Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the BPH6 prospective, multicentre, randomized study.

OBJECTIVES: To compare prostatic urethral lift (PUL) with transurethral resection of the prostate (TURP) with regard to symptoms, recovery experience, sexual function, continence, safety, quality of life, sleep and overall patient perception. PATIENTS AND METHODS: A total of 80 patients with lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) were enrolled in a prospective, randomized, controlled, non-blinded study conducted at 10 European centres. The BPH6 responder endpoint assessed symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation and safety. Additional evaluations of patient perspective, quality of life and sleep were prospectively collected, analysed and presented for the first time. RESULTS: Significant improvements in International Prostate Symptom Score (IPSS), IPSS quality of life (QoL), BPH Impact Index (BPHII), and maximum urinary flow rate (Qmax ) were observed in both arms throughout the 2-year follow up. Change in IPSS and Qmax in the TURP arm were superior to the PUL arm. Improvements in IPSS QoL and BPHII score were not statistically different between the study arms. PUL resulted in superior quality of recovery, ejaculatory function preservation and performance on the composite BPH6 index. Ejaculatory function bother scores did not change significantly in either treatment arm. TURP significantly compromised continence function at 2 weeks and 3 months. Only PUL resulted in statistically significant improvement in sleep. CONCLUSION: PUL was compared to TURP in a randomised, controlled study which further characterized both modalities so that care providers and patients can better understand the net benefit when selecting a treatment option.

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

PURPOSE: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). METHODS: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. RESULTS: In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. CONCLUSION: When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.

Quality of life improvement in patients treated with degarelix versus leuprorelin for advanced prostate cancer.

PURPOSE: We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix. MATERIALS AND METHODS: We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12® and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms. Utility was tested for relationships with aspects of the symptom and side effect burden that may be affected by degarelix treatment, that is prostate specific antigen progression and adverse events. RESULTS: Average utility in patients without prostate specific antigen progression or an adverse event was 0.742, similar to previously published utilities for nonprogressed prostate cancer states. Prostate specific antigen progression was associated with a utility decrement of between 0.062 and 0.134 depending on the mapping algorithm used. Of adverse events considered in our analysis musculoskeletal events were associated with the greatest effects on patient utility with a decrement of between 0.029 and 0.086. The 4 mapping algorithms generated similar utility estimates, although values derived from SF-12 were consistently lower than those derived from EORTC QLQ-C30. CONCLUSIONS: Prostate specific antigen progression status and the incidence of treatment and disease related adverse events result in significant decrements to patient health related quality of life. By slowing prostate specific antigen progression degarelix may improve patient utility and the health related quality of life burden.

Development of male genital lichen sclerosus in penile reconstruction skin grafts after cancer surgery: an unreported complication.

OBJECTIVE: • To describe the incidence of the development of male genital lichen sclerosus (LS) in non-genital skin grafts used in penile reconstruction after cancer surgery. PATIENTS AND METHODS: • Between 1997 and 2009, 177 patients received surgical treatment for penile cancer in the Urology Department at Sunderland Royal Hospital, the regional penile cancer centre for the north-east of England. • Patients who had organ-sparing surgery and non-genital penile graft reconstructions were identified. • Histology reports for specimens obtained from those grafts were reviewed to identify the presence of male genital LS and the incidence of recurrence of squamous cell carcinoma (SCC). RESULTS: • The mean (range) age of patients at diagnosis was 61.8 (32-89) years. Of the 177 patients, 139 had SCC, 32 had carcinoma in situ and six had verrucous carcinoma. • In total, 56 penile reconstructive procedures were performed using split-thickness skin grafts obtained from the inner thigh. • From those grafts, 18 specimens were obtained later for cosmetic, diagnostic or curative purposes. • Male genital LS was found in six of the 18 specimens, and one of them was associated with recurrent verrucous carcinoma. CONCLUSIONS: • This is the first published series to describe the incidence of male genital LS in penile skin grafts taken from a remote site after penile cancer surgery. • These results represent new information that might help explain the aetiology of male genital LS.

Prospective, randomized, multinational study of prostatic urethral lift versus transurethral resection of the prostate: 12-month results from the BPH6 study.

BACKGROUND: Transurethral resection of the prostate (TURP) is considered the gold standard for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, TURP may lead to sexual dysfunction and incontinence, and has a long recovery period. Prostatic urethral lift (PUL) is a treatment option that may overcome these limitations. OBJECTIVE: To compare PUL to TURP with regard to LUTS improvement, recovery, worsening of erectile and ejaculatory function, continence and safety (BPH6). DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, controlled trial at 10 European centers involving 80 men with BPH LUTS. INTERVENTION: PUL or TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The BPH6 responder endpoint assesses symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation, and safety. Noninferiority was evaluated using a one-sided lower 95% confidence limit for the difference between PUL and TURP performance. RESULTS AND LIMITATIONS: Preservation of ejaculation and quality of recovery were superior with PUL (p<0.01). Significant symptom relief was achieved in both treatment arms. The study demonstrated not only noninferiority but also superiority of PUL over TURP on the BPH6 endpoint. Study limitations were the small sample size and the inability to blind participants to enrollment arm. CONCLUSIONS: Assessment of individual BPH6 elements revealed that PUL was superior to TURP with respect to quality of recovery and preservation of ejaculatory function. PUL was superior to TURP according to the novel BPH6 responder endpoint, which needs to be validated in future studies. PATIENT SUMMARY: In this study, participants who underwent prostatic urethral lift responded significantly better than those who underwent transurethral resection of the prostate as therapy for benign prostatic hyperplasia with regard to important aspects of quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT01533038.

Prostate gland lengths and iceball dimensions predict micturition functional outcome following salvage prostate cryotherapy in men with radiation recurrent prostate cancer.

INTRODUCTION: Tissue cryoablation is a potential curative option for solid malignancies, including radiation recurrent prostate cancer (RRPC). Case series of salvage cryotherapy (SCT) in RRPC have reported promising disease free survival (DFS) outcomes and acceptable toxicity profile. While many men receive SCT, no predictive factors for treatment induced side effects are known. The aim of this study is to validate the oncologic outcome of SCT in a large multi-centre patient cohort and to identify potential parameters associated with an increased risk of micturition symptoms. PATIENTS AND METHODS: In this retrospective analysis, we studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres (between 2001 and 2011). Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites. We analysed clinico-pathological factors against tumour response. Functional outcomes were assessed by continence status and IPSS questionnaire. Predictive factors for SCT-induced micturition symptoms were analysed in a sub-group (n=42) of consecutive cases. RESULTS: We found that nadir post-SCT PSA levels strongly associated with DFS. The DFS rates at 12- and 36-month were 84% and 67% for the ≤ 1 ng/ml group and 56% and 14% for the >1 ng/ml group, respectively (p<0.001). Correlative analysis revealed highly significant association between patients' post-SCT micturition status with prostate gland and iceball lengths following SCT. Finally, in a reduction model, both gland length and maximal length of iceball were highly associated with patients' IPSS outcome (p<0.001). CONCLUSION: We report the largest European patient cohort treated with SCT for RRPC. Oncologic outcome guided by nadir PSA of <1 ng/ml is consistent with earlier single-centre series. For the first time, we identified physical parameters to predict micturition symptoms following SCT. Our data will directly assist on-going and future trial design in cryotherapy in prostate cancer.

Cryotherapy for the prostate: an in vitro and clinical study of two new developments; advanced cryoneedles and a temperature monitoring system.

OBJECTIVES: To assess the characteristics of two new developments in cryotherapy for the prostate, IceRods (Oncura, Amersham, UK; 17 G cryoneedles with an advanced heat exchanger which produces a precise ice-ball comparable in size to those with larger diameter cryoneedles) and the Multitemp 1601 temperature monitoring system (TMS, InvivoSense, Trondheim, Norway) probes, in an in vitro model and in a clinical setting, to assess their usefulness, focusing in particular on the TMS probes. PATIENTS, MATERIALS AND METHODS: We assessed the temperature profile and performance of the IceRods in several different configurations, in conjunction with the TMS probes for temperature mapping, in a phantom prostate model. Subsequently 20 patients with prostate cancer were treated with cryosurgery either as a primary or secondary treatment for radiation failure; all had a standard treatment protocol. The temperatures throughout the procedure were recorded accurately and analysed. RESULTS The IceRods were better able to freeze tissue, reaching lower temperatures than conventional cryoneedles. The IceRods were also capable of forming ice-balls with a maximum diameter of >6 cm after freezing at full power for 10 min. The TMS probes depicted real-time temperature gradients over either four or eight points in a linear array, enabling more thorough monitoring of the temperature changes during a treatment cycle. In the clinical setting, in all 20 patients, therapeutic freezing of <-40 degrees C was achieved in both the cycles. Temperatures of approximately - 40 degrees C were attained in the area just outside the prostate, as measured by the TMS probes, but with variation along the longitudinal axis. The rectal and external urinary sphincter temperatures did not fall below 0 degrees C at any of the points along the eight-point temperature probe, but there was variation in temperature along the prostate. CONCLUSION: IceRods and the TMS probes are clinically useful, requiring fewer cryoneedles and with more efficient temperature monitoring; this would be expected to reduce morbidity and increase safety without compromising an adequate oncological outcome. The IceRods were useful in larger prostates of >3.5 cm long, which obviated the need for a 'pull-back' technique. The TMS probes showed convincingly the variation in temperatures along one line, suggesting that single-point temperature monitoring might not accurately depict the lowest temperatures reached during treatment, which is particularly important in the rectum. This is a significant development in cryosurgery and would make the procedure safer, reproducible and allow interested clinicians to learn the technique safely and more quickly.