Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy.

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Prevalence of urinary tract cancer in the Spanish cohort of the IDENTIFY study.

INTRODUCTION: Malignant tumors of the urinary tract are associated with high morbidity and mortality, and their prevalence can vary worldwide. Recently, the IDENTIFY study has published results on the prevalence of urinary tract cancer at a global level. This study evaluates the prevalence of cancer within the Spanish cohort of the IDENTIFY study to determine whether the published results can be extrapolated to our population. PATIENTS AND METHODS: An analysis of the data from the Spanish cohort of patients in the IDENTIFY study was performed. This is a prospective cohort of patients referred to secondary care with suspected cancer, predominantly due to hematuria. Patients were recruited between December 2017 and December 2018. RESULTS: A total of 706 patients from 9 Spanish centers were analyzed. Of these, 277 (39.2%) were diagnosed with cancer: 259 (36.7%) bladder cancer, 10 (1.4%) upper tract urothelial carcinoma, 9 (1.2%) renal cancer and 5 (0.7%) prostate cancer. Increasing age (OR 1.05 (95% CI 1.03-1.06; P < 0.001)), visible hematuria (VH) OR 2.19 (95% CI 1.13-4.24; P = 0.02)) and smoking (ex-smokers: OR 2.11(95% CI 1.30-3.40; P = 0.002); smokers: OR 2.36 (95% CI 1.40-3.95; P = 0.001)) were associated with higher probability of bladder cancer. CONCLUSION: This study highlights the risk of bladder cancer in patients with VH and smoking habits. Bladder cancer presented the highest prevalence; higher than the prevalence reported in previous series and presented in the IDENTIFY study. Future work should evaluate other associated factors that allow us to create cancer prediction models to improve the detection of cancer in our patients.

A prospective clinical, cost and environmental analysis of a clinician-led virtual urology clinic.

INTRODUCTION: A virtual clinic is a form of telemedicine where contact between clinical teams and patients occur without face-to-face consultation. Our study aims to quantify the clinical, financial and environmental benefits of our virtual urology clinic. MATERIAL AND METHODS: We collected data prospectively from our weekly follow-up virtual clinic over a continuous four-month period between July and September 2017. RESULTS: In total, we reviewed 409 patients. Following virtual clinic consultation, 68.5% of our patients were discharged from further follow-up. The majority of our patients (male 57.7%, female 55.5%) were of working age. The satisfaction scores were high, at 90.1%, and there were no reported adverse events as a result of using the virtual clinic. Our calculated cost savings were £18,744, with a predicted 12-month cost saving of £56,232. The creation of additional face-to-face clinic capacity has created an estimated 12-month increase in tariff generation for our unit of £72,072. In total, 4623 travel miles were avoided by patients using the virtual clinic, with an estimated avoided carbon footprint of 0.35-1.45 metric tonnes of CO2e, depending on mode of transport. Our predicted 12-month avoided carbon footprint is 1.04-4.04 metric tonnes of CO2e. CONCLUSIONS: Our virtual clinic model has demonstrated a trifecta of positive outcomes, namely, clinical, financial and environmental benefits. The environmental importance and benefits of a virtual clinic should be promoted as a social enterprise value when engaging stakeholders in setting up such a urological service. We propose the adoption of our virtual clinic model in those urological units considering this method of telemedicine.

Beam distortion due to gold fiducial markers during salvage high-intensity focused ultrasound in the prostate.

PURPOSE: High intensity focused ultrasound (HIFU) provides a non-invasive salvage treatment option for patients with recurrence after external beam radiation therapy (EBRT). As part of EBRT the prostate is frequently implanted with permanent fiducial markers. To date, the impact of these markers on subsequent HIFU treatment is unknown. The objective of this work was to systematically investigate, using computational simulations, how these fiducial markers affect the delivery of HIFU treatment. METHODS: A series of simulations was performed modelling the propagation of ultrasound pressure waves in the prostate with a single spherical or cylindrical gold marker at different positions and orientations. For each marker configuration, a set of metrics (spatial-peak temporal-average intensity, focus shift, focal volume) was evaluated to quantify the distortion introduced at the focus. An analytical model was also developed describing the marker effect on the intensity at the focus. The model was used to examine the marker's impact in a clinical setting through case studies. RESULTS: The simulations show that the presence of the marker in the pre-focal region causes reflections which induce a decrease in the focal intensity and focal volume, and a shift of the maximum pressure point away from the transducer's focus. These effects depend on the shape and orientation of the marker and become more pronounced as its distance from the transducer's focus decreases, with the distortion introduced by the marker greatly increasing when placed within 5 mm of the focus. The analytical model approximates the marker's effect and can be used as an alternative method to the computationally intensive and time consuming simulations for quickly estimating the intensity at the focus. A retrospective review of a small patient cohort selected for focal HIFU after failed EBRT indicates that the presence of the marker may affect HIFU treatment delivery. CONCLUSIONS: The distortion introduced by the marker to the HIFU beam when positioned close to the focus may result in an undertreated region beyond the marker due to less energy arriving at the focus, and an overtreated region due to reflections. Further work is necessary to investigate whether the results presented here justify the revision of the patient selection criteria or the markers' placement protocol.

A multi-centre cohort study evaluating the role of inflammatory markers in patient's presenting with acute ureteric colic (MIMIC).

BACKGROUND: Spontaneous Stone Passage (SSP) rates in acute ureteric colic range from 47 to 75%. There is conflicting evidence on the role of raised inflammatory markers in acute ureteric colic. The use of an easily applicable biomarker that could predict SSP or need for intervention would improve the management of obstructing ureteric stones. Thus, there is a need to determine in an appropriately powered study, in patients who are initially managed conservatively, which factors at the time of acute admission can predict subsequent patient outcome such as SSP and the need for intervention. Particularly, establishing whether levels of white cell count (WBC) at presentation are associated with likelihood of SSP or intervention may guide clinicians on the management of these patients' stones. DESIGN: Multi-center cohort study disseminated via the UK British Urology Researchers in Surgical Training (BURST) and Australian Young Urology Researchers Organisation (YURO). PRIMARY RESEARCH QUESTION: What is the association between WBC and SSP in patients discharged from emergency department after initial conservative management? PATIENT POPULATION: Patients who have presented with acute renal colic with CT KUB evidence of a solitary ureteric stone. A minimum sample size of 720 patients across 15 centres will be needed. HYPOTHESIS: A raised WBC is associated with decreased odds of spontaneous stone passage. PRIMARY OUTCOME: The occurrence of SSP within six months of presentation with acute ureteric colic (YES/NO). SSP was defined as absence of need for intervention to assist stone passage. STATISTICAL ANALYSIS PLAN: A multivariable logistic regression model will be constructed, where the outcome of interest is SSP using data from patients who do not undergo intervention at presentation. A random effect will be used to account for clustering of patients within hospitals/institutions. The model will include adjustments for gender, age as control variables.

PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.

BACKGROUND: Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. METHODS: An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases. RESULTS: Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). CONCLUSIONS: In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA responders, however, with significant morbidity. Additionally, post-HIFU PSA nadir appears to be an important predictor for both progression and survival. Further research on focal salvage ablation in order to reduce toxicity while retaining disease control rates is required.

Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer.

BACKGROUND: Localized recurrent prostate cancer after primary radiotherapy can be curatively treated using salvage iodine-125 ((125)I) brachytherapy. Selection is hampered by a lack of predictive factors for cancer control. This study aims to develop and internally validate a prognostic model for biochemical failure (BF) after salvage (125)I brachytherapy. METHODS AND MATERIALS: Whole-gland salvage (125)I brachytherapy patients were treated between 1993 and 2010 in two radiotherapy centers in the Netherlands. Multivariable Cox regression was performed to assess the predictive value of clinical parameters related to BF (Phoenix-definition [prostate-specific antigen [PSA]-nadir + 2.0 ng/mL]). Missing data were handled by multiple imputation. The model's discriminatory ability was assessed with Harrell's C-statistic. Internal validation was performed using bootstrap resampling (2000 data sets). Goodness-of-fit was evaluated with calibration plots. All analyses were performed using the recently published TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement. RESULTS: After median followup of 74 months (range 5-138), 43 of a total 62 patients developed BF. In multivariable analysis, disease-free survival interval (DFSI) after primary therapy and pre-salvage prostate-specific antigen doubling time (PSADT) were predictors of BF: corrected hazard ratio (HR) 0.99 (95% confidence interval 0.97-0.999; p = 0.04) and 0.94 (95% confidence interval 0.89-0.99; p = 0.03), both for a 1-month increase (optimism-adjusted C-statistic 0.70). Calibration was accurate up to 36 months. Of patients with PSADT >30 months and DFSI >60 months, 36-month biochemical disease-free survival was >75%. Every 12-month increase in DFSI will allow 3-month decrease in PSADT while maintaining the same biochemical recurrence-free rates. CONCLUSIONS: We have presented results from a cohort of patients undergoing salvage (125)I-brachytherapy. Our data show that better selection of patients is possible with the DFSI and PSADT.

[Focal therapy for prostate cancer: German version]. / Fokale Therapie des Prostatakarzinoms : Deutsche Version.

Focal therapy is a treatment strategy for men with localized prostate cancer that may serve as an alternative option to radical therapy. A number of minimally invasive ablative technologies are available to deliver treatment, and the energies most commonly used include high-intensity focused ultrasound and cryotherapy. The benefit of a tissue-preserving approach is the limitation of damage to key structures such as the neurovascular bundles, external urinary sphincter, rectal mucosa and bladder neck. This in turn minimizes side effects typically associated with radical therapies whilst also aiming to maintain oncological control. Over 30 single-centre studies of focal therapy have been published to date reporting excellent continence rates, good potency rates and acceptable short-term oncological outcomes. However, there are a number of controversial aspects associated with focal therapy including the index lesion hypothesis, patient selection criteria, assessment of treatment effect and the lack of medium- and long-term oncological outcomes. In the process of the adoption of new technology, there is a limited window of opportunity to provide this evidence in well-designed prospective trials. Men should be allowed to benefit from the potential advantages of this novel treatment whilst under close surveillance. An English version of this article is available under dx.doi.org/10.1007/s00120-014-3734-7.

Subacute physeal abscess: case report to illustrate treatment with a minimally invasive incision and drainage technique.

INTRODUCTION: Brodie's abscess is a form of subacute osteomyelitis characterised by a low grade pyogenic abscess found most commonly in the metaphysis. One rare form found in children crosses the physeal growth plate and into the epiphysis. Due to the rarity of this subtype and apprehension associated with treatment of the transphyseal abscess, no clear guidance exists on its management. CASE HISTORY: We present a case of delayed diagnosis of Brodie's abscess crossing the physis in a 14-year-old boy. He gave a one-year history of pain in the right knee and early x-rays had shown lucent areas in the tibia. However, these were only noted to be significant at presentation one year later. We also describe an improvised minimally invasive and atraumatic technique of modifying a laminar suction catheter for accessing and draining the abscess. CONCLUSIONS: From our experience and reports in the literature it is clear that antibiotic treatment is generally advocated with varying degrees of surgical intervention. Outcomes are largely favourable. Nevertheless, initial drainage allows samples to be sent for microbiological and histological assessment to aid subsequent management and may prevent subsequent leg length discrepancy from failed conservative treatment. We believe that management of a transphyseal abscess must include early drainage and a prolonged course of antibiotics. The antibiotic choice and duration will be governed by culture results and local policy but is commonly given for up to six weeks in the literature and must include one antistaphylococcal drug.

An atypical presentation of aortic rupture: intuition and investigation can avoid disaster.

INTRODUCTION: Patients with an acute abdomen are a common presentation for those participating in emergency surgery cover. The aetiology of this presentation incorporates the spectrum of organ systems and is often not identified satisfactorily. Nevertheless, certain diagnoses will always be difficult to make and some presentations can be deceptive. Radiological investigations increasingly play a role in establishing an accurate diagnosis and frequently allow prompt management to be instituted. INTRODUCTION: Patients with an acute abdomen are a common presentation for those participating in emergency surgery cover. The aetiology of this presentation incorporates the spectrum of organ systems and is often not identified satisfactorily. Nevertheless, certain diagnoses will always be difficult to make and some presentations can be deceptive. Radiological investigations increasingly play a role in establishing an accurate diagnosis and frequently allow prompt management to be instituted. INTRODUCTION: Ruptured AAA should be considered as a differential diagnosis in all elderly patients presenting with acute severe abdominal pain who may be haemodynamically stable. Atypical history and examination with inconsistent or equivocal clinical signs should raise the suspicion of aneurysm, particularly in elderly men with known arterial disease. There should be a low threshold for both requesting and justifying definitive imaging (ie CT) in such cases if a catastrophic outcome through misdiagnosis is to be avoided.