Salvage vesiculectomy for local prostate cancer recurrence: surgical technique and early post-operative outcomes.

PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.

Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience.

OBJECTIVES: To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer. PATIENTS AND METHODS: Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant. RESULTS: The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P < 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level >1.0 ng/mL (HR 6.8, P < 0.001). CONCLUSION: This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level >1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.

Robot-assisted salvage seminal vesicle excision for isolated recurrence after low-dose-rate prostate brachytherapy.

OBJECTIVES: To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) for the focal treatment of isolated seminal vesical (SV) recurrence after treatment for prostate cancer by low-dose-rate brachytherapy. PATIENTS AND METHODS: Patients with rising prostate-specific antigen (PSA) after low-dose-rate prostate brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) of the prostate and 11 C-Choline or 68 Ga-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) scan, followed by targeted transperineal biopsy of the prostate and SVs. Isolated SV recurrence were identified in 17 (0.38%) LDR-PB patients. These 17 patients were offered RA-SVE. RESULTS: The median total operative time was 90 min and blood loss 50 mL with no postoperative transfusions required. The median hospital stay was 1 day. No intra- or postoperative complications were documented. Continence status was unaffected, no patient required urinary pads. Postoperative pathology confirmed SV invasion in all specimens. Surgical margins were positive in seven (41%) patients. All patients had at least one positive imaging study, although three (18%) mp-MRI and five (29%) PET/CT assessments were negative. One (6%) pre-SVE biopsy was also negative but with positive imaging. Salvage SVE failure, defined as three consecutive PSA rises or the need for further treatment, occurred in six patients of whom three had a positive margin. Overall failure-free survival rates were 86%, 67%, and 53% at 1, 2, and 3 years after SVE, respectively. CONCLUSIONS: Salvage RA-SVE appears to be a safe focal treatment, with very low morbidity, for patients with localised SV recurrence after LDR-PB. It permits deferral of androgen deprivation therapy in selected patients. Bilateral SVE is mandatory. This surgical option should be considered in patients with isolated prostate cancer recurrence to the SV.

Hemi-ablative low-dose-rate prostate brachytherapy for unilateral localised prostate cancer.

OBJECTIVES: To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness of hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer. PATIENTS AND METHODS: Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole-gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models. RESULTS: Pre-treatment demography was similar between the 30 HG patients and 362 WG controls. Post-implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post-implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre-treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post-implant prostate-specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32-67 months after implant. CONCLUSION: This pilot study suggests that treatment-related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.

Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer.

OBJECTIVES: To report oncological and functional outcomes of men treated with low-dose-rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment. PATIENTS AND METHODS: Of 3262 patients treated with LDR brachytherapy at our centre up to June 2016, we retrospectively identified 597 patients aged ≤60 years at treatment with ≥3-years post-implantation follow-up and four prostate-specific antigen (PSA) measurements, of which one was at baseline. Overall survival (OS), prostate cancer-specific survival (PCSS) and relapse free survival (RFS) were analysed together with prospectively collected physician-reported adverse events and patient-reported symptom scores. RESULTS: The median (range) age was 57 (44-60) years, follow-up was 8.9 (1.5-17.2) years, and PSA follow-up 5.9 (0.8-15) years. Low-, intermediate- and high-risk disease represented 53%, 37% and 10% of the patients, respectively. At 10 years after implantation OS and PCSS were 98% and 99% for low-risk, 99% and 100% for intermediate-risk, and 93% and 95% for high-risk disease, respectively. At 10 years after implantation RFS, using the PSA level nadir plus 2 ng/mL definition, was 95%, 90% and 87% for low-, intermediate-, and high-risk disease, respectively. Urinary stricture was the most common genitourinary adverse event occurring in 19 patients (3.2%). At 5 years after implantation erectile function was preserved in 75% of the patients who were potent before treatment. CONCLUSION: LDR brachytherapy is an effective treatment with long-term control of prostate cancer in men aged ≤60 years at time of treatment. It was associated with low rates of treatment-related toxicity and can be considered a first-line treatment for prostate cancer in this patient group.

Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse.

OBJECTIVES: To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised prostate cancer. PATIENTS AND METHODS: Analysis of clinical outcomes from a prospective cohort of patients treated with LDR-PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse-free survival (RFS), overall survival (OS), prostate cancer-specific survival (PCSS), and metastases-free survival (MFS), were analysed together with patient-reported symptom scores and physician-reported adverse events. RESULTS: The NICE and NCCN criteria identified 267 and 202 high-risk patients, respectively. NICE-defined patients had significantly lower pre-treatment PSA levels, Gleason scores <7, and a greater proportion of patients who received LDR-PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log-rank P = 0.637), and OS 93% and 94%, respectively (log-rank P = 0.481). All of the survival estimates were similar between LDR-PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment-related toxicity was also similar between the treatment methods. CONCLUSION: LDR-PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR-PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high-risk factors.

Surgical Quality Predicts Length of Stay in Patients with Congenital Heart Disease.

Historically, the primary marker of quality for congenital cardiac surgery has been postoperative mortality. The purpose of this study was to determine whether additional markers (10 surgical metrics) independently predict length of stay (LOS), thereby providing specific targets for quality improvement. Ten metrics (unplanned ECMO, unplanned cardiac catheterization, revision of primary repair, delayed closure, mediastinitis, reexploration for bleeding, complete heart block, vocal cord paralysis, diaphragm paralysis, and change in preoperative diagnosis) were defined in 2008 and subsequently collected from 1024 consecutive index congenital cardiac cases, yielding 990 cases. Four patient characteristics and 22 case characteristics were used for risk adjustment. Univariate and multivariable analyses were used to determine independent associations between each metric and postoperative LOS. Increased LOS was independently associated with revision of the primary repair (p = 0.014), postoperative complete heart block requiring a permanent pacemaker (p = 0.001), diaphragm paralysis requiring plication (p < 0.001), and unplanned postoperative cardiac catheterization (p < 0.001). Compared with patients without each metric, LOS was 1.6 (95 % CI 1.1-2.2, p = 0.014), 1.7 (95 % CI 1.2-2.3, p = 0.001), 1.8 (95 % CI 1.4-2.3, p < 0.001), and 2.0 (95 % CI 1.7-2.4, p < 0.001) times as long, respectively. These effects equated to an additional 4.5-7.8 days in hospital, depending on the metric. The other 6 metrics were not independently associated with increased LOS. The quality of surgery during repair of congenital heart disease affects outcomes. Reducing the incidence of these 4 specific surgical metrics may significantly decrease LOS in this population.

Modified transurethral resection of the prostate (TURP) for men with moderate lower urinary tract symptoms (LUTS) before brachytherapy is safe and feasible.

OBJECTIVE: To report the urinary toxicity outcomes for patients at greater risk of voiding symptoms and retention who received a modified limited transurethral resection of the prostate (TURP) before low-dose rate (LDR) brachytherapy. PATIENTS AND METHOD: Data were analysed from patients receiving the above procedures between 2006 to present, taken from the prospective brachytherapy database of 2000 patients at the St. Luke's Cancer Centre. The limited TURP (TURP(BXT) ) was performed at a median (range) of 64 (25-205) days before seed implantation with a median resection weight of 1.15 g. Selection criteria were based on patients with moderate lower urinary tract symptoms, poor flow or post-void residual urine volume (PVR), or a prominent middle lobe or high bladder neck on transrectal ultrasonography. Baseline prostate cancer characteristics, uroflowmetry, International Prostate Symptom Score (IPSS) and quality-of-life QoL scores were collected and compared with follow-up IPSS and QoL scores. RESULTS: Data for 112 patients was gathered from the database. The TURP(BXT) resulted in statistically significant improvements before LDR brachytherapy in maximum urinary flow rate (Qmax ) and PVR, IPSS and QoL scores (the mean Qmax before vs after the TURP(BXT) was 11.3 vs 16.7 mL/s). The IPSS and QoL scores at 6 months after seed implantation were increased compared with baseline values before the TURP(BXT) (mean IPSS at 6 months 11.7 vs 9.2 before TURP(BXT) ), but no difference at 1 year (mean IPSS 9), and improved scores at 2, 3, 4 and 5 years follow-up (mean IPSS of 7.9, 5.6, 5.3 and 7.4, respectively). CONCLUSION: The present study suggests patients at increased risk of deteriorating voiding symptoms, including urinary retention, are no longer contraindicated against LDR brachytherapy if they receive a modified TURP before seed implantation. This procedure does not appear to carry the risk of urinary incontinence thought to be associated with a conventional TURP before LDR brachytherapy.

Abnormal myocardial blood flow in children with mild/moderate aortic stenosis.

OBJECTIVE: To quantify myocardial blood flow in infants and children with mild or moderate aortic stenosis using adenosine-infusion cardiac magnetic resonance. BACKGROUND: It is unclear whether asymptomatic children with mild/moderate aortic stenosis have myocardial abnormalities. In addition, cardiac magnetic resonance-determined normative myocardial blood flow data in children have not been reported. METHODS: We studied 31 infants and children with either haemodynamically normal hearts (n=20, controls) or mild/moderate aortic stenosis (n=11). The left ventricular myocardium was divided into six segments, and the change in average segmental signal intensity during contrast transit was used to quantify absolute flow (ml/g/minute) at rest and during adenosine infusion by deconvolution of the tissue curves with the arterial input of contrast. RESULTS: In all the cases, adenosine was well tolerated without complications. The mean pressure gradient between the left ventricle and the ascending aorta was higher in the aortic stenosis group compared with controls (24 versus 3 mmHg, p<0.001). Left ventricular wall mass was slightly higher in the aortic stenosis group compared with controls (65 versus 50 g/m², p<0.05). After adenosine treatment, both the absolute increase in myocardial blood flow (p<0.0001) and the hyperaemic flow significantly decreased (p<0.001) in children with mild/moderate aortic stenosis compared with controls. CONCLUSION: Abnormal myocardial blood flow in children with mild/moderate aortic stenosis may be an important therapeutic target.

Importance of HOX genes in normal prostate gland formation, prostate cancer development and its early detection.

The aims of this paper were to review the published literature on the role of HOX genes in the development of the normal prostate gland and in prostate cancer and to discuss the potential role of the HOX family member, Engrailed-2 (EN2), as a diagnostic test of PCa. Hox genes were first described in the fruit fly Drosphila melanogaster, where they specify the body plan and control the formation of body segments. They belong to a family of homeodomain-containing transcription factors that determine cell and tissue identity during normal embryonic development. They have been shown to be re-expressed by several different types of cancers. Studies have shown that different Hox genes are responsible for the development of the separate lobes of the prostate gland, the seminal vesicles and the epididymis. All HOX13 paralogues are expressed in the adult human prostate, suggesting the possibility of similarities between the function and expression of HOX genes within urological structures at similar anterior-posterior positions. The oncogenic and tumour suppressor signalling pathways associated with PCa converge on the HOX gene network, which ultimately controls gene expression, affecting tumour formation and metastatic progression. The Engrailed genes (EN1 and EN2) from the HOX gene family show a very high degree of functional conservation during embryonic development. Urinary EN2 is being investigated as a potential diagnostic marker of early PCa. It is secreted into the urine by PCa cells but not by normal prostatic tissue. A recent study has shown an association between urinary EN2 levels and cancer volume in radical prostatectomy specimens. The ability to predict tumour volume could inform the treatment decision-making process for patients with localized PCa choosing between active surveillance and radical treatment options.

Does prostate HistoScanning™ play a role in detecting prostate cancer in routine clinical practice? Results from three independent studies.

OBJECTIVES: To evaluate the ability of prostate HistoScanning™ (PHS; Advanced Medical Diagnostics, Waterloo, Belgium) to detect, characterize and locally stage prostate cancer, by comparing it with transrectal ultrasonography (TRUS)-guided prostate biopsies, transperineal template prostate biopsies (TTBs) and whole-mount radical prostatectomy specimens. SUBJECTS AND METHODS: Study 1. We recruited 24 patients awaiting standard 12-core TRUS-guided biopsies of the prostate to undergo PHS immediately beforehand. We compared PHS with the TRUS-guided biopsy results in terms of their ability to detect cancer within the whole prostate and to localize it to the correct side and to the correct region of the prostate. Lesions that were suspicious on PHS were biopsied separately. Study 2. We recruited 57 patients awaiting TTB to have PHS beforehand. We compared PHS with the TTB pathology results in terms of their ability to detect prostate cancer within the whole gland and to localize it to the correct side and to the correct sextant of the prostate. Study 3. We recruited 24 patients awaiting radical prostatectomy for localized prostate cancer to undergo preoperative PHS. We compared PHS with standardized pathological analysis of the whole-mount prostatectomy specimens in terms of their measurement of total tumour volume within the prostate, tumour volume within prostate sextants and volume of index lesions identified by PHS. RESULTS: The PHS-targeted biopsies had an overall cancer detection rate of 38.1%, compared with 62.5% with standard TRUS-guided biopsies. The sensitivity and specificity of PHS for localizing tumour to the correct prostate sextant, compared with standard TRUS-guided biopsies, were 100 and 5.9%, respectively. The PHS-targeted biopsies had an overall cancer detection rate of 13.4% compared with 54.4% for standard TTB. PHS had a sensitivity and specificity for cancer detection in the posterior gland of 100 and 13%, respectively, and for the anterior gland, 6 and 82%, respectively. We found no correlation between total tumour volume estimates from PHS and radical prostatectomy pathology (Pearson correlation coefficient -0.096). Sensitivity and specificity of PHS for detecting tumour foci ≥0.2 mL in volume were 63 and 53%. CONCLUSIONS: These three independent studies in 105 patients suggest that PHS does not reliably identify and characterize prostate cancer in the routine clinical setting.

Net survival of men with localized prostate cancer after LDR brachytherapy.

OBJECTIVES: To compare survival of patients who received LDR prostate brachytherapy relative to that of peers in the general population of England, UK. PATIENTS AND METHODS: Net survival was estimated for 2472 cases treated between 2002 and 2016 using population-based analysis guidelines. Life tables adjusted for social deprivation in England from the Office for National Statistics were used to match patients by affluence based on their postcode. RESULTS: The median (range) age at time of brachytherapy was 66 (55-84) years, 84% resided in Southeast England, 51% under an index of deprivation quintile 5 (most affluent), 55% were clinical stage T1 and the remainder T2. Death from any cause occurred in 270 patients at a median (range) of 7 (1-17) years postimplant. Five and 10-year estimates (95% CI) of overall survival were 96% (95-97) and 90% (89-92), and net survival 103% (102-104) and 109% (107-110) respectively. The net survival remained above 100% in all age-at-treatment and clinical stage groups. CONCLUSION: Net survival above 100% indicates patients survive longer than the matched general population. The study shows for the first time the net survival of patients treated with a radical therapy for localized prostate cancer in England. The impact of treatment choice on the long-term net survival advantage requires further investigation.

The neonatal hypoplastic aortic arch: decisions and more decisions.

Neonatal patients with hypoplasia of the aortic arch constitute a heterogeneous group with a wide spectrum of severity. The milder end of the spectrum comprises patients with aortic coarctation and isthmus hypoplasia. At the other end of the spectrum are patients with severe transverse arch hypoplasia or hypoplastic left heart syndrome. The aim of this paper is to discuss the various strategies and surgical approaches available for this group of patients, focusing on the surgical decisions that influence individual patient management. Many of the things discussed are applicable to any neonatal arch problem. We also describe and discuss in detail our surgical technique for patients who undergo neonatal repair of a hypoplastic aortic arch via median sternotomy.

First case of intracardiac foregut cyst occurring in the left-ventricular outflow tract.

An 11 day-old female infant underwent resection of a mass in the subaortic region secondary to critical aortic stenosis. At 3 months of age, recurrent severe left-ventricular outflow obstruction (LVOT) in the setting of heart failure prompted redo surgery, and the resected mass revealed an intracardiac foregut cyst, which is a rare finding. To our knowledge, this is the first case describing obstruction of the LVOT.

4D Brachytherapy, a novel real-time prostate brachytherapy technique using stranded and loose seeds.

What's known on the subject? and What does the study add? There are a number of techniques used successfully to perform brachytherapy, including 2-stage procedures and realtime techniques using loose seeds. This study demonstrates a one-stage realtime brachytherapy technique using stranded seeds with improved time efficiency and clinical outcome: 4D Brachytherapy. This paper reviews the development of a new one-stage prostate brachytherapy technique (4D Brachytherapy) using a combination of stranded and loose seeds. This novel technique utilizes a nomogram constructed from over 1000 procedures to calculate the seed requirement in advance of the implant. This allows stranded seeds to be pre-ordered and loaded prior to the procedure rather than per-operatively, resulting in a more efficient use of operating room time. The use of both stranded and loose seeds may reduce the risk of migration from peripherally placed seeds via the venous plexus, whilst maintaining the flexibility to optimize the dose within the prostate and especially at the apex of the gland. Prospectively collected data show significantly improved dosimetry: median D(90) 143 and 153 Gy (P < 0.005) and median V(100) 88% and 93% (P < 0.005) for the Seattle technique and 4D Brachytherapy implant technique, respectively. Also there was a reduced short-term urinary morbidity as assessed by the change in International Prostate Symptom Score (IPSS) at 3 months and 1 year compared with the Seattle technique. Mean (sd) change in IPSS from baseline at 1 year was 2.73 (5.92) and 0.97 (5.10) for the Seattle and 4D Brachytherapy series, respectively (P < 0.049).

A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy.

UNLABELLED: Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Men with prostate cancer have higher rates of non-cancer mortality and CV morbidity and some of that excess risk has been attributed to the treatment they receive. ADT is an established treatment option for men with locally-advanced and metastatic prostate cancer and, although it has been shown to confer a disease-free survival advantage, it has also been associated with an increased incidence of CV disease and the metabolic syndrome (characterized by a cluster of CV risk factors, including insulin resistance). The benefits of the insulin sensitizer metformin and lifestyle intervention for reducing the incidence of metabolic syndrome have been shown in patients with impaired glucose tolerance. At the time of writing, the present study is the first to use metformin and lifestyle intervention in men with prostate cancer with the aim of reducing the risk of developing ADT-related CV morbidity and the metabolic syndrome. The study shows that lifestyle changes and metformin may indeed reduce the complications of androgen suppression in these men. Although further investigations are needed to establish which of the two interventions may be most beneficial, the favourable effects of a combination of these interventions on patients' quality of life and the potential for improved overall survival are of clinical significance. OBJECTIVE: To investigate the effects of metformin and lifestyle changes on the development of androgen deprivation therapy (ADT)-related metabolic syndrome. PATIENTS AND METHODS: Men with prostate cancer due to receive ADT were recruited and randomized. Controls received ADT alone. Men in the intervention arm received ADT with 6 months of metformin, a low glycaemic index diet and an exercise programme. All patients were investigated pretreatment and at 6 months for the metabolic syndrome, as well as for related biochemical and physical parameters. RESULTS: In total, 40 men were recruited and randomized (20 to each arm). After 6 months, significant improvements in abdominal girth (P= 0.05), weight (P < 0.001), body mass index (P < 0.001) and systolic blood pressure (P= 0.01) were seen in the intervention arm compared to controls. Biochemical markers of insulin resistance did not differ significantly. CONCLUSIONS: The present study shows the potential benefits of metformin and lifestyle changes in ADT-treated men. Further studies will aim to determine which intervention is most important, and may show that overall survival can be improved.

Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? There are a lot of potential prostate cancer biomarkers being evaluated. All aim to improve on the sensitivity and specificity of PSA. EN2 was recently shown by our group to have better sensitivity and specificity than PSA. EN2 is a simple ELISA test and is not dependent on other parameters, even PSA, unlike all the other current biomarkers under evaluation. To date, no marker correlates with the amount of cancer present - the present study shows this positive correlation with EN2 in men undergoing prostatectomy. The potential utility of this work is that by knowing that the level of EN2 corresponds to the amount of cancer present, irrelevant of tumour grade and number of cancer foci, we can define an EN2 level corresponding to small cancers, which can then undergo surveillance. We are conducting a further study that is aimed at determining whether the levels of EN2 in urine can indicate 'significant' vs 'non-significant cancer' using the threshold of 0.5 mL cancer (after Epstein's work). OBJECTIVES: To evaluate the relationship between levels of a recently described prostate cancer biomarker engrailed-2 (EN2) in urine and cancer volume in men who had undergone radical prostatectomy (RP) for prostate cancer. To date, prostate-specific antigen (PSA) levels have not reliably predicted prostate cancer volume. Reliable volume indicator biomarker(s) may aid management decisions, e.g. active treatment vs active surveillance. PATIENTS AND METHODS: Archived patient samples from the Aarhus Prostate Cancer Project, Denmark, were assessed. Pre-treatment mid-stream urines, without preceding prostatic massage, were collected and stored at -80 °C. Urinary EN2 levels were measured by a recently published enzyme-linked immunosorbent assay. RESULTS: In all, 88 of the whole cohort of 125 men (70%) were positive for EN2 in their urine (>42.5 µg/L); 38/58 (65%) men where cancer volume data was available. There was no statistical relationship between urinary EN2 levels and serum PSA levels. PSA levels did not correlate with tumour stage, combined Gleason grade, total prostatic weight or cancer volume. There was a strong statistical relationship between urinary EN2 and prostate cancer volume by linear regression (P = 0.006). Higher EN2 levels correlated with tumour stage T1 vs T2 (P = 0.027). CONCLUSIONS: Pre-surgical urinary EN2 levels were associated with increasing tumour stage and closely reflected the volume of cancer in RP specimens. Given the ease of collection (no prostatic massage required) and the simplicity, low cost and robustness of the assay, EN2 may become a useful biomarker in not only identifying which patients have prostate cancer but may also facilitate risk stratification by indicating the burden of tumour volume.

Report of a consensus meeting on focal low dose rate brachytherapy for prostate cancer.

What's known on the subject? and What does the study add? Whole gland brachytherapy has been used to successfully treat prostate cancer but the protocol for focal therapy has not previously been established. The consensus findings provide guidance on patient selection for focal brachytherapy as well as recommendations for conducting therapy and patient follow-up. Low dose rate prostate brachytherapy is an effective treatment for localized prostate cancer. Recently, it has been considered for use in a focused manner whereby treatment is targeted only to areas of prostate cancer. The objective of focal brachytherapy is to provide effective cancer control for low-risk disease but with reduced genitourinary and rectal side-effects in a cost-effective way. We report on the outputs of a consensus meeting of international experts in brachytherapy and focal therapy convened to consider the feasibility and potential development of focal brachytherapy. A number of factors were considered for focal brachytherapy including optimal patient selection, disease characterization and localization, treatment protocols and outcome measures. The consensus meeting also addressed the design of a clinical trial that would assess the oncological outcomes and side-effect profiles resulting from focal brachytherapy.