Current Clinical Practice Guidelines for the Treatment of Renal Cell Carcinoma: A Systematic Review and Critical Evaluation.

The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of nephron-sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non-clear-cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti-VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines. IMPLICATIONS FOR PRACTICE: Currently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.

Technical solutions to improve the management of non-muscle-invasive transitional cell carcinoma: summary of a European Association of Urology Section for Uro-Technology (ESUT) and Section for Uro-Oncology (ESOU) expert meeting and current and future perspectives.

The aim of the present review was to compare state-of-the-art care and future perspectives for the detection and treatment of non-muscle-invasive transitional cell carcinoma (TCC) of the bladder. We provide a summary of the third expert meeting on 'Optimising the management of non-muscle-invasive bladder cancer, organized by the European Association of Urology Section for Uro-Technology (ESUT) in collaboration with the Section for Uro-Oncology (ESOU), including a systematic literature review. The article includes a detailed discussion on the current and future perspectives for TCC, including photodynamic diagnosis, optical coherence tomography, narrow band imaging, the Storz Professional Image Enhancement system, magnification and high definition techniques. We also provide a detailed discussion of future surgical treatment options, including en bloc resection and tumour enucleation. Intensive research has been conducted to improve tumour detection and there are promising future perspectives, that require proven clinical efficacy. En bloc resection of bladder tumours may be advantageous, but is currently considered to be experimental.

Vitamin D and benign prostatic hyperplasia -- a review.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a more common form of lower urinary tract symptoms (LUTS). BPH is due to the excessive growth of both stromal and epithelial cells of the prostate. Fifty percent of men over the age of 50 will have this disease, along with the probability that 90% of men at the age of 80 will have an enlarged prostate. The prevalence of vitamin D deficiency in the male urological population may represent a connection between BPH and vitamin D. MATERIAL AND METHODS: This review is geared to provide the most relevant data on the correlation between vitamin D and BPH. A comprehensive review was conducted on all studies on the specific topic and compiled into a complete article. RESULTS: Data suggests that vitamin D has an inhibitory effect on the RhoA/ROCK pathway, along with cyclooxygenase-2 expression and prostaglandin E2 production in BPH stromal cells. Increasing intake of vitamin D from diet and supplements has shown a correlation with decreased BPH prevalence. Vitamin D analogues of up to 6000 IU/day have shown to decrease prostate volume in BPH patients. Pre-clinical trials have shown vitamin D to not only decrease BPH cell and prostate cell proliferation alone, but also when induced by known growth promoting molecules such as IL-8, Des (1-3) IGF-1, testosterone and dihydrotestosterone. Among all the studies there has not been any side effects or negative implications with increased vitamin D intake. CONCLUSION: The impact of vitamin D on prostate volume and BPH has shown promising results, thus proposing further studies on vitamin D and BPH be conducted.

Laser prostatectomy: holmium laser enucleation and photoselective laser vaporization of the prostate.

Historically, transurethral resection of the prostate has been the gold standard for the treatment of benign prostatic hyperplasia (BPH). Laser technology has been used to treat BPH for > 15 years. Over the past decade, it has gained wide acceptance by experienced urologists. This review provides an evidence-based update on laser surgery for BPH with a focus on photoselective laser vaporization and holmium laser enucleation of the prostate surgeries and assesses the safety, efficacy, and durability of these techniques.

Primary testicular leiomyosarcoma.

Primary testicular leiomyosarcoma is an extremely rare tumor, and, to the best of our knowledge, only 20 cases in adults have been reported in the literature to date. Herein, we present a case of a 68-year-old man who complained of left scrotal swelling for 2 months. Radiological examination revealed a left testicular tumor with no metastases to other organs. A left inguinal orchiectomy was carried out and histopathologic examination revealed an intratesticular leiomyosarcoma. The patient was treated successfully by orchiectomy and received no adjuvant therapy. During follow up until 12 months after surgery, there has been no recurrence or metastases of the disease.

Hormonal manipulation of benign prostatic hyperplasia.

PURPOSE OF REVIEW: We provide new viewpoints of hormonal control of benign prostatic hyperplasia (BPH). The latest treatment findings with 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride, refined indications, efficacy, and safety are discussed and compared. We also discuss potential new 5-ARIs and other hormonal treatments. RECENT FINDINGS: Finasteride and dutasteride have equal efficacy and safety for the treatment and prevention of progression of BPH. 5-ARIs are especially recommended for prostates greater than 40 ml and PSA greater than 1.5 ng/ml. Combination therapy is the treatment of choice in these patients, but with prostate volume greater than 58 ml or International Prostate Symptom Score of at least 20, combinations have no advantage over 5-ARI monotherapy. Updates on the recent developments on BPH therapy with luteinizing hormone-releasing hormone (LHRH) antagonist are also reviewed and analyzed. Preclinical studies suggest that growth hormone-releasing hormone (GHRH) antagonists effectively shrink experimentally enlarged prostates alone or in combination with LHRH antagonists. SUMMARY: New 5-ARIs seem to be the promising agents that need further study. Preclinical studies revealed that GHRH and LHRH antagonists both can cause a reduction in prostate volume. Recent data indicate that prostate shrinkage is induced by the direct inhibitory action of GHRH and of LHRH antagonists exerted through prostatic receptors. The adverse effects of 5ARIs encourage alternative therapy.

Correlation between benign prostatic hyperplasia and inflammation.

PURPOSE OF REVIEW: This review aims to evaluate the available evidence on the role of prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). RECENT FINDINGS: Although there is still no evidence of a causal relation, accumulating evidence suggests that inflammation may contribute to the development of BPH and lower urinary tract symptoms (LUTS). Inflammatory infiltrates are frequently observed in prostate tissue specimens from men with BPH and the presence or degree of inflammation has been found to be correlated with prostate volume and weight. The inflammatory injury may contribute to cytokine production by inflammatory cells driving local growth factor production and angiogenesis in the prostatic tissue. This proinflammatory microenvironment is closely related to BPH stromal hyperproliferation and tissue remodeling with a local hypoxia induced by increased oxygen demands by proliferating cells which supports chronic inflammation as a source of oxidative stress leading to tissue injury in infiltrating area. SUMMARY: Although the pathogenesis of BPH is not yet fully understood and several mechanisms seem to be involved in the development and progression, recent studies strongly suggest that BPH is an immune inflammatory disease. The T-cell activity and associated autoimmune reaction seem to induce epithelial and stromal cell proliferation. Further understanding of the role of inflammation in BPH and clinical detection of this inflammation will expand the understanding of BPH pathogenesis and its histologic and clinical progression, allow risk stratification for patients presenting with BPH-related LUTS, and suggest novel treatment strategies.

Imaging in benign prostatic hyperplasia: what is new?

PURPOSE OF REVIEW: This article discusses the new imaging techniques in diagnosis and treatment of benign prostatic hyperplasia by reviewing the most recent publications. RECENT FINDINGS: Imaging study for the evaluation of patients with lower urinary tract symptoms is not suggested by American Urology Association guidelines; however, European Association of Urology recommends the assessment of the upper urinary tract by modalities like ultrasound. Several new imaging indices like resistive index of capsular artery, presumed circle area ratio, prostatic urethral angle, intraprostatic protrusion, and detrusor wall thickness are used to find a noninvasive way for bladder outlet obstruction diagnosis. In addition to them, 3D transrectal ultrasound, near infrared spectroscopy, and MRI are used to add more practical findings in patient management. SUMMARY: Urologists have requested more imaging studies than expected for benign prostatic hyperplasia patients in recent years, and several studies have been done to find a noninvasive way to diagnose bladder outlet obstruction. However, none of them could play the urodynamic studies role in bladder outlet obstruction diagnosis.

Evaluation of erectile function after laparoscopic radical prostatectomy in a single center.

INTRODUCTION: To evaluate erectile function among men who had undergone laparoscopic radical prostatectomy and received postoperative medical therapy for erectile dysfunction. MATERIALS AND METHODS: We performed a prospective study in men who underwent laparoscopic radical prostatectomy between September 2003 and November 2005 at our center and who received penile rehabilitation after surgery. All patients had antegrade interfascial dissection. They received 10 mg tadalafil on the fifth postoperative day and continued to receive it every other day, regardless of erectile function. Intracavernous injection of alprostadil was initiated at 3 or 6 months depending on response to treatment with tadalafil. Follow up evaluations were done at 3, 6, 12, 18 and 24 months. Oncologic and functional outcomes and compliance were assessed. Patients filled in International Index of Erectile Function-5 (IIEF-5) questionnaires. RESULTS: Of 1078 men who underwent laparoscopic radical prostatectomy during this time, 586 patients met inclusion criteria, complied with the study medication, and had complete data for 24 months. The patients had a median preoperative baseline IIEF-5 score of 22. A total of 150 patients (26%) underwent unilateral nerve-sparing surgery, while 436 patients (74%) had bilateral nerve-sparing surgery. At 24 months, 35% of patients who underwent unilateral nerve-sparing surgery and 68% of patients who underwent bilateral nerve-sparing surgery reported having sufficient erectile function for intercourse without using intracavernous injection of alprostadil. At 24 months after surgery, the median IIEF-5 score was 13 (1-25) for the whole cohort, 5 (1-25) for patients who had undergone unilateral nerve-sparing surgery, and 15 (1-25) for patients who had undergone bilateral nerve-sparing surgery. CONCLUSIONS: The findings suggest that adequate patient selection and postoperative medical intervention allows the preservation or recovery of erectile function after laparoscopic radical prostatectomy. Inaccurate selection of patients and postoperative assessment might explain inferior erectile function results following this surgery.

Role of testosterone in managing advanced prostate cancer.

Androgen deprivation therapy is frequently used to treat patients with advanced prostate cancer. New therapies for metastatic castration-resistant prostate cancer have drawn increased attention to serum and intratumoral testosterone levels. The present review examines the role of testosterone in prostate cancer progression, discusses the nuances and potential pitfalls in measuring serum testosterone using available assays, and summarizes current data relevant to the arguments for and against achieving and maintaining the lowest possible testosterone levels during androgen deprivation therapy, including the adverse effects of such treatment. Incorporating this information, we have made recommendations incorporating testosterone evaluation and its effect on the clinical decision-making process.

Revival of thermotherapy for benign prostatic hyperplasia.

PURPOSE OF REVIEW: Transurethral resection of the prostate (TURP) has long been held as the gold standard for treatment of benign prostatic hyperplasia (BPH); however, there has been significant innovation in other less invasive alternative treatments for BPH in recent years. BPH treatment guidelines now recommend minimally invasive therapy be considered as a treatment option alongside TURP and medical management. Our purpose is to review the current evidence supporting the safety, effectiveness, and durability of transurethral microwave thermotherapy (TUMT) as a minimal invasive technique. RECENT FINDINGS: Recent clinical studies of TUMT have provided significant evidence regarding safety, efficacy, and durability. TUMT has now become a minimally invasive office-based alternative to both standard TURP and medical therapy in the treatment of bladder outlet obstruction and lower urinatry tract symptoms due to BPH. SUMMARY: TUMT treatment has improved with the advent of later generation devices. This well tolerated, effective, and durable therapy for the treatment of BPH has definitively found its place as one of the alternatives to TURP. Anestheisa-free outpatient capability, lack of sexual side-effects, and avoidance of actual surgery are attractive to patient and clinician alike. TUMT deserves reconsideration in clinical practices as a suitable treatment alternative to TURP and medical therapy.

α-Blockers for benign prostatic hyperplasia: the new era.

PURPOSE OF REVIEW: α1-Adrenoceptor blockers are the most frequently prescribed medical therapy in the treatment of lower urinary tract symptom suggestive of benign prostatic hyperplasia (LUTS/BPH). The purpose of this review is to highlight the evolution of adrenoceptor blockers with emphasis on newly approved drugs. RECENT FINDINGS: Over the past years new formulations of several α1-adrenoceptor blockers were introduced to the market. Five long-acting α1-blockers are currently approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, alfuzosin and silodosin. Silodosin is the only adrenoceptor blocker that exhibits true selectivity for the α1-adrenoceptor subtypes. This unique adrenoceptor selectivity profile likely accounts for the very favorable cardiovascular safety profile. SUMMARY: Tamsulosin, alfuzosin slow release and silodosin do not require dose titration. Alfuzosin, terazosin, doxazosin and silodosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size. Low incidence of orthostatic hypotension has been reported for silodosin, but abnormal ejaculation is the most commonly reported adverse effect.

American Urological Association and European Association of Urology guidelines in the management of benign prostatic hypertrophy: revisited.

PURPOSE OF REVIEW: The purpose of this review is to provide a complete revision of two of the most widely used clinical guidelines in the management of lower urinary tract symptoms induced by benign prostatic hyperplasia and their importance and compliance among urologists. RECENT FINDINGS: Updates of the American Association of Urology and European Association of Urology clinical practice guidelines (CPGs) were reviewed and analyzed. Literature concerning compliance and application of these two CPGs in the different working scenarios of practicing has been evaluated. SUMMARY: Urology has moved to an era in which costs and quality of care are being scrutinized, and compliance to CPGs will be assessed. Practicing urologists do not have the time to keep up to date with the continuous incoming literature and CPGs are a great tool to give the highest quality of care to our patients.

Testosterone in prostate cancer: the Bethesda consensus.

OBJECTIVE: • Androgen stimulation of prostate cancer (PCa) cells has been extensively studied. The increasing trend of using serum testosterone as an absolute surrogate for castration state means that the diagnostic measurement of testosterone and the values potentially influencing prognosis must be better understood. This is especially important when PCa progresses from an endocrine to an intracrine status. PATIENTS AND METHODS: • We performed a literature review using the MEDLINE database for publications on: (i) hormonal changes with androgen deprivation therapy (ADT); (ii) monitoring hormonal therapy with testosterone measurement; (iii) the efficacy of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation; (iv) the underlying mechanisms of castration-resistance; and (v) novel treatments for castration-resistant PCa (CRPCa). RESULTS: • The optimum serum castration levels to be achieved with ADT are still debated. Recently, the 50 ng/dL threshold has been questioned because of reports indicating worse outcomes when levels between 20 and 50 ng/dL were studied. Instead, a 20 ng/dL threshold for serum testosterone after ADT in patients with advanced prostate cancer was recommended. CONCLUSION: • Understanding the mechanisms of androgen biosynthesis relating to PCa as well as prognostic implications might achieve a consensus regarding the role of ADT for both the androgen-sensitive and -insensitive disease state.

Blood loss during radical prostatectomy: impact on clinical, oncological and functional outcomes and complication rates.

UNLABELLED: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? It is generally accepted in the medical community that total and intra-operative blood loss after RALP is significantly lower in comparison with ORRP. This has led to speculation that less bleeding results in better visualization of the operative field resulting in superior potency and continence. Blood loss (BL) during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with RALP would not be expected to improve functional or oncological outcomes. OBJECTIVE: To determine the short- and long-term impact of blood loss (BL) on clinical, oncological and functional outcomes as well as complication rates after an open radical retropubic prostatectomy (ORRP). PATIENTS AND METHODS: Between 2000 and 2008, 1567 men who underwent an ORRP participated in our prospective longitudinal outcomes study. Haematocrit (Hct) levels, transfusion rates, BL and complications were recorded prospectively. Validated, self-administered quality-of-life (QoL) questionnaires were completed at baseline, 3, 6 and 12 months and yearly thereafter. Urinary function and erectile dysfunction were assessed using AUA Symptom Score and the UCLA Prostate Cancer Index and analysis of variance (anova)/chi-square tests were used to compare clinical, BL, biochemical recurrence (BCR) and QoL outcomes amongst the three groups for continuous/categorical variables. RESULTS: The mean estimated BL was 742.7 (45 to 3500) mL and 5.4% and 3.8% received an autologous (AU) or allogeneic (AL) blood transfusions, respectively. The average baseline, induction, postoperative and discharge Hct was 43.8%, 48.3%, 35.7% and 34.1%, respectively. The estimated BL and the rate of change of Hct correlated moderately (r=0.41, P<0.0001). Tertiles of BL were based on the difference between induction and discharge Hct (Delta 1) and the average Delta 1 for Groups 1, 2 and 3 were 7.9%, 12.7% and 17.2%, respectively. Intra-operative, early/delayed complications, length of hospital stay (LoS), SM surgical margins status, anastomotic stricture and BCR were not statistically different (P<0.001) and the mean AUASS, UCLA Prostate Cancer urinary bother scores, urinary function scores, sexual bother/function scores at 24 months were similar amongst all tertiles (P>0.05). CONCLUSIONS: BL during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with robotic-assisted laparoscopic prostatectomy (RALP) in and of itself would not be expected to improve functional or oncological outcomes.

Immunotherapy in the treatment of advanced prostate cancer.

Prostate cancer is a complex disease, and treatment selection is informed by numerous variables depending on the stage of disease. Moreover, patient expectations and the impact of treatment-related adverse events may influence treatment choices. Available treatment options over the course of the disease have included surgery, radiation therapy, hormonal therapy, immunotherapy, and chemotherapy. This complexity requires an understanding of a wide range of treatment options and the support of a multidisciplinary team that involves urologists, radiation oncologists, diagnostic radiologists, pathologists, and medical oncologists. Collaboration among these physicians allows for a comprehensive treatment strategy that addresses the individual needs of the patient throughout the course of his disease. Prior to 2004, treatment options for metastatic castrate-resistant prostate cancer (CRPC) were limited to therapies for palliation of pain and reduction of skeletal-related events. Over the past 7 years, four therapeutic options-three within the last 2 years-that provide a survival benefit in this setting have been approved. These therapies have diverse mechanisms, perhaps reflecting the complex nature of advanced prostate cancer. Among them is sipuleucel-T, the first autologous immunotherapy approved for any cancer. This review will discuss the rapidly changing treatment environment for metastatic CRPC and the increased exploration of immunotherapeutic approaches to advanced prostate cancer.