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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., (© 2014 The Authors. BJU International © 2014 BJU International.)

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., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: To report on the long-term toxicity outcome for patients with prostate cancer treated by low-dose rate (LDR) brachytherapy (BXT)., Patients and Methods: The study population comprised a cohort of men treated in our centre between March 1999 and April 2004 with LDR BXT for prostate cancer who had at least 5 years of follow-up post-implant. Patients who had died or experienced biochemical failure were excluded. We contacted eligible patients and asked them to complete a questionnaire to assess current urinary, erectile and bowel function. Urinary and erectile function was compared pre- and post-treatment and outcomes were assessed by treatment modality., Results: Of the 226 LDR BXT-treated patients with >5 years of follow-up, 174 (77.0%) responded to the questionnaire. The mean International Prostate Symptom Score (IPSS) increased from 6.70 pre-BXT to 7.91 at follow-up (P = 0.003). Of the patients with mild symptoms pre-BXT (IPSS, 0-7), 64.2% retained mild symptoms at follow-up, 31.2% developed moderate symptoms (IPSS, 8-9) and 4.6% reported severe symptoms (IPSS, 20-35). A good or acceptable quality of life (QoL) secondary to urinary symptoms (IPSS QoL, 0-4) was reported by 98.0% of respondents. Of those patients potent (International Index of Erectile Function-5 ≥11) pre-BXT, 62.9% remained potent at follow-up. There were no differences in the proportion of patients who were potent when analyzed by the number of years post-implant. At follow-up, 51.7% and 45.4% of patients, respectively, had normal or mild bowel symptoms as indicated by the European Organisation for the Research and Treatment of Cancer questionnaire (QLQ-C30/PR25 scores, 4-8). Moderate bowel symptoms (QLQ-C30/PR25 scores, 9-12) were reported by 2.9% of respondents; none reported severe symptoms., Conclusion: The present study shows low morbidity after LDR BXT over the long-term for a large cohort of patients., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

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)., (© 2011 The Authors. BJU International © 2011 BJU International.)

Objective: To report our clinical experience and 5-year prostate-specific antigen (PSA) relapse-free survival rate for early-stage prostate cancer after (125)I low-dose-rate prostate brachytherapy., Patients and Methods: In all, 300 patients were treated between March 1999 and April 2003, and followed prospectively. Patients were stratified into low-, intermediate- and high-risk groups, and those receiving neoadjuvant androgen deprivation (NAAD) or not. Kaplan-Meier estimates of PSA relapse-free survival and PSA nadirs were obtained for all patients and for the risk groups. Toxicity, as urinary and erectile dysfunction (ED), were reported from a prospective database., Results: The median (range) follow-up was 45 (33-82) months. The actuarial PSA relapse-free survival was 93% at 5 years; 21 (7%) of patients had evidence of biochemical failure as defined by the American Society of Therapeutic Radiation Oncology criteria. There was no significant difference in actuarial survival for patients in the different risk groups, or between those receiving NAAD or not (low-risk 96%, intermediate 89%, high 93%, P = 0.12; NAAD 92%, no NAAD 95%, P = 0.30). Overall the 3-year median PSA level was 0.3 ng/mL (192 men). There was no significant difference in median 3-year PSA levels for different risk groups, or for those treated with or with no NAAD. The 3- and 4-year PSA nadir of <0.5 ng/mL was achieved by 71% and 86% of men, respectively. The acute urinary retention rate was 7%; 5.6% of men developed urethral strictures requiring dilatation, while 2.7% required a transurethral resection of the prostate after implantation, for obstructive symptoms. Of patients with no ED before treatment, 62% had no ED at 2 years, and of these 60% used a phosphodiesterase inhibitor., Conclusion: This prospective series confirms the excellent overall biochemical survival after (125)I brachytherapy; the treatment was tolerated well, with early and late urinary toxicity and ED similar to other published results.

Objective: To report the results from the first 100 consecutive patients treated with 125I transperineal interstitial prostate brachytherapy between March 1999 and June 2001, and to determine if the International Prostate Symptom Score (IPSS), prostate volume or urodynamic variables correlate with acute morbidity., Patients and Methods: Patients were assessed prospectively by uroflowmetry, the IPSS, a physical examination and transrectal ultrasonography. Of the 100 patients, 57 had a full urodynamic assessment, 61 presented with lower urinary tract symptoms (LUTS), 25 were screen-detected and 14 presented with other problems. The IPSS was recorded at 1, 6 and 12 weeks, and then at 3-monthly intervals after treatment; significant events, e.g. acute urinary retention (AUR) and rectal symptoms, were recorded prospectively; the mean follow-up was 16 months., Results: No patients were incontinent after treatment. There was a temporary deterioration in IPSS in 89% of patients. Peak symptoms occurred at 6 weeks and a statistically significant deterioration in IPSS persisted until 9 months, but continued to improve throughout the follow-up. AUR affected seven patients, with a further 20 using clean intermittent self-catheterization (CISC) for symptoms. In most patients the symptoms resolved spontaneously to the levels before treatment, with only two patients requiring surgery for bladder outlet obstruction. The IPSS before treatment did not predict urodynamic obstruction. Urodynamically unobstructed patients did not require catheterization. By 2 years after implantation the mean IPSS was better than before treatment. Five patients had mild, transient proctitis., Conclusion: Selecting patients with a low prostate volume and IPSS is likely to optimize the outcome of brachytherapy. Urodynamic studies may be helpful in predicting the risk of AUR and symptoms requiring CISC. Despite many patients presenting with LUTS, acute morbidity was no worse than that reported in large American series of predominantly screening-detected cancers. Prostate brachytherapy is well tolerated and may be safely delivered to patients with prostate cancer in the UK.