Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

• ? To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well‐studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS

• ? A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution.
• ? The results were classified into two groups based on the total serum testosterone: group1, <3 ng/mL; group 2, ≥3 ng/mL.
• ? Student’s t‐test was used to compare continuous variables, and Fisher’s exact test or the chi‐squared test was used to compare categorical variables.
• ? Survival curves were established using the Kaplan–Meier method and compared using the log‐rank test. In all tests, P < 0.05 was considered to indicate statistical significance.

RESULTS

• ? All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co‐morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels.
• ? In pathological specimens, low total testosterone (<3 ng/mL) was an independent risk factor for high Gleason score (>7) and for locally advanced pathological stage (pT3 and pT4).
• ? Higher preoperative testosterone correlated with disease confined to the gland.
• ? There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other.

CONCLUSION

• ? Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

     

Biopsy Gleason score and the duration of testosterone suppression among men treated with external beam radiation and 6 months of combined androgen blockade

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The return of testosterone to normal levels following short‐course androgen blockade in prostate cancer is variable. Factors associated with a longer time to recovery include older age and lower baseline testosterone level. In this study, we found that among men treated with 6 months of combined androgen blockade and radiation therapy, higher biopsy Gleason grade was associated with a shorter time to testosterone normalization.

OBJECTIVE

• ? To determine whether the biopsy Gleason score is associated with duration of testosterone suppression following 6 months of combined androgen blockade (CAB) and radiation therapy (RT) in men with prostate cancer (PCa).

PATIENTS AND METHODS

• ? The study cohort consisted of 221 men with PCa treated with RT and 6 months of CAB between 1996 and 2005.
• ? We defined the duration of testosterone suppression as the time between the last day of CAB and the date the testosterone returned to ≥252 ng/dL. We used Cox regression multivariable analysis to relate biopsy Gleason score to duration of testosterone suppression following cessation of CAB.

RESULTS

• ? A biopsy Gleason score of 8–10 had an adjusted hazard ratio (AHR) of 1.56 (95% confidence interval [CI] 1.04, 2.34; P= 0.03) for a shorter time to testosterone normalization relative to Gleason 6. Specifically, the 51 men with biopsy Gleason score of 8–10 had a median time to testosterone normalization of 17.0 months compared with 22.1 months and 23.8 months for those with biopsy Gleason ≤6 and 7, respectively.
• ? Increasing age was significantly associated with a longer duration of testosterone suppression (AHR of 0.95 [95% CI 0.92, 0.97; P < 0.001]) as was a higher baseline PSA (AHR 0.82 [95% CI 0.69, 0.97; P= 0.02]).

CONCLUSION

• ? A biopsy Gleason score of 8–10 was associated with a shorter period of testosterone suppression following 6 months of CAB and RT. These data are consistent with the hypothesis that a factor released from high‐grade PCa cells may impact on testosterone production.

     

Outcomes of clomiphene citrate treatment in young hypogonadal men

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Hypogonadism is a prevalent problem, increasing in frequency as men age. It is most commonly treated by testosterone supplementation therapy but in younger patients this can lead to testicular atrophy with subsequent exogenous testosterone dependency and may impair spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment in these patients with hypogonadism when maintenance of fertility is desired. This study shows that CC is a safe and efficacious drug to use as an alternative to exogenous testosterone. Not only have we validated previous findings of other papers but have proven our findings over a much longer period (mean duration of treatment 19 months). This prospective study is the largest to date assessing both the objective hormone response to CC therapy as well as the subjective response based on a validated questionnaire.

OBJECTIVE

• ? To prospectively assess the andrological outcomes of long‐term clomiphene citrate (CC) treatment in hypogonadal men.

PATIENTS AND METHODS

• ? We prospectively evaluated 86 men with hypogonadism (HG) as confirmed by two consecutive early morning testosterone measurements <300 ng/dL.
• ? The cohort included all men with HG presenting to our clinic between 2002 and 2006 who, after an informed discussion, elected to have CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every other day. The target testosterone level was 550 ± 50 ng/dL.
• ? Testosterone (free and total), sex hormone binding globulin, oestradiol, luteinizing hormone and follicle stimulating hormone were measured at baseline and during treatment on all patients. Once the desired testosterone level was achieved, testosterone/gonadotropin levels were measured twice per year.
• ? To assess subjective response to treatment, the androgen deficiency in aging males (ADAM) questionnaire was administered before treatment and during follow‐up.

RESULTS

• ? Patients' mean (standard deviation [sd ]; range) age was 29 (3; 22–37) years. Infertility was the most common reason (64%) for seeking treatment. The mean (sd ) duration of CC treatment was 19 (14) months.
• ? At the last evaluation, 70% of men were using 25 mg CC every other day, and the remainder were using 50 mg every other day.
• ? All mean testosterone and gonadotropin measurements significantly increased during treatment.
• ? Subjectively, there was an improvement in all questions (except loss of height) on the ADAM questionnaire. More than half the patients had an improvement in at least three symptoms.
• ? There were no major side effects recorded and the presence of a varicocele did not have an impact on the response to CC.

CONCLUSION

• ? Long‐term follow‐up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility.

     

A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Testosterone deficiency syndrome can be treated with testosterone replacement in the form of injectable, transdermal, buccal and oral preparations. Long‐acting i.m. testosterone undecanoate 1000 mg, which is given at 10?14 week intervals, has been shown to be adequate for sustaining normal testosterone levels in hypogonadal men. This study confirms that long‐acting i.m. testosterone undecanoate is effective in improving the health‐related quality of life in men with testosterone deficiency syndrome as assessed by the improvement in the Aging Male Symptoms scale. Testosterone treatment can be indicated in men who have poor health‐related quality of life resulting from testosterone deficiency syndrome.

OBJECTIVE

• ? To evaluate the effect of i.m. injection of testosterone undecanoate 1000 mg over 12 months on the Aging Male Symptom (AMS) scale scores in men with testosterone deficiency syndrome (TDS).

PATIENTS AND METHODS

• ? A total of 120 men >40 years old with TDS (total testosterone < 12 nmol/L and total AMS scores ≥ 27) were randomized into i.m. injection of either placebo or testosterone undecanoate 1000 mg.
• ? In all, 56 and 58 participants from the active treatment and placebo groups, respectively completed the study.
• ? An i.m. injection of either placebo or testosterone undecanoate 1000 mg was given at weeks 0, 6, 18, 30 and 48.
• ? Self‐administered AMS questionnaires were completed at weeks 0, week 18 and week 48.

RESULTS

• ? Improvement in the total AMS score was significantly greater in the treatment group than in the placebo group (F: 4.576, P= 0.017) over the 48‐week period.
• ? The mean (sd ) total AMS score was 38.46 (11.85) at baseline and 33.59 (1.69) at 48 weeks for the placebo group, and 41.73 (12.73) at baseline and 32.61 (9.67) at 48 weeks for the treatment group.
• ? The mean change in the total AMS score was ?12.6% in the placebo group and ?21.9% in the treatment group.
• ? The mean psychological and somatovegetative domain scores decreased significantly more in the treatment group than in the placebo group (?2.8 vs ?1.2, P= 0.03; and ?3.2 vs ?1.8, P= 0.016).
• ? The difference in change between the randomized groups for the sexual domain scores followed the same trend, though the difference was not significant.

CONCLUSION

• ? Long‐acting testosterone is effective in improving health‐related quality of life as assessed by the AMS scale in men with TDS.

     

Non-transecting anastomotic bulbar urethroplasty: a preliminary report

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Excision of a stricture and end‐to‐end anastomosis of the two ends is thought to be the best form of treatment for short strictures of the proximal bulbar urethra but involves transecting the main blood supply of the corpus spongiosum and the urethra. This is a preliminary report of achieving the same goal but without transecting the blood supply of the corpus spongiosum of the urethra.

OBJECTIVE

• ? To report our early experience with a novel approach to the excision and end‐to‐end anastomotic repair of bulbar urethral strictures.

PATIENTS AND METHODS

• ? A total of 22 patients underwent excision and end‐to‐end anastomosis of a proximal bulbar urethral stricture using a technique in which the corpus spongiosum is not transected, so as to maintain its blood supply intact.
• ? The range of follow‐up was 6–21 months and for 16 patients the follow up was ≥1year.

RESULTS

• ? At 1 year of follow‐up there was no evidence of a recurrent stricture on symptomatic assessment or uroflowmetry in the 16 patients.
• ? On urethrography one patient has a urethral calibre 80% of normal. In the other 15 the calibre is normal or greater than normal.

CONCLUSION

• ? The non‐transecting anastomotic bulbar urethroplasty technique used appears to give results that are as good as those of traditional anastomotic urethroplasty with less surgical trauma.

     

Side effects of intradetrusor botulinum toxin injections on ejaculation and fertility in men with spinal cord injury: preliminary findings

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The beneficial effect of intradetrusor botulinum toxin (BT) injections on hyperactive bladders in individuals with spinal cord injury is known from the literature, but its potential effect on ejaculation and fertility through diffusion is not. As BT injection paralyses the bladder muscle, it may also paralyse the muscular envelopes of the adjacent reproductive organs and lead to potential negative side effects, which have not been studied yet. This study provides preliminary data on the potential negative side effects of BT injections on semen volume and retrograde ejaculation, as well as some potential beneficial effects on semen quality.

OBJECTIVE

• ? To investigate the effect of botulinum neurotoxin A on ejaculation potential and fertility. Intradetrusor injection of botulinum neurotoxin A is most commonly used nowadays to treat overactive bladder in patients with spinal cord injury (SCI).

PATIENTS AND METHODS

• ? Retrospective analyses were carried out of 11 patients with complete lesions from C5 to T6 who had received botulinum (BT) injections for their overactive bladder and who had undergone ejaculation tests before and after BT treatment.

RESULTS

• ? BT treatment was found effective in improving bladder function in up to 85% of the cases.
• ? While no patients maintained natural ejaculation following their SCI, BT treatment was found to increase the incidence of retrograde ejaculation (vibrostimulation) in 46% of cases and to diminish semen volume in 77% of cases, from an average of 1.8 mL to 1 mL.
• ? Semen quality was slightly improved following BT treatment, sperm mobility increased in 67% of cases, sperm vitality in 50% and semen culture improved in 43%.

CONCLUSIONS

• ? BT treatment has beneficial and detrimental effects on ejaculation function. The detrimental effects involve retrograde ejaculation and reduced semen volume, which are explained by the spread of toxin to the bladder neck, reducing its tonus, and to the smooth muscle sexual accessory organs, reducing the strength of their contraction.
• ? The beneficial effects are explained by the reduced contamination of the semen by urinary infection, which may improve spermatogenesis and subsequent semen quality.
• ? The results are discussed in terms of their clinical implications and advice to patients.

     

Expression of the tumour antigen T21 is up-regulated in prostate cancer and is associated with tumour stage

What's known on the subject? and What does the study add? T21 is an immunogenic prostate‐associated tumor antigen identified by SEREX expression cloning and shown to have a highly restricted mRNA expression profile. This study shows the expression of T21 at the protein level in a panel of tissues and cell lines and demonstrates increasing levels of T21 protein expression in patients with more advanced stage prostate cancer.

OBJECTIVES

• ? To define the expression pattern of the tumour antigen T21 at the protein level in prostate tissues, prostate cell lines and a panel of normal tissues.
• ? To correlate the expression pattern of T21 in prostate cancer with clinical parameters.

PATIENTS AND METHODS

• ? Tissue samples were collected from 79 patients presenting at clinic with either prostate cancer (63 patients) or benign prostatic hyperplasia (BPH, 16 patients).
• ? A tissue microarray (TMA) was constructed from 44 of the prostate cancer tissues and areas of benign disease (43 patients) from these tissues were also included on the TMA. The remaining tissues (prostate cancer 19 patients and BPH 16 patients) were mounted fresh frozen onto cork boards and sectioned.
• ? Full ethical approval was granted for all aspects of the study and informed patient consent was taken before tissue collection.
• ? Immunohistochemistry was used on the prostate tumour TMA, the normal tissue TMA and the fresh‐frozen prostate tissues. Fluorescent microscopy and flow cytometry was performed on prostate cell lines.

RESULTS

• ? Expression of T21 was highly restricted within normal tissues with only the stomach, ovary, breast and prostate having detectable T21 expression.
• ? T21 was significantly over‐expressed in prostate cancer glands compared with benign tissue and was present in >80% of the malignant specimens analysed.
• ? Increased expression was positively correlated to pathological stage of prostate tumours.
• ? Additionally, T21 was associated with Gleason grade and prostate‐specific antigen recurrence, although statistical significance was not reached in this restricted cohort of patients.

CONCLUSION

• ? Taken together these results show that T21 is a potential new biomarker for advanced disease and that elevated levels of T21 appear relevant to prostate cancer development.

     

Evaluation of maximum voided volume in Korean children by use of a 48-h frequency volume chart

Study Type – Diagnostic (validating cohort) Level of Evidence 2a What's known on the subject? and What does the study add? The relationship between the maximum voided volume followed a linear curve. The formula presented, bladder capacity (mL) = 12 ×[age (years) + 11], is thought to be a reasonable one for Korean children. Korean children have a smaller bladder capacity than that reported in previous Western studies.

OBJECTIVE

• ? To develop practical guidelines for the prediction of normal bladder capacity in Korean children measured by a frequency volume chart (FVC), maximum voided volume (MVV) is an important factor in the diagnosis of children with abnormal voiding function.

SUBJECTS AND METHODS

• ? In all, 298 children, aged 3–13 years, with no history of voiding disorders volunteered for the study. The MVV was determined in 219 subjects by use of a completely recorded FVC.

RESULTS

• ? Linear regression analysis was used to define the exact relationship between age and bladder capacity. An approximate formula related age to bladder capacity as follows: bladder capacity (mL) = 12 ×[age (years) + 11].

CONCLUSIONS

• ? The relationship between the MVV measured by a FVC by age (3–13 years) of Korean children followed a linear curve.
• ? When applied to normal voiding patterns, the formula presented appears to be a reasonable one for Korean children.

     

Association between obesity and alteration of sperm DNA integrity and mitochondrial activity

Study Type – Prognosis (cohort) Level of Evidence 3a What's known on the subject? and What does the study add? The relationship between high levels of BMI and changes in altered standard semen analysis parameters are described in the literature. However, the functional characteristics of the sperm are essential to complete the evaluation of male infertility. Thus, this study provides important information about the functionality of the sperm of men with different levels of BMI.

OBJECTIVE

• ? To assess the effect of obesity on semen analysis, sperm mitochondrial activity and DNA fragmentation.

MATERIALS AND METHODS

• ? A transversal study of 305 male patients, presenting for clinical evaluation, was carried out. The patients were divided into three groups according to body mass index (BMI) as follows: eutrophic (BMI < 25 kg/m², n= 82), overweight (BMI ≥ 25 kg/m² and <30, n= 187) and obese (BMI ≥ 30 kg/m², n= 36).
• ? The variables analysed were semen analysis, rate of sperm DNA fragmentation and sperm mitochondrial activity.
• ? Groups were compared using one‐way analysis of variance followed by a least significant difference post‐hoc test. A P‐value of <0.05 was considered to indicate statistical significance.

RESULTS

• ? No differences were observed in age, ejaculatory abstinence, ejaculate volume, sperm vitality, morphology or round cell and neutrophil count among the groups.
• ? The eutrophic group had a higher percentage of sperm with progressive motility (P= 0.001). Mitochondrial activity was lower in the obese group (P= 0.037) when compared to the eutrophic, and the percentage of sperm with DNA damage was higher in the obese group (P= 0.004) than the other two groups.

CONCLUSION

• ? Increased BMI values are associated with decreased mitochondrial activity and progressive motility and increased DNA fragmentation.

     

Achieving the 'bifecta' using salvage cryotherapy for locally recurrent prostate cancer: analysis of the Cryo On-Line Data (COLD) registry data

Study Type – Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The cancer‐specific outcomes of salvage cryotherapy for locally recurrent prostate cancer have been well established within contemporary scientific literature. However, very little is known about the outcomes of salvage cryotherapy encompassing health‐related quality of life considerations such as continence after treatment. We think the present study is quite novel, as it proposes a new therapeutic endpoint to evaluate the efficacy and outcomes of salvage therapies for locally recurrent prostate cancer, which we have termed the ‘bifecta’. In addition, we report that in a large multicentre data registry, such as the COLD Registry, the therapeutic ‘bifecta’ can be achieved in most patients.

OBJECTIVES

• ? To evaluate the contemporary outcomes of salvage cryotherapy for locally recurrent prostate cancer using the Cryo On‐Line Data (COLD) Registry.
• ? We also evaluate the outcomes of salvage cryotherapy in achieving the therapeutic ‘bifecta’ consisting of: (i) achieving a post‐cryotherapy nadir serum PSA level of <0.6 ng/mL and (ii) no urinary incontinence.

PATIENTS AND METHODS

• ? A prospectively, centrally collected secure online database has been developed of patients undergoing salvage cryoablation for locally recurrent prostate cancer. Of the patients undergoing salvage cryotherapy (in the absence of neoadjuvant hormonal ablative therapy) included within the COLD Registry, complete medical records pertaining to continence status and serial PSA measurements after treatment were available in 183 patients.

RESULTS

• ? The therapeutic ‘bifecta’ was achieved in 133 of these patients (72.7%).
• ? Of the patients achieving the ‘bifecta’, the mean (sd ) age at presentation was 71.5 (6.6) years.
• ? Most patients (91%) had a baseline pre‐salvage total serum PSA level of <10 ng/mL and a pre‐treatment biopsy Gleason score of <8 (85%).
• ? The mean duration of follow‐up of patients achieving the ‘bifecta’ was 36.5 months.

CONCLUSIONS

• ? The therapeutic ‘bifecta’, a new surrogate benchmark for salvage therapies, can be achieved in most patients undergoing salvage cryotherapy.
• ? Therefore, salvage cryotherapy is a reasonable treatment choice for locally recurrent prostate cancer in appropriately selected patients.

     

New treatment paradigm for prostate cancer: abarelix initiation therapy for immediate testosterone suppression followed by a luteinizing hormone-releasing hormone agonist

Study Type – Therapy (prospective cohort) Level of Evidence 2a What's known on the subject? and What does the study add? The sequential administration of a GnRH antagonist followed by an LHRH agonist in the management of prostate cancer patients has not been studied, but such a program would provide a more physiologic method of achieving testosterone suppression and avoid the obligatory testosterone surge and need for concomitant antiandrogens that accompany LHRH agonist therapy. The current study which uses abarelix initiation therapy for 12 weeks followed by either leuprolide or goserelin demonstrates the ability to more rapidly achieve testosterone suppression, avoid the obligatory LHRH induced testosterone surge, avoid the necessity of antiandrogens, all of which were accomplished safely, without inducing either additional or novel safety issues.

OBJECTIVE

• ? To demonstrate the safety and endocrinological and biochemical efficacy of initiating treatment with the gonadotropin‐releasing hormone (GnRH) antagonist, abarelix, followed by administration of an luteinizing hormone‐releasing hormone (LHRH) agonist in patients with advanced and metastatic prostate cancer.

PATIENTS AND METHODS

• ? A multicentre, open‐label design study was conducted at 22 centres in the US involving patients with: localized, locally advanced or metastatic disease; with a rising prostate‐specific antigen (PSA) after definitive local treatment; patients undergoing neoadjuvant hormonal therapy before local therapy (radical prostatectomy, radiation therapy or cryosurgery); and patients in whom intermittent therapy was the planned treatment.
• ? All patients received abarelix for 12 weeks followed by an LHRH agonist (either leuprolide or goserelin) for 8 weeks
• ? The primary efficacy endpoint was achievement and maintenance of castration defined as testosterone <50 ng/dL from day 29 through to day 141 and whether abarelix initiation therapy could eliminate the testosterone surge after two consecutive doses of LHRH agonist therapy.
• ? PSA, LH and follicle‐stimulating hormone (FSH) levels were measured and adverse events were monitored.

RESULTS

• ? A total of 176 patients were enrolled into the present study, the majority of whom had localized prostate cancer (82%) and a PSA level <10 ng/mL (62%).
• ? At the end of the abarelix treatment period (day 85), 93.8% of patients achieved castrate levels; during the first week of switch over to the LHRH agonist therapy (days 85–92) the rate was 86.5% and during the week after the second LHRH agonist injection (days 114–12) it was 93.3%.
• ? A small, transient increase in testosterone occurred during the first injection of the LHRH agonist; mean (standard deviation [sd ]) values increased from 17 (17.8) ng/dL at day 85 to 37.3 (51.07) ng/dL at day 86.
• ? Mean (sd ) PSA levels decreased from 20.5 (56.6) ng/mL at baseline to 3.7 (23.5) ng/mL on day 85 and remained stable throughout the LHRH agonist treatment phase.
• ? Treatment‐related adverse events occurred in 84% of patients overall; a similar incidence was reported during the two treatment phases.

CONCLUSIONS

• ? Abarelix initiation therapy results in the desired effect of achieving rapid testosterone suppression; testosterone surges after subsequent LHRH agonist therapy are greatly abrogated or completely eliminated.
• ? This treatment paradigm (abarelix initiation followed by agonist maintenance) obviates the need for an antiandrogen.
• ? Abarelix was well tolerated and no clinically meaningful or novel adverse events were observed during abarelix treatment or in the transition to LHRH agonist maintenance therapy.

     

MRI and its role in the evaluation and surgical decision making in patients with challenging IPP presentations: descriptions of MRI findings and algorithm for patient management

Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that magnetic resonance imaging (MRI) is safe and effective for imaging patients with inflatable penile prostheses (IPPs). Previous series have reported results of MRI for imaging series of patients with IPPs. The impact on management in particular with regard to salvage procedures is not well defined. This study represents the largest known experience with MRI evaluation of IPPs. This also provides an algorithm that assists with decisions regarding utilization of MRI and treatment planning based on results.

OBJECTIVE

• ? In some patients who undergo placement of an inflatable penile prosthesis (IPP) the device may function inadequately. We describe the use of magnetic resonance imaging (MRI) for anatomical localization and detection of prosthesis malrotation, angulation, displacement and erosion in IPPs with equivocal clinical examination.

PATIENTS AND METHODS

• ? We prospectively performed MRI by a defined protocol including T1‐weighted imaging, and transaxial, sagittal and coronal fat‐saturated fast spin‐echo T2‐weighted imaging in both deflated and inflated states to evaluate patients seen at our referral centre for IPP‐related complaints.
• ? We retrospectively reviewed 32 such MRI studies performed as a supplement to clinical examination between 2000 and 2008.

RESULTS

• ? Of 32 cases, 75% (24/32) underwent surgical intervention. Of these, 45% (11/24) underwent device salvage procedures including cylinder revision in 33% (8/24), cylinder replacement in 8% (2/24) and pump replacement in 4% (1/24).
• ? MRI was most useful for determination of surgical approach in those with abnormal physical examination, and for justification of either surgical or expectant management in those with indeterminate physical examination.

CONCLUSIONS

• ? MRI is safe and effective for imaging genitourinary prostheses.
• ? We found MRI to be a valuable adjunct for evaluation of IPP‐related complaints when clinical examination is equivocal as it detected a variety of prosthetic and corporal abnormalities and impacted management decisions regarding observation, replacement or device salvage procedures.
• ? We provide technique, results and an algorithm that can be beneficial in this complex subset of patients.

     

The use of estramustine phosphate in the modern management of advanced prostate cancer

What’s known on the subject? and What does the study add? Estramustine phosphate has anti‐tumour properties and it improves patient outcomes if combined with other chemotherapy agents such as doeetaxel. The efficacy of estramustine phosphate in selected patients and its safety profile, provided used with any low‐molecular‐weight heparin support its use as a second‐line treatment in hormone‐resistant prostate cancer.

OBJECTIVES

• ? Estramustine phosphate is a nitrogen mustard derivative of estradiol‐17β‐phosphate and has anti‐tumour properties.
• ? Interest in estramustine has been renewed because of the results of clinical studies showing improved patient outcomes if estramustine is combined with other chemotherapy agents such as docetaxel.

PATIENTS AND METHODS

• ? Relevant clinical studies using chemotherapy combinations including estramustine are discussed.
• ? Efficacy and safety outcomes are summarized.

RESULTS

• ? Combination therapy with estramustine and docetaxel can increase PSA response rates, improve quality of life and increase median patient survival compared with chemotherapy regimens that do not include estramustine.
• ? Although the overall tolerability of estramustine is favourable, its use can be associated with an increased risk of thromboembolic events.

CONCLUSIONS

• ? The identification of suitable patient groups and the effective management of the risk of thromboembolism with the adjunct of low‐molecular‐weight heparins support the use of estramustine as an effective second‐line treatment strategy in hormone‐resistant prostate cancer.
• ? These promising findings warrant further investigation in a randomized clinical trial.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

Study Type – Diagnostic (case series) Level of Evidence 4

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.

     

Natural history of lower urinary tract symptoms in Japanese men from a 15-year longitudinal community-based study

Study Type – Symptom prevalence (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? There have been few longitudinal community‐based studies on LUTS suggestive of BPH. It is important to determine the natural history of LUTS suggestive of BPH among men in various countries because it is known that there are differences according to race. Although we previously reported a cross‐sectional community‐based survey on LUTS suggestive of BPH in Japanese men, no longitudinal data were available. The present study provides 15‐year longitudinal data on LUTS suggestive of BPH and related variables in Japanese men.

OBJECTIVE

• ? To report the natural history of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in Japanese men.

PATIENTS AND METHODS

• ? From 1992 to 1993, we conducted a cross‐sectional community‐based study on LUTS suggestive of BPH in Japanese men aged 40–79 years.
• ? After 15 fifteen years, a follow‐up study was conducted to determine their longitudinal changes of LUTS.
• ? Of the 319 participants taking part in the initial study, 135 participated again in the follow‐up study.
• ? We investigated International Prostate Symptom Score (IPSS), quality of life index and bother score using a questionnaire, and measured prostate volume (PV), prostate‐specific antigen (PSA) level and peak urinary flow rate (Q_max) using a method that we have employed previously.

RESULTS

• ? The change in the total IPSS during 15 years was significant (P= 0.001) and its mean (sd ) annual change was 0.11 (0.40).
• ? Although there was little change in the bother score, a significant correlation was observed between changes in the IPSS and bother score (r= 0.528, P < 0.001).
• ? For the individual IPSS and bother scores, only changes in urgency, weak stream and nocturia were significant.
• ? The changes in PV, PSA level and Q_max were significant.
• ? The change in the total IPSS did not correlate with the changes in these variables.

CONCLUSION

• ? In a 15‐year‐longitudinal community‐based study for Japanese men, we have shown that the IPSS and quality of life index deteriorated, PV and PSA level increased, and Q_max decreased.

     

Incidence and clinical significance of arterial injury in varicocele repair

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

• ? This study was performed to histologically determine the rate of arterial injury in varicocele ligation surgery and to determine the clinical significance of these arterial injuries.

MATERIALS AND METHODS

• ? 41 men who underwent varicocele ligation surgery, and had segments of each ligated vessel examined histologically.
• ? The patients were followed prospectively to determine the effect of arterial injury on surgical results and clinical complications.

RESULTS

• ? Arterial ligation was identified in 6 of 41 patients (12%), and in 7 of 132 specimens (5%), which is higher than previous reports.
• ? Arterial injury was not associated with testicular atrophy and there was no apparent effect of arterial injury on surgical outcome.

CONCLUSION

• ? The rate of arterial injury during varicocele repair is higher than previously reported, but the clinical significance of these injuries appears to be limited.

     

In the era of micro‐dissection sperm retrieval (m‐TESE) is an isolated testicular biopsy necessary in the management of men with non‐obstructive azoospermia?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There are a number of ways to retrieve sperm from the testis however there is no universal consensus as to which is the best approach. Furthermore, there is controversy as to whether a diagnostic biopsy has a role in management of non‐obstructive azoospermia (NOA). This study gives support to the growing consensus that micro‐dissection TESE (m‐TESE) is the optimum approach to retrieve sperm in patients with NOA even when previous attempts have failed. Moreover, it strongly suggests that histology is unreliable in determining success rates with m‐TESE and therefore isolated diagnostic biopsies should not be performed.

OBJECTIVES

• ? To assess the outcome of sperm retrieval using micro‐dissection‐TESE (m‐TESE) and simultaneous diagnostic biopsy in NOA to determine if the final definitive histology correlated with the outcome of sperm retrieval by m‐TESE in men with NOA.
• ? To determine if there was a correlation between FSH levels and positive sperm retrieval rates and assessed the success rate of m‐TESE as either a primary or a salvage procedure after previous negative sperm retrieval.
• ? The EAU guidelines (2010) recommend that in men with non obstructive azoospermia ‘a testicular biopsy is the best procedure to define the histological diagnosis and the possibility of finding sperm’. However, these guidelines do not identify which patients should have a diagnostic biopsy and if this biopsy should be performed as an isolated procedure or synchronously with sperm retrieval. It is also suggested that there is a correlation between the histological diagnosis and possibility of finding sperm on testis biopsy.

PATIENTS AND METHODS

• ? 100 men with NOA underwent a m‐TESE sperm retrieval between 2005 and 2010 at a single centre.
• ? All patients underwent hormonal analysis (serum FSH, Testosterone and LH levels) and genetic analyses after full counselling including; Y‐deletion, CF‐gene analysis and karyotype.
• ? Thirty five men had previously undergone unsuccessful TESA/TESE or diagnostic biopsy at other centres. All patients underwent synchronous sperm retrieval and biopsy of the testis, which was sent for histopathological examination on the day of an ICSI cycle or as an isolated procedure.

RESULTS

• ? Mean age of patients was 37.25 (range 29–56 years). The mean serum FSH levels in the Sertoli cell only, maturation arrest and hypospermatogenesis groups were 21.3 IU/L (2.8–75), 16.18 (1.6–67) and 14.17 IU/L (0.8–42.3) respectively. SR rates in the respective groups were 42.85%, 26.6% and 75.86% (P= 0.023). There were no post‐operative complications.
• ? In the 35 men who had previously undergone unsuccessful procedures elsewhere, the SR rates were 57.1%. The overall sperm retrieval rate was 50%. There was no correlation between SR and FSH levels (P= 0.28).

CONCLUSION

• ? M‐TESE should be considered the gold standard for retrieval of testicular sperm in NOA, even in cases where there has been previously unsuccessful attempts. FSH levels and histology cannot be used to predict the success of sperm retrieval. An isolated diagnostic testicular biopsy is not recommended in men with NOA, as a significant proportion of men undergoing m‐TESE will have successful a sperm retrieval irrespective of previous histology or previous unsuccessful surgery.

     

Will the implementation of the 2007 National Institute for Health and Clinical Excellence (NICE) guidelines on childhood urinary tract infection (UTI) in the UK miss significant urinary tract pathology?

What's known on the subject? and What does the study add? Most centres continue to investigate children extensively after a urinary tract infection. These investigations are invasive, time consuming and expensive and despite their widespread application they have not had a significant impact on the rates of chronic renal failure secondary to infection. Despite this evidence the National Institute for Health and Clinical Excellence (NICE) guidelines generated significant controversy that abnormalities would be missed, placing children at increased risk of renal injury, thus reducing their implementation. Significant underlying abnormalities of the urinary tract will not be missed if the NICE guidelines are followed. This will reduce the unpleasant investigations that children will be subjected to and it should lead to considerable cost savings. The NICE guidelines are safe and should be widely implemented.

OBJECTIVE

• ? To investigate whether the implementation of the August 2007 National Institute for Health and Clinical Excellence (NICE) guidelines would miss significant urinary tract pathology in children with urinary tract infection (UTI).

PATIENTS AND METHODS

• ? All ultrasound (US) performed in children aged >6 months, during the year 1 August 2006 to 31 July 2007 for UTI, were retrospectively studied.
• ? Each US scan in the study population of 346 was categorised dependent on whether it was appropriate or inappropriate to have been performed under the new guidelines and whether the US scan was normal or abnormal.
• ? The records of each patient with an inappropriate abnormal US scan were re‐analysed to see if patient management was affected by the US scan.
• ? In 2011 patients with an original inappropriate abnormal US scan were re‐evaluated to identify if any had presented with further urinary pathology.

RESULTS

• ? In accordance with the NICE guidelines patients were divided by age.
• ? Children aged 0.5–3 years: 78/95 (82%) US scans were inappropriate of which 12 (15%) were abnormal and four of these had a further documented UTI. After careful assessment of the US abnormalities it was judged that only one would have benefited from the initial US scan.
• ? Children aged >3 years: 146/251 (58%) US scans were inappropriate of which 21(14%) were abnormal and six of these (29%) had a further documented UTI. After careful assessment of the US abnormalities it was judged that only three of 21 (14%) would have benefited from the initial US scan.

CONCLUSIONS

• ? The vast majority of anomalies detected on the inappropriate US scans were of little clinical significance.
• ? It is difficult to identify any patient who would have been truly disadvantaged if the US scan had not been performed after the initial UTI.
• ? The NICE guidelines are safe to follow.

     

Contrast-enhanced ultrasound using a time-intensity curve for the diagnosis of renal cell carcinoma

Study Type – Diagnosis (non‐consecutive series) Level of Evidence 3b What’s known on the subject? and What does the study add? In terms of imaging differentiation, distinguishing complex cystic renal masses that require surgery from those that do not remains a common and difficult diagnostic problem. Magnetic resonance imaging (MRI) is useful for characterizing complex cystic renal masses. But there are some cases that are difficult to diagnose differentially on computed tomography (CT) or MRI. We evaluated the usefulness of contrast‐enhanced ultrasound (CEUS) for the diagnosis of cystic renal cell carcinoma by using a time‐intensity curve (TIC). Assessments of blood flow in the solid component of a cystic tumour by CEUS using a second‐generation US contrast agent and TIC analysis have made it easier to objectively diagnose cystic renal cancer.

OBJECTIVE

• ? To evaluate the usefulness of contrast‐enhanced ultrasound (CEUS) for the diagnosis of renal cell carcinoma by employing a time‐intensity curve (TIC).

PATIENTS AND METHODS

• ? From May 2008 to October 2009, CEUS was performed prior to surgery in 30 patients with renal masses.
• ? In all, 10 of the 30 patients had cystic renal masses. The final diagnoses of all patients were pathologically confirmed. Contrast enhancement as a function of time was measured in two (tumour or solid component of cystic lesions and normal parenchyma) regions of interest (ROI) and TICs were obtained.
• ? The time to the contrast enhancement peak (TTP), intensity change from the baseline to peak (ΔI) and ΔI/TTP of the tumour and the normal parenchyma were measured from the TIC.

RESULTS

• ? Pathological diagnoses were renal cell carcinoma in 30 patients.
• ? The TTP of the cancer was shorter than that of the normal parenchyma in all cases (6.0 ± 2.0 vs 10.4 ± 3.0 s; P < 0.0001).
• ? The ΔI did not differ between the cancer and normal parenchyma [21.3 ± 5.9 vs 20.9 ± 7.0 decibels (db); P= 0.68]; the ΔI/TTP of the cancer was significantly higher than that of the normal parenchyma (3.9 ± 1.4 vs 2.2 ± 0.94 db/s; P < 0.0001).
• ? TIC patterns of solid cancer and cystic cancer were very similar.

CONCLUSIONS

• ? An objective and quantitative diagnosis of renal cell carcinoma by CEUS using a second‐generation ultrasound contrast agent can be made by employing a TIC.
• ? The TIC patterns of solid and cystic cancers were very similar, despite their morphological and vascular differences.
• ? CEUS using TIC is a promising tool in the diagnosis of cystic renal cancer.

     

Outcomes in patients with Gleason score 8-10 prostate cancer: relation to preoperative PSA level

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐grade prostate cancers are associated with poor disease‐specific outcomes. A proportion of these tumours produce little PSA. This study demonstrates that among Gleason 8–10 prostate cancers, some of the worst survival outcomes are associated with the lowest PSA levels.

OBJECTIVE

• ? To assess outcomes of patients with Gleason score 8–10 prostate cancer (CaP) with a low (≤2.5 ng/mL) vs higher preoperative serum PSA levels.

PATIENTS AND METHODS

• ? From 1983 to 2003, 5544 patients underwent open radical prostatectomy, of whom 354 had a Gleason 8–10 tumour in the prostatectomy specimen.
• ? Patients were stratified according to preoperative PSA level into four strata: ≤2.5 ng/mL (n= 31), 2.6–4 ng/mL (n= 31), 4.1–10 ng/mL (n= 174), and >10 ng/mL (n= 118).
• ? We compared biochemical progression‐free survival (PFS), metastasis‐free survival (MFS), and cancer‐specific survival (CSS) as a function of preoperative PSA level.

RESULTS

• ? Patients with PSA level ≤2.5 ng/mL were more likely to have seminal vesicle invasion (P= 0.003).
• ? On Kaplan–Meier survival analysis, patients with a PSA level ≤2.5 ng/mL had proportionately worse outcomes than their counterparts with higher PSA levels.
• ? The 7‐year PFS in the PSA ≤2.5 ng/mL stratum was lower than those of the PSA 2.6–4 ng/mL and 4–10 ng/mL strata (36% vs 50 and 42%, respectively); however, the lowest 7‐year PFS was found in those with a PSA level >10 ng/mL (32%, P= 0.02).
• ? Gleason score 8–10 tumours with a PSA level ≤2.5 ng/mL also tended to have the lowest 7‐year MFS (75, 93, 89 and 92% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.2) and CSS (81, 100, 94 and 90% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.3), although these differences were not statistically significant.
• ? In the subset with palpable disease, Gleason grade 8–10 disease with PSA level ≤2.5 ng/mL also was associated with a worse prognosis.

CONCLUSIONS

• ? In patients with Gleason grade 8–10 disease, a proportion of these tumours are so poorly differentiated that they produce relatively little PSA.
• ? Patients with high‐grade, low‐PSA tumours had less favourable outcomes than many of those with higher PSA levels.