Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

BACKGROUND: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. METHODS: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 µg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. FINDINGS: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). INTERPRETATION: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. FUNDING: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.

Bladder neck sparing in radical prostatectomy.

The role of a bladder neck sparing (BNS) technique in radical prostatectomy (RP) remains controversial. The potential advantages of improved functional recovery must be weighed against oncological outcomes. We performed a literature review to evaluate the current knowledge regarding oncological and functional outcomes of BNS and bladder neck reconstruction (BNr) in RP. A systematic literature review using on-line medical databases was performed. A total of 33 papers were identified evaluating the use of BNS in open, laparoscopic and robotic-assisted RP. The majority were retrospective case series, with only one prospective, randomised, blinded study identified. The majority of papers reported no significant difference in oncological outcomes using a BNS or BNr technique, regardless of the surgical technique employed. Quoted positive surgical margin rates ranged from 6% to 32%. Early urinary continence (UC) rates were ranged from 36% to 100% at 1 month, with long-term UC rate reported at 84-100% at 12 months if the bladder neck (BN) was spared. BNS has been shown to improve early return of UC and long-term UC without compromising oncological outcomes. Anastomotic stricture rate is also lower when using a BNS technique.

Urological litigation in the UK National Health Service (NHS): an analysis of 14 years of successful claims.

OBJECTIVES: • To present a summary of the collected data on urological litigation within the UK National Health Service (NHS). • Knowledge of the main areas of litigation is essential for maintaining good clinical practice as well as risk management procedures in any specialty. MATERIALS AND METHODS: • Details of all claims closed with indemnity payment pertaining to the specialty of urology as practiced by urologists, general surgeons and paediatric surgeons was obtained from the NHS Litigation Authority (NHSLA) for the years since its creation in 1995 to 2009. • The data was then classified and analysed. RESULTS: • In all, 493 cases were closed with indemnity payment with a total of £20,508,686.18 paid. The average payment per claim was £41,599.77. • Most of the claims were related to non-operative events (232), followed by postoperative events (168) and intraoperative events (92). • The most common reason for non-operative-related claims was failure to diagnose/treat cancer (69), perforation/organ injury (38) was the highest intraoperative-related claim and a forgotten ureteric stent (23) was the most frequent postoperative-related claim. • The five most commonly implicated procedures were ureteroscopy/ureteric stenting (45), transurethral resection of the prostate (30), nephrectomy (26), vasectomy (19) and urethral catheterisation (15). CONCLUSIONS: • The present study once again emphasizes the importance of thorough clinical assessment, record keeping and follow-up as well as informed consent and good communication with patients. • Recognising the areas of highest risk and improving practice should limit future claims.

Early prostate cancer--which treatment do men prefer and why?

STUDY TYPE: Preference (prospective cohort). LEVEL OF EVIDENCE: 1b. What's known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients' views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient's final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE: To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment. PATIENTS AND METHODS: 768 men with prostate cancer (stage T1/2, Gleason≤7, PSA<20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons for choice were recorded. Post-treatment satisfaction was examined via postal questionnaire. RESULTS: Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n=63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n=64, 39%). Active surveillance was chosen by patients for more varied reasons. Post-treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again. CONCLUSION: Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.

Long-term results of extracorporeal shockwave therapy for Peyronie's disease.

PURPOSE: To analyze the long-term results in patients undergoing extracorporeal shockwave therapy (ESWT) for Peyronie's disease. PATIENTS AND METHODS: Patients treated with ESWT (3000 shockwaves on a Storz Minilith SL lithotripter) for Peyronie's disease were included. The mean disease duration prior to treatment was 23.2 months (range 4-60 months). Penile angulation was measured before and after treatment by artificial vacuum induction of erection. Pain during erection was measured using a visual analog scale (VAS 0-5). The average number of ESWT sessions was 3.4 (range 2-9). The mean follow-up post-treatment was 44.1 months (range 42-48 months). Of 44 eligible patients, 38 patients (86.4%) were contactable for evaluation. RESULTS: Of the 38 patients, 10 (26%) subsequently underwent corrective surgery for failed ESWT. Of the remaining 28 patients, 18 (47% of the total) had a statistically significant reduction in angulation, with a mean reduction of 33.2 degrees +/- 14.4 degrees (SD) (range 10 degrees -75 degrees ) (P < 0.001). Nine patients (24%) obtained no benefit, and one had an increase in angulation of 10 degrees . Of the 24 patients with pain, 16 (66.6%) reported relief after ESWT, the mean reduction being 2.5 (range 0.5-4.0) on the VAS (P < 0.001). Of the 28 patients who had not undergone surgical correction, 18 (65%) reported erections suitable for intercourse; 14 (48%) were satisfied with ESWT, 8 (30%) dissatisfied, and 6 (22%) uncertain. Although one patient complained of some penile shortening, no other long-term adverse events were noted. CONCLUSION: Although a quarter of ESWT patients resorted to surgery, in the absence of other effective nonsurgical treatments, ESWT may provide a useful, safe, conservative management option. Extracorporeal shockwave therapy cannot yet be recommended as standard for Peyronie's disease, and randomized controlled studies are required to validate its efficacy and identify the subset of patients most likely to benefit.

Prevalence of prostatic calcification subtypes and association with prostate cancer.

OBJECTIVE: To evaluate the prevalence and to classify prostatic calcification on transrectal ultrasonography (TRUS) and correlate the findings with histology. METHODS: A prospective, blinded study of men undergoing TRUS and prostatic biopsy was designed. A standardized reproducible technique was used with a BK 7.5- to 12.5-MHz multiplanar probe. Representative images of the calcification in the sagittal and transverse planes were captured. Blind analysis by an experienced observer was performed. TRUS findings were categorized using a novel classification and correlated with histologic data. RESULTS: A total of 274 patients (58.8%) had prostate cancer, 88 patients (18.9%) inflammation, and 104 patients (22.3%) had benign pathology. Interface calcification was present in 42.3% of patients. Peripheral or transitional zone calcification was unusual (6.8% and 9.0%, respectively). Of the peripheral zone calcification group patients, 78.1% had cancer on histology examination (P = .020). CONCLUSION: Prevalence and characteristics of prostatic calcification have been described using this novel and practical classification. Although interface calcification is common and not associated with any particular pathology, peripheral zone calcification appears to be strongly associated with prostate cancer.

Acute urinary retention in women due to urethral calculi: A rare case.

We present a case of a 51-year-old woman with acute urinary retention caused by a urethral calculus. Urethral calculi in women are extremely rare and are usually formed in association with underlying genitourinary pathology. In this case, however, no pathology was detected via thorough urological evaluation. We discuss the pathogenesis, clinical presentation and treatment of urethral calculi. To our knowledge, this is the second reported case of a primary urethral calculus in a female with an anatomically normal urinary tract and the first in a middle-aged Caucasian female.

Embryology and adult urology - Not always mutually exclusive: A case report on true hermaphroditism at an adult urology clinic.

True hermaphrodite (TH) is one of the rarest varieties of disorders of sexual differentiation. Most patients present early in the life and are managed by pediatricians. We present a rare case of an adult TH which was first diagnosed by a urologist. We discuss the pathology of TH and its clinical relevance. Knowledge and awareness of embryology are vital to all specialties.

A rare case of testicular metastasis of bladder transitional cell carcinoma.

Metastases from bladder transitional cell carcinoma (TCC) to the testis are very rare. These are usually found on autopsy and occur in advanced or metastatic bladder cancers. More common, known primary tumors that metastasize to the testis include prostate, lungs, melanoma, gastro-intestinal tract and the kidney. We report a rare case of solitary and synchronous metastatic TCC of the bladder to the testis, discovered on histological examination. This case illustrates that metastatic neoplasm to uncommon sites should be considered in the differential diagnosis for patients with a history of advanced bladder TCC.

Diethylstilboestrol for the treatment of prostate cancer: past, present and future.

The aim of this review was to discuss the most recent data from current trials of diethylstilboestrol (DES) to identify its present role in advanced prostate cancer treatment as new hormonal therapies emerge. The most relevant clinical studies using DES in castration-refractory prostate cancer (CRPC) were identified from the literature. The safety, efficacy, outcomes and mechanisms of action are summarized. In the age of chemotherapy this review highlights the efficacy of oestrogen therapy in CRPC. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

The '2-week wait' rule for referrals for suspected urological cancers--urgent need for refinement of criteria.

INTRODUCTION: All NHS-suspected cancers should be seen within 2 weeks of referral and are referred under government guidelines (Health Service Circular 205; HSC 205). This policy will be subject to review in 2009. Review is vital to allow the appropriate detection of malignancy without overburdening the premium clinic slots with the healthy. PATIENTS AND METHODS: A total of 170 consecutive patients were referred from January-June 2005. Referral details, patient information, events and time to diagnosis were recorded. RESULTS: Of these 170 patients, 143 were suitable for analysis. Forty-three patients (30%) were referred with frank haematuria, of whom 30% had bladder cancer. Nine percent of patients (n = 13) had microscopic haematuria none of whom had cancer. A quarter of the patients (n = 35) were referred with suspected testis cancer but none had cancer. Forty-one patients were referred with serum prostate-specific antigen (PSA) elevation; 18 cancers were detected in this group. Ten men had PSA values greater than 50 ng/ml. Only two cancers were suitable for radical prostatectomy. No cancer was found in patients less than 50 years of age. CONCLUSIONS: A high cancer incidence was found (27.9%), the majority of which was bladder cancer or advanced prostate cancer. Out of the 143 patients, no malignancy was diagnosed in any patient less than 50 years of age, no malignancy was diagnosed in any of the microscopic haematuria group and there was no cancer diagnosed in the group of patients referred with scrotal swellings. We suggest that some guidelines are leading to referral of patients with low cancer risk. When the HSC 205 is revised in 2009, we hope studies such as ours are taken into consideration in order to improve resource utilisation.

Diethylstilboestrol versus bicalutamide in hormone refractory prostate carcinoma: a prospective randomized trial.

OBJECTIVE: To compare the efficacy of diethylstilboestrol (DES) with bicalutamide in the treatment of hormone refractory prostate cancer in relation to its effect on prostate-specific antigen (PSA) and survival. METHODS: Patients on LHRH analogues for prostate carcinoma with evidence of biochemical or clinical progression were randomized into one of the treatment arms (n=58). The first group (group A, n=26) received 1 mg of DES with 75 mg of aspirin per day in addition to the primary hormonal treatment. The second group (group B, n=32) received bicalutamide at a dose of 50 mg/day in addition to the primary treatment. Patients were followed up every 3 months with their PSA being checked and were also monitored for any clinical progression and adverse effects as a result of treatment. Any adverse event occurring after patients were started on treatment was attributed to the drug and patients were clinically assessed at each visit. Failure of treatment was defined as a 50% or greater increase in PSA after commencing treatment. Once randomized, all patients were followed up for survival regardless of failure of second-line hormonal manipulation. RESULTS: The mean age of the patients was 76.7 years (60-88, SD 7.4) in group A and 76 years (67-86, SD 6.9) in group B. Twelve patients in each group had metastatic disease. The median follow-up periods for both groups were 24 months (range 6-48 in group A, range 3-54 in group B). 65% of the patients in group A (17/26) and 43.5% (14/32) in group B had a fall in their PSA levels (p=0.08, Fisher's exact test) with 23% (6/26) and 31% (10/32) having a >50% response respectively (p=0.34, Fisher's exact test). Mean PSA nadir in those who responded were 20.6 ng/ml (range 1.6-59.4) and 7.41 ng/ml (range 0.1-42.6) in groups A and B respectively. The median duration of response was 9 months (3-18 months) for group A and 12 months (3-18 months) for group B. Seven patients in group A and 6 in group B experienced adverse events. Three of the 7 in the group A experienced cardiovascular related adverse effects (1 congestive cardiac failure, 1 pulmonary embolism and 1 stroke). At the end of the study period, 14 (54%) of group A patients were alive and 12 (46%) were dead. In group B, 15 (47%) were alive, 16 (50%) were dead and 1 (3%) lost to follow-up. At the completion of the study, 3 patients in each group were still on treatment. CONCLUSION: Low-dose DES and 50 mg of bicalutamide per day are equally effective in hormone refractory prostate carcinoma with respect to biochemical response, although DES has more severe adverse effects. This is a small sample and larger multicentre trials are needed to give us a definite conclusion.

Troponin T and N-terminal pro-brain natriuretic peptide changes in patients undergoing transurethral resection of the prostate.

PURPOSE: We investigated whether transurethral resection of the prostate (TURP) caused subclinical myocardial damage or cardiac dysfunction by measuring troponin T (Trop T) and N-terminal pro-brain natriuretic peptide (pro-BNP). MATERIALS AND METHODS: A total of 52 consenting patients took part in this study. All had a detailed medical history including cardiac history taken. On the day of the operation all patients had troponin T, pro-BNP, full blood count and urea, electrolytes and creatinine measured preoperatively. A preoperative and postoperative electrocardiogram was performed. Patients in renal failure were excluded from analysis. During the operations factors such as blood loss, operative time, tissue resected and fluid absorption were monitored. On postoperative day 1 all the previously mentioned tests were repeated. RESULTS: Mean patient age was 71 years (range 52 to 85). Eight patients had a history of associated cardiac problems. Mean preoperative and postoperative hemoglobin were 14.1 gm/dl (range 10.5 to 17) and 13.3 gm/dl (range 9.9 to 16.2), respectively. None of the patients had significant (greater than 1,000 ml) fluid absorption during TURP, which was calculated using ethanol tagged glycine. Mean blood loss measured with a photometer was 129.7 ml (range 0 to 1,800). Mean operative time was 28.4 minutes (range 5 to 50) and mean weight of prostatic tissue resected was 15.2 gm (range 1 to 47). Preoperative Trop T was less than 0.01 mcg/ml in all patients and mean pro-BNP was 39.2 pg/ml (range 0.5 to 866). Postoperative Trop T was less than 0.01 mcg/ml in all but 1 patient who experienced chest pain after TURP and had an increased Trop T (0.28 mcg/ml). Mean postoperative pro-BNP was 54.57 pg/ml (range 1 to 679). A total of 37 patients had an increase in pro-BNP which was still within the reference range for the age group. There were no significant electrocardiogram changes postoperatively. The Trop T changes were not statistically significant (Wilcoxon sign ranked test p = 0.31) although they may be clinically significant. CONCLUSIONS: Our study indicates that in patients with no prior cardiac history TURP does not cause myocardial damage indicated by nonincrease of Trop T. There are slight increases in pro-BNP after TURP in some patients although the exact clinical significance is uncertain.

Nitrous oxide vs periprostatic nerve block with 1% lidocaine during transrectal ultrasound guided biopsy of the prostate: a prospective, randomized, controlled trial.

PURPOSE: We compared the efficacy of Entonox (BOC Gases, Manchester, United Kingdom), a mixture of 50% nitrous oxide and oxygen, with periprostatic infiltration of 1% lidocaine to provide analgesia during transrectal ultrasound (TRUS) guided biopsy of the prostate. MATERIALS AND METHODS: The study included 235 consecutive men undergoing TRUS guided biopsy of the prostate for elevated prostate specific antigen or abnormal digital rectal examination. Patients were randomized to 3 groups, including group 1-84 controls who did not receive any form of analgesia prior to the procedure, group 2-75 who received periprostatic infiltration with 10 ml 1% lidocaine with biopsies performed 5 minutes after infiltration and group 3-76 who received Entonox for 2 minutes through a breath activated device prior to the procedure and thereafter according to patient preference. All patients were asked to indicate the level of pain experienced before and after the procedure on a 10 cm, nonnumerical, horizontal visual analog score. Results were analyzed using 1-way ANOVA. RESULTS: Mean patient age was 68.8, 64.9 and 65.2 years, and mean visual analog score was 2.9, 1.6 and 2.2 in groups 1 to 3, respectively. Patients in groups 2 (1% lidocaine infiltration) and 3 (Entonox) experienced significantly less pain during the procedure compared with group 1 controls (p <0.001 and 0.028, respectively). There was no statistical difference in pain scores between groups 2 and 3 (p = 0.08). CONCLUSIONS: Inhalation of Entonox or periprostatic infiltration with 1% lidocaine can be used for analgesia during TRUS guided biopsy of the prostate since each provides significant and similar pain relief.

Over expression of metallothionein predicts resistance of transitional cell carcinoma of bladder to intravesical mitomycin therapy.

PURPOSE: Metallothionein, a low molecular weight intracellular protein, binds mitomycin with high affinity protecting the tumor DNA. We prospectively studied the relationship of metallothionein expression in bladder transitional cell carcinoma and resistance to intravesical mitomycin. MATERIALS AND METHODS: A series of 45 consecutive patients with superficial transitional cell carcinoma treated with intravesical mitomycin were studied. Resected tumor tissues were stained with metallothionein monoclonal antibody E9. Two pathologists scored staining intensity and distribution. All patients were followed with regular flexible cystoscopy. RESULTS: Median patient age was 73 years (range 44 to 89). Tumor grade was 1 to 3 in 6, 33 and 6 cases, respectively. In 20 patients (44.44%) tumor recurred after mitomycin therapy. Median cytoplasmic staining scores for recurrent and nonrecurrent tumors were 5 (range 0 to 61) and 0 (0 to 14), respectively. Median nuclear staining scores for recurrent and nonrecurrent tumors were 3 (range 0 to 56) and 0 (0 to 11), respectively. Median followup of patients without recurrence was 18 months (range 12 to 36). Nuclear and cytoplasmic staining scores were significantly higher in recurrent than in nonrecurrent tumors. There was no significant relationship of metallothionein expression with tumor grade. CONCLUSIONS: Over expression of metallothionein predicts the resistance of bladder transitional cell carcinoma to intravesical mitomycin therapy.