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Video: Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores

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Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores

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Abstract

Objectives

To apply the standard PADUA and RENAL nephrometry score variables to three‐dimensional (3D) virtual models (VMs) produced from standard bi‐dimensional imaging, thereby creating three‐dimensional (3D)‐based (PADUA and RENAL) nephrometry scores/categories for the reclassification of the surgical complexity of renal masses, and to compare the new 3D nephrometry score/category with the standard 2D‐based nephrometry score/category, in order to evaluate their predictive role for postoperative complications.

Materials and Methods

All patients with localized renal tumours scheduled for minimally invasive partial nephrectomy (PN) between September 2016 and September 2018 underwent 3D and 2D nephrometry score/category assessments preoperatively. After nephrometry score/category evaluation, all the patients underwent surgery. Chi‐squared tests were used to evaluate the individual patients’ grouping on the basis of the imaging tool (3D VMs and 2D imaging) used to assess the nephrometry score/category, while Cohen’s κ coefficient was used to test the concordance between classifications. Receiver‐operating characteristic curves were produced to evaluate the sensitivity and specificity of the 3D nephrometry score/category vs the 2D nephrometry score/category in predicting the occurrence of postoperative complications. A general linear model was used to perform multivariable analyses to identify predictors of overall and major postoperative complications.

Results

A total of 101 patients were included in the study. The evaluation of PADUA and RENAL nephrometry scores via 3D VMs showed a downgrading in comparison with the same scores evaluated with 2D imaging in 48.5% and 52.4% of the cases. Similar results were obtained for nephrometry categories (29.7% and 30.7% for PADUA risk and RENAL complexity categories, respectively). The 3D nephrometry score/category demonstrated better accuracy than the 2D nephrometry score/category in predicting overall and major postoperative complications (differences in areas under the curve for each nephrometry score/category were statistically significant comparing the 3D VMs with 2D imaging assessment). Multivariable analyses confirmed 3D PADUA/RENAL nephrometry category as the only independent predictors of overall (P = 0.007; P = 0.003) and major postoperative complications (P = 0.03; P = 0.003).

Conclusions

In the present study, we showed that 3D VMs were more precise than 2D standard imaging in evaluating the surgical complexity of renal masses according to nephrometry score/category. This was attributable to a better perception of tumour depth and its relationships with intrarenal structures using the 3D VM, as confirmed by the higher accuracy of the 3D VM in predicting postoperative complications.

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Video: Cost–utility analysis of focal HIFU vs AS for low‐ to intermediate‐risk prostate cancer using a Markov multi‐state model

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Cost–utility analysis of focal high‐intensity focussed ultrasound vs active surveillance for low‐ to intermediate‐risk prostate cancer using a Markov multi‐state model

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Abstract

Objectives

To estimate the relative cost‐effectiveness of focal high‐intensity focussed ultrasound (F‐HIFU) compared to active surveillance (AS) in patients with low‐ to intermediate‐risk prostate cancer, in France.

Patients and Methods

A Markov multi‐state model was elaborated for this purpose. Our analyses were conducted from the French National Health Insurance perspective, with a time horizon of 10 years and a 4% discount rate for cost and effectiveness. A secondary analysis used a 30‐year time horizon. Costs are presented in 2016 Euros (€), and effectiveness is expressed as quality‐adjusted life years (QALYs). Model parameters’ value (probabilities for transitions between health states, and cost and utility of health states) is supported by systematic literature reviews (PubMed) and random effect meta‐analyses. The cost of F‐HIFU in our model was the temporary tariff attributed by the French Ministry of Health to the overall treatment of prostate cancer by HIFU (€6047).

Our model was analysed using Microsoft Excel 2010 (Microsoft Corp., Redmond, WA, USA). Uncertainty about the value of the model parameters was handled through probabilistic analyses.

Results

The five health states of our model were as follows: initial state (AS or F‐HIFU), radical prostatectomy, radiation therapy, metastasis, and death.

Transition probabilities from the initial F‐HIFU state relied on four articles eligible for our meta‐analyses. All were non‐comparative studies. Utilities relied on a single cohort in San Diego, CA, USA.

For a fictive cohort of 1000 individuals followed for 10 years, F‐HIFU would be €207 520 more costly and would yield 382 less QALYs than AS, which means that AS is cost‐effective when compared to F‐HIFU. For a threshold value varying from €0 to 100 000/QALY, the probability of AS being cost‐effective compared to F‐HIFU varied from 56.5% to 60%. This level of uncertainty was in the same range with a 30‐year time horizon.

Conclusion

Given existing published data, our results suggest that AS is cost‐effective compared to F‐HIFU in patients with low‐ and intermediate‐risk prostate cancer, but with high uncertainty. This uncertainty must be scaled down by continuing to supply the model with new published data and ideally through a randomised clinical trial that includes cost‐effectiveness analyses.

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Video: Guideline of guidelines: testosterone therapy for testosterone deficiency

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Guideline of guidelines: testosterone therapy for testosterone deficiency

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Abstract

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations.

All the organisations were in general agreement concerning the following key points:

  • Only men meeting the criteria for testosterone deficiency (TD) should be treated.
  • Consider screening asymptomatic men with certain conditions that increase the risk of TD.
  • Exogenous TTh causes impairment of spermatogenesis.
  • There is no evidence that TTh causes prostate cancer.
  • Men on TTh require careful laboratory monitoring.
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Video: Use of mpMRI and fusion‐guided biopsies to properly select and follow African‐American men on active surveillance

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Use of multiparametric magnetic resonance imaging and fusion‐guided biopsies to properly select and follow African‐American men on active surveillance

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Abstract

Objectives

To determine the rate of Gleason Grade Group (GGG) upgrading in African‐American (AA) men with a prior diagnosis of low‐grade prostate cancer (GGG 1 or GGG 2) on 12‐core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non‐AA) population.

Patients and methods

A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan–Meier curves were generated for AA men and non‐AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log‐rank test.

Results

AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non‐AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non‐AA men then continued AS, with a median (interquartile range) follow‐up of 39.19 (24.24–56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80).

Conclusions

AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non‐AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

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Video: mpMRI and follow-up to avoid prostate biopsy in 4259 men

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Multiparametric magnetic resonance imaging and follow-up to avoid prostate biopsy in 4259 men

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Abstract

Objective

To determine the proportion of men avoiding biopsy because of negative multiparametric magnetic resonance imaging (mpMRI) findings in a prostate MRI expert centre, and to assess the number of clinically significant prostate cancers (csPCa) detected during follow‐up.

Patients and methods

Retrospective study of 4259 consecutive men having mpMRI of the prostate between January 2012 and December 2017, with either a history of previous negative transrectal ultrasonography‐guided biopsy or biopsy naïve. Patients underwent mpMRI in a referral centre. Lesions were classified according to Prostate Imaging Reporting And Data System (PI‐RADS) versions 1 and 2. Negative mpMRI was defined as an index lesion PI‐RADS ≤2. Follow‐up until 13 October 2018 was collected by searching the Dutch Pathology Registry (PALGA). Gleason score ≥3 + 4 was considered csPCa. Kaplan–Meier analysis and univariable logistic regression models were used in the cohort of patients with negative mpMRI and follow‐up.

Results

Overall, in 53.6% (2281/4259) of patients had a lesion classified as PI‐RADS ≤2. In 320 patients with PI‐RADS 1 or 2, follow‐up mpMRI was obtained after a median (interquartile range) of 57 (41–63) months. In those patients, csPCa diagnosis‐free survival (DFS) was 99.6% after 3 years. Univariable logistic regression analysis revealed age as a predictor for csPCa during follow‐up (P < 0.05). In biopsied patients, csPCa was detected in 15.8% (19/120), 43.2% (228/528) and 74.5% (483/648) with PI‐RADS 3, 4 and 5, respectively.

Conclusion

More than half of patients having mpMRI of the prostate avoided biopsy. In those patients, csPCa DFS was 99.6% after 3 years.

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Video: The global prevalence of erectile dysfunction

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The global prevalence of erectile dysfunction: a review

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Abstract

Objective

To evaluate the global prevalence of erectile dysfunction (ED); as well as its association with physiological and pathological ageing by examining the relationship between ED and cardiovascular disease (CVD), benign prostatic hyperplasia (BPH), and dementia. We also aimed to characterise discrepancies caused by the use of different ED screening tools.

Methods

The Excerpta Medica dataBASE (EMBASE) and Medical Literature Analysis and Retrieval System Online (MEDLINE) were searched to find population‐based studies investigating the prevalence of ED and the association between ED and CVD, BPH, and dementia in the general population.

Results

The global prevalence of ED was 3–76.5%. ED was associated with increasing age. Use of the International Index of Erectile Function (IIEF) and Massachusetts Male Aging Study (MMAS)‐derived questionnaire identified a high prevalence of ED in young men. ED was positively associated with CVD. Men with ED have an increased risk of all‐cause mortality odds ratio (OR) 1.26 (95% confidence interval [CI] 1.01–1.57), as well as CVD mortality OR 1.43 (95% CI 1.00–2.05). Men with ED are 1.33–6.24‐times more likely to have BPH then men without ED, and 1.68‐times more likely to develop dementia than men without ED.

Conclusion

ED screening tools in population‐based studies are a major source of discrepancy. Non‐validated questionnaires may be less sensitive than the IIEF and MMAS‐derived questionnaire. ED constitutes a large burden on society given its high prevalence and impact on quality of life, and is also a risk factor for CVD, dementia, and all‐cause mortality.

 

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Video: Current status of artificial intelligence applications in urology

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Current status of artificial intelligence applications in urology and their potential to influence clinical practice

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Abstract

Objective

To investigate the applications of artificial intelligence (AI) in diagnosis, treatment and outcome prediction in urologic diseases and evaluate its advantages over traditional models and methods.

Materials and methods

A literature search was performed after PROSPERO registration (CRD42018103701) and in compliance with Preferred Reported Items for Systematic Reviews and Meta‐Analyses (PRISMA) methods. Articles between 1994 and 2018 using the search terms “urology”, “artificial intelligence”, “machine learning” were included and categorized by the application of AI in urology. Review articles, editorial comments, articles with no full‐text access, and non-urologic studies were excluded.

Results

Initial search yielded 231 articles, but after excluding duplicates and following full‐text review and examination of article references, only 111 articles were included in the final analysis. AI applications in urology include: utilizing radiomic imaging or ultrasonic echo data to improve or automate cancer detection or outcome prediction, utilizing digitized tissue specimen images to automate detection of cancer on pathology slides, and combining patient clinical data, biomarkers, or gene expression to assist disease diagnosis or outcome prediction. Some studies employed AI to plan brachytherapy and radiation treatments while others used video based or robotic automated performance metrics to objectively evaluate surgical skill. Compared to conventional statistical analysis, 71.8% of studies concluded that AI is superior in diagnosis and outcome prediction.

Conclusion

AI has been widely adopted in urology. Compared to conventional statistics AI approaches are more accurate in prediction and more explorative for analyzing large data cohorts. With an increasing library of patient data accessible to clinicians, AI may help facilitate evidence‐based and individualized patient care.

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Video: Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA

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Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23‐gene panel with utility for non‐invasive diagnosis and risk stratification

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Abstract

Objectives

To develop a focused panel of somatic mutations (SMs) present in the majority of urothelial bladder cancers (UBCs), to investigate the diagnostic and prognostic utility of this panel, and to compare the identification of SMs in urinary cell‐pellet (cp) DNA and cell‐free (cf) DNA as part of the development of a non‐invasive clinical assay.

Patients and Methods

A panel of SMs was validated by targeted deep‐sequencing of tumour DNA from 956 patients with UBC. In addition, amplicon and capture‐based targeted sequencing measured mutant allele frequencies (MAFs) of SMs in 314 urine cpDNAs and 153 urine cfDNAs. The association of SMs with grade, stage and clinical outcomes was investigated by univariate and multivariate Cox models. Concordance between SMs detected in tumour tissue and cpDNA and cfDNA was assessed.

Results

The panel comprised SMs in 23 genes: TERT (promoter), FGFR3, PIK3CA, TP53, ERCC2, RHOB, ERBB2, HRAS, RXRA, ELF3, CDKN1A, KRAS, KDM6A, AKT1, FBXW7, ERBB3, SF3B1, CTNNB1, BRAF, C3orf70, CREBBP, CDKN2A and NRAS; 93.5–98.3% of UBCs of all grades and stages harboured ≥1 SM (mean: 2.5 SMs/tumour). RAS mutations were associated with better overall survival (P = 0.04). Mutations in RXRA, RHOB and TERT (promoter) were associated with shorter time to recurrence (P < 0.05). MAFs in urinary cfDNA and cpDNA were highly correlated; using a capture‐based approach, >94% of tumour SMs were detected in both cpDNA and cfDNA.

Conclusions

SMs are reliably detected in urinary cpDNA and cfDNA. The technical capability to identify very low MAFs is essential to reliably detect UBC, regardless of the use of cpDNA or cfDNA. This 23‐gene panel shows promise for the non‐invasive diagnosis and risk stratification of UBC.

 

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Video: Global, regional and national burden of testicular cancer

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Global, regional and national burden of testicular cancer, 1990–2016: results from the Global Burden of Disease Study 2016

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Abstract

Objective

To provide estimates of the global incidence, mortality and disability‐adjusted life‐years (DALYs) associated with testicular cancer (TCa) between 1990 and 2016, using findings from the Global Burden of Disease (GBD) 2016 study.

Materials and Methods

For the GBD 2016 study, cancer registry data and a vital registration system were used to estimate TCa mortality. Mortality to incidence ratios were used to transform mortality estimates to incidence, and to estimate survival, which was then used to estimate 10‐year prevalence. Prevalence was weighted using disability weights to estimate years lived with disability (YLDs). Age‐specific mortality and a reference life expectancy were used to estimate years of life lost (YLLs). DALYs are the sum of YLDs and YLLs.

Results

Global incidence of TCa showed a 1.80‐fold increase from 37 231 (95% uncertainty interval [ UI] 36 116–38 515) in 1990 to 66 833 (95% UI 64 487–69 736) new cases in 2016. The age‐standardized incidence rate also increased from 1.5 (95% UI 1.45–1.55) to 1.75 (95% UI 1.69–1.83) cases per 100 000. Deaths from TCa remained stable between 1990 and 2016 [1990: 8394 (95% UI 7980–8904), 2016: 8651 (95% UI 8292–9027)]. The TCa age‐standardized death rate decreased between 1990 and 2016, from 0.39 (95% UI 0.37–0.41) to 0.25 (95% UI 0.24–0.26) per 100 000; however, the decreasing trend was not similar in all regions. Global TCa DALYs decreased by 2% and reached 391 816 (95% UI 372 360–412 031) DALYs in 2016. The age‐standardized DALY rate also decreased globally between 1990 and 2016 (10.31 [95% UI 9.82–10.84]) per 100 000 in 2016).

Conclusion

Although the mortality rate for TCa has decreased over recent decades, large disparities still exist in TCa mortality, probably as a result of lack of access to healthcare and oncological treatment. Timely diagnosis of this cancer, by improving general awareness, should be prioritized. In addition, improving access to effective therapies and trained healthcare workforces in developing and under‐developed areas could be the next milestones.

by @ErfanAmini and @FarhadPishgar

 

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Video: Risk of metastatic disease on 68-Ga‐PSMA PET/CT scan for primary staging of 1253 men with PCa

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Risk of metastatic disease on 68Gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer

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Abstract

Objective

To determine the number of men with 68gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography (68Ga‐PSMA PET/CT) avid metastasis at diagnosis, as most data on 68Ga‐PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with 68Ga‐PSMA PET/CT.

Patients and Methods

A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for 68Ga‐PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018.

The primary outcome measure was to determine the risk of metastasis based on 68Ga‐PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate‐specific antigen (PSA) level, and staging with pre‐biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results.

Results

The median PSA level was 6.5 ng/mL and median ISUP grade was 3, with high‐risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of <10 ng/mL and 43% with a PSA level of >20 ng/mL. Metastases were identified in 6.4% with ISUP grade 2–3 and 21% with ISUP grade 4–5. Pre‐biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate‐risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high‐risk disease.

Conclusions

These results support the use of 68Ga‐PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis.

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