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Video: Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study

Abstract

Objective

To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function.

Patients and Methods

Patients with cT2aN0NxM0 clear‐cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7–10 mg, was administered twice daily, for 2–6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib.

Results

Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5  (70–98) mm and 11 (7–11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III–V post‐surgery complications. At 2‐year follow‐up, six patients had metastatic progression, and two had a recurrence.

Conclusion

Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.

Video: Prostatic capsular incision during RP has important oncological implications. A systematic review and meta‐analysis

Prostatic capsular incision during radical prostatectomy has important oncological implications. A systematic review and meta‐analysis

Abstract

Introduction

Capsular Incision (CapI) is an iatrogenic breach of the prostatic capsule during radical prostatectomy that can cause positive surgical margins (PSM) in organ‐confined (pT2) prostate cancer (PCa), or the retention of benign prostatic tissue. We systematically interrogated the literature in order to clarify the definition of CapI, and the implications of this event for rates of PSM and biochemical recurrence (BCR).

Methods

A literature search was conducted according to PRISMA criteria using the search terms ‘CapI’ AND ‘prostatectomy’ and variations of each. 18 studies were eligible for inclusion.

Results

A total of 51,057 radical prostatectomy specimens were included. The incidence of CapI ranged from 1.3‐54.3%. CapI definitions varied, and included a breach of the prostatic capsule “exposing both benign or malignant PCa cells”, “malignant tissue only”, or “benign tissue only”. The incidence of PSM due to CapI ranged from 2.8 – 71.7%. Our meta‐analysis results found that when CapI was defined as “exposing malignant tissue only in organ‐confined prostate cancer” there was an increased risk of BCR compared to patients with pT2 disease and no CapI (RR 3.53, 95%CI 2.82‐4.41; p < 0.00001).

Conclusions

The absolute impact of CapI on oncological outcomes is currently unclear due to inconsistent definitions. However, the data implies an association between CapI and PSM and BCR. Reporting of possible areas of CapI on the operation note, or marking areas of concern on the specimen, are critical to assist CapI recognition by the pathologist.

 

Video: The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

 

Abstract

Objective

To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.

Materials and Methods

The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses.

Results

This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.

Conclusions

We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.

Video: In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function?

In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function?

Abstract

 

Objectives

To evaluate the first 100 cases of in utero myelomeningocele (MMC) repair and urological outcomes in a prospective analysis aiming to define possible improvement in bladder function.

Patients and methods

We used a protocol consisting of a detailed medical history, urinary tract ultrasonography, voiding cystourethrography, and urodynamic evaluation. Patients were categorised into four groups: normal, high risk (overactive bladder with a detrusor leak‐point pressure >40 cm H2O and high filling pressures also >40 cm H2O), incontinent, and underactivity (underactive bladder with post‐void residual urine), and patients were treated accordingly.

Results

We evaluated 100 patients, at a mean age of 5.8 months (median 4 months), classified as high risk in 52.6%, incontinent in 27.4%, with underactive bladder in 4.2%, and only 14.7% had a normal bladder profile. Clean intermittent catheterisation was initiated in 57.3% of the patients and anticholinergics in 52.6%. Antibiotic prophylaxis was initiated in 19.1% of the patients presenting with vesico‐ureteric reflux.

Conclusion

The high incidence of abnormal bladder patterns suggests little benefit of in utero MMC surgery concerning the urinary tract.

 

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Video: Ultrasound characteristics of MRI suspicious regions predict the likelihood of clinically significant cancer on MRI-ultrasound fusion-targeted biopsy

The ultrasound characteristics of regions identified as suspicious by magnetic resonance imaging (MRI) predict the likelihood of clinically significant cancer on MRI–ultrasound fusion‐targeted biopsy

 
 

Abstract

Objective

To determine whether the presence of an ultrasound hypoechoic region at the site of a region of interest (ROI) on magnetic resonance imaging (MRI) results in improved prostate cancer (PCa) detection and predicts clinically significant PCa on MRI–ultrasonography fusion‐targeted prostate biopsy (MRF‐TB).

Materials and Methods

Between July 2011 and June 2017, 1058 men who underwent MRF‐TB, with or without systematic biopsy, by a single surgeon were prospectively entered into an institutional review board‐approved database. Each MRI ROI was identified and scored for suspicion by a single radiologist, and was prospectively evaluated for presence of a hypoechoic region at the site by the surgeon and graded as 0, 1 or 2, representing none, a poorly demarcated ROI‐HyR, or a well demarcated ROI‐HyR, respectively. The interaction of MRI suspicion score (mSS) and ultrasonography grade (USG), and the prediction of cancer detection rate by USG, were evaluated through univariate and multivariate analysis.

Results

For 672 men, the overall and Gleason score (GS) ≥7 cancer detection rates were 61.2% and 39.6%, respectively. The cancer detection rates for USGs 0, 1 and 2 were 46.2%, 58.6% and 76.0% (P < 0.001) for any cancer, and 18.7%, 35.2% and 61.1% (P < 0.001) for GS ≥7 cancer, respectively. For MRF‐TB only, the GS ≥7 cancer detection rates for USG 0, 1 and 2 were 12.8%, 25.7% and 52.0%, respectively (P < 0.001). On univariate analysis, in men with mSS 2–4, USG was predictive of GS ≥7 cancer detection rate. Multivariable regression analysis showed that USG, prostate‐specific antigen density and mSS were predictive of GS ≥7 PCa on MRF‐TB.

Conclusions

Ultrasonography findings at the site of an MRI ROI independently predict the likelihood of GS ≥7 PCa, as men with a well‐demarcated ROI‐HyR at the time of MRF‐TB have a higher risk than men without.
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Video: Four-year outcomes from a multiparametric MRI based active surveillance programme

Four‐year outcomes from a multiparametric magnetic resonance imaging (MRI)‐based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies

 

Abstract

Objectives

To report outcomes from a multiparametric (mp) magnetic resonance imaging (MRI)‐based active surveillance programme that did not include performing protocol biopsies after the first confirmatory biopsy.

Patients and Methods

All patients diagnosed with Gleason 3 + 3 prostate cancer because of a raised PSA level who underwent mpMRI after diagnosis were included. Patients were recorded in a prospective clinical database and followed up with PSA monitoring and repeat MRI. In patients who remained on active surveillance after the first MRI (with or without confirmatory biopsy), we investigated PSA dynamics for association with subsequent progression. Comparison between first and second MRI scans was undertaken. Outcomes assessed were: progression to radical therapy at first MRI/confirmatory biopsy and progression to radical therapy in those who remained on active surveillance after first MRI.

Results

A total of 211 patients were included, with a median of 4.2 years of follow‐up. The rate of progression to radical therapy was significantly greater at all stages among patients with visible lesions than in those with initially negative MRI (47/125 (37.6%) vs 11/86 (12.8%); odds ratio 4.1 (95% CI 2.0–8.5), P < 0.001). Only 1/56 patients (1.8%) with negative initial MRI scans who underwent a confirmatory systematic biopsy had upgrading to Gleason 3 + 4 disease. PSA velocity was significantly associated with subsequent progression in patients with negative initial MRI (area under the curve 0.85 [95% CI 0.75–0.94]; P <0.001). Patients with high‐risk visible lesions on first MRI who remained on active surveillance had a high risk of subsequent progression 19/76 (25.0%) vs 9/84 (10.7%) for patients with no visible lesions, despite reassuring targeted and systematic confirmatory biopsies and regardless of PSA dynamics.

Conclusion

Men with low‐risk Gleason 3 + 3 prostate cancer on active surveillance can forgo protocol biopsies in favour of MRI and PSA monitoring with selective re‐biopsy.

 

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Video: Does the robot have a role in radical cystectomy?

Does the robot have a role in radical cystectomy

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Abstract

Between 2014 and 2015, 3742 radical cystectomies (RCs) were performed in the UK. The majority of these were open RCs (ORCs), and only 25% were performed with robot assistance. These data contrast starkly with the picture in radical prostatectomy (RP), for which most operations are robot assisted (79.4% of the 7673 in 2016). Given that most pelvic surgeons have access to robotic facilities (as shown by the RP trends) and urologists are typically early adopters, one must question why many surgeons have yet to be convinced by robot‐assisted RC (RARC). This question is particularly perplexing given that RC is a more morbid operation than RP and most patients with bladder cancer are considerably less fit than the average man with prostate cancer, and therefore, reductions in morbidity are especially rewarding in this cohort.

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Video: Immediate versus delayed exercise in men initiating androgen deprivation

Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition

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Abstract

Objectives

To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen‐deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft‐tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

Patients and methods

In all, 104 patients with prostate cancer, aged 48–84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X‐ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months.

Results

There was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (−0.4% vs −1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (−1.4% to −2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12‐month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively).

Conclusions

Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment‐related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT.

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Video: APAC APCCC 2018

Management of patients with advanced prostate cancer in the Asia Pacific region: ‘real‐world’ consideration of results from the Advanced Prostate Cancer Consensus Conference 2017

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Abstract

Objective

The Asia Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2018) brought together 20 experts from 15 APAC countries to discuss the real‐world application of consensus statements from the second APCCC held in St Gallen in 2017 (APCCC 2017).

Findings

Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration‐naïve prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor‐targeting agents appear to be well tolerated in Asian men with metastatic castration‐resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision‐making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower‐income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side‐effect profiles of some drugs and influence prescribing.

 

Conclusions

As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team‐based approach to treatment planning and care, delivery of best‐practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.

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Video: Cognitive training for technical and non‐technical skills in robotic surgery

Cognitive training for technical and non‐technical skills in robotic surgery: a randomised controlled trial

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Abstract

Objective

To investigate the effectiveness of motor imagery (MI) for technical skill and non‐technical skill (NTS) training in minimally invasive surgery (MIS).

Subjects and Methods

A single‐blind, parallel‐group randomised controlled trial was conducted at the Vattikuti Institute of Robotic Surgery, King’s College London. Novice surgeons were recruited by open invitation in 2015. After basic robotic skills training, participants underwent simple randomisation to either MI training or standard training. All participants completed a robotic urethrovesical anastomosis task within a simulated operating room. In addition to the technical task, participants were required to manage three scripted NTS scenarios. Assessment was performed by five blinded expert surgeons and a NTS expert using validated tools for evaluating technical skills [Global Evaluative Assessment of Robotic Skills (GEARS)] and NTS [Non‐Technical Skills for Surgeons (NOTSS)]. Quality of MI was assessed using a revised Movement Imagery Questionnaire (MIQ).

Results

In all, 33 participants underwent MI training and 29 underwent standard training. Interrater reliability was high, Krippendorff’s α = 0.85. After MI training, the mean (sd) GEARS score was significantly higher than after standard training, at 13.1 (3.25) vs 11.4 (2.97) (P = 0.03). There was no difference in mean NOTSS scores, at 25.8 vs 26.4 (P = 0.77). MI training was successful with significantly higher imagery scores than standard training (mean MIQ score 5.1 vs 4.5, P = 0.04).

Conclusions

Motor imagery is an effective training tool for improving technical skill in MIS even in novice participants. No beneficial effect for NTS was found.

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