Multiparametric MRI and 18F-PSMA-1007 PET/CT for the Detection of Clinically Significant Prostate Cancer.

Background Multiparametric MRI (mpMRI) is effective for detecting prostate cancer (PCa); however, there is a high rate of equivocal Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions and false-positive findings. Purpose To investigate whether fluorine 18 (18F) prostate-specific membrane antigen (PSMA) 1007 PET/CT after mpMRI can help detect localized clinically significant PCa (csPCa), particularly for equivocal PI-RADS 3 lesions. Materials and Methods This prospective study included participants with elevated prostate-specific antigen (PSA) levels referred for prostate mpMRI between September 2020 and February 2022. 18F-PSMA-1007 PET/CT was performed within 30 days of mpMRI and before biopsy. PI-RADS category and level of suspicion (LOS) were assessed. PI-RADS 3 or higher lesions at mpMRI and/or LOS 3 or higher lesions at 18F-PSMA-1007 PET/CT underwent targeted biopsies. PI-RADS 2 or lower and LOS 2 or lower lesions were considered nonsuspicious and were monitored during a 1-year follow-up by means of PSA testing. Diagnostic accuracy was assessed, with histologic examination serving as the reference standard. International Society of Urological Pathology (ISUP) grade 2 or higher was considered csPCa. Results Seventy-five participants (median age, 67 years [range, 52-77 years]) were assessed, with PI-RADS 1 or 2, PI-RADS 3, and PI-RADS 4 or 5 groups each including 25 participants. A total of 102 lesions were identified, of which 80 were PI-RADS 3 or higher and/or LOS 3 or higher and therefore underwent targeted biopsy. The per-participant sensitivity for the detection of csPCa was 95% and 91% for mpMRI and 18F-PSMA-1007 PET/CT, respectively, with respective specificities of 45% and 62%. 18F-PSMA-1007 PET/CT was used to correctly differentiate 17 of 26 PI-RADS 3 lesions (65%), with a negative and positive predictive value of 93% and 27%, respectively, for ruling out or detecting csPCa. One additional significant and one insignificant PCa lesion (PI-RADS 1 or 2) were found at 18F-PSMA-1007 PET/CT that otherwise would have remained undetected. Two participants had ISUP 2 tumors without PSMA uptake that were missed at PET/CT. Conclusion 18F-PSMA-1007 PET/CT showed good sensitivity and moderate specificity for the detection of csPCa and ruled this out in 93% of participants with PI-RADS 3 lesions. Clinical trial registration no. NCT04487847 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Extended pelvic lymph node dissection in robot-assisted radical prostatectomy is an independent risk factor for major complications.

The aim of this study is to evaluate the major postoperative complication rate after robot-assisted radical prostatectomy (RARP) and to identify related risk factors. A consecutive series of patients who underwent RARP between September 2016 and May 2021, with or without extended pelvic lymph node dissection (ePLND) were analyzed for postoperative complications that occurred within 30 days following surgery. Potential risk factors related to complications were identified by means of a multivariate logistic analysis. Electronic medical records were retrospectively reviewed for the occurrence of major complications (Clavien-Dindo grade III or higher) on a per patient level. A multivariate logistic regression with risk factors was performed to identify contributors to complications. In total, 1280 patients were included, of whom 79 (6.2%) experienced at least 1 major complication. Concomitant ePLND was performed in 609 (48%) of patients. The majority of all complications were likely related to the surgical procedure, with anastomotic leakage and lymphoceles being the most common. Upon multivariate analysis, performing ePLND remained the only significant risk factor for the occurrence of major complications (OR 2.26, p = 0.001). In contrast to robot-assisted radical prostatectomy alone, the combination with extended pelvic lymph node dissection (ePLND) has a substantial risk of serious complications. Since the ePLND is performed mainly for staging purpose, the clinical contribution of the ePLND has to be reconsidered with the present use of the PSMA-PET/CT.

Prostate-Specific Membrane Antigen-Targeted Radioguided Pelvic Lymph Node Dissection in Newly Diagnosed Prostate Cancer Patients with a Suspicion of Locoregional Lymph Node Metastases: The DETECT Trial.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) aims to optimize the peroperative detection and removal of PSMA-avid lymph node (LN) metastases (LNMs) and has been described in patients with recurrent prostate cancer (PCa). In newly diagnosed PCa patients undergoing pelvic LN dissections, PSMA RGS could guide the urologist toward PSMA-expressing LNMs as identified on preoperative 18F-PSMA PET/CT imaging. The objective was to evaluate the safety and feasibility of 111In-PSMA RGS in primary PCa patients with one or more suggestive LNs on preoperative 18F-PSMA PET/CT. Methods: This prospective, phase I/II study included 20 newly diagnosed PCa patients with at least 1 suggestive LN on preoperative 18F-PSMA PET/CT. PSMA RGS was performed 24 h after 111In-PSMA-I&T administration, and postoperative 18F-PSMA PET/CT was performed to verify successful removal of the suggestive lesions. The primary endpoint was determination of the safety and feasibility of 111In-PSMA RGS. Safety was assessed by monitoring adverse events. Feasibility was described as the possibility to peroperatively detect suggestive LNs as identified on preoperative imaging. Secondary outcomes included the accuracy of 111In-PSMA RGS compared with histopathology, tumor- and lesion-to-background ratios, and biochemical recurrence. Results: No tracer-related adverse events were reported. In 20 patients, 43 of 49 (88%) 18F-PSMA PET-suggestive lesions were successfully removed. 111In-PSMA RGS facilitated peroperative identification and resection of 29 of 49 (59%) RGS-target lesions, of which 28 (97%) contained LNMs. Another 14 of 49 (29%) resected LNs were not detected with 111In-PSMA RGS, of which 2 contained metastases. Conclusion: 111In-PSMA RGS is a safe and feasible procedure that allows peroperative detection of 18F-PSMA PET/CT-suggestive lesions in newly diagnosed PCa patients. The use of a radioactive PSMA tracer and a detection device (γ-probe) during surgery helps in identifying LNs that were suggestive of PCa metastases on the 18F-PSMA PET/CT before surgery and thus may improve the peroperative identification and removal of these LNs.

Validation of Claims Data for Absorbing Pads as a Measure for Urinary Incontinence after Radical Prostatectomy, a National Cross-Sectional Analysis.

The use of healthcare insurance claims data for urinary incontinence (UI) pads has the potential to serve as an objective measure for assessing post-radical prostatectomy UI rates, but its validity for this purpose has not been established. The aim of this study is to correlate claims data with Patient Reported Outcome Measures (PROMs) for UI pad use. Patients who underwent RP in the Netherlands between September 2019 and February 2020 were included. Incontinence was defined as the daily use of ≥1 pad(s). Claims data for UI pads at 12-15 months after RP were extracted from a nationwide healthcare insurance database in the Netherlands. Participating hospitals provided PROMS data. In total, 1624 patients underwent RP. Corresponding data of 845 patients was provided by nine participating hospitals, of which 416 patients were matched with complete PROMs data. Claims data and PROMs showed 31% and 45% post-RP UI (≥1 pads). UI according to claims data compared with PROMs had a sensitivity of 62%, specificity of 96%, PPV of 92%, NPV of 75% and accuracy of 81%. The agreement between both methods was moderate (κ = 0.60). Claims data for pads moderately align with PROMs in assessing post-prostatectomy urinary incontinence and could be considered as a conservative quality indicator.

The Development and External Validation of Artificial Intelligence-Driven MRI-Based Models to Improve Prediction of Lesion-Specific Extraprostatic Extension in Patients with Prostate Cancer.

Adequate detection of the histopathological extraprostatic extension (EPE) of prostate cancer (PCa) remains a challenge using conventional radiomics on 3 Tesla multiparametric magnetic resonance imaging (3T mpMRI). This study focuses on the assessment of artificial intelligence (AI)-driven models with innovative MRI radiomics in predicting EPE of prostate cancer (PCa) at a lesion-specific level. With a dataset encompassing 994 lesions from 794 PCa patients who underwent robot-assisted radical prostatectomy (RARP) at two Dutch hospitals, the study establishes and validates three classification models. The models were validated on an internal validation cohort of 162 lesions and an external validation cohort of 189 lesions in terms of discrimination, calibration, net benefit, and comparison to radiology reporting. Notably, the achieved AUCs ranged from 0.86 to 0.91 at the lesion-specific level, demonstrating the superior accuracy of the random forest model over conventional radiological reporting. At the external test cohort, the random forest model was the best-calibrated model and demonstrated a significantly higher accuracy compared to radiological reporting (83% vs. 67%, p = 0.02). In conclusion, an AI-powered model that includes both existing and novel MRI radiomics improves the detection of lesion-specific EPE in prostate cancer.

MRI-Guided Salvage Focal Cryoablation: A 10-Year Single-Center Experience in 114 Patients with Localized Recurrent Prostate Cancer.

Patients with localized recurrent prostate cancer (PCa) are eligible for androgen-deprivation therapy, salvage radical prostatectomy (RP) or radiation therapy. These treatments are associated with serious side-effects, illustrating the need for alternative local treatment options with lower morbidity rates. All patients who underwent magnetic resonance imaging (MRI)-guided salvage focal cryoablation (SFC) with localized recurrent PCa between 2011-2021 (n = 114) were included. Two subgroups were formed: patients without (n = 99) and with prior RP (n = 15). We assessed the recurrence- (RFS) and treatment-free survival (TFS), measured from date of treatment to date of recurrence or initiation of additional salvage treatment, using Kaplan-Meier plots. Complications were reported using the Clavien-Dindo (CD) scale. Overall 1-year and 5-year RFS were 76.0% and 25.1%, and overall 1-year and 5-year TFS were 91.5% and 58.2%, respectively. Patients without prior RP showed a significantly higher 1-year (78.5% vs. 52.5%) and 5-year RFS (28.1% vs. 0.0%; p = 0.03), and a trend towards a higher 1-year (92.6% vs. 79.0%) and 5-year TFS (60.2% vs. 23.0%; p = 0.10) compared to those with prior RP. A total of 46 complications occurred in 37 patients, and the overall complication rate was 32.4% (37/114 patients). The majority (41/46; 89.1%) of complications were minor (CD 1-2). Overall (31.3 vs. 40.0%) and major (3.0 vs. 13.3%) complication rates were lower in patients without compared to those with prior RP, respectively. MRI-guided SFC is an effective and safe therapy for patients with recurrent PCa, and has proved to delay and potentially prevent the initiation of salvage treatments. Patients with locally recurrent PCa after prior RP had an increased risk of recurrence, a shortened time to additional treatment, and more complications compared to those without prior RP, which should be considered when selecting patients for SFC.

Cost Effectiveness of Rectal Culture-based Antibiotic Prophylaxis in Transrectal Prostate Biopsy: The Results from a Randomized, Nonblinded, Multicenter Trial.

Background: Culture-based antibiotic prophylaxis is a plausible strategy to reduce infections after transrectal prostate biopsy (PB) related to fluoroquinolone-resistant pathogens. Objective: To assess the cost effectiveness of rectal culture-based prophylaxis compared with empirical ciprofloxacin prophylaxis. Design setting and participants: The study was performed alongside a trial in 11 Dutch hospitals investigating the effectiveness of culture-based prophylaxis in transrectal PB between April 2018 and July 2021 (trial registration number: NCT03228108). Intervention: Patients were 1:1 randomized for empirical ciprofloxacin prophylaxis (oral) or culture-based prophylaxis. Costs for both prophylactic strategies were determined for two scenarios: (1) all infectious complications within 7 d after biopsy and (2) culture-proven Gram-negative infections within 30 d after biopsy. Outcome measurements and statistical analysis: Differences in costs and effects (quality-adjusted life-years [QALYs]) were analyzed from a healthcare and societal perspective (including productivity losses, and travel and parking costs) using a bootstrap procedure presenting uncertainty surrounding the incremental cost-effectiveness ratio in a cost-effectiveness plane and acceptability curve. Results and limitations: For the 7-d follow-up period, culture-based prophylaxis (n = 636) was €51.57 (95% confidence interval [CI] 6.52-96.63) more expensive from a healthcare perspective and €16.95 (95% CI -54.29 to 88.18) from a societal perspective than empirical ciprofloxacin prophylaxis (n = 652). Ciprofloxacin-resistant bacteria were detected in 15.4%. Extrapolating our data, from a healthcare perspective, 40% ciprofloxacin resistance would lead to equal cost for both strategies. Results were similar for the 30-d follow-up period. No significant differences in QALYs were observed. Conclusions: Our results should be interpreted in the context of local ciprofloxacin resistance rates. In our setting, from a healthcare perspective, culture-based prophylaxis was significantly more expensive than empirical ciprofloxacin prophylaxis. From a societal perspective, culture-based prophylaxis was somewhat more cost effective against the threshold value customary for the Netherlands (€80.000). Patient summary: Culture-based prophylaxis in transrectal prostate biopsy was not associated with reduced costs compared with empirical ciprofloxacin prophylaxis.

Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand.

PURPOSE: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting of a DOTA chelator for 111In labeling and a fluorophore/photosensitizer IRDye700DX (PSMA-N064). We evaluated the efficacy of PSMA-tPDT using PSMA-N064 in cell viability assays, a mouse xenograft model and in an ex vivo incubation study on fresh human PCa tissue. METHODS: In vitro, therapeutic efficacy of PSMA-N064 was evaluated using PSMA-positive LS174T cells and LS174T wild-type cells. In vivo, PSMA-N064-mediated tPDT was tested in immunodeficient BALB/c mice-bearing PSMA-positive LS174T xenografts. Tumor growth and survival were compared to control mice that received either NIR light or ligand injection only. Ex vivo tPDT efficacy was evaluated in excised fresh human PCa tissue incubated with PSMA-N064. RESULTS: In vitro, tPDT led to a PSMA-specific light- and ligand dose-dependent loss in cell viability. In vivo, tPDT-induced tumor cell apoptosis, delayed tumor growth, and significantly improved survival (p = 0.004) of the treated PSMA-positive tumor-bearing mice compared with the controls. In fresh ex vivo human PCa tissue, apoptosis was significantly increased in PSMA-tPDT-treated samples compared to non-treated control samples (p = 0.037). CONCLUSION: This study showed the feasibility of PSMA-N064-mediated tPDT in cell assays, a xenograft model and excised fresh human PCa tissue. This paves the way to investigate the impact of in vivo PSMA-tPDT on surgical outcome in PCa patients.

Cohort profile - the Renal cell cancer: Lifestyle, prognosis and quality of life (ReLife) study in the Netherlands.

PURPOSE: The Renal cell cancer: Lifestyle, prognosis and quality of life (ReLife) study is set up to obtain insight into the association of patient and tumour characteristics, lifestyle habits and circulating biomarkers with body composition features in patients with localised renal cell cancer (RCC). Further, it aims to assess the association of body composition features, lifestyle habits and circulating biomarkers with clinical outcomes, including health-related quality of life. PARTICIPANTS: The ReLife study is a multicentre prospective cohort study involving 368 patients with newly diagnosed stages I-III RCC recruited from January 2018 to June 2021 from 18 hospitals in the Netherlands. At 3 months, 1 year and 2 years after treatment, participants fill out a general questionnaire and questionnaires about their lifestyle habits (eg, diet, physical activity, smoking and alcohol consumption), medical history and health-related quality of life. At all three time points, patients wear an accelerometer and have blood samples taken. CT scans for body composition analysis are being collected. Permission is asked for collection of tumour samples. Information about disease characteristics, treatment of the primary tumour and clinical outcomes is being collected from medical records by the Netherlands Cancer Registry. FINDINGS TO DATE: A total of 836 invited patients were eligible and 368 patients were willing to participate and were included (response rate 44%). The mean age of patients was 62.5±9.0 years and 70% was male. The majority had stage I (65%) disease and were treated with radical nephrectomy (57%). Data collection at 3 months and 1 years after treatment have been finalised. FUTURE PLANS: Data collection at 2 years after treatment is expected to be finalised in June 2023 and longitudinal clinical data will continue to be collected. Results of studies based on this cohort are important to develop personalised evidence-based lifestyle advice for patients with localised RCC to enable them to get more control over their disease course.

Confocal laser microscopy for assessment of surgical margins during radical prostatectomy.

OBJECTIVE: To evaluate the feasibility of confocal laser microscopy (CLM) for intraoperative margin assessment as faster alternative to neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Surgical margins were assessed during 50 RARP procedures in patients scheduled for NeuroSAFE. Posterolateral sections were cut and imaged with CLM and further processed to conform with the NeuroSAFE protocol. Secondary resection (SR) was performed in case a positive surgical margin (PSM) was observed with NeuroSAFE. Afterwards, the CLM images were non-blinded assessed for the presence of PSMs. The accuracy of both NeuroSAFE and CLM was compared with conventional histopathology. Agreement for detection of PSMs between NeuroSAFE and CLM was evaluated with Cohen's kappa coefficient. Procedure times were compared with a Wilcoxon signed-ranks test. RESULTS: In total, 96 posterolateral sections of RP specimens were evaluated for the presence of PSMs. CLM identified 15 (16%) PSMs and NeuroSAFE identified 14 (15%) PSMs. CLM had a calculated sensitivity, specificity, positive predictive value and negative predictive value of 86%, 96%, 80% and 98% respectively for the detection of PSMs compared to definite pathology. After SR, residual tumour was found in six of 13 cases (46%), which were all identified by both techniques. There was a substantial level of agreement between CLM and NeuroSAFE (κ = 0.80). The median procedure time for CLM was significantly shorter compared to NeuroSAFE (8 vs 50 min, P < 0.001). The main limitation of this study was the non-blinded assessment of the CLM images. CONCLUSIONS: Compared to NeuroSAFE, CLM is a promising technique for intraoperative margin assessment and is able to reduce the time of intraoperative margin assessment.

Rectal Culture-Based Versus Empirical Antibiotic Prophylaxis to Prevent Infectious Complications in Men Undergoing Transrectal Prostate Biopsy: A Randomized, Nonblinded Multicenter Trial.

BACKGROUND: An increase in infections after transrectal prostate biopsy (PB), related to an increasing number of patients with ciprofloxacin-resistant rectal flora, necessitates the exploration of alternatives for the traditionally used empirical prophylaxis of ciprofloxacin. We compared infectious complication rates after transrectal PB using empirical ciprofloxacin prophylaxis versus culture-based prophylaxis. METHODS: In this nonblinded, randomized trial, between 4 April 2018 and 30 July 2021, we enrolled 1538 patients from 11 Dutch hospitals undergoing transrectal PB. After rectal swab collection, patients were randomized 1:1 to receive empirical prophylaxis with oral ciprofloxacin (control group [CG]) or culture-based prophylaxis (intervention group [IG]). Primary outcome was any infectious complication within 7 days after biopsy. Secondary outcomes were infectious complications within 30 days, and bacteremia and bacteriuria within 7 and 30 days postbiopsy. For primary outcome analysis, the χ2 test stratified for hospitals was used. Trial registration number: NCT03228108. RESULTS: Data from 1288 patients (83.7%) were available for analysis (CG, 652; IG, 636). Infection rates within 7 days postbiopsy were 4.3% (n = 28) (CG) and 2.5% (n = 16) (IG) (P value = .08; reduction: -1.8%; 95% confidence interval, -.004 to .040). Ciprofloxacin-resistant bacteria were detected in 15.2% (n = 1288). In the CG, the presence of ciprofloxacin-resistant rectal flora resulted in a 6.2-fold higher risk of early postbiopsy infection. CONCLUSIONS: Our study supports the use of culture-based prophylaxis to reduce infectious complications after transrectal PB. Despite adequate prophylaxis, postbiopsy infections can still occur. Therefore, culture-based prophylaxis must be weighed against other strategies that could reduce postbiopsy infections. Clinical Trials Registration. NCT03228108.

The Effect of Different Types of Prostate Biopsy Techniques on Post-Biopsy Infectious Complications.

PURPOSE: The aim of our study was to compare infectious complication rates between different prostate biopsy techniques with various number of biopsy cores. MATERIALS AND METHODS: In this retrospective study, all patients from 2 hospitals who underwent prostate biopsy between 2012 and 2019 were identified. Cohorts with different types of prostate biopsies were compiled within these hospitals. Primary outcome measure was any registered infectious complication within 7 days post-biopsy. Secondary outcomes were infectious complications within 30 days, hospitalization and bacteremia. To compare the risk of infection following different prostate biopsy techniques, data was fitted into a logistic regression model adjusting for potential confounders. RESULTS: In total, 4,233 prostate biopsies in 3,707 patients were included. After systematic transrectal ultrasound-guided prostate biopsy (TRUSPB; 12±1.4 biopsy cores), 4.0% (2,607) of all patients had infectious complications within 7 days post-biopsy. Transperineal magnetic resonance imaging (MRI)-ultrasound fusion guided prostate biopsy (16±3.7 biopsy cores) was associated with significantly lower infection rates than systematic TRUSPB (adjusted OR: 0.29 [0.09-0.73] 95% confidence interval [CI]). Transrectal targeted MRI-ultrasound fusion guided prostate biopsy (3.1±0.8 biopsy cores) and transrectal targeted in-bore MRI guided prostate biopsy (2.8±0.8 biopsy cores) also showed fewer infectious complications than systematic TRUSPB (adjusted OR: 0.41 [0.12-1.12] 95% CI and 0.68 [0.37-1.20] 95% CI, respectively). CONCLUSIONS: Transperineal prostate biopsy, or transrectal prostate biopsy with reduced number of biopsy cores, could lower the risk of infectious complications.

Skeletal muscle radiodensity and visceral adipose tissue index are associated with survival in renal cell cancer - A multicenter population-based cohort study.

INTRODUCTION: Body composition has been associated with disease outcome in several cancer types. Results for localized and metastatic renal cell cancer (RCC) are limited and inconsistent. Our aim was to examine the association between body composition and survival in RCC. METHODS: We conducted a population-based historical cohort study including patients diagnosed with RCC from 2008 to 2012. Diagnostic Computed Tomography images at the third lumbar vertebra (L3) were assessed for skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI). Clinical data was retrieved from medical records. Multivariable Cox regressions with restricted cubic splines were used to determine hazard ratios (HRs) and 95% confidence intervals (95%CIs) for 10-unit increases in body composition features with overall survival (OS) and recurrence-free survival (RFS). RESULTS: We included 719 stage I-III (of whom 254 (35.3%) died and 148 (21.9%) experienced recurrence) and 320 stage IV RCC patients (of whom 298 (93.1%) died). Median follow-up was 6.35 years (interquartile range; 1.41-8.23). For stage I-III, higher SMD was associated with better OS (men: HR 0.86; 95% CI 0.68-1.08; women: HR 0.69; 95% CI 0.50-0.95). Lower compared to median VATI was associated with worse OS for both men (HR 1.38; 95%CI 1.05-1.83 for VATI = 25) and women (HR 1.67; 95%CI 1.01-2.78 for VATI = 20). For stage IV, higher SMD and higher VATI were associated with better OS among men (HR 0.74; 95% CI 0.59-0.94 and HR 0.93; 95% CI 0.88-0.99, respectively). Results for women were similar but non-significant. No statistically significant associations were found for SMI or SATI. CONCLUSION: Higher SMD and higher VATI were marginally associated with better survival in RCC patients and might be useful for better prognostication. However, the added value to current prognostic scores needs to be investigated.

The association of body composition with postoperative complications and length of hospital stay after radical or partial nephrectomy in patients with renal cell cancer: a multicenter population-based cohort study.

Background: Body mass index (BMI) and body composition have been associated with postoperative outcomes in oncological surgery. Evidence in renal cell cancer (RCC) is limited and inconsistent. Therefore, we examined BMI and body composition in relation to postoperative outcomes in patients with RCC. Methods: We conducted a multicenter population-based historical cohort study including 801 patients with RCC treated with radical (79%) or partial (21%) nephrectomy between 2008-2012. Computed Tomography images at third lumbar vertebrae were assessed for skeletal muscle (SM) index, SM density, visceral adipose tissue (VAT) index and subcutaneous adipose tissue index (SATI). Multivariable multilevel logistic regression analyses were used to examine associations between BMI, body composition and (major) postoperative complications and extended length of hospital stay (LOHS) (≥7 days). Discrimination of models for major complications was compared using receiver operating characteristics (ROC) curves. Results: In total, 19.6% of the patients had postoperative complications (6.2% Clavien grade ≥III) and 24.1% had extended LOHS. A 10-unit increase in SM density was inversely associated with extended LOHS [odds ratio (OR) 0.58; 95% confidence interval (95% CI): 0.44-0.78]. Associations of high BMI and lower SM density with risk of major complications and of higher VAT index with extended LOHS were also observed but statistical significance differed according to surgical procedure. Models predicting major complications with or without body composition parameters were not different. Conclusions: Lower SM density was associated with extended LOHS and non-significantly associated with higher risk of major postoperative complications. High BMI was associated with higher risk of major postoperative complications. Higher VAT was non-significantly associated with higher risk of extended LOHS. Results by surgical procedure were in the same direction but were only statistically significant for some subgroups. Validation of these results and investigation of the added value of body composition parameters to anatomic classification systems is needed.

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. METHODS: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. RESULTS: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1-6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2-7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1-2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3-4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09-19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. CONCLUSIONS: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up.

Acceptability of innovative culture-based antibiotic prophylaxis strategies: a multi-method study on experiences regarding transrectal prostate biopsy.

BACKGROUND: The acceptability of innovative medical strategies among healthcare providers and patients affects their uptake in daily clinical practice. OBJECTIVES: To explore experiences of healthcare providers and patients with culture-based antibiotic prophylaxis in transrectal prostate biopsy with three swab-screening scenarios: self-sampling at home, self-sampling in the hospital and sampling by a healthcare provider. METHODS: We performed focus group interviews with urologists and medical microbiologists from 11 hospitals and six connected clinical microbiological laboratories. We used Flottorp's comprehensive checklist for identifying determinants of practice to guide data collection and analysis. The experiences of 10 laboratory technicians from five laboratories and 452 patients from nine hospitals were assessed using a questionnaire. RESULTS: Overall, culture-based prophylaxis strategies were experienced as feasible in daily clinical practice. None of the three swab-screening scenarios performed better. For urologists (n = 5), implementation depended on the effectiveness of the strategy. In addition, it was important to them that the speed of existing oncology care pathways is preserved. Medical microbiologists (n = 5) and laboratory technicians (n = 8) expected the strategy to be fairly easy to implement. Patients (n = 430; response rate 95.1%) were generally satisfied with the screening scenario presented to them. To meet the various patients' needs and preferences, multiple scenarios within a hospital are probably needed. CONCLUSIONS: This multi-method study has increased our understanding of the acceptability of culture-based prophylaxis strategies in prostate biopsy, which can help healthcare providers to offer high-quality patient-centred care. The strategy seems relatively straightforward to implement as overall acceptance appears to be high.

Reassessment of Prostate Biopsy Specimens for Patients Referred for Robot-assisted Radical Prostatectomy Rarely Influences Surgical Planning.

BACKGROUND: The minimum volume standard is 100 robot-assisted radical prostatectomy (RARP) procedures per hospital in the Netherlands, so patients have to be referred to high-volume surgical centers for RARP. During preoperative work-up, prostate biopsies taken elsewhere are reassessed, with upgrading or downgrading of the initial Gleason grade group a possible consequence. OBJECTIVE: To determine if prostate biopsy reassessment leads to adjustment of the surgical plan regarding a nerve-sparing approach and extended pelvic lymph node dissection (ePLND) during RARP. DESIGN SETTING AND PARTICIPANTS: For 125 men who were referred to the Prosper prostate center at Canisius Wilhelmina Hospital (CWH) in the Netherlands between 2013 and 2016, results for the initial assessment of prostate biopsy by a local uropathologist were compared to results for biopsy reassessment by dedicated uropathologists at CWH. RESULTS AND LIMITATIONS: The pathologists reached agreement in 80% of the cases. In cases for which there was disagreement (n = 25), biopsy revision involved upgrading of the initial grade group in 68% and downgrading in 32%. Biopsy reassessment led to a change in surgical plan in ten cases (8%). As a result of upgrading, ePLND was performed in three patients (2%). ePLND was omitted in one patient (1%) because of downgrading. For three patients (2%) a non-nerve-sparing procedure was planned after upgrading of the initial grade group. For four patients (3%), a unilateral nerve-sparing procedure was performed after downgrading. CONCLUSIONS: This study shows that there is large interobserver agreement between uropathologists in the assessment of Gleason grade group in prostate biopsy specimens. Reassessment rarely leads to a change in surgical plan regarding the indication for a nerve-sparing approach and ePLND. Therefore, reassessment of prostate biopsy before radical prostatectomy can be omitted when the initial pathological assessment was performed by a dedicated uropathologist. PATIENT SUMMARY: Reassessment of the initial prostate biopsy specimen for patients referred to a specialist center for robot-assisted removal of the prostate rarely influences surgical planning and can be omitted.

The Effects of Multidisciplinary Team Meetings on Clinical Practice for Colorectal, Lung, Prostate and Breast Cancer: A Systematic Review.

OBJECTIVE: The aim of our systematic review is to identify the effects of multidisciplinary team meetings (MDTM) for lung, breast, colorectal and prostate cancer. METHODS: Our systematic review, performed following PRISMA guidelines, included studies examining the impact of MDTMs on treatment decisions, patient and process outcomes. Electronic databases PUBMED, EMBASE, Cochrane Library and Web of Science were searched for articles published between 2000 and 2020. Risk of bias and level of evidence were assessed using the ROBINS-I tool and GRADE scale. RESULTS: 41 of 13,246 articles were selected, evaluating colorectal (21), lung (10), prostate (6) and breast (4) cancer. Results showed that management plans were changed in 1.6-58% of cases after MDTMs. Studies reported a significant impact of MDTMs on surgery type, and a reduction of overall performed surgery after MDTM. Results also suggest that CT and MRI imaging significantly increased after MDTM implementation. Survival rate increased significantly with MDTM discussions according to twelve studies, yet three studies did not show significant differences. CONCLUSIONS: Despite heterogeneous data, MDTMs showed a significant impact on management plans, process outcomes and patient outcomes. To further explore the impact of MDTMs on the quality of healthcare, high-quality research is needed.

Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Radium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy. MATERIALS AND METHODS: In this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings. RESULTS: We observed a substantial decrease in absolute lymphocyte counts (-0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets - the regulatory T cells and the monocytic MDSCs - increased throughout treatment. These findings were not more pronounced in patients with an alkaline phosphatase response during therapy. CONCLUSION: Immune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.