Annals of Urology Vol I Issue 1

An Overview of the Potential Applications of Choline PET/CT in Prostate Cancer

The aim of this review is to offer an overview about the potential applications of choline PET/CT in prostate cancer patients. The potential use of molecular imaging in the field of prostate cancer comes from the lack of accuracy of conventional imaging methods such as a CT, MR, or bone scan. It is a known fact that conventional imaging methods gives poor results either in cancer detection, stage, or restage of the disease in the case of biochemical recurrence. Choline PET/CT has been used in all steps of the natural history of the disease; however, it can be summarized that the most important application of choline PET/CT is represented by the restaging of the disease in the case of biochemical relapse. A main advantage of PET/CT is the detection of lymph node metastasis and small initial bone metastases. In particular, choline PET/CT could play a crucial role as a first diagnostic procedure in prostate cancer patients who show fast PSA kinetics.

Urodynamics: State of Art Review of Literature and Recent Controversies

INTRODUCTION

There is ongoing debate about the diagnostic utility of urodynamic studies (UDS) in the management of women with urinary incontinence given the conflicting statements by various governing bodies. Most patients with urinary incontinence will respond well to conservative measures and/or minimally invasive anti-incontinence surgery without the need for routine urodynamic testing. Furthermore several controversies continue to exist on the utility of UDS in the preoperative investigation value, degree of detrusor- or bladder neck-related voiding dysfunction, application of leak point pressures and urethral pressure profile, and the need for UDS in healthy, treatment-naive woman with no history of prior incontinence or prolapsed surgery.

OBJECTIVES

To highlight the arguments surrounding the current controversies and explore the value of UDS based on published literature.

MATERIALS AND METHODS

The Pubmed and Medline database were searched for recent articles published over the last 5 years. Only peer-reviewed articles published in English were evaluated and specific emphasis on major international guidelines, statements from major urinary and continence organizations, and published studies from randomized controlled multicenter trials were placed. The search terms were urodynamics, recent controversies, preoperative and surgical outcome, valsalva leak point pressure, and cost-effectiveness.

RESULTS

Many issues pertaining to UDS remain unresolved but UDS should be considered in women with prior stress-incontinent and/or pelvic surgery or radiation, concomitant large pelvic organ prolapse, or who have history of neurological conditions.

CONCLUSION

Further research is needed to determine the role of UDS in preoperative patient counseling and surgical success.

Urethral Cancer: An Overview

Urethral cancer is an extremely rare lesion, with fewer than 2000 reported cases. Although once believed that urethral cancer was four times more common in women than men, recent literature suggests that primary urethral cancer is nearly three times more common in males. Fifty-five percent of primary urethral are transitional cell carcinomas, 21.5% and 16.4% being squamous cell carcinomas and adenocarcinomas, respectively. The signs and symptoms of urethral cancer vary and are neither diagnostic nor pathognomonic. The main prognostic factors for these tumors are age, stage, grade, systemic metastases, histological type, site, size, and the presence of pelvic lymph node extension. As with most tumors, early detection affords the best chance of cure. Cystourethroscopy and biopsy of the lesion helps to determine the diagnosis and histological subtype. The magnetic resonance imaging (MRI) of the pelvis is the test of choice for clinical staging and provides reliable data on tumor extent and local invasion. Urethral carcinoma can spread by direct extension to adjacent structures, usually involving the vascular spaces of the corpus spongiosum and the periurethral tissues, vagina, bladder neck, rectum, or it can metastasize through lymphatic embolization to regional lymph nodes. Hematogenous dissemination is uncommon except in advanced disease. Little progress has been made regarding the definitive treatment options due to its low incidence and subtle clinical findings. The primary form of treatment for urethral carcinoma is surgical excision. Multimodality therapy appears to be the mainstay treatment to achieve the longest survival without evidence of disease. Patients who survived the longest without disease received combination therapy that consisted of either chemotherapy with radiotherapy or neoadjuvant chemotherapy with radiotherapy prior to surgery.

Surgical Management of Metastases to the Adrenal Gland

The adrenal gland can be the site of metastatic disease in the setting of a number of primary malignancies. Differentiating a metastatic lesion from a primary adrenal lesion is important and may require the use of radiologic imaging, an endocrinologic evaluation, and adrenal biopsy. Adrenal biopsy may be especially useful in those patients with a known primary malignancy in order to determine whether the patient is a candidate for metastatectomy or systemic therapy. Patients with isolated adrenal metastases may have superior outcomes from adrenalectomy as compared to chemotherapy. In the past, open adrenalectomy was the standard of care for patients with an isolated adrenal metastasis, but recently laparoscopic adrenalectomy has been utilized with favorable outcomes. Appropriate patient selection for the surgical approach is critical to determine the best treatment for the individual patient.

Urodynamic Evaluation of Experimental Rat Models of Urinary Bladder Overactivity: A Systematic Review of the Literature

BACKGROUND

Many in vivo experimental models of overactive bladder (OAB) have been frequently used as tools to explore the pathophysiology and therapeutical options for the treatment of OAB. However, there is no standard recommendation according to the OAB model.

PURPOSE

Our aim was to perform a systematic revision of the literature to identify articles devoted to the experimental models of OAB. The following review is focused on the backgrounds, methodology, and outcomes of the described models.

EVIDENCE ACQUISITION

This review is based on a systemic literature research. The MedLine, Embase, and Web of Science databases were browsed in order to identify original and review articles, as well as editorials relating to “overactive bladder,” “urodynamic evaluation,” “cystometry,” “experimental model,” “methodology,” and “rat” in urinary bladder dysfunction. The controlled vocabulary of the Medical Subject Headings (MeSH) database was used to ensure sensitivity of the searches.

EVIDENCE SYNTHESIS AND CONCLUSIONS

Different OAB models in conscious and anesthetized rats were described. However, a wide range of differences in experimental protocols concerning urodynamic evaluation of bladder motor activity was observed. Also, in the majority of papers the way of calibration of intravesical pressure measurement systems is not mentioned. All these factors could exert influence on bladder motor activity recordings and, consequently, could lead to differences in cystometrogram traces and cystometric parameters values even though the same experimental protocol was used. Therefore, the standardization of cystometric protocol seems to be pivotal for correct bladder motor activity assessment. Based on our experience and the previously described studies we suggest some steps that should always be taken to minimize the artifacts occurrence during cystometry.

Population-Based Screening for Prostate Cancer: Improved Outcomes in African American Men

INTRODUCTION

African American men have a higher incidence of prostate cancer (PCa) and are more likely to die from the disease than men of other race. The PCa incidence is lower in Hispanics but the stage of the disease is more advanced at the time of diagnosis.

OBJECTIVE

To examine how ethnic diversity affects PCa screening accounting for body mass index (BMI).

METHODS

From the population-based San Antonio Center for Biomarkers of Risk for prostate cancer (SABOR) cohort, 2358 participants comprising African Americans, Hispanics, and non-Hispanic White males 55 years or older were included for analysis. Area under the receiver operating characteristic curves (AUCs) of prostate-specific antigen (PSA), BMI-adjusted PSA, Prostate Cancer Prevention Trial (PCPT) PCa risk and high-grade PCa (Gleason ≥7) risk, and BMI-adjusted PCPT risks were compared among different ethnic groups.

RESULTS

The AUCs (95% confidence intervals) for PSA were .79 (.72, .86), .80 (.76, .84), and .90 (.85, .95) for Hispanics, non-Hispanic Whites and African Americans, respectively; for BMI-adjusted PSA, .79 (.73, .86), .79 (.76, .83), and .90 (.86, .95), respectively; for PCPT risks, .84 (.78, .9), .85 (.82, .88), and .92 (.88, .96), respectively; and for BMI-adjusted PCPT risks, .84 (.78, .90), .84 (.81, .88), and .93 (.89, .97), respectively.

CONCLUSIONS

In this cohort, the original and BMI-adjusted PCPT risk calculators performed significantly better for PCa detection than PSA alone for Hispanics and non-Hispanic Whites. All screening modalities, including PSA, performed markedly better for African Americans than for other race/ethnic groups.

Antenatal Hydronephrosis: A Review of Postnatal Evaluation

The diagnosis, workup, and management of prenatal hydronephrosis has undergone a change from preemptive surgical treatment to a more conservative approach as the natural history of the differential diagnoses becomes more appreciated. A review of the more common differential diagnoses of prenatal hydronephrosis, evaluation, and current treatment options for ureteropelvic junction (UPJ) obstruction, vesicoureteral reflux, ureteroceles, ectopic ureters, megaureters, multicystic dysplastic kidney (MCDK), and posterior urethral valves is undertaken.

Laparoscopic, Robotic, and Laparoendoscopic Single-Site (LESS) Surgery: Applications in Female Urology and Urogynecology

REVIEW ARTICLE

Michael S Ingber¹ and Courtenay K Moore²

Affiliations: ¹Department of Urology and Urogynecology, Saint Clare’s Hospital, Denville, NJ, USA and ²Glickman Urological and Kidney Institute, Cleveland Clinic,
Cleveland, OH, USA

ABSTRACT

Traditional pelvic reconstructive and incontinence surgery required large abdominal incisions and carried significant morbidity for the patient. The introduction of laparoscopy and robotic-assisted laparoscopic surgery provided patients the option to have the same long-term outcomes with much smaller incisions and a significantly shorter recovery. Surgical technology has further evolved, and we are now offering patients laparoendoscopic single-site (LESS) surgery, which can be performed through a single incision, often through a natural orifice such as the umbilicus. This manuscript reviews the available literature on these minimally invasive techniques and how they have been applied in the field of female urology and urogynecology.

Keywords: laparoscopy, robotics, pelvic organ prolapse, incontinence, stress, surgical procedures, minimally invasive

Correspondence: Michael Ingber, Morris Urology Associates, 16 Pocono Rd, Suite 205, Denville, NJ 07834, USA. Tel: +1 (973) 627-0060; Fax: +1 (973) 627-6821; email: ingbermd@aol.com

Castration Resistant Prostate Cancer: Current Treatments and Future Prospects

REVIEW ARTICLE

Emre Can Akinsal and Mustafa Sofikerim

Affiliation: Department of Urology, Erciyes University Faculty of Medicine, Kayseri, Turkey

ABSTRACT

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. Unfortunately, most of these patients will fail and inevitably progress to hormone-independent disease. Prostate cancer that progresses in the presence of androgen blockade is defined as castration resistant prostate cancer (CRPC). No effective "standard" chemotherapy exists for these patients, in which median survival is 6-9 months.

Treatment options for CRPC are secondary hormonal manipulations, immunotherapy, chemotherapy, inhibition of invasion and metastases, inhibition and/or blockade of growth factor receptors or growth factor receptor pathways, inhibition of neoangiogenesis, and supportive care.

Docetaxel and prednisone are the first-line therapies for CRPC and they prolong overall survival. Although many clinical studies have been done, currently there is still no effective second-line treatment modality for CRPC. Better understanding of the mechanisms of drug resistance, discovery of new agents, and targeting of new pathways in the emergence of CRPC would ultimately lead to a better chance of survival with the use of standard and evolving combination therapies.

Keywords: prostate cancer, castration resistant, chemotherapy, treatment

Correspondence: Mustafa Sofikerim, Department of Urology, Faculty of Medicine, Erciyes University, 38030 Kayseri, Turkey. Tel: +90 352 4374937 21455; Fax: +90 0352 4377613; e-mail: mustafasofikerim@yahoo.com

Castration-Resistant Prostate Cancer: Definition, Biology, and Novel Therapeutic Intervention Strategies

ETS Gene Fusions in Castration-Resistant Prostate Cancer

Castration-Resistant Prostate Cancer: Current Status and Future Directions

REVIEW ARTICLE

Saadettin Eskicorapci, Ali Ersin Zumrutbas, Tahir Turan and Omer Levent Tuncay

Affiliation: Department of Urology, Pamukkale University Medical School, Denizli, Turkey

ABSTRACT

Over the past decade, the treatment alternatives of castration-resistant prostate cancer (CRPC) have developed significantly, especially with the revelation of the docetaxel-based chemotherapy regimes. However, despite several attempts, the median survival for men with metastatic CRPC remains as 1–2 years. The purpose of this article is to discuss the current status and recent developments in the field of CRPC, focusing particularly on the new agents that are most encouraging. Nonetheless, there are serious improvements being made in the development of more effective antiandrogens and cytochrome P17 inhibitors (abiraterone, MDV3100), novel chemotherapy regimens, targeted therapies, and immunotherapies (sipuleucel-T). For the most part, new therapeutic agents are being combined with chemotherapy, similar to the approach taken in other tumors. However, the development of new approaches to the treatment of castration resistant prostate cancer presents many challenges that will demand collaboration and consensus building with respect to biomarkers for patient selection, clinical endpoints, and trial designs.

Keywords: castration-resistant prostate cancer, chemotherapy, immunotherapy, hormonal therapy, targeted therapeutics, vascular endothelial growth factor, androgens

Correspondence: Saadettin Eskicorapci, Department of Urology, Pamukkale University Medical School, Denizli, Turkey. Tel: +90 258 444 0 728; Fax: 0090 2582134922; e-mail: drsye@yahoo.com

CT Scanning in the Management and ESWL of Patients with Renal Calculi

REVIEW ARTICLE

Briony Varda and Manoj Monga

Affiliation: Department of Urologic Surgery, University of Minnesota, Minneapolis, Minnesota, USA

ABSTRACT

This review article aims to summarize the value of computed tomography (CT) in determining treatment, specifically shockwave lithotripsy, for patients with renal calculi. Both CT and shockwave the lithotripsy SWL were new technologies three decades ago and have since evolved both in parallel and synergistically over time. Although initially CT was only a diagnostic tool, advances in its use and postprocessing techniques have allowed for the determination of several stone and patient characteristics that guide therapy. Over time, CT has evolved into a distinctive application as a prognostic tool for SWL. Caution must be observed, however, in over using CT due to the long-term risks of radiation exposure. Ultimately a balance must be struck between clinical utility and patient protection.

Keywords: extracorporeal shockwave lithotripsy, renal calculi, computed tomography, attenuation, Hounsfield units, skin-to-stone distance, low-dose radiation protocols

Correspondence: Manoj Monga, Department of Urologic Surgery, University of Minnesota, 420 Delaware St. SE, MMC 394, Minneapolis, MN 55455, USA. Tel: +1 612 625 7486; Fax: +1 612 624 4430; e-mail: endourol@yahoo.com

Sequencing of Therapeutic Agents in the Treatment of Advanced Renal Cell Carcinoma: Focus on Mechanism of Action

REVIEW ARTICLE

Stéphane Oudard^1, Alain Ravaud^2, and Bernard Escudier³

Affiliations: ¹Oncology Department, Georges Pompidou Hospital, Paris Cedex, France; ²Department of Oncology, Bordeaux University Hospital, Place Amelie Raba Léon, Bordeaux Cedex, France; and ³Institut Gustave Roussy, rue Camille-Desmoulins, Villejuif, France

ABSTRACT

INTRODUCTION
Recent introductions of numerous targeted agents (the antivascular endothelial growth factor [VEGF] monoclonal antibody bevacizumab; the VEGF receptor tyrosine kinase inhibitors [VEGFR-TKI] sorafenib, sunitinib, and pazopanib; and the mammalian target of rapamycin [mTOR] inhibitors everolimus and temsirolimus) have provided additional therapeutic options for patients with metastatic renal cell carcinoma (mRCC).

OBJECTIVES
We sought to collect evidence that may guide optimization of the therapeutic course subsequent to the inevitable progression of disease.

METHODS
We reviewed the published medical literature for data from studies of sequential targeted therapy in mRCC.

RESULTS
Due to similar safety profiles of agents with similar mechanisms of action, sequential treatment may be preferable to combination therapy because it reduces the risk of cumulative toxicity. Retrospective studies suggested that following one VEGFR-TKI with a second VEGFR-TKI could provide clinical benefit; however, prospective studies have not replicated these findings, but have evidenced increased toxicity with the second VEGFR-TKI. In contrast, targeting a different pathway with everolimus after VEGFR-TKI failure in a pivotal clinical study had clear efficacy without evidence of excess toxicity. Preliminary indications of tumor resensitization to VEGFR-TKIs after blocking mTOR activation are intriguing but must be verified in prospective studies. Future studies are focused on better understanding tumor biology and biomarkers in RCC to allow the optimal treatment sequences to be based on individual patient characteristics.

CONCLUSION
Currently, the best-supported strategy after failure of VEGFR-TKI therapy in patients with mRCC remains treatment with everolimus.

Keywords: mammalian target of rapamycin (mTOR), metastatic cancer, renal cell carcinoma, sequential therapy, tumor escape, vascular endothelial growth factor

Correspondence: Stéphane Oudard, Hôpital Européen Georges Pompidou, Service de Cancérologie Médicale, 20 rue Leblanc 75908, Paris Cedex 15, France. Tel: +33 1 56 093 003; Fax: +33 1 56 092 803; e-mail: stephane.oudard@egp.aphp.fr

Current Advances in Castration Resistant Prostate Cancer

REVIEW ARTICLE


Romain Mathieu^1, Grégory Verhoest^1, Sébastien Vincendeau^1, Andréa Manunta^1, Renaud De Crevoisier^2, François Guillé¹ and Karim Bensalah¹

Affiliations: ¹Department of Urology, Rennes University Hospital, Rennes, Cedex, France and ²Department of Oncology, Rennes University Hospital, Rennes, Cedex, France

ABSTRACT

Androgen blockade is the standard treatment of metastatic PCa. However, after a limited period of time, tumoral cells invariably become resistant to hormone therapy. Docetaxel-based chemotherapy is the standard option when hormonal treatment fails. New chemotherapeutic agents are being evaluated. Some of them, including cabazitaxel, have shown significant results. Research is ongoing and numerous agents undergo evaluation through phase II and III trials. Better understanding of biological pathways involved in castration resistant prostate cancer (CRPC) could lead to the development of new efficient therapeutic agents. Specific drugs targeting androgen receptors, the angiogenesis pathway, bone tissue, apoptosis, or the immune system have recently emerged. Some of them such as denosumab and sipuleucel have shown interesting results and could be used in a clinical setting in the future. This article is a review of the literature and ongoing trials that describes most recent advances in chemotherapy, hormonal, and targeted therapies for the management of CRPC.

Keywords: prostate cancer, chemotherapy, targeted therapies

Correspondence: Karim Bensalah, Service d'Urologie, Centre Hospitalier Universitaire de Rennes, 2 rue Henri Le Guilloux, 35033 Rennes, Cedex, France. Tel: +33 2 99 28 42 69; Fax: +33 2 99 28 41 13; e-mail: Karim.Bensalah@chu-rennes.fr

Overactive Bladder in Middle Age Women: The Frustration of Baby Boomers with OAB Symptoms

ORIGINAL ARTICLE


Nancy Muller

Affiliation: National Association For Continence (NAFC), Charleston, South Carolina, USA

ABSTRACT

In 2009, NAFC sponsored a nationwide survey of women aged 40 to 65 with overactive bladder (OAB). The purpose was to learn more about what drives women to seek treatment for OAB symptoms and what factors might precipitate stopping or changing treatment. Using a nonexperimental correlational design, descriptive demographic data were collected on respondents to examine correlations with their self-reported symptoms, behavior, attitudes, and feelings about OAB. The most salient findings of the primary research were: (1) women are significantly more likely to express feeling annoyed and frustrated about their symptoms of OAB than they are embarrassed or stigmatized and (2) frustration abounds among those in treatment. More research is needed to support the suggestion that female baby boomers are not necessarily obstructed by embarrassment or stigma associated with bladder control in seeking solutions to conditions such as OAB. Practitioners are encouraged to be more interactive and instructional with patients by offering a combination therapy approach to managing symptoms. Greater public health education is warranted to make more people aware of their treatment options.



Keywords: overactive bladder, stigmatization, quality of life, urinary incontinence, help-seeking behavior

Correspondence: Nancy Muller, National Association for Continence (NAFC), PO Box 1019, 62 Columbus Street, Charleston, SC 29403, USA. Tel: +1 843 377 0900, ext. 207; Fax: +1 843 377 0905; e-mail: nmuller@nafc.org

Hypoactive Sexual Desire Disorder: What the Urologist Needs to Know

Endothelin Receptor Antagonism: A Novel Therapeutic Option in Castration-Resistant Prostate Cancer

REVIEW ARTICLE


Michael Borre

Affiliation: Department of Urology, Aarhus University Hospital, Skejby, Denmark

ABSTRACT

Treatment with chemotherapy results in limited therapeutic and quality of life improvements in patients with castration-resistant prostate cancer (CRPC), and new efficacious and well-tolerated therapies are needed to more effectively treat this disease, before resorting to the use of cytotoxic agents. The endothelin (ET) axis, which comprises ET-1, ET-2, ET-3 and the ETA and ETB receptors, performs important physiological functions, as a modulator of vasomotor tone, and in tissue differentiation, cell proliferation and hormone production. The role of the endothelin system has also been investigated in malignant disease, and the ET-1/ETA interaction has been implicated in the growth and progression of a variety of tumours. Subsequently, novel therapeutic interventions have been developed that inhibit ETA receptor interactions. A broad range of data is available on the impact of ETA receptor antagonists in a number of urological, gynaecological and breast cancers. The clinical investigations of the selective ETA receptor antagonist atrasentan in prostate cancer have shown promise. Antitumour activity, control of metastatic bone involvement and reductions in cancer-associated pain have all been documented. However, significant improvements in time to progression and overall survival have not been demonstrated. Preliminary clinical data from trials investigating the specific ETA receptor antagonist zibotentan are encouraging, and a promising overall survival signal has been achieved, despite non-significant effects on progression-free survival. A large Phase 3 programme currently ongoing with this agent should further define the role of ETA receptor antagonists in treating CRPC.

Keywords: Atrasentan, clinical trial, endothelin, endothelin receptor antagonist, metastasis, prostate cancer, zibotentan

Correspondence: Michael Borre, Department of Urology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. Tel: + 45 8949 5909; Fax: + 45 89 49 6006; e-mail: borre@ki.au.dk

Therapeutic Options for Men with Castrate-Resistant Prostate Cancer

REVIEW ARTICLE

Reid V Graves, Nicholas A Laryngakis, S. Bruce Malkowicz and Thomas J Guzzo

Affiliation: Division of Urology, Department of Surgery, The Hospital of the University of Pennsylvania, Philadelphia, PA, USA

ABSTRACT

Prostate cancer (PCa) is the most common malignancy diagnosed in American men. Men with the clinically localized disease typically have an excellent prognosis; however, the overall survival of those with castrate-resistant metastatic prostate cancer is poor. Until recently, therapeutic options for men with castrate-resistant prostate cancer (CRPC) were limited. Further understanding of the complex molecular biology of the androgen receptor (AR) has led to the development of novel therapeutic strategies for men with CRPC. This article reviews both the current state of CRPC therapy and the potential future therapeutic struggles.


Keywords: prostate cancer, castrate-resistant prostate cancer

Correspondence: Thomas J Guzzo, Assistant Professor of Urology, Division of Urology, Department of Surgery, The Hospital of the University of Pennsylvania, Philadelphia, PA 19106, USA. Tel: +1-215-662-7018; Fax: +215-662-3955; email: thomas.guzzo@uphs.upenn.edu