Second generation of temporary implantable nitinol device (iTind) in men with LUTS: 2 year results of the MT-02-study.

OBJECTIVES: Assessing medium-term functional results of a novel minimally-invasive treatment for lower urinary tract symptoms due to BPO with the second generation of the temporary implantable nitinol device (iTind; Medi-Tate Ltd®, Israel): 2-year follow-up of a single-arm, prospective, international multicenter study. Further, we aimed to identify preoperative baseline parameters predicting response to iTind treatment. METHODS: Following local ethical committee approval in every participating centre, 81 men with symptomatic BPO (IPSS ≥ 10, peak urinary flow < 12 ml/s, and prostate volume < 75 ml) were enrolled in this study. Patients with PVR > 250 ml, obstructive median lobe, previous prostatic surgery, confounding bladder or sphincter dysfunction based on medical history, active urinary infection and unable to interrupt antithrombotic or antiplatelet treatment were exclusion criteria. A wash-out period of 1 month for alpha-blockers and 6 months for 5-ARIs was mandatory to avoid confounders. The procedure was performed as previously described: implantation under light sedation and removal 5-7 days later with topical sedation. Patients were assessed for perioperative results including OR-time, pain (VAS) and complications (Clavien-Dindo-Grading System); and for functional results (PVR, Qmax, IPSS) and quality of life (QoL) including sexual and ejaculatory function using two yes/no questions. Follow-up assessments were done at 1, 3, and 6 months, and 1 and 2 years. RESULTS: Of the 81 patients initially enrolled in this study, follow-up included 67 men at 1 year and 51 men at 2 years. For the 51 men included in the present analysis, the median age was 65 years, median prostate volume 37 ml (range 16-65 ml). Baseline values for IPSS and QoL were 20.51 ± 4.58, 3.96 ± 0.87. Qmax and PVR were 7.62 ± 2.25 ml/s and 65.84 ± 38.46, respectively. No intraoperative complications were observed and the average pain level recorded on the visual analogue scale (VAS) was 3.2 ± 1.6. A significant reduction in symptoms and improvement in urinary flow was observed (p < 0.0001) at all assessment points: IPSS-score and QoL improved to 8.51 ± 5.51 and 1.76 ± 1.32, respectively; and Qmax increased to 16.00 ± 7.43 ml/s. None of the patients who were previously sexually active reported a deterioration in sexual or ejaculatory functions according to two yes/no questions over the follow-up period. Excluding the patients lost at follow-up, five patients underwent surgery between 12 and 24 months. Upon investigation, it was discovered that four of the five patients requiring surgery had median lobes and were protocol deviators. A failure analysis was carried out for all 81 patients in order to identify baseline parameters that could predict treatment failure. 58.33% of patients in the failure group (7 out of 12) had median lobes which was found to be statistically significant (p < 0.0001). None of the other preoperative variables (age, prostate volume, IPSS scores, Qmax, PVR, and PSA) were found to predict response to iTind treatment. CONCLUSION: iTind treatment for BPO-related LUTS showed marked and durable reduction in symptoms and improvement of functional parameters and quality of life at 24 months of follow-up. It was found that median lobe may predict failure of iTind treatment. According to the yes/no questions, ejaculatory and sexual functions do not seem to be effected following treatment, however, this finding must be supported with further studies using the accepted tools.

Second-generation of temporary implantable nitinol device for the relief of lower urinary tract symptoms due to benign prostatic hyperplasia: results of a prospective, multicentre study at 1 year of follow-up.

OBJECTIVES: To report the clinical experience with a second-generation of temporary implantable nitinol device (iTIND; Medi-Tate Ltd, Or-Akiva, Israel) for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) after 1 year of follow-up. PATIENTS AND METHODS: In all, 81 patients with LUTS, International Prostate Symptom Score (IPSS) ≥10, maximum urinary flow rate (Qmax ) ≤12 mL/s, and prostate volume <75 mL, were enrolled in this prospective Research Ethics Committee-approved multicentre study. The main exclusion criteria were: haemostatic disorders, post-void residual urine volume (PVR) >250 mL, obstructive median lobe, and previous prostate surgery. The iTIND was implanted within the bladder neck and the prostatic urethra under light sedation, using a rigid cystoscope. The device was removed 5-7 days later in an outpatient setting. Demographics, perioperative results, complications (according to the Clavien-Dindo system), functional results and quality of life (QoL) were evaluated. Follow-up assessments were conducted at 1, 3, 6 and 12 months postoperatively. RESULTS: The mean (sd) patient age was 65 (8.9) years, prostate volume was 40.5 (12.25) mL, Qmax was 7.3 (2.6) mL/s, IPSS was 22.5 (5.6), and the median (interquartile range) IPSS QoL score was 4 (2-5). All the implantations were successful, with no intraoperative complications recorded; all patients were discharged on the same day of surgery. The devices were retrieved at a mean (SD) of 5.9 (1.1) days after implantation, typically under topical anaesthesia. No Clavien-Dindo Grade >II complications were recorded. The mean (SD) Qmax at the 1 month follow-up visit was 11.2 (5.7) mL/s and continued to improve thereafter, reaching 14.7 (8.1) mL/s at the 12-month follow-up visit (+100%). The mean (SD) IPSS urinary symptom scores were 11.7 (8.0) after 1 month and further improved to 8.8 (6.4) at the 12-month follow-up (-60%). In parallel, the mean (SD) IPSS QoL score drop reached 1.6 (1.3) by the end of the study. During the 12-month period, two patients (2.4%) required medical therapy for BPH, two patients (2.4%) required transurethral resection of the prostate, whilst 10 patients were lost to follow-up (12.3%). As compared to baseline, none of the 61 sexually active patients who completed the 12-month follow-up period reported sexual or ejaculatory dysfunction. CONCLUSION: iTIND implantation is feasible, safe and effective in providing relief of BPH-related symptoms, at least until 12 months postoperatively. Sexual and ejaculatory functions are fully preserved. Further studies with a longer follow-up period are needed to assess the durability of these results and to clearly define the indications for iTIND implantation.

Clinical Outcomes and Testosterone Levels Following Continuous Androgen Deprivation in Patients with Relapsing or Locally Advanced Prostate Cancer: A Post Hoc Analysis of the ICELAND Study.

PURPOSE: Lower serum testosterone levels correlate with improved cause specific survival and longer time to progression in year 1 of continuous androgen deprivation in men with prostate cancer. ICELAND was a large European study demonstrating the efficacy of leuprorelin (Eligard®) during continuous androgen deprivation. In this post hoc analysis we investigated serum testosterone levels within year 1 of continuous androgen deprivation to determine survival and time to progression. MATERIALS AND METHODS: In ICELAND (ClinicalTrials.gov NCT00378690) patients with locally advanced or relapsing nonmetastatic prostate cancer and with prostate specific antigen 1 ng/ml or less following 6-month induction with leuprorelin 3-month depot 22.5 mg (plus bicalutamide 50 mg per day for 1 month) were randomized 1:1 to continuous androgen deprivation (361) or intermittent androgen deprivation (340) with leuprorelin for 36 months. Patients receiving continuous androgen deprivation were stratified by minimum, median and maximum testosterone levels during year 1 of therapy into 20 or less, greater than 20 to 50 and greater than 50 ng/dl subgroups. Cause specific survival and time to prostate specific antigen (castrate resistant prostate cancer) progression were analyzed. RESULTS: A total of 90.1%, 83.5% and 74.5% of patients receiving continuous androgen deprivation achieved minimum, median and maximum serum testosterone levels of 20 ng/dl or less, respectively. Cause specific survival rates and time to prostate specific antigen progression did not differ among the testosterone subgroups. CONCLUSIONS: In patients receiving continuous androgen deprivation cause specific survival and time to prostate specific antigen progression did not differ according to testosterone levels in year 1 of therapy. This finding may in part be due to the induction period and the effectiveness of leuprorelin in lowering testosterone.

Novel anti-biofilm mechanism for wireless capsule endoscopy in the urinary tract: preliminary study in a sheep model.

OBJECTIVE: To develop and test the safety and feasibility of a novel anti-biofilm mechanism configured for wireless capsule endoscopy (WCE) in a sheep bladder model. MATERIALS AND METHODS: A WCE mechanism, designed for long-term bladder monitoring, was developed and introduced into a sheep bladder for 5 months. The transparency of the surface was assessed by evaluating a resolution target placed inside the capsule at serial intervals using cystoscopy under general anaesthesia. Animal behaviour, voiding patterns and urine cultures were monitored throughout the study. At study termination, the capsule was extracted and assessed using scanning electron microscopy. RESULTS: The resolution target was visualized clearly at all investigation points. No notable adverse effects were noted during the entire follow-up period and no urinary tract infection occurred. Scanning electron microscopy confirmed the efficacy of the technology to prevent biofilm formation and surface encrustation. CONCLUSIONS: We report a novel technology that effectively prevents biofilm formation on the outer surface of foreign objects in the urinary tract. Further studies are under way to test the applicability of this technology in bladder WCE to enable high-quality wireless image transmission.

Temporary implantable nitinol device for benign prostatic hyperplasia-related lower urinary tract symptoms: over 48-month results.

BACKGROUND: This study (MT02) reports >48-month (50-79 months) results of a prospective, single-arm, multicenter study (NCT02145208) of temporary implantable nitinol device (iTind®) in men with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS). METHODS: Men with symptomatic BPH (International Prostate Symptom Score [IPSS] ≥10, Maximum flow rate [Qmax] <12 mL/s, and prostate volume <75 mL) from 9 centers were enrolled from December 2014 to December 2016. Total 50/81 (62%) patients at 3/9 sites (Italy, Switzerland, and Belgium), pursued the study beyond 36 months following iTind® device, per study protocol. Due to COVID-19, follow-up was amended. Each patient was assessed once during 50-79 months postoperatively for IPSS and IPSS-quality of life (IPSS-QoL), change in medication, need for surgical re-treatment and adverse events telephonically. RESULTS: Post 36 month-follow-up, 5 patients were lost to follow-up and 2 patients died unrelated to iTind® device placement. Two patients (36-48 months follow-up) required surgical re-treatments (1 transurethral resection of prostate, 1 Thulium laser enucleation of prostate). >48 months results were available for 41 patients wherein iTind® device treatment showed significant improvement in symptoms (IPSS: -45.3%, P<0.0001 and IPSS-QoL: -45.1%, P<0.0001) from baseline to 79 months post-procedure; mean±SD of 11.26±7.67 and 2.10±1.41 points, respectively. No complications were recorded between 36 up to 79 months; no patient required additional medication. CONCLUSIONS: iTind® device provided significant and durable symptom reduction and improved IPSS-QoL for >48 months post treatment. No late postoperative complications were reported beyond 36 months of follow-up. Surgical re-treatment rate for >36 months was 4%.

Localising prostate cancer: comparison of endorectal magnetic resonance (MR) imaging and 3D-MR spectroscopic imaging with transrectal ultrasound-guided biopsy.

BACKGROUND: Magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) have been gaining acceptance as tools in the evaluation of prostate cancer. We compared the accuracy of transrectal ultrasound (TRUS)-guided biopsy and dynamic contrast-enhanced MRI combined with three-dimensional (3D) MRSI in locating prostate tumours and determined the influence of prostate weight on MRI accuracy. PATIENTS AND METHODS: Between March 1999 and October 2006, 507 patients with localised prostate cancer underwent radical prostatectomy (RP) at the Jules Bordet Institute. Of these, 220 had undergone endorectal MRI (1.5 T Siemens Quantum Symphony) and 3D-MRSI prior to RP. We retrospectively reviewed data on tumour location and compared the results obtained by MRI and by TRUS-guided biopsy with those obtained on histopathology of the RP specimen. RESULTS: Patient data were as follows: median age 62.4 years (45-74); median PSA 6.36 ng/ml (0.5-22.6); 73.6% of patients had non-palpable disease (T1c); median biopsy Gleason score 6 (3-9); median RP specimen weight 50 g (12-172); median pathological Gleason score 7 (4-10); 68.64% of patients had organ-confined (pT2) disease. Tumour localisation was correlated with RP data in a significantly higher percentage of patients when using MRI rather than TRUS-guided biopsy (47.4 vs. 36.6%, p < 0.0001). MRI was marginally superior to TRUS-guided biopsy in detecting malignancy at the prostate apex (48.3 vs. 41.9%, p = 0.0687) and somewhat better at the prostate base (46 vs. 39.1%, p = 0.0413). It was highly significantly better at mid-gland (52 vs. 41.1%, p = 0.0015) and in the transition zone (40.1 vs. 24.3%, p < 0.0001). MRI had higher sensitivity in larger (≥50 g) than smaller (<50 g) prostates (50.3 vs. 42.2%, p = 0.0017). CONCLUSIONS: MRI was superior to TRUS-guided biopsy in locating prostate tumours except at the gland apex. MRI was more accurate in larger (≥50 g) than smaller prostates.

3-Year results following treatment with the second generation of the temporary implantable nitinol device in men with LUTS secondary to benign prostatic obstruction.

BACKGROUND: To report the 3-year results of a prospective, single arm, multicenter, international clinical study with the second generation of the temporary implantable nitinol device (iTIND; Medi-Tate Ltd®, Israel) on men suffering lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). METHODS: Eighty-one men with symptomatic BPO (IPSS ≥ 10, peak urinary flow <12 ml/s, and prostate volume <75 ml) were enrolled in this study between December 2014 and December 2016. Subjects were washed-out 1 month for alpha-blockers and 6 months for 5-ARIs. The implantation was performed under light sedation and the removal 5-7 days later with topical anesthesia. Perioperative results including OR-time, pain (VAS) postoperative complications (Clavien-Dindo-Grading System), functional results (Qmax, IPSS, PVR) and quality of life (QoL) were assessed at 1, 3, 6 months, 1, 2, and 3 years. Sexual and ejaculatory function were evaluated using two yes/no questions. RESULTS: Thirty-six month functional results were available for 50 patients and demonstrated that iTIND efficacy remained stable through 3 years, with averages IPSS, QOL, Qmax and PVR of 8.55 + 6.38, 1.76 + 1.32, 15.2 + 6.59 ml/s and 9.38 + 17.4 ml, improved from baseline by -58.2, -55.6, +114.7, and -85.4% (all significantly different from their corresponding baseline values, p < 0.0001). Even considering the Intention to Treat analysis (ITT), the 36-month results confirmed significant improvements of the functional outcomes if compared with baselines values (all p < 0.0001). No late post-operative complications were observed between 12 and 36 months. Sexual function was stable through 3 years, with no reports of sexual or ejaculatory dysfunctions. No patients underwent alternative treatments between 24 and 36 months. CONCLUSION: Treatment of BPO-related LUTS with iTIND demonstrated a significant and durable reduction in symptoms and improvement of functional parameters and quality of life at 3 years of follow-up. No late post-operative complications, ejaculatory dysfunction or additional treatment failures were observed between 24 and 36 months.

Endocrine aspects of male sexual dysfunctions.

INTRODUCTION: Endocrine disorders may adversely affect men's sexual function. AIM: To provide recommendations based on best evidence for diagnosis and treatment of endocrine-related male sexual dysfunctions. METHODS: The Endocrine Aspects of Male Sexual Dysfunctions Committee, including 11 members from eight countries and four continents, collaborated with the Endocrine subcommittee of the Standards Committee of the International Society for Sexual Medicine. Medical literature was reviewed in detail, followed by extensive internal committee discussion over 2 years, then public presentation and discussion with the other experts before finalizing the report. MAIN OUTCOME MEASURE: Recommendations based on grading of evidence-base medical literature and interactive discussion. RESULTS: From animal studies, it is derived that testosterone modulates mechanisms involved in erectile machinery, including expression of enzymes that both initiate and terminate erection. In addition, testosterone is essential for sexual motivation. Whether these findings could be extrapolated to human erections is unclear. Testosterone plays a broad role in men's overall health. Recent studies have established strong associations between low testosterone and metabolic and cardiovascular imbalances. In some studies, low testosterone decreased longevity; however, longitudinal studies do not support the predictive value of low testosterone for further cardiovascular events. The article proposes a standardized process for diagnosis and treatment of endocrine-related male sexual dysfunctions, updating the knowledge on testosterone and prostate safety. There is no compelling evidence that testosterone treatment causes prostate cancer or its progression in men without severe testosterone deficiency (TD). The possible roles of prolactin and thyroid hormones are also examined. CONCLUSIONS: Men with erectile dysfunction, hypoactive sexual desire and retarded ejaculation, as well as those with visceral obesity and metabolic diseases, should be screened for TD and treated. Prospective interventional studies are required before screening for TD in more conditions, including cardiovascular diseases, and considering correction as preventive medicine as much data suggests.

Trends in urologic oncology clinical practice and medical education under COVID-19 pandemic: An international survey of senior clinical and academic urologists.

OBJECTIVE: Ad-hoc guidelines for managing the COVID-19 pandemic are published worldwide. We investigated international applications of such policies in the urologic-oncology community. METHODS: A 20-item survey was e-mailed via SurveyMonkey to 100 international senior urologic-oncology surgeons. Leaders' policies regarding clinical/surgical management and medical education were surveyed probing demographics, affiliations, urologic-oncologic areas of interest, and current transportation restrictions. Data on COVID-19 burden were retrieved from the ECDC. Statistical analyses employed non-parametric tests (SPSS v.25.0, IBM). RESULTS: Of 100 leaders from 17 countries, 63 responded to our survey, with 58 (92%) reporting university and/or cancer-center affiliations. Policies on new-patient visits remained mostly unchanged, while follow-up visits for low-risk diseases were mostly postponed, for example, 83.3% for small renal mass (SRM). Radical prostatectomy was delayed in 76.2% of cases, while maintaining scheduled timing for radical cystectomy (71.7%). Delays were longer in Europe than in the Americas for kidney cancer (SRM follow-up, P = 0.014), prostate cancer (new visits, P = 0.003), and intravesical therapy for intermediate-risk bladder cancer (P = 0.043). In Europe, COVID-19 burden correlated with policy adaptation, for example, nephrectomy delays for T2 disease (r = 0.5, P =0.005). Regarding education policies, trainees' medical education was mainly unchanged, whereas senior urologists' planned attendance at professional meetings dropped from 6 (IQR 1-11) to 2 (IQR 0-5) (P < 0.0001). CONCLUSION: Under COVID-19, senior urologic-oncology surgeons worldwide apply risk-stratified approaches to timing of clinical and surgical schedules. Policies regarding trainee education were not significantly affected. We suggest establishment of an international consortium to create a directive for coping with such future challenges to global healthcare.

Is there a rationale for the chronic use of phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia?

OBJECTIVES: To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both highly prevalent in men aged > or =50 years, as PDE5-Is are very effective as a first-line therapy for ED, and attractive for further physiological functional investigations. METHODS: We searched Medline for peer-reviewed articles in English, from 1991 to 2008, to provide a critical contemporary review of PDE5 pertaining to the potential interest of findings supporting a role for PDE5-Is in LUTS due to BPH. The selection of papers was based on the relevance of subject matter. A critical analysis of available fundamental and clinical data is reported. RESULTS: Several studies assessed the role of the nitric oxide/cGMP signalling pathway in the regulation of the prostate tone, with the support of clinical observations. PDE5-Is can also represent a potential mode of action allowing the targeting of transcriptional activity implicated in the regulation of the progression of the inflammatory process involved in BPH. PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. New targeting hypotheses of pathophysiological processes are also reported. CONCLUSIONS: There is evidence that LUTS and ED are strongly linked. This analysis of the regulatory basis of PDE5 biology could indicate several directions of investigation. However, it is necessary to devise well-designed large prospective studies that would produce significant data before this approach becomes a standard of care.

Prostate cancer: a serious disease suitable for prevention.

Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life-expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5alpha-reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk-reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk-reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment.

Health-related quality of life instruments in studies of adult men with testosterone deficiency syndrome: a critical assessment.

INTRODUCTION: Health-related quality of life (HRQOL) is a multidimensional concept, which subjectively measures a patient's physical, social, and emotional well-being. This information is becoming increasingly important in policy and clinical decisions. With such a wide range of tools available, careful selection is required to ensure they adequately reflect patient's concerns. AIM: To critically assess HRQOL instruments used in studies of testosterone deficiency syndrome (TDS) to see whether they accurately measure these concerns. METHODS: A systematic review identified published articles. Studies were included if the population was adult men with TDS, with or without comorbid disease; used one or more HRQOL tools; and described the impact of treatment, the impact of TDS on the patient or the development of a questionnaire. Measurement properties and their use in clinical studies were described. Each study was assessed against 10 clinical face validity criteria to evaluate whether the questionnaires reflected issues that were of concern to patients. MAIN OUTCOME MEASURE: Review of published literature. RESULTS: The study identified 29 articles that included 14 HRQOL questionnaires selected for use in 20 intervention studies, seven studies of the impact of TDS on the patient, and two studies describing the development of a HRQOL tool. Questionnaires displayed variable measurement properties and only nine studies complied with more than 50% of the clinical face validity criteria. Disease-specific instruments achieved a higher rate of compliance and more often demonstrated a positive effect of treatment on HRQOL compared to generic instruments. CONCLUSION: Instruments used to measure HRQOL display variable measurement properties and often lack adequate clinical face validity. There are well-validated disease-specific HRQOL measures for age-related TDS, but none for classical TDS patients. Clinical and political decision-makers require HRQOL information using a combination of well-validated generic questionnaires and patient-focused, disease specific instruments relevant to the target TDS population under study.

Tamsulosin modified release and oral controlled absorption system in the management of lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

BACKGROUND: Tamsulosin MR has been on the market for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) for many years. Recently, tamsulosin OCAS was introduced, which has improved pharmacokinetics. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin. METHODS: Literature was identified through a PubMed search using the term 'tamsulosin' and by screening reference lists of review articles. RESULTS: Tamsulosin rapidly improves LUTS/BPH, with benefits maintained in the long-term. The overall tolerability of tamsulosin MR 0.4 mg is comparable to that of placebo. While the efficacy of tamsulosin OCAS and MR is comparable, tamsulosin OCAS is slightly better tolerated. CONCLUSION: Tamsulosin OCAS 0.4 mg has a favourable efficacy/safety profile and should be considered the treatment of choice for patients requiring optimal symptom control without increasing the risk of cardiovascular adverse events.

Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer.

PURPOSE: To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy. PATIENTS AND METHODS: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity. RESULTS: At 2 years, 33% of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes. CONCLUSION: Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.

The role of bisphosphonates in the treatment of prostate cancer: recommendations from an expert panel.

In this study, we provide consensus guidelines for the use of bisphosphonates in men with prostate cancer. To this end, an expert panel composed of urologists, medical oncologists, radiation oncologists, and endocrinologists met to review current clinical evidence for the use of bisphosphonates in patients with different stages of prostate cancer to derive consensus recommendations. Physicians should be proactive in monitoring bone loss in patients receiving long-term androgen-deprivation therapy for prostate cancer. Further study is needed before recommending the routine use of bisphosphonates in men with nonmetastatic prostate cancer. However, if a patient has clinically significant bone loss, use of a bisphosphonate to prevent further compromise of bone integrity should be strongly considered, regardless of hormonal and metastatic status. Bone scans are the preferred method for the identification of bone metastases. In patients with hormone-refractory prostate cancer and bone metastases, zoledronic acid is the only bisphosphonate indicated for the prevention of skeletal complications. In conclusion, patients with prostate cancer are at high risk for skeletal morbidity. Bisphosphonates have been shown to prevent cancer treatment-induced bone loss in men receiving androgen-deprivation therapy as well as skeletal complications in men with bone metastases. However, further study of the use of bisphosphonates across the clinical spectrum of prostate cancer is needed.

PSA: an update.

We know there is no cut-off of PSA that can rule out prostate cancer, a little more than zero and you may be at risk, the problem is to know if you are at risk of dying from of this disease or not. So PSA is not so specific, and we know also that between 2 and 8 ng/ml there is no big difference, and that PSA is partly related to the transition zone. PSA is related to age and to the size of the transition zone, which is BPH, so you have to exclude this, and keep in mind the reference data that Joe Oesterling published in the JAMA in 1996 which is that PSA is age dependeant. I would say that for patients who are at high risk of dying of the disease, those who have a life expectancy of 10 or 15 years, that are under 60 and have high Gleason, if you consider treatment, then you have to treat them early if you want to cure them. But let's not overtreat patients who have no risk or limited risk of dying from prostate cancer, let's be more conservative. The difficulty is to define criteria. Age, of course, is the major criteria. High Gleason, i.e., a Gleason with pattern 4 or 5, and PSA velocity is very important.

Increased body mass index as a risk factor in localized prostate cancer treated by radical prostatectomy.

BACKGROUND: The association between obesity and aggressive forms of prostate cancer is controversial. We compared preoperative body mass index (BMI) and prostate-specific antigen (PSA) levels as predictive risk factors for increased prostate weight and disease aggressiveness. MATERIALS AND METHODS: This retrospective review of 464 patients with localized prostate cancer who underwent radical prostatectomy between March 1999 and October 2006 examined relationships among clinicopathological variables (BMI, preoperative serum PSA, biopsy and pathologic Gleason score [GS], and whole prostate weight) using linear and multinomial logistic regression analysis. We used multivariate regression modeling adjusting for age, year of surgery, PSA or BMI, pathologic stage, and GS. RESULTS: Median age of patients (51% cT1c, 69% pT2) was 61 years (41-76), mean BMI 26.50kg/m(2) (standard deviation = 4.82), mean PSA 6.8ng/ml (0.67-27.2), median prostate weight 51g (12-200), median biopsy GS 6 (3-9), and median pathologic GS 7 (4-10). GS was upgraded in 227 patients (49%) from median GS 6 to 7 (P<0.00001). Mean prostate weight was 47±13.7g for BMI<25kg/m(2) (n = 170), 47±15g for BMI 25 to 30kg/m(2) (n = 224), and 59±26g for BMI>30kg/m(2) (n = 69) (P<0.00184). Mean prostate weight was significantly higher for BMI>30 than BMI<25 (47±13g vs. 59±25g, P<0.00015). Mean PSA was significantly higher for BMI>30 than for all other patients combined (8.56 [95% CI: 6.94-10.18] vs. 8.34 [7.23-9.45]; P = 0.001). PSA was positively associated with high biopsy GS for BMI≥25 (P = 0.048) and BMI≥30 (P = 0.009) but not for BMI≤25 (P = 0.151). BMI≥30 was associated with higher pT stage (odd ratio = 1.279 [1.5-1.56]; P = 0.015). In multivariate analyses, higher BMI was associated with higher prostate weight (P = 0.036) and pT stage (P = 0.008), and higher PSA with higher biopsy GS (P = 0.002). Neither BMI nor PSA was associated with GS upgrading. CONCLUSIONS: Higher BMI was associated with higher prostate weight and PSA, as well as with higher pT stage and pathologic GS in men undergoing radical prostatectomy, providing further evidence that obese men are more likely to have aggressive cancer. BMI thus constitutes an additional risk factor besides PSA.

Testosterone Therapy in Men With Prostate Cancer.

CONTEXT: The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. OBJECTIVE: To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. EVIDENCE ACQUISITION: We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. EVIDENCE SYNTHESIS: The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. CONCLUSIONS: An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life-and the ability of testosterone therapy to mitigate these effects-has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency. PATIENT SUMMARY: In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.

Intermittent Versus Continuous Androgen Deprivation Therapy in Patients with Relapsing or Locally Advanced Prostate Cancer: A Phase 3b Randomised Study (ICELAND).

BACKGROUND: Intermittent androgen deprivation (IAD) has received increasing attention; however, the current literature is still limited, especially in nonmetastatic prostate cancer (PCa), and the relative efficacy and safety benefits of IAD versus continuous androgen deprivation (CAD) remain unclear. OBJECTIVE: To add to the knowledge base regarding efficacy and potential benefits, including reduced side effects and improved quality of life (QoL), of IAD versus CAD in patients with nonmetastatic relapsing or locally advanced PCa. DESIGN, SETTING, AND PARTICIPANTS: A 42-mo phase 3b open-label randomised study in 933 patients from 20 European countries. INTERVENTION: Following a 6-mo induction with leuprorelin acetate (Eligard) 22.5mg 3-mo depot, patients were randomised to CAD or IAD with leuprorelin for 36 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was time to prostate-specific antigen (PSA) progression while receiving luteinising hormone-releasing hormone agonist, defined as three consecutive increasing PSA values ≥ 4 ng/ml ≥ 2 wk apart. Secondary end points included PSA progression-free survival (PFS), overall survival (OS), testosterone levels, performance status, and QoL. RESULTS AND LIMITATIONS: A total of 933 patients entered the induction phase; 701 were randomised. The median number of injections administered after randomisation was 12 (range: 1-12) for the CAD group and 3 (range: 1-10) for the IAD group. There were no statistically significant or clinically relevant differences between the groups for time to PSA progression, PSA PFS, OS, mean PSA levels over time, or QoL. A similar number of adverse events was observed in each group; the most common were hot flushes and hypertension. Study limitations include the open-label design and absence of formal testosterone recovery assessment. CONCLUSIONS: IAD and CAD demonstrated similar efficacy, tolerability, and QoL in men with nonmetastatic PCa. The principal benefit of IAD compared with CAD is a potential cost reduction with comparable OS rates. There are no apparent QoL benefits. PATIENT SUMMARY: This randomised trial showed that both intermittent and continuous hormone therapy had similar efficacy, tolerability, and quality-of-life profiles in patients with relapsing M0 or locally advanced prostate cancer. Intermittent therapy may be a valid option for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00378690.

Fundamental Concepts Regarding Testosterone Deficiency and Treatment: International Expert Consensus Resolutions.

To address widespread concerns regarding the medical condition of testosterone (T) deficiency (TD) (male hypogonadism) and its treatment with T therapy, an international expert consensus conference was convened in Prague, Czech Republic, on October 1, 2015. Experts included a broad range of medical specialties including urology, endocrinology, diabetology, internal medicine, and basic science research. A representative from the European Medicines Agency participated in a nonvoting capacity. Nine resolutions were debated, with unanimous approval: (1) TD is a well-established, clinically significant medical condition that negatively affects male sexuality, reproduction, general health, and quality of life; (2) symptoms and signs of TD occur as a result of low levels of T and may benefit from treatment regardless of whether there is an identified underlying etiology; (3) TD is a global public health concern; (4) T therapy for men with TD is effective, rational, and evidence based; (5) there is no T concentration threshold that reliably distinguishes those who will respond to treatment from those who will not; (6) there is no scientific basis for any age-specific recommendations against the use of T therapy in men; (7) the evidence does not support increased risks of cardiovascular events with T therapy; (8) the evidence does not support increased risk of prostate cancer with T therapy; and (9) the evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes. These resolutions may be considered points of agreement by a broad range of experts based on the best available scientific evidence.