68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery). RESULTS: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%. CONCLUSIONS: SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

Alvimopan as part of the Enhanced Recovery After Surgery protocol following radical cystectomy is associated with decreased hospital stay.

OBJECTIVE: To study the effect of alvimopan and the Enhanced Recovery After Surgery protocol on length of hospital stay in patients undergoing radical cystectomy. METHODS: Our retrospective study involved 296 consecutive patients undergoing radical cystectomy for bladder cancer at our institution from 2010 through 2018. Patients were grouped according to three stages of the Enhanced Recovery After Surgery protocol implementation: (i) pre-Enhanced Recovery After Surgery (group A; n = 146); (ii) pre-alvimopan Enhanced Recovery After Surgery (group B; n = 102); and (iii) Enhanced Recovery After Surgery plus alvimopan (group C; n = 48). The primary outcome was the length of hospital stay. Secondary outcomes were time to first bowel movement, time to tolerate a regular diet, the incidence of postoperative ileus, postoperative complications and 30-day readmission rate. RESULTS: Group C showed a significantly shorter median length of hospital stay (7 days, P = 0.003), shorter gastrointestinal recovery time (4 days, P = 0.018) and a lower rate of postoperative ileus (14.6%, P = 0.005). The reduction in length of hospital stay, gastrointestinal recovery time and a lower rate of postoperative ileus was significant after controlling for other confounders on multivariable regression analysis. With the open approach, group C showed a significantly shorter length of hospital stay and gastrointestinal recovery time (P = 0.005, P = 0.001, respectively); however, in robotic cohorts, no significant differences were observed. There was no difference among groups in the 30-day readmission rate or postoperative complications. CONCLUSIONS: Patients undergoing radical cystectomy and managed by an Enhanced Recovery After Surgery protocol experience a significantly shorter length of hospital stay when receiving alvimopan as part of the protocol. Patients seem to derive the optimum benefits of alvimopan when it is used with an open approach; however, these benefits become less obvious with the robotic approach.

Drain fluid creatinine-to-serum creatinine ratio as an initial test to detect urine leakage following cystectomy: A retrospective study.

INTRODUCTION: Urine leak following radical cystectomy is a known complication. Among the various methods to diagnose this, assessment of drain fluid creatinine is a relatively easy procedure. We aimed to ascertain the validity of the drain fluid creatinine-to-serum creatinine ratio (DCSCR) as an initial indicator of urinary leak in patients undergoing radical cystectomy. METHODS: We retrospectively identified consecutive patients with documentation of drain fluid creatinine in the postoperative period following cystectomy and urinary diversion at our institution between January 2009 and December 2018. All continent diversions and any patient with a DCSCR >1.5:1 underwent contrast study postoperatively. A diagnosis of urine leak was made following confirmatory imaging. Receiver operative characteristic curves were created, and Youden's index was used to determine the strength and clinical utility of DCSCR as a diagnostic test. RESULTS: Two hundred forty-four of the 340 patients included in the study underwent cystectomy with conduit and 81 underwent neobladder creation. Sixteen out of 340 (4.7%) patients had radiologically confirmed urinary leak. DCSCR was elevated in all ureteric anastomotic leaks and in 1 out of the 7 neobladder-urethral anastomotic (NUA) leaks. The sensitivity and specificity of DCSCR to predict all urinary leaks were 68.8% and 80.9% at 1.12 (area under the curve [AUC] = 0.838), whereas at a value of 1.18 (AUC = 0.876) and with the exclusion of NUA leaks, the sensitivity was 77.8% and specificity was 87.6%. CONCLUSIONS: DCSCR is a good preliminary test for identifying patients who need prompt confirmatory testing for localizing urinary leaks. A drain creatinine level just 18% higher than the serum creatinine level can signify a urine leak. This is different from general assumptions of a higher DCSCR.

Detection and localisation of primary prostate cancer using 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology.

OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.

The fate of urological systematic reviews registered in PROSPERO.

PURPOSE: To identify urologic systematic reviews (SRs) registered to PROSPERO that resulted in a publication, and to evaluate their methodological quality and concordance with their stated a priori protocols. METHODS: We searched PubMed to identify urologic SR protocols registered in PROSPERO that resulted in a publication and assessed their methodological quality and protocols in relation to their stated a priori protocols in PROSPERO. RESULTS: Of the 576 urologic SR protocols registered in PROSPERO up to December 2017, 201 (34.9%) resulted in a full SR publication, but only 40 (17.7%) updated their registration record accordingly. Publications were spread over 100 different journals, with a median time-to-publication of 29 months (95% CI 25.0-33.0). The most common topic by far was prostate cancer (59.7%), followed by voiding issues (15.3%), and renal transplantation (15.3%). Only little over half the reviews (52.74%) explicitly stated primary outcome(s) that matched the primary outcome of their corresponding PROSPERO protocol. Notable methodologic deviations from registered protocols included planned restriction on study design (33%), heterogeneity analysis (42%) and planned risk of bias analysis (65.2%). CONCLUSION: SR authors in urology are increasingly using PROSPERO to register their titles, but our findings indicate that registration alone is not a guarantor of a high-quality SR product. There appears to be a critical need to raise the bar for review authors registering protocols in PROSPERO, with an emphasis on transparency in their publication status updates as well as deviations from their a priori protocols.

Robotic Assisted Radical Cystectomy vs Open Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: We performed an updated systematic review and meta-analysis of outcomes important to patients in those undergoing robot-assisted and open radical cystectomy. MATERIALS AND METHODS: Multiple scientific databases were searched up to July 2018 for randomized, controlled trials comparing robot-assisted and open radical cystectomy. The primary outcomes of interest were disease progression, major (Clavien III-V) complications and 90-day quality of life. The quality of evidence was evaluated according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Five studies with a total of 540 participants were included in this review. There was no difference between robot-assisted and open radical cystectomy in disease progression (RR 0.94, 95% CI 0.69-1.29), major complications (RR 1.06, 95% CI 0.75-1.49) or quality of life (standardized mean difference -0.03, 95% CI -0.27-0.21). However, robot-assisted radical cystectomy demonstrated a reduced risk of perioperative blood transfusion (RR 0.58, 95% CI 0.43-0.80) and a marginally shorter hospital stay (RR -0.63 days, 95% CI -1.21-0.05). Operative time was longer in the robot-assisted group (mean difference 68.51 minutes, 95% CI 30.55-105.48). There was no statistically significant difference in local recurrence rates between the procedures (RR 2.08, 95% CI 0.96-4.50) but this difference may be clinically significant and it favored open radical cystectomy. The overall quality of evidence was judged to be moderate. CONCLUSIONS: Surgical approach does not have a considerable impact on oncologic, safety and quality of life outcomes in patients who undergo radical cystectomy. The benefits conferred by robot-assisted radical cystectomy are a decreased need for blood transfusion and earlier hospital discharge.

Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer.

OBJECTIVE: To assess, in men undergoing active surveillance (AS) for low-risk prostate cancer, whether saturation or transperineal biopsy altered oncological outcomes, compared with standard transrectal biopsy. PATIENTS AND METHODS: Retrospective analysis of prospectively collected data from two cohorts with localised prostate cancer (1998-2012) undergoing AS. Prostate cancer-specific, metastasis-free and treatment-free survival, unfavourable disease and significant cancer at radical prostatectomy (RP) were compared for standard (<12 core, median 10) vs saturation (>12 core, median 16), and transrectal vs transperineal biopsy, using multivariate analysis. RESULTS: In all, 650 men were included in the analysis with a median (mean) follow-up of 55 (67) months. Prostate cancer-specific, metastasis-free and biochemical recurrence-free survival were 100%, 100% and 99% respectively. Radical treatment-free survival at 5 and 10 years were 57% and 45% respectively (median time to treatment 7.5 years). On Kaplan-Meier analysis, saturation biopsy was associated with increased objective biopsy progression requiring treatment (log-rank P = 0.01). On multivariate Cox proportional hazards analysis, saturation biopsy (hazard ratio 1.68, P < 0.01) but not transperineal approach (P = 0.89) was associated with increased objective biopsy progression requiring treatment. On logistic regression analysis of 179 men who underwent RP for objective progression, transperineal biopsy was associated with lower likelihood of unfavourable RP pathology (odds ratio 0.42, P = 0.03) but saturation biopsy did not alter the likelihood (P = 0.25). Neither transperineal nor saturation biopsy altered the likelihood of significant vs insignificant cancer at RP (P = 0.19 and P = 0.41, respectively). CONCLUSIONS: AS achieved satisfactory oncological outcomes. Saturation biopsy increased progression to treatment on AS; longer follow-up is needed to determine if this represents beneficial earlier detection of significant disease or over-treatment. Transperineal biopsy reduced the likelihood of unfavourable disease at RP, possibly due to earlier detection of anterior tumours.

Combined Utility of 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Predicting Prostate Biopsy Pathology.

BACKGROUND: 68Gallium-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions. OBJECTIVE: To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 200 men who underwent 68Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary outcomes were detection of grade group (GG) 3-5 and GG 2-5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via 68Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy. RESULTS AND LIMITATIONS: The median SUVmax was greater for GG 3-5 tumours (6.40, interquartile range [IQR] 4.47-11.0) than for benign and GG 1-2 tumours (3.14, IQR 2.55-3.91; p < 0.001). The median SUVmax was greater for GG 3 (5.70, IQR 3.68-8.67) than for GG 2 (3.47, IQR 2.70-4.74; p < 0.001). For GG 3-5 disease, sensitivity was 86.5%, 95.9%, and 98.6%, and the negative predictive value (NPV) was 88.4%, 88.5%, and 93.3% using SUVmax ≥4, a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3-5, and both, respectively. This combined model detected more GG 3-5 disease than mpMRI alone (98.6% vs 95.9%; p = 0.04). SUVmax was an independent predictor of csPCa for GG 3-5 disease only (odds ratio 1.27 per unit, 95% confidence interval 1.13-1.45). Our results are limited by the retrospective study design. CONCLUSIONS: Greater SUVmax on 68Ga-PSMA-11 PET/CT is associated with detection of GG 3-5 cancer on biopsy. The combination of PI-RADS score and SUVmax provides higher sensitivity and NPV than either alone. 68Ga-PSMA-11 PET/CT may be useful alongside mpMRI in improving risk stratification for localised disease. PATIENT SUMMARY: The amount of a radioactive tracer taken up in the prostate during a type of scan called PET (positron emission tomography) can predict whether aggressive prostate cancer is likely to be found on biopsy. This may complement the more usual type of scan, MRI (magnetic resonance imaging), used to detect prostate cancer.

Automatic Segmentation of Kidneys and Kidney Tumors: The KiTS19 International Challenge.

Purpose: Clinicians rely on imaging features to calculate complexity of renal masses based on validated scoring systems. These scoring methods are labor-intensive and are subjected to interobserver variability. Artificial intelligence has been increasingly utilized by the medical community to solve such issues. However, developing reliable algorithms is usually time-consuming and costly. We created an international community-driven competition (KiTS19) to develop and identify the best system for automatic segmentation of kidneys and kidney tumors in contrast CT and report the results. Methods: A training and test set of CT scans that was manually annotated by trained individuals were generated from consecutive patients undergoing renal surgery for whom demographic, clinical and outcome data were available. The KiTS19 Challenge was a machine learning competition hosted on grand-challenge.org in conjunction with an international conference. Teams were given 3 months to develop their algorithm using a full-annotated training set of images and an unannotated test set was released for 2 weeks from which average Sørensen-Dice coefficient between kidney and tumor regions were calculated across all 90 test cases. Results: There were 100 valid submissions that were based on deep neural networks but there were differences in pre-processing strategies, architectural details, and training procedures. The winning team scored a 0.974 kidney Dice and a 0.851 tumor Dice resulting in 0.912 composite score. Automatic segmentation of the kidney by the participating teams performed comparably to expert manual segmentation but was less reliable when segmenting the tumor. Conclusion: Rapid advancement in automated semantic segmentation of kidney lesions is possible with relatively high accuracy when the data is released publicly, and participation is incentivized. We hope that our findings will encourage further research that would enable the potential of adopting AI into the medical field.

The state of the art in kidney and kidney tumor segmentation in contrast-enhanced CT imaging: Results of the KiTS19 challenge.

There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.

The role of open radical nephrectomy in contemporary management of renal cell carcinoma.

Radical nephrectomy (RN) remains a cornerstone of the management of localised renal cell carcinoma (RCC). RN involves the en bloc removal of the kidney along with perinephric fat enclosed within Gerota's fascia. Key principles of open RN include appropriate incision for adequate exposure, dissection and visualisation of the renal hilum, and early ligation of the renal artery and subsequently renal vein. Regional lymph node dissection (LND) facilitates local staging but its therapeutic role remains controversial. LND is recommended in patients with high risk clinically localised disease, but its benefit in low risk node-negative and clinically node-positive patients is unclear. Concomitant adrenalectomy should be reserved for patients with large tumours with radiographic evidence of adrenal involvement. Despite a recent downtrend in utilisation of open RN due to nephron-sparing and minimally invasive alternatives, there remains a vital role for open RN in the management of RCC in three domains. Firstly, open RN is important to the management of large, complex tumours which would be at high risk of complications if treated with partial nephrectomy (PN). Secondly, open RN plays a crucial role in cytoreductive nephrectomy (CN) for metastatic RCC, in which the laparoscopic approach achieves similar results but is associated with a high reoperation rate. Finally, open RN is the current standard of care in the management of inferior vena caval (IVC) tumour thrombus. Management of tumour thrombus requires a multidisciplinary approach and varies with cranial extent of thrombus. Higher level thrombus may require hepatic mobilisation and circulatory support, whilst the presence of bland thrombus may warrant post-operative filter insertion or ligation of the IVC.

Public Perceptions of Artificial Intelligence and Robotics in Medicine.

Objective: To understand better the public perception and comprehension of medical technology such as artificial intelligence (AI) and robotic surgery. In addition to this, to identify sensitivity to their use to ensure acceptability and quality of counseling. Subjects and Methods: A survey was conducted on a convenience sample of visitors to the MN Minnesota State Fair (n = 264). Participants were randomized to receive one of two similar surveys. In the first, a diagnosis was made by a physician and in the second by an AI application to compare confidence in human and computer-based diagnosis. Results: The median age of participants was 45 (interquartile range 28-59), 58% were female (n = 154) vs 42% male (n = 110), 69% had completed at least a bachelor's degree, 88% were Caucasian (n = 233) vs 12% ethnic minorities (n = 31) and were from 12 states, mostly from the Upper Midwest. Participants had nearly equal trust in AI vs physician diagnoses. However, they were significantly more likely to trust an AI diagnosis of cancer over a doctor's diagnosis when responding to the version of the survey that suggested that an AI could make medical diagnoses (p = 9.32e-06). Though 55% of respondents (n = 145) reported that they were uncomfortable with automated robotic surgery, the majority of the individuals surveyed (88%) mistakenly believed that partially autonomous surgery was already happening. Almost all (94%, n = 249) stated that they would be willing to pay for a review of medical imaging by an AI if available. Conclusion: Most participants express confidence in AI providing medical diagnoses, sometimes even over human physicians. Participants generally express concern with surgical AI, but they mistakenly believe that it is already being performed. As AI applications increase in medical practice, health care providers should be cognizant of the potential amount of misinformation and sensitivity that patients have to how such technology is represented.

Adherence to Active Surveillance Protocols for Low-risk Prostate Cancer: Results of the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance Initiative.

BACKGROUND: Active surveillance (AS) enrolment criteria and follow-up schedules for low-risk prostate cancer vary between institutions. However, uncertainty remains about adherence to these protocols. OBJECTIVE: To determine adherence to institution-specific AS inclusion criteria and follow-up schedules within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively assessed the data of 15 101 patients from 25 established AS cohorts worldwide between 2014 and 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adherence to individual AS inclusion criteria was rated on a five-point Likert scale ranging from poor to excellent. Nonadherence to follow-up schedules was defined as absence of repeat biopsy 1 yr after the scheduled date. Cohorts were pooled into annual and Prostate Cancer Research International: Active Surveillance (PRIAS)-based biopsy schedules, and a generalised linear mixed model was constructed to test for nonadherence. RESULTS AND LIMITATIONS: Serum prostate-specific antigen (PSA) inclusion criteria were followed in 92%, Gleason score (GS) criteria were followed in 97%, and the number of positive biopsy cores was followed in 94% of men. Both age and tumour stage (T stage) criteria had 99% adherence overall. Pooled nonadherence rates increased over time-8%, 16%, and 34% for annual schedules and 11%, 30%, and 29% for PRIAS-based schedules at 1, 4, and 7 yr, respectively-and did not differ between biopsy schedules. A limitation is that our results do not consider the use of multiparametric magnetic resonance imaging. CONCLUSIONS: In on-going development of evidence-based AS protocols, variable adherence to PSA and GS inclusion criteria should be considered. Repeat biopsy adherence reduces with increased duration of surveillance, independent of biopsy frequency. This emphasises the importance of risk stratification at the commencement of AS. PATIENT SUMMARY: We studied adherence to active surveillance protocols for prostate cancer worldwide. We found that inclusion criteria were generally followed well, but adherence to repeat biopsy reduced with time. This should be considered when optimising future active surveillance protocols.