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.

Correlation between prostate brachytherapy-related urethral stricture and peri-apical urethral dosimetry: a matched case-control study.

BACKGROUND AND PURPOSE: Radiation dose to the bulbomembranous urethra has been shown to correlate with urethral stricture formation. This retrospective case-control study was designed to explore the relationship between dose to the apical/peri-apical regions of the urethra and development of brachytherapy (BXT)-related urethral stricture. MATERIALS AND METHODS: Cases were patients who developed urethral stricture after treatment with BXT as monotherapy and who had urethral dosimetry post-implant. Each case was matched with a control that had not developed urethral stricture. Dosimetry was compared between cases and controls. RESULTS: Twenty-three cases were pair matched with 23 controls. There were no significant differences between the two groups in terms of age, presenting Prostate Specific Antigen (PSA), International Prostate Symptom Score (IPSS) or Gleason score. The dose delivered to the peri-apical and apical urethra was significantly higher for cases when compared with controls (peri-apical urethra: mean V(150) 1.1 Vs 0.8 cc [p=0.02]; apical urethra: mean dose 200 Vs 174 Gy [p=0.01]). The distance from the prostate apex to isodose lines was also found to be significant in predicting stricture formation. CONCLUSION: There was evidence to suggest that the development of BXT-related stricture was associated with radiation dose at the apical and peri-apical urethra. Attention to the dose delivered to those areas may minimise the risk of developing such morbidity.

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.

Long-term toxicity and quality of life up to 10 years after low-dose rate brachytherapy for prostate cancer.

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.

A randomized controlled trial investigating the effects of celecoxib in patients with localized prostate cancer.

UNLABELLED: Cyclooxygenase-2 (COX-2) is associated with tumour promotion, inhibition of apoptosis, angiogenesis and metastasis. Celecoxib, a selective COX-2 inhibitor was investigated, in patients with clinically localized prostate cancer using immunohistochemistry. PATIENTS AND METHODS: Patients with cT1-2 prostate cancer (n=45) were randomized to celecoxib 400mg b.d. or no treatment for four weeks prior to radical prostatectomy. Histological sections of preoperative biopsy and matched radical prostatectomy specimens were stained for markers of cell proliferation (MIB-1/Ki-67), microvessel density (CD-31 with Weidner scoring), COX-2, apoptosis (TUNEL analysis), angiogenic factors (VEGF and KDR) and HIF-1. RESULTS: Celecoxib decreased tumour cell proliferation, microvessel density, angiogenesis and HIF-1 whilst enhancing apoptosis. These effects approached statistical significance in a multivariate model and the cell proliferation index approached statistical significance on univariate analysis. CONCLUSION: In this pilot study a 4 week regimen of celecoxib resulted in measurable biological effects in prostate cancer tissue. These findings warrant further investigation.

Novel prostate brachytherapy technique: improved dosimetric and clinical outcome.

PURPOSE: Erectile dysfunction following prostate brachytherapy is reported to be related to dose received by the penile bulb. To minimise this, whilst preserving prostate dosimetry, we have developed a technique for I-125 seed brachytherapy using both stranded seeds and loose seeds delivered with a Mick applicator, and implanted via the sagittal plane on trans-rectal ultrasound. MATERIALS AND METHODS: Post-implant dosimetry and potency rates were compared in 120 potent patients. In Group 1, 60 patients were treated using a conventional technique of seeds implanted in a modified-uniform distribution. From January 2005, a novel technique was developed using stranded seeds peripherally and centrally distributed loose seeds implanted via a Mick applicator (Group 2). The latter technique allows greater flexibility when implanting the seeds at the apex. Each patient was prescribed a minimum peripheral dose of 145 Gy. No patients received external beam radiotherapy or hormone treatment. There was no significant difference in age or pre-implant potency score (mean IIEF-5 score 22.4 vs. 22.6, p=0.074) between the two groups. RESULTS: The new technique delivers lower penile bulb doses (D(25) as %mPD - Group 1: 61.2+/-35.7, Group 2: 29.7+/-16.0, p<0.0001; D(50) as %mPD - Group 1: 45.8+/-26.9, Group 2: 21.4+/-11.7, p<0.0001) whilst improving prostate dosimetry (D(90) - Group 1: 147 Gy+/-21.1, Group 2: 155 Gy+/-16.7, p=0.03). At 2 years, the potency rate was also improved: Group 1: 61.7%; Group 2: 83.3% (p=0.008). CONCLUSIONS: In this study, the novel brachytherapy technique using both peripheral stranded seeds and central loose seeds delivered via a Mick applicator results in a lower penile bulb dose whilst improving prostate dosimetry, and may achieve higher potency rates.

Biochemical (prostate-specific antigen) relapse-free survival and toxicity after 125I low-dose-rate prostate brachytherapy.

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.

Quality of life following treatment for early prostate cancer: does low dose rate (LDR) brachytherapy offer a better outcome? A review.

OBJECTIVE: Due to a lack of evidence from randomised studies, there is little agreement on the best form of treatment among men who require curative treatment for prostate cancer. The relative impact of the various treatments on symptoms and health-related quality of life is also controversial. We review the literature on quality of life changes following low dose rate brachytherapy (BXT) and compare BXT to other treatments for early prostate cancer. METHODS: Systematic literature review 1988-2003 (Medline). KEYWORDS: Brachytherapy; Radical prostatectomy; External beam radiotherapy; Quality of life; Symptoms. RESULTS: Review of the current literature suggests that radical prostatectomy, external beam radiotherapy and BXT either alone or in combination with supplementary external beam radiotherapy offer good long-term health-related quality of life. However differences exist in the toxicity of treatment in terms of erectile function, voiding difficulty, incontinence and bowel function. These differences seem to persist for at least 3-5 years post-treatment though longer-term quality of life outcomes from modern techniques are unknown. CONCLUSION: BXT offers a high probability of maintaining continence, potency and normal rectal function though both storage and voiding urinary symptoms have been reported. Addition of androgen deprivation and EBRT to BXT may increase urinary, bowel and sexual toxicity of treatment. Quality of life outcome following brachytherapy compares favourably with other radical treatment options for the management of early prostate cancer.

Identification of pubic arch interference in prostate brachytherapy: simplifying the transrectal ultrasound technique.

PURPOSE: We report a simplified technique allowing identification of pubic arch interference (PAI) using transrectal ultrasound (TRUS). METHODS AND MATERIALS: Fifty consecutive brachytherapy patients implanted using a two-stage technique were studied. The pubic arch was outlined using a marker pen on the ultrasound monitor screen during the dose planning ultrasound. Where pubic arch interference (PAI) was identified attempted needle passage was used to confirm PAI (n = 3). RESULTS: Mean time to perform PAI assessment was 90 s. Three of 50 patients had PAI, which was confirmed by attempted needle passage. No patients required modification to the implant plan during the implant procedure. CONCLUSIONS: TRUS reliably identifies PAI. This simple technique may be used with any TRUS scanner and avoids the need for CT scanning or specific software to identify PAI. Our low incidence of PAI may be related to lower prostate volumes at implantation due to patient selection, neoadjuvant androgen deprivation, or improved patient positioning.

A Spanner in the works: the use of a new temporary urethral stent to relieve bladder outflow obstruction after prostate brachytherapy.

PURPOSE: Assessment of the Spanner, a new temporary urethral stent to relieve bladder outflow obstruction and urinary symptoms after brachytherapy. METHODS AND MATERIALS: Five patients with unusually severe urinary morbidity after (125)I brachytherapy were recruited. The mean time after implant was 40 days (range 25-90). Spanner intraprostatic stents were introduced using topical anesthetic without complication. RESULTS: All patients were able to void spontaneously with no post-void residual volume of urine. The flow rates increased in all cases (p=0.03) and the International Prostate Symptom Scores were significantly improved after stent insertion in all patients (p=0.03). All patients experienced some degree of pain or dysuria during stent use. CONCLUSIONS: Bladder outflow obstruction was effectively treated with the Spanner intraprostatic stent, however pain limited the use of the device in the early post-brachytherapy patient group. Pharmacotherapy, stent design modification, or smaller stent diameter may increase the utility of stents after brachytherapy.