ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males

The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.     

迟发性睾丸功能减退筛查量表的研究与应用现状

随着迟发性睾丸功能减退(LOH)研究的深入,LOH筛查量表研究逐渐完善。常用筛查量表有AMS量表、ADAM问卷、MMAS问卷,量表的主要作用是筛查或者诊断LOH以及治疗效果的评估,目前研究主要集中在量表的应用、敏感性和特异性的验证、量表评价结果或者某些项目与血清激素水平之间的相关性、不同量表之间的比较等方面。本文综述筛查量表的研究、应用现状,并对其敏感性、特异性进行了总结。     

Gonadotropin Suppression in Normal Males and Males with 1° Hypogonadism: Evaluation of Four Androgens

Serum concentrations of FSH and LH have been evaluated during treatment with four commonly prescribed androgens. In the first study, five adult males with primary gonadal failure were treated for four weeks with each of four regimens: 17α-methyl testosterone [MT] (40 mg/day or 50 mg/day), fluoxymesterone [F] (50 mg/day), and testosterone cypionate [TC] (200 mg). LH was not suppressed by either dose of MT but was suppressed by F ( P < 0.02). Both FSH and LH were suppressed for up to 3 weeks ( P < 0.05) after a single injection of TC. In the second study, testosterone enanthate [TE] was evaluated as a contraceptive in 20 normal men. After two weeks (200 mg/week), the concentration of testosterone increased from 661 ± 29 ng/dl to approximately 1050 ng dl ( P < 0.001) and serum gonadotropins had fallen to very low or undetectable levels. After 12 weeks of this regimen, 11 men had ≤ 1 million sperm/ml of semen, but 3 had ≥ 10 million sperm/ml. When 200 mg of TE was given every 3 weeks, serum levels of FSH and LH normalized and sperm density increased.
These studies indicate that exogenous androgens can be used to suppress gonadotropins and spermatogenesis; however, each of these four available androgens has limitations. A more potent, longer acting androgen with low toxicity is needed if this approach to the development of a male contraceptive is to be pursued.     

Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines

Context

New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC.

Objective

To review the new EAU guidelines for MiM-BC with a specific focus on treatment.

Evidence acquisition

New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence.

Evidence synthesis

Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available.

Conclusions

In the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.     

EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced,Relapsing, and Castration-Resistant Prostate Cancer

ObjectiveTo present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).Evidence acquisitionThe working panel performed a literature review of the new data (2011–2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews.Evidence synthesisLuteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they may be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel at 75 mg/m² every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.ConclusionsThe knowledge in the field of advanced, metastatic, and castration-resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or at www.uroweb.org.Patient summaryWe present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they might be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy. Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Multiparametric magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of castration-resistant CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel 75 mg/m² every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.The guidelines reported should be adhered to in daily routine to improve the quality of care in PCa patients. As we have shown recently, guideline compliance is only in the area of 30–40%.     

EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer

Objectives

Our aim is to present a summary of the 2010 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).

Methods

The working panel performed a literature review of the new data emerging from 2007 to 2010. The guidelines were updated, and the levels of evidence (LEs) and/or grades of recommendation (GR) were added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.

Results

Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). Although LHRH antagonists decrease testosterone without any testosterone surge, their clinical benefit remains to be determined. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation (IAD) results in equivalent oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and ¹¹C-choline positron emission tomography/computed tomography (CT) are of limited importance if the PSA is <2.5 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include screening for the metabolic syndrome and an analysis of PSA and testosterone levels. Treatment of castration-resistant prostate cancer (CRPC) includes second-line hormonal therapy, novel agents, and chemotherapy with docetaxel at 75 mg/m² every 3 wk. Cabazitaxel as a second-line therapy for relapse after docetaxel might become a future option. Zoledronic acid and denusomab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.

Conclusion

The knowledge in the field of advanced, metastatic, and CRPC is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or online at www.uroweb.org.     

8～17周岁男性FSH、LH、PRL、E2、T的调查分析

目的:通过对8~17周岁男性青少年FSH、LH、PRL、E2、T的测定,了解不同年龄的FSH、LH、PRL、E2、T的变化。方法:对627例体检合格的8~17周岁男性血清使用Access全自动微粒子化学发光免疫分析仪进行FSH、LH、PRL、E2、T的检测,并使用免疫分析质控液进行质量控制。结果:FSH在8~10周岁处于较低水平,11周岁时开始增高;LH和T在12周岁前处于较低水平,13周岁开始增高;E2在13周岁前较低,14周岁后开始增高(P均<0.01)。结论:男性青少年FSH、LH分别在11、12周岁时明显增高,T在13周岁时明显增高,标志性发育的开始。     

To Treat or Not to Treat with Testosterone Replacement Therapy: a Contemporary Review of Management of Late-Onset Hypogonadism and Critical Issues Related to Prostate Cancer

Over the last 10 years there has been a dramatic increase in the number of patients identified and treated with testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH). By virtue of age, race, and family history, many of these patients are concurrently at risk for harboring indolent prostate cancer. Other men are at increased risk for prostate cancer as a result of an elevated serum PSA level or having had a prior prostate biopsy showing prostatic intraepithelial neoplasia (PIN) or atypical small acinar proliferation (ASAP). The clinician is often challenged with the decision whether to initiate TRT in these patients. This review presents a contemporary overview of the rationale for TRT, as well as the relationship between testosterone (endogenous and exogenous) and premalignant and malignant lesions of the prostate. We will discuss preliminary data from several recent series demonstrating that TRT may be safely administered in select patients with certain premalignant and bona fide malignant tumors of the prostate. In the absence of a large randomized clinical trial with long-term outcome data evaluating TRT, we hope that this overview will provide clinicians with an evidence-based approach to managing these anxiety-provoking – and often frustrating – clinical scenarios.     

江苏省3551例中老年男性健康调查

目的:了解我省中老年男性健康的基本情况。方法:对苏南、苏北、苏中随机收集3551例46~69岁的男性进行常规体检;按照勃起功能国际指数(IIEF-5)、老年男性雄激素部分缺乏(PADAM)自我评估表等进行询问。实验室检测肝肾功能和血糖、血脂指标;用放射免疫法测定血清睾酮和游离睾酮;B超检查前列腺体积及残余尿情况。结果:各年龄组B超检查的前列腺体积有明显差异(P<0.05)。各年龄组之间睾酮的差异无显著性(P>0.05),而游离睾酮随着年龄的增加而降低,有明显差异,在有更年期症状者中随着年龄的增加下降更为明显(P<0.05)。勃起功能障碍(ED)和PADAM的发病率与年龄的增加显著相关(P<0.001)。结论:男性在中老年期随着年龄的增加,体能、性功能水平下降,前列腺体积增大,ED、PADAM发病率明显增加。     

EAU Guidelines on Prostate Cancer. Part 1: Screening,Diagnosis, and Local Treatment with Curative Intent—Update 2013

Context

The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011.

Objective

To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa.

Evidence acquisition

A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.

Evidence synthesis

A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur.

Conclusions

Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Patient summary

A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level.     

White Knight: ASRA, ASA, and the formation of the ABA

The original American Society of Regional Anesthesia (1924-1940) was instrumental in the formation of the American Board of Anesthesiology, whereupon competence in anesthesiology was placed on the same footing as every other specialty practice in the United States.     

Patients With Chronic Obstructive Pulmonary Disease Exacerbations: Recommendations for Diagnosis,Treatment and Care

ObjectiveTo describe an evidence- and experience-based expert consensus on the most relevant issues of patients with COPD exacerbations.MethodsThe Delphi technique was used. Evidence was reviewed by a scientific committee and 60 experts. A questionnaire was prepared containing 3 sections: diagnosis of the exacerbator; treatment, and healthcare processes. The survey was answered in 2 rounds by 60 pneumologists on an online platform. Statements were scored on a Likert scale from 1 (total disagreement) to 9 (total agreement). Agreement and disagreement were defined as a score of 7–9 or 1–3, respectively, given by more than two thirds of the participants.ResultsA total of 48 statements were included, one of which was added in the second round. Consensus was reached in 37 items (78.7%) after the first round (agreement), and in 43 (89.5%) after the second round (42 agreement, 1 disagreement). The statements with the highest proportion of experts agreeing were as follows: in exacerbators, chronic bronchial infection favors lung function decline (93.1%); long-acting bronchodilators should not be withdrawn (93.1%); treatment must be personalized if new exacerbations occur despite optimal bronchodilator treatment (96.6%); management must be coordinated between primary care and the respiratory medicine department (93.1%), and patients must be followed up in specific integrated multicomponent programs (94.8%).ConclusionsThe findings of this study could assist in the diagnosis and treatment of COPD exacerbators in our area.