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.

99mTcPSMA-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 prognostic value of lymph node staging with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and extended pelvic lymph node dissection in node-positive patients with prostate cancer.

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

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.

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.

A standardized method to measure the membranous urethral length (MUL) on MRI of the prostate with high inter- and intra-observer agreement.

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

3D-Reconstructed Contact Surface Area and Tumour Volume on Magnetic Resonance Imaging Improve the Prediction of Extraprostatic Extension of Prostate Cancer.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p < 0.001). Multivariable logistic regression analysis showed that the radiological tumour stage (p = 0.001), tumour volume (p < 0.001), prostate CSA (p < 0.001), and tumour CSA (p ≤ 0.001) were independent predictors of pathological EPE. A 3D reconstruction of tumour locations in the prostate improves prediction of extraprostatic extension. Tumours with a higher 3D-reconstructed volume, a higher surface area of tumour in contact with the prostate capsule, and higher surface area of prostate capsule in contact with the tumour are at increased risk of side-specific extraprostatic extension.

Prospective analysis of clinically significant prostate cancer detection with [18F]DCFPyL PET/MRI compared to multiparametric MRI: a comparison with the histopathology in the radical prostatectomy specimen, the ProStaPET study.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is a well-established imaging method for localizing primary prostate cancer (PCa) and for guiding targeted prostate biopsies. [18F]DCFPyL positron emission tomography combined with MRI (PSMA-PET/MRI) might be of additional value to localize primary PCa. The aim of this study was to assess the diagnostic performance of [18F]DCFPyL-PET/MRI vs. mpMRI in tumour localization based on histopathology after robot-assisted radical-prostatectomy (RARP), also assessing biopsy advice for potential image-guided prostate biopsies. METHODS: Thirty prospectively included patients with intermediate to high-risk PCa underwent [18F]DCFPyL-PET/MRI and mpMRI prior to RARP. Two nuclear medicine physicians and two radiologists assessed tumour localization on [18F]DCFPyL-PET/MRI and on mpMRI respectively, and gave a prostate biopsy advice (2 segments) using a 14-segment model of the prostate. The uro-pathologist evaluated the RARP specimen for clinically significant PCa (csPCa) using the same model. csPCa was defined as any PCa with Grade Group (GG) ≥ 2. The biopsy advice based on imaging was correlated with the final histology in the RARP specimen for a total-agreement analysis. An additional near-agreement correlation was performed to approximate clinical reality. RESULTS: Overall, 142 of 420 (33.8%) segments contained csPCa after pathologic examination. The segments recommended for targeted biopsy contained the highest GG PCa segment in 27/30 patients (90.0%) both for [18F]DCFPyL-PET/MRI and mpMRI. Areas under the receiver operating characteristics curves (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the total-agreement detection of csPCa per segment using [18F]DCFPyL-PET/MRI were 0.70, 50.0%, 89.9%, 71.7%, and 77.9%, respectively. These results were 0.75, 54.2%, 94.2%, 82.8%, and 80.1%, respectively, for mpMRI only. CONCLUSION: Both [18F]DCFPyL-PET/MRI and mpMRI were only partly able to detect csPCa on a per-segment basis. An accurate detection (90.0%) of the highest GG lesion at patient-level was observed when comparing both [18F]DCFPyL-PET/MRI and mpMRI biopsy advice with the histopathology in the RARP specimen. So, despite the finding that [18F]DCFPyL-PET/MRI adequately detects csPCa, it does not outperform mpMRI.

Predicting early outcomes in patients with intermediate- and high-risk prostate cancer using prostate-specific membrane antigen positron emission tomography and magnetic resonance imaging.

OBJECTIVES: To identify predictors of early oncological outcomes in patients who opt for robot-assisted laparoscopic radical prostatectomy (RARP) for localized prostate cancer (PCa), including conventional prognostic variables as well as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET). PATIENTS AND METHODS: This observational study included 493 patients who underwent RARP and extended pelvic lymph node dissection (ePLND) for unfavourable intermediate- or high-risk PCa. Outcome measurement was biochemical progression of disease, defined as any postoperative prostate-specific antigen (PSA) value ≥0.2 ng/mL, or the start of additional treatment. Cox regression analysis was performed to assess predictors for biochemical progression, including initial PSA value, biopsy Grade Group (GG), T-stage on mpMRI, and lymph node status on PSMA PET imaging (miN0 vs miN1). RESULTS: The median (interquartile range) total follow-up of all included patients without biochemical progression was 12.6 (7.5-22.7) months. When assessing biochemical progression after surgery, initial PSA value (per doubling; odds ratio [OR] 1.22, 95% confidence interval [CI] 1.07-1.40; P = 0.004), biopsy GG ≥4 vs GG 1-2 (OR 1.83, 95% CI 1.18-2.85; P = 0.007), T-stage on mpMRI (rT3a vs rT2: OR 2.13, 95% CI 1.39-3.27; P = 0.001; ≥rT3b vs rT2: OR 4.78, 95% CI 3.20-7.16; P < 0.001) and miN1 on PSMA PET imaging (OR 2.94, 95% CI 2.02-4.27; P < 0.001) were independent predictors of early biochemical progression of disease. CONCLUSION: Initial PSA value, biopsy GG ≥4, ≥rT3 disease on mpMRI and miN1 disease on PSMA PET were predictors of early biochemical progression after RARP. Identifying these patients with an increased risk of early biochemical progression after surgery may have major implications for patient counselling in radical treatment decisions and on patient selection for modern (neo-)adjuvant and systematic treatments.

Standardised uptake values as determined on prostate-specific membrane antigen positron emission tomography/computed tomography is associated with oncological outcomes in patients with prostate cancer.

OBJECTIVES: To investigate the association between intraprostatic, intratumoral maximum standardised uptake values (SUVmax ) on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer (PCa) prior to robot-assisted radical prostatectomy (RARP) and pathology outcomes, including pathological International Society of Urological Pathology score (pISUP) and lymph node (LN) status (pN0/pN1). PATIENTS AND METHODS: A bi-centric, secondary analysis of two previous, prospective cohort studies was performed in 318 patients with biopsy confirmed PCa and who were scheduled for RARP. Before surgery, patients received a PSMA PET/CT with either 68 Ga-PSMA-11 (59% of the patients) or 18 F-PSMA (DCFPyL; 41%) as radiotracer. PET/CT images were analysed both visually and semi-quantitatively by measuring the SUVmax of the most intense suspect lesion in the prostate. The association between the SUVmax of the primary tumour and pre- and postoperative variables was analysed. RESULTS: The SUVmax was associated with clinical and biopsy preoperative variables, as well as with pISUP score and pathological tumour stage. Patients with a pISUP of ≤2 showed significantly lower SUVmax compared to patients with a pISUP of >2 for both tracers (SUVmax18 F-PSMA: median 5.1 vs 9.6, P = 0.002; SUVmax68 Ga-PSMA-11: 6.6 vs 8.6, P = 0.003). Moreover, patients with pN1 had significantly higher median SUVmax than those with pN0/pNx for both tracers (SUVmax18 F-PSMA: 7.9 vs 12.3, P = 0.04; SUVmax68 Ga-PSMA-11: 7.6 vs 12.0, P < 0.001). On multivariable logistic regression analysis, the intraprostatic SUVmax was an independent predictor of pN1 for both 68 Ga-PSMA-11 (per doubling: odds ratio [OR] 1.96, 95% confidence interval [CI] 1.27-3.01)) and 18 F-PSMA (per doubling: OR 1.79, 95% CI 1.06-3.03). CONCLUSION: Intraprostatic, intratumoral PSMA intensity on PET/CT, as semi-quantitatively expressed by SUVmax , may be a valuable innovative biomarker in patients with localised PCa, as it is highly associated with known conventional prognostic factors, such as pISUP and LN status.

Quality of early prostate cancer follow-up care from the patients' perspective.

PURPOSE: To develop optimal cancer survivorship care programs, this study assessed the quality of prostate cancer follow-up care as experienced by patients shortly after completion of primary treatment. METHODS: We surveyed 402 patients with localized prostate cancer participating in a randomized controlled trial comparing specialist versus primary care-based follow-up. For the current study, we used patient-reported data at the time of the first follow-up visit at the hospital, prior to randomization. We assessed patients' ratings of the quality of follow-up care using the Assessment of Patient Experiences of Cancer Care survey. This survey includes 13 scales about different aspects of care and an overall rating of care. Multivariable linear regression analysis was used to identify factors associated with perceived follow-up quality. RESULTS: Patients reported positive experiences at first follow-up for 9 of 13 scales, with mean (M) scores ranging from 79 to 97 (on a 0-100 response scale). Patients reported most frequently (over 70%) suboptimal care regarding symptom management (84%; M = 44, SD = 37), health promotion (75%; M = 45, SD = 39), and physician's knowledge about patients' life (84%; M = 65, SD = 23). Overall, patients' lower quality of follow-up ratings were associated with younger age, higher education level, having more than one comorbid condition, having undergone primary surgery, and experiencing significant symptoms. CONCLUSION: Patients with prostate cancer are generally positive about their initial, hospital-based follow-up care. However, efforts should be made to improve symptom management, health promotion, and physician's knowledge about patients' life. These findings point to areas where prostate cancer follow-up care can be improved.

The Predictive Value of Preoperative Negative Prostate Specific Membrane Antigen Positron Emission Tomography Imaging for Lymph Node Metastatic Prostate Cancer.

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

Intraoperative Strategies to Reduce Catheter-Related Bladder Discomfort in the Early Postoperative Period after Robot-Assisted Radical Prostatectomy.

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

Prostate Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography in the Evaluation of Initial Response in Candidates Who Underwent Salvage Radiation Therapy after Radical Prostatectomy for Prostate Cancer.

PURPOSE: We assessed predictors of short-term oncologic outcomes of patients who underwent salvage radiation therapy for biochemical recurrence after robot-assisted laparoscopic radical prostatectomy without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography. MATERIALS AND METHODS: We retrospectively analyzed 194 patients with biochemical recurrence after robot-assisted laparoscopic radical prostatectomy who underwent prostate specific membrane antigen positron emission tomography/computerized tomography prior to salvage radiation therapy. Patients with lymph node or distant metastases on restaging imaging or at the time of extended pelvic lymph node dissection during robot-assisted laparoscopic radical prostatectomy were excluded, as were patients who received androgen deprivation therapy during or prior to salvage radiation therapy. A multivariable logistic regression analysis was performed to assess predictors of treatment response, defined as prostate specific antigen value ≤0.1 ng/ml after salvage radiation therapy. RESULTS: Overall treatment response after salvage radiation therapy was 75% (146/194 patients). On multivariable analysis, prostate specific antigen value at initiation of salvage radiation therapy (OR 0.42, 95% CI 0.27-0.62, p <0.001), pathological T stage (pT3a vs pT2 OR 0.28, 95% CI 0.11-0.69, p=0.006; pT3b vs pT2 OR 0.26, 95% CI 0.09-0.71, p=0.009) and local recurrent disease on imaging (OR 5.53, 95% CI 1.96-18.52, p=0.003) were predictors of treatment response. CONCLUSIONS: Salvage radiation therapy in patients without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography showed a good overall treatment response of 75%. Higher treatment response rates were observed in patients with lower prostate specific antigen values at initiation of salvage radiation therapy, those with local recurrent disease on imaging and those with lower pathological T stage (pT2 vs pT3a/b).

Management impact of 18F-DCFPyL PET/CT in hormone-sensitive prostate cancer patients with biochemical recurrence after definitive treatment: a multicenter retrospective study.

PURPOSE: The aim of this study was to investigate whether an early, accurate identification of disease using 18F-DCFPyL PET/CT imaging resulted in a change of decision on treatment management, for individual patients with biochemically recurrent (BCR), hormone-sensitive prostate cancer. METHODS: In this retrospective study, a total of 253 patients with BCR who underwent restaging 18F-DCFPyL PET/CT were assessed. Two urologists specialized in uro-oncology were asked to formulate a preferred treatment for each patient before and after knowing the results of the 18F-DCFPyL PET/CT. RESULTS: Out of 253 patients, 191 (75%) underwent robot-assisted radical prostatectomy (RARP) as primary therapy, and 62 (25%) external beam radiation therapy (EBRT). In 103/253 cases (40.7%), a preferred treatment change based on the 18F-DCFPyL PET/CT findings was reported. In patients post-RARP, a positive 18F-DCFPyL PET/CT (OR 6.21; 95%CI 2.78-13.8; p < 0.001) and positive pathological lymph node status (pN1) (OR 2.96; 95%CI 1.15-7.60; p = 0.024) were significant predictors for an intended change of management, whereas a positive surgical margin (OR 0.42; 95%CI 0.20-0.88; p = 0.022) was inversely associated with an intended change of management. CONCLUSION: In this study, we found a significant impact of 18F-DCFPyL PET/CT on the intended management of patients with biochemically recurrent hormone-sensitive prostate cancer. A positive 18F-DCFPyL PET/CT scan, positive pathological lymph node status, and a negative surgical margin status were significantly associated with increased odds of having a change of management based on 18F-DCFPyL PET/CT findings.

Machine learning-based analysis of [18F]DCFPyL PET radiomics for risk stratification in primary prostate cancer.

PURPOSE: Quantitative prostate-specific membrane antigen (PSMA) PET analysis may provide for non-invasive and objective risk stratification of primary prostate cancer (PCa) patients. We determined the ability of machine learning-based analysis of quantitative [18F]DCFPyL PET metrics to predict metastatic disease or high-risk pathological tumor features. METHODS: In a prospective cohort study, 76 patients with intermediate- to high-risk PCa scheduled for robot-assisted radical prostatectomy with extended pelvic lymph node dissection underwent pre-operative [18F]DCFPyL PET-CT. Primary tumors were delineated using 50-70% peak isocontour thresholds on images with and without partial-volume correction (PVC). Four hundred and eighty standardized radiomic features were extracted per tumor. Random forest models were trained to predict lymph node involvement (LNI), presence of any metastasis, Gleason score ≥ 8, and presence of extracapsular extension (ECE). For comparison, models were also trained using standard PET features (SUVs, volume, total PSMA uptake). Model performance was validated using 50 times repeated 5-fold cross-validation yielding the mean receiver-operator characteristic curve AUC. RESULTS: The radiomics-based machine learning models predicted LNI (AUC 0.86 ± 0.15, p < 0.01), nodal or distant metastasis (AUC 0.86 ± 0.14, p < 0.01), Gleason score (0.81 ± 0.16, p < 0.01), and ECE (0.76 ± 0.12, p < 0.01). The highest AUCs reached using standard PET metrics were lower than those of radiomics-based models. For LNI and metastasis prediction, PVC and a higher delineation threshold improved model stability. Machine learning pre-processing methods had a minor impact on model performance. CONCLUSION: Machine learning-based analysis of quantitative [18F]DCFPyL PET metrics can predict LNI and high-risk pathological tumor features in primary PCa patients. These findings indicate that PSMA expression detected on PET is related to both primary tumor histopathology and metastatic tendency. Multicenter external validation is needed to determine the benefits of using radiomics versus standard PET metrics in clinical practice.

A systematic review on mutation markers for bladder cancer diagnosis in urine.

OBJECTIVES: To systematically summarise the available evidence on urinary bladder cancer (BC) mutation markers. Gene mutations are expected to provide novel biomarkers for urinary BC diagnosis. To date, evidence on urinary BC mutation markers has not proven sufficient to be adopted by clinical guidelines. In the present systematic review, diagnostic accuracy of urinary mutation analysis is separately assessed for primary BC diagnosis (BC detection) and for follow-up of BC patients (BC surveillance). METHODS: A literature search (PubMed, Embase.com and Wiley/Cochrane Library) and systematic review was performed up to 31 October 2019. As studies were too heterogeneous, no quantitative analysis could be performed. RESULTS: In total, 25 studies were summarised by qualitative analysis. For BC detection, diagnostic accuracy differed considerably for single mutation markers (sensitivity 1-85%, specificity 84-100%), and for marker panels (sensitivity 50-94%, specificity 43-97%). Similarly, for BC surveillance, diagnostic accuracy was highly variable for single mutation markers (sensitivity 0-85%, specificity 66-100%), and for marker panels (sensitivity 51-84%, specificity 66-96%). CONCLUSION: Urinary mutation analysis showed to be a promising diagnostic tool for non-invasive BC diagnosis. Nonetheless, we observed substantial differences in diagnostic accuracy of urinary BC mutation markers among publications. To translate the data summarised in the present review to future clinical practice, heterogeneity in research design, BC population, mutation analysis technique and urinary DNA should be considered. Eventual clinical implementation of urinary BC mutation markers can only be achieved by collecting more and stronger evidence. Combining different molecular assays might overcome current shortcomings of urinary mutation analysis.

Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial.

BACKGROUND: In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting. METHODS & DESIGN: This study compares 177Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on 18F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq 177Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another 18F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive 177Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression. DISCUSSION: This is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of 177Lu-PSMA-I&T for patients with oHSPC. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04443062 .

Use of gallium-68 prostate-specific membrane antigen positron-emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature.

OBJECTIVES: To review the literature to determine the sensitivity and specificity of gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron-emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68 Ga-PSMA PET in patients with BCR after radical prostatectomy (RP). MATERIALS AND METHODS: We performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were '(PSMA, 68 Ga-PSMA, 68 Gallium-PSMA, Ga-68-PSMA or prostate-specific membrane antigen)' and '(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)'. Relevant abstracts were reviewed and full-text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. RESULTS: Nine retrospective and two prospective studies described the sensitivity and specificity of 68 Ga-PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68 Ga-PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68 Ga-PSMA PET in patients with BCR after RP in the PSA subgroups <0.2 ng/mL, 0.2-0.49 ng/mL and 0.5 to <1.0 ng/mL ranged from 11.3% to 50.0%, 20.0% to 72.7% and 25.0% to 87.5%, respectively. CONCLUSION: The review results showed that 68 Ga-PSMA PET had a high specificity for the detection of pelvic lymph node metastases in primary PCa. Furthermore, 68 Ga-PSMA PET had a very high positive predictive value in detecting lymph node metastases in patients with BCR. By contrast, sensitivity was only moderate; therefore, based on the currently available literature, 68 Ga-PSMA PET cannot yet replace pelvic lymph node dissection to exclude lymph node metastases. In the salvage phase, 68 Ga-PSMA PET had both a high detection rate and impact on radiotherapy planning in early BCR after RP.