted SUL showed a mean difference of 0.64 - 1.86mm difference versus human annotators, but with significant deviation (SD 3.28 - 3.56). Conclusion This study shows that an AI image segmentation model can predict vital structures during RARP urethral dissection with moderate to fair accuracy. SUL estimation derived from it showed large deviations and outliers when compared to human annotators, but with a very small mean difference (<2mm). This is a promising development for further research on AI-assisted RARP. Keywords Prostate cancer, Anatomy recognition, Artificial intelligence, Continence, Urethral length.

Current Standards for Training in Robot-assisted Surgery and Endourology: A Systematic Review.

BACKGROUND AND OBJECTIVE: Different training programs have been developed to improve trainee outcomes in urology. However, evidence on the optimal training methodology is sparse. Our aim was to provide a comprehensive description of the training programs available for urological robotic surgery and endourology, assess their validity, and highlight the fundamental elements of future training pathways. METHODS: We systematically reviewed the literature using PubMed/Medline, Embase, and Web of Science databases. The validity of each training model was assessed. The methodological quality of studies on metrics and curricula was graded using the MERSQI scale. The level of evidence (LoE) and level of recommendation for surgical curricula were awarded using the educational Oxford Centre for Evidence-Based Medicine classification. KEY FINDINGS AND LIMITATIONS: A total of 75 studies were identified. Many simulators have been developed to aid trainees in mastering skills required for both robotic and endourology procedures, but only four demonstrated predictive validity. For assessment of trainee proficiency, we identified 18 in robotics training and six in endourology training; however, the majority are Likert-type scales. Although proficiency-based progression (PBP) curricula demonstrated superior outcomes to traditional training in preclinical settings, only four of six (67%) in robotics and three of nine (33%) in endourology are PBP-based. Among these, the Fundamentals of Robotic Surgery and the SIMULATE curricula have the highest LoE (level 1b). The lack of a quantitative synthesis is the main limitation of our study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Training curricula that integrate simulators and PBP methodology have been introduced to standardize trainee outcomes in robotics and endourology. However, evidence regarding their educational impact remains restricted to preclinical studies. Efforts should be made to expand these training programs to different surgical procedures and assess their clinical impact. PATIENT SUMMARY: Simulation-based training and programs in which progression is based on proficiency represent the new standard of quality for achieving surgical proficiency in urology. Studies have demonstrated the educational impact of these approaches. However, there are still no standardized training pathways for several urology procedures.

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.

Strong Correlation Between SUVmax on PSMA PET/CT and Numeric Drop-In γ-Probe Signal for Intraoperative Identification of Prostate Cancer Lesions.

Prostate-specific membrane antigen (PSMA) PET is used to select patients with recurrent prostate cancer for metastasis-directed therapy. A surgical approach can be achieved through radioguided surgery (RGS), using a Drop-In γ-probe that traces lesions that accumulate the radioactive signal. With the aim of guiding patient selection for salvage surgery, we studied the correlation between the SUVmax of lesions on preoperative PSMA PET/CT and their intraoperative counts/s measured using the Drop-In γ-probe. Methods: A secondary analysis based on the prospective, single-arm, and single-center feasibility study was conducted (NCT03857113). Patients (n = 29) with biochemical recurrence after previous curative-intent therapy and a maximum of 3 suggestive lesions within the pelvis on preoperative PSMA PET/CT were included. Patients treated with androgen deprivation therapy within 6 mo before surgery were excluded. All patients received an intravenous injection of 99mTc-PSMA-I&S 1 d before surgery. Radioguidance was achieved using a Drop-In γ-probe. Correlation was determined using the Spearman rank correlation coefficient (ρs). Subgroup analysis was based on the median SUVmax Results: In total, 33 lesions were visible on the PSMA PET/CT images, with a median overall SUVmax of 6.2 (interquartile range [IQR], 4.2-9.7). RGS facilitated removal of 31 lesions. The median Drop-In counts/s were 134 (IQR, 81-220) in vivo and 109 (IQR, 72-219) ex vivo. The intensity of the values correlated with SUVmax (ρs = 0.728 and 0.763, respectively; P < 0.001). Subgroup analysis based on median SUVmax in the group with an SUVmax of less than 6 showed no statistically significant correlation with the numeric signal in vivo (ρs = 0.382; P = 0.221) or the signal-to-background-ratio (ρs = 0.245; P = 0.442), whereas the group with an SUVmax of 6 or more showed respective statistically significant positive correlations (ρs = 0.774 [P < 0.001] and ρs = 0.647 [P = 0.007]). Conclusion: Our findings indicate that there is a direct relation between SUVmax on PSMA PET/CT and the readout recorded by the surgical Drop-In probe, thereby indicating that SUVmax can be used to select patients for PSMA RGS. For more definitive subgroup definitions for treatment recommendations, further studies are necessary to validate the present findings.

Review on the Role of BRCA Mutations in Genomic Screening and Risk Stratification of Prostate Cancer.

(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only "landmark" publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1.2% and 3.2%. However, BRCA2 and BRCA1 mutations are responsible for most cases of hereditary PCa, increasing the risk by 3-8.6 times and up to 4 times, respectively. These mutations are correlated with aggressive disease and poor prognosis. Gene testing should be offered to patients with metastatic PCa, those with 2-3 first-degree relatives with PCa, or those aged < 55 and with one close relative with breast (age ≤ 50 years) or invasive ovarian cancer. (4) Conclusions: The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.

Penile cancer care in the Netherlands: increased incidence, centralisation, and improved survival.

OBJECTIVE: To evaluate penile squamous cell carcinoma (PSCC) incidence and centralisation trends in the Netherlands over the past three decades, as well as the effect of centralisation of PSCC care on survival. PATIENTS AND METHODS: In the Netherlands PSCC care is largely centralised in one national centre of expertise (Netherlands Cancer Institute [NCI], Amsterdam). For this study, the Netherlands Cancer Registry, an independent nationwide cancer registry, provided per-patient data on age, clinical and pathological tumour staging, follow-up, and vital status. Patients with treatment at the NCI were identified and compared to patients who were treated at all other centres. The age-standardised incidence rate was calculated with the European Standard Population. The probability of death due to PSCC was estimated using the relative survival. Multivariable Cox regression analysis was performed to evaluate predictors of survival. RESULTS: A total of 3160 patients were diagnosed with PSCC between 1990 and 2020, showing a rising incidence (P < 0.001). Annual caseload increased at the NCI (1% in 1990, 65% in 2020) and decreased at other (regional) centres (99% to 35%). Despite a relatively high percentage of patients with T2-4 (64%) and N+ (33%) at the NCI, the 5-year relative survival was higher (86%, 95% confidence interval [CI] 82-91%) compared to regional centres (76%, 95% CI 73-80%, P < 0.001). Patients with a pathological T2 tumour were treated with glans-sparing treatment more often at the reference centre than at the regional centres (16% vs 5.0%, P < 0.001). After adjusting for age, histological grading, T-stage, presence of lymph node involvement and year of diagnosis, treatment at regional centres remained a predictor for worse survival (hazard ratio 1.22, 95% CI 1.05-1.39; P = 0.006). CONCLUSION: The incidence of PSCC in the Netherlands has been gradually increasing over the past three decades, with a noticeable trend towards centralisation of PSCC care and improved relative survival rate.

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.

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.

European Association of Urology Biochemical Recurrence Risk Classification as a Decision Tool for Salvage Radiotherapy-A Multicenter Study.

BACKGROUND: The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP). OBJECTIVE: To assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT). DESIGN, SETTING, AND PARTICIPANTS: Analyses of 2379 patients who developed BCR after RP (1989-2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group. RESULTS AND LIMITATIONS: Overall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1). CONCLUSIONS: Improved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up. PATIENT SUMMARY: The impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR.

Membranous urethral length measurement on preoperative MRI to predict incontinence after radical prostatectomy: a literature review towards a proposal for measurement standardization.

OBJECTIVES: To investigate the membranous urethral length (MUL) measurement and its interobserver agreement, and propose literature-based recommendations to standardize MUL measurement for increasing interobserver agreement. MUL measurements based on prostate MRI scans, for urinary incontinence risk assessment before radical prostatectomy (RP), may influence treatment decision-making in men with localised prostate cancer. Before implementation in clinical practise, MRI-based MUL measurements need standardization to improve observer agreement. METHODS: Online libraries were searched up to August 5, 2022, on MUL measurements. Two reviewers performed article selection and critical appraisal. Papers reporting on preoperative MUL measurements and urinary continence correlation were selected. Extracted information included measuring procedures, MRI sequences, population mean/median values, and observer agreement. RESULTS: Fifty papers were included. Studies that specified the MRI sequence used T2-weighted images and used either coronal images (n = 13), sagittal images (n = 18), or both (n = 12) for MUL measurements. 'Prostatic apex' was the most common description of the proximal membranous urethra landmark and 'level/entry of the urethra into the penile bulb' was the most common description of the distal landmark. Population mean (median) MUL value range was 10.4-17.1 mm (7.3-17.3 mm), suggesting either population or measurement differences. Detailed measurement technique descriptions for reproducibility were lacking. Recommendations on MRI-based MUL measurement were formulated by using anatomical landmarks and detailed descriptions and illustrations. CONCLUSIONS: In order to improve on measurement variability, a literature-based measuring method of the MUL was proposed, supported by several illustrative case studies, in an attempt to standardize MRI-based MUL measurements for appropriate urinary incontinence risk preoperatively. CLINICAL RELEVANCE STATEMENT: Implementation of MUL measurements into clinical practise for personalized post-prostatectomy continence prediction is hampered by lack of standardization and suboptimal interobserver agreement. Our proposed standardized MUL measurement aims to facilitate standardization and to improve the interobserver agreement. KEY POINTS: • Variable approaches for membranous urethral length measurement are being used, without detailed description and with substantial differences in length of the membranous urethra, hampering standardization. • Limited interobserver agreement for membranous urethral length measurement was observed in several studies, while preoperative incontinence risk assessment necessitates high interobserver agreement. • Literature-based recommendations are proposed to standardize MRI-based membranous urethral length measurement for increasing interobserver agreement and improving preoperative incontinence risk assessment, using anatomical landmarks on sagittal T2-weighted images.

The Impact of Positron Emission Tomography Imaging and Tumor Molecular Profiling on Risk Stratification, Treatment Choice, and Oncological Outcomes of Patients with Primary or Relapsed Prostate Cancer: An International Collaborative Review of the Existing Literature.

CONTEXT: The clinical introduction of next-generation imaging methods and molecular biomarkers ("radiogenomics") has revolutionized the field of prostate cancer (PCa). While the clinical validity of these tests has thoroughly been vetted, their clinical utility remains a matter of investigation. OBJECTIVE: To systematically review the evidence to date on the impact of positron emission tomography (PET) imaging and tissue-based prognostic biomarkers, including Decipher, Prolaris, and Oncotype Dx, on the risk stratification, treatment choice, and oncological outcomes of men with newly diagnosed PCa or those with biochemical failure (BCF). EVIDENCE ACQUISITION: We performed a quantitative systematic review of the literature using the MEDLINE, EMBASE, and Web of Science databases (2010-2022) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. The validated Quality Assessment of Diagnostic Accuracy Studies 2 scoring system was used to assess the risk of bias. EVIDENCE SYNTHESIS: A total of 148 studies (130 on PET and 18 on biomarkers) were included. In the primary PCa setting, prostate-specific membrane antigen (PSMA) PET imaging was not useful in improving T staging, moderately useful in improving N staging, but consistently useful in improving M staging in patients with National Comprehensive Cancer Network (NCCN) unfavorable intermediate- to very-high-risk PCa. Its use led to a management change in 20-30% of patients. However, the effect of these treatment changes on survival outcomes was not clear. Similarly, biomarkers in the pretherapy primary PCa setting increased and decreased the risk, respectively, in 7-30% and 32-36% of NCCN low-risk and 31-65% and 4-15% of NCCN favorable intermediate-risk patients being considered for active surveillance. A change in management was noted in up to 65% of patients, with the change being in line with the molecular risk-based reclassification, but again, the impact of these changes on survival outcomes remained unclear. Notably, in the postsurgical primary PCa setting, biomarker-guided adjuvant radiation therapy (RT) was associated with improved oncological control: Δ↓ 2-yr BCF by 22% (level 2b). In the BCF setting, the data were more mature. PSMA PET was consistently useful in improving disease localization-Δ↑ detection for T, N, and M staging was 13-32%, 19-58%, and 9-29%, respectively. Between 29% and 73% of patients had a change in management. Most importantly, these management changes were associated with improved survival outcomes in three trials: Δ↑ 4-yr disease-free survival by 24.3%, Δ↑ 6-mo metastasis-free survival (MFS) by 46.7%, and Δ↑ androgen deprivation therapy-free survival by 8 mo in patients who received PET-concordant RT (level 1b-2b). Biomarker testing in these patients also appeared to be helpful in risk stratifying and guiding the use of early salvage RT (sRT) and concomitant hormonal therapy. Patients with high-genomic-risk scores benefitted from treatment intensification: Δ↑ 8-yr MFS by 20% with the use of early sRT and Δ↑ 12-yr MFS by 11.2% with the use of hormonal therapy alongside early sRT, while low-genomic-risk score patients did equally well with initial conservative management (level 3). CONCLUSIONS: Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited. PATIENT SUMMARY: In this review, we evaluated the utility of prostate-specific membrane antigen positron emission tomography and tumor molecular profiling in guiding the care of men with prostate cancer (PCa). We found that these tests augmented risk stratification, altered management, and improved cancer control in men with a new diagnosis of PCa or for those experiencing a relapse.

Delphi consensus project on prostate-specific membrane antigen (PSMA)-targeted surgery-outcomes from an international multidisciplinary panel.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients. METHODS: One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey®. Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method. RESULTS: Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of "cannot answer" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions). CONCLUSIONS: This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines.

Impact of persistent PSA after salvage radical prostatectomy: a multicenter study.

BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

Reliable Visualization of the Treatment Effect of Transperineal Focal Laser Ablation in Prostate Cancer Patients by Magnetic Resonance Imaging and Contrast-enhanced Ultrasound Imaging.

Background: Transperineal focal laser ablation (TPLA) treatment for prostate cancer (PCa) is an experimental focal ablative therapy modality with low morbidity. However, a dosimetry model for TPLA is lacking. Objective: To determine (1) the three-dimensional (3D) histologically defined ablation zone of single- and multifiber TPLA treatment for PCa correlated with magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) and (2) a reliable imaging modality of ablation zone volumetry. Design setting and participants: This was a prospective, multicenter, and interventional phase I/II pilot study with an ablate-and-resect design. TPLA was performed in 12 patients with localized prostate cancer divided over four treatment regimens to evaluate potential variation in outcomes. Intervention: TPLA was performed approximately 4 wk prior to robot-assisted radical prostatectomy (RARP) in a daycare setting using local anesthesia. Outcome measurements and statistical analysis: Four weeks after TPLA, ablation zone volumetry was determined on prostate MRI and CEUS by delineation and segmentation into 3D models and correlated with whole-mount RARP histology using the Pearson correlation index. Results and limitations: Twelve office-based TPLA procedures were performed successfully under continuous transrectal ultrasound guidance using local perineal anesthesia. No serious adverse events occurred. A qualitative analysis showed a clear demarcation of the ablation zone on T2-weighted MRI, dynamic contrast-enhanced MRI, and CEUS. On pathological evaluation, no remnant cancer was observed within the ablation zone. Ablation zone volumetry on CEUS and T2-weighted MRI compared with histology had a Pearson correlation index of r = 0.94 (95% confidence interval [CI] 0.74-0.99, p < 0.001) and r = 0.93 (95% CI 0.73-0.98, p < 0.001), respectively. Conclusions: CEUS and prostate MRI could reliably visualize TPLA ablative effects after minimally invasive PCa treatment with a high concordance with histopathological findings and showed no remnant cancer. Patient summary: The treatment effects of a novel minimally invasive ablation therapy device can reliably be visualized with radiological examinations. These results will improve planning and performance of future procedures.