New Agents for the Treatment of Advanced Bladder Cancer.

Despite recent advances in the management of a wide variety of solid tumors, the outcomes for patients with metastatic urothelial carcinoma (MUC) remain extremely poor. Cisplatin-based combination chemotherapy remains the standard of care for first-line systemic treatment of MUC, and for more than 20 years there have been no other US Food and Drug Administration-approved treatment options available for these patients. Finally there appears to be hope on the horizon, with an ever-increasing number of precisely targeted agents being developed for use in MUC, resulting in improved survival rates. These targeted agents have now entered the cancer treatment arena, a direct result of a greater understanding of the genetic background of MUC. In this review article, we summarize the current state of development of these targeted agents, used either alone or in combination with traditional chemotherapy in MUC. Our discussion focuses on the most promising novel agents, including therapies targeting receptors for fibroblast growth factor and endothelial growth factor; antiangiogenesis agents (bevacizumab); tyrosine kinase inhibitors (cabozantinib); and immune checkpoint inhibitors that target proteins in the immune checkpoint-regulation pathway (anti-programmed death 1 and anti-programmed death ligand 1).

Role of complimentary therapy for male LUTS.

Phytotherapy, the use of plant based extracts (derived from fruits, seeds, roots, or bark) as medicines or health-promoting agents are often used as first-line treatments for bothersome male lower urinary tract symptoms (LUTS). Their use, either as monotherapy or in conjunction with conventional pharmaceutical treatments is becoming increasingly popular worldwide. There are now over 30 of these phytotherapeutic compounds available, with saw palmetto and pygeum being the most widely used. This paper discusses the mechanism of action, reported efficacies and potential side effects of a number of the most common phytotherapies being used for male LUTS, as well as summarizes outcome data relevant to these agents from the most current peer-reviewed publications.

Comparison of biochemical failure definitions for predicting local cancer recurrence following cryoablation of the prostate.

BACKGROUND: Various definitions of biochemical failure (BF) have been used to predict cancer recurrence following prostate cryoablation. However to date, none of these definitions have been validated for this use. We have reviewed several definitions of BF to determine their accuracy in predicting biopsy-proven local recurrence following prostate cryoablation. METHODS: The Columbia University Urologic Oncology Database was queried for patients who underwent prostate cryoablation between 1994 and 2010, and who subsequently underwent surveillance biopsy due to clinical suspicion of prostate cancer recurrence. Serial postoperative prostate-specific antigen (PSA) results were used to determine BF according to various definitions of BF. Biopsy results were used to determine local recurrence. Sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curve area were calculated for each of the BF definitions. RESULTS: A total of 110 patients met inclusion criteria for the study. These patients were treated with primary full-gland (n = 38), primary focal (n = 24), or salvage cryoablation (n = 48). On surveillance biopsy, 66 patients (60%) were found to have locally recurrent prostate cancer. The most accurate BF definition overall was PSA nadir plus 2 ng/ml (Phoenix definition), with sensitivity, specificity, and ROC curve area of 68%, 59%, and 0.64, respectively. CONCLUSIONS: Overall, the Phoenix definition best predicted local cancer recurrence following prostate cryoablation. These preliminary data may be useful for researchers evaluating the short-term efficacy of cryoablation, and for urologists assessing their patients for potential cancer recurrence.

Alpha particles as radiopharmaceuticals in the treatment of bone metastases: mechanism of action of radium-223 chloride (Alpharadin) and radiation protection.

Approximately 85% to 90% of men with castration-resistant prostate cancer (CRPC) have radiological evidence of bone metastases. To date, however, therapies to manage bone metastases have been primarily palliative. Among CRPC patients with bone metastases, there is a significant unmet need for active antitumor treatment options that are highly efficacious and have a favorable safety profile. This article will present current information about alpha-pharmaceuticals, a new class of targeted cancer therapy for the treatment of patients with CRPC and bone metastases. It will review preclinical and clinical studies of the experimental radiopharmaceutical radium-223 chloride (Alpharadin), a first-in-class, highly targeted and well-tolerated alpha-pharmaceutical under development to improve survival in patients with bone metastases from advanced prostate cancer. Alpharadin kills cancer cells via alpha radiation from the decay of radium-223, a calcium mimetic that naturally self-targets to bone metastases. The mechanism of action of Alpharadin and specifics of administration, radiation protection, and patient management will be discussed.

Vitamin D deficiency in the urological population: a single center analysis.

PURPOSE: Vitamin D has a well-known role in calcium metabolism and bone health. It may also help prevent a number of chronic diseases, including cardiovascular disease, diabetes and malignancies such as breast, colorectal and prostate cancer. To our knowledge the prevalence of vitamin D deficiency has never been reported in the general urological population. We evaluated the vitamin D status of this population at a large academic center. MATERIALS AND METHODS: We retrospectively reviewed the records of 3,763 male and female patients from a urology database at a single academic institution. Patients were identified whose levels of serum 25-hydroxyvitamin D were measured for the first time between 1997 and 2010. We determined the prevalence of normal--greater than 30, insufficient--20 to 29 and deficient--less than 20 ng/ml 25-hydroxyvitamin D. Logistic regression analysis was performed to identify risk factors for vitamin D deficiency. RESULTS: Overall 2,559 patients (68%) had suboptimal 25-hydroxyvitamin D (less than 30 ng/ml), of whom 1,331 (52%) were frankly deficient (less than 20 ng/ml) in the vitamin. Vitamin D deficiency was more common in patients younger than age 50 years (44.5%), black (53.2%) and Hispanic (41.6%) patients (p <0.001), and patients without an existing urological malignancy (35.4%, p <0.001). On multivariate analysis race, age, season and cancer diagnosis were independent predictors of vitamin D status. CONCLUSIONS: Vitamin D deficiency is extremely common in urological patients at a major urban medical center. Urologists should consider recommending appropriate supplementation during the initial assessment of all patients.

Gleason score concordance on biopsy-confirmed prostate cancer: is pathological re-evaluation necessary prior to radical prostatectomy?

OBJECTIVES: • Gleason sum from prostate biopsy (bGS) is an important tool in classifying severity of disease, ultimately influencing clinical management. • Commonly, pathology specimens are re-evaluated internally prior to surgery. • We evaluate agreement of bGS with prostatectomy Gleason sum (pGS) and the impact of re-grading on prediction of true underlying tumor architecture. MATERIALS AND METHODS: • Retrospective analysis of men who underwent robotic-assisted radical prostatectomy (RARP) by two surgeons from 2005-2009. Initial transrectal ultrasound (TRUS) biopsy demonstrated carcinoma at an outside lab. Specimens were re-evaluated by our GU pathologists prior to surgery. Biopsy data were correlated with pGS. • Kappa (κ) statistics for agreement and linear regression analyses were used for categorical variables. Coefficient of concordance was used for continuous variables. RESULTS: • 100 patients had 331 positive biopsies. Agreement (κ) for bGS between outside labs and our pathologists was 0.55 (p < 0.001). • Internal read was twice as likely to upgrade vs. downgrade outside bGS (23% vs. 11%). • When re-evaluation resulted in a change in bGS, agreement with pGS was κ= 0.29, vs. κ=-0.04 for agreement of initial (outside) bGS with pGS. • When no change was made to bGS, agreement with pGS was κ= 0.40 (p < 0.001). CONCLUSION: • Good reproducibility seen between outside labs and our institution on bGS. Internal pathology re-reads correlated better with pGS than original community bGS. When re-reads result in a change in bGS, there is a marked improvement in prediction of underlying tumor architecture confirming the value of re-evaluating all external biopsies prior to definitive surgery.

Diet and prostate cancer - a holistic approach to management.

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.

Assessment of lymph node yield after pelvic lymph node dissection in men with prostate cancer: a comparison between robot-assisted radical prostatectomy and open radical prostatectomy in the modern era.

BACKGROUND AND PURPOSE: Studies of radical prostatectomy (RP) suggest that higher lymph node yield (LNY) improves tumor staging. Robot-assisted radical prostatectomy (RARP) is becoming increasingly popular, yet LNY data are not well reported. We compare LNY from contemporary open RP (ORP) with RARP at an academic center. PATIENTS AND METHODS: A retrospective study was conducted of an Urologic Oncology Database. Between January 2005 and November 2009, 217 men underwent ORP with pelvic lymph node dissection (PLND); 99 underwent RARP with PLND by a single surgeon during the same period. Men were stratified according to the D'Amico risk criteria. For intermediate and high-risk disease, an extended PLND was performed. Patient demographic, operative, and pathologic variables were measured, and LNY was compared across groups. RESULTS: No significant differences were seen between groups for race, body mass index, preoperative prostate-specific antigen level or biopsy Gleason score. Patients were younger for RARP vs ORP (P = 0.003) and had higher clinical tumor stage (P = 0.02). Operative time was longer (P = 0.03) and estimated blood loss was greater (P < 0.001) in the ORP group. Overall, only a borderline significant difference was seen in LNY between ORP and RARP (7.49 vs 6.35 nodes, respectively, P = 0.06). No difference was seen for intermediate and high-risk patients, with 7.7 vs 6.8 nodes for ORP and RARP, respectively (P = 0.27). The lymph node metastasis rate was 6.3%, with more positive nodes detected during ORP vs RARP: 19/217 (8.8%) vs 1/99 (1.0%), P = 0.009. CONCLUSIONS: No significant differences were seen in LNY during RARP and ORP for intermediate and high-risk men. For experienced surgeons, RARP can achieve equivalent LNY as ORP. A future study with a larger sample size is necessary to make a definitive statement of equivalence.

Use of a flexible carbon dioxide laser fiber for precise dissection of the neurovascular bundle during robot-assisted laparoscopic prostatectomy.

INTRODUCTION: Carbon dioxide (CO(2)) lasers deliver energy with minimal thermal spread to tissues during dissection. Excess thermal spread during dissection of the neurovascular bundle (NVB) can affect potency in men after robot-assisted radical prostatectomy (RARP). We report on a novel delivery mechanism for CO(2) laser energy through a flexible fiber to enhance accuracy of NVB dissection during RARP. MATERIALS: A feasibility study of the OmniGuide BeamPath URO-LG CO(2) laser fiber for NVB dissection was performed on 10 patients with primary Gleason 3 T1c prostate cancer during RARP. Bilateral lateral fascial antegrade nerve sparing was performed. We evaluated fiber performance, safety, and efficacy. RESULTS: The fiber was inserted through the 12-mm assistant's port and easily manipulated by robotic instruments. Once pedicles were clipped and dissected, the laser fiber was effective in establishing planes of dissection between prostatic capsule and NVB. The endoscopically discernable thermal laser footprint was small, with minimal thermal spread during nerve sparing, meticulous dissection of NVB, and fascial layer identification. Although the laser did provide extremely accurate dissection, it was unable to serve as an adequate means of larger vessel coagulation. CONCLUSIONS: The flexible CO(2) laser fiber was easily manipulated. Identification of fascial layers during nerve sparing was facilitated with the fiber. Long-term follow-up is necessary to determine efficacy of this technology versus conventional techniques on the NVB. Larger studies are currently in progress to determine if use of the flexible CO(2) laser fiber results in improvements in functional outcomes with regard to return of sexual potency after RARP.

An evaluation of patient selection criteria on predicting progression-free survival after primary focal unilateral nerve-sparing cryoablation for prostate cancer: recommendations for follow up.

PURPOSE: Focal cryoablation targets unilateral disease, sparing healthy tissue and the ipsilateral neurovascular bundle. Given half the prostate is spared, proper patient selection is imperative to optimize outcomes. We report focal cryotherapy outcome data and evaluate the accuracy of the 2007 Task Force patient selection criteria at predicting disease recurrence. MATERIALS AND METHODS: This is a retrospective patient chart review from a single academic institution. Inclusion criterion is having unilateral prostate cancer treated with primary hemicryoablation. Patients were stratified using the Task Force selection criteria. Exclusion criterion is having had past radiation or hormone therapy. Progression-free survival was calculated using follow-up TRUS biopsy (biopsy done with transrectal ultrasound) and serial prostate-specific antigen (PSA) results (Phoenix criteria). Kaplan-Meier curves were constructed and Cox regression analyses performed, comparing outcomes across patient selection cohorts. RESULTS: From 2002 to 2009, 77 men underwent primary focal cryosurgery: mean age, 69.5 (SD, 6.7) years; median follow-up time, 24 months (range, 0-87 months); mean precryosurgical PSA, 6.5 (SD, 4.9) ng/mL; median Gleason score, 6 (range, 5-8). There were 44, 31, and 2 men who had D'Amico low-, intermediate-, and high-risk disease, respectively. Seventeen men met Focal Task Force Selection Criteria. After treatment, 22 patients underwent prostate biopsy for suspicion of recurrent disease. Of the 22 patients, 10 (45.5%) had confirmed prostate cancer. Of the 10 patients, 2 had ipsilateral disease, 7 had contralateral disease, and 1 had bilateral disease. Overall biochemical and pathological progression-free survival rates were 72.7% and 87%. The cumulative incidence of biochemical disease progression, using the Kaplan-Meier method, was greater than 75% at 3 years for men with more than 2 positive preoperative biopsy cores and greater than 50% at 5 years for men with 2 or less positive preoperative biopsy cores. No survival differences were seen across cohorts. Pretreatment PSA level, pretreatment Gleason score, number positive cores, and total tumor length were associated with disease progression. CONCLUSIONS: Focal cryotherapy is a promising option for carefully selected patients, although optimization of inclusion criteria is required. Current selection criteria are associated with cancer-free survival. Given no accurate definitions for biochemical failure after focal cryotherapy exist combined with our high biochemical failure rate, mandating 12-month follow-up TRUS biopsy may improve accurate detection of cancer progression. Further follow up will determine optimal patient selection criteria and follow-up protocols for patients undergoing primary focal unilateral nerve-sparing prostate cancer treatment.

Does the presence of robotic surgery affect demographics in patients choosing to undergo radical prostatectomy? A multi-center contemporary analysis.

We report on differences in patient demographics in those men choosing to undergo radical prostatectomy in a UK center where there is no influence of robotic surgery and in those choosing radical prostatectomy in a US center where there is a strong robotic influence. Demographic and pathologic data were prospectively recorded in parallel for 78 consecutive men undergoing robot-assisted radical prostatectomy in a tertiary care academic US center and 69 consecutive men concurrently undergoing open radical prostatectomy in a similar UK center. Although average patient age was significantly younger in the US cohort (58.8 years, range 43.1-77.6 vs. 62.2 years, range 51.7-70.5; P = 0.002), the US cohort encompassed a wider age range and older patients than the UK cohort. Average preoperative prostate-specific antigen (PSA) was significantly lower in the US group (6.0, range 2.0-6.0 vs. 8.60, range 4.6-12.6; P < 0.01). Biopsy Gleason score, clinical stage, final pathology Gleason score, pathologic staging and positive margin rate were not significantly different between the two groups. Blood loss and transfusion rate were significantly lower in the US group. 16.7% of men in the US cohort had overall positive surgical margins compared to 29% in the UK group (P = 0.07). This data confirms our belief that patient age ranges are different in a setting influenced by robotic surgery. Although pathologic parameters were similar, the age distribution of robotic surgery patients was much wider, suggesting robotics attracts men previously reluctant to undergo surgery in the open setting or to pursue active surveillance protocols. Larger studies are needed to verify this finding.

La dieta y el cáncer de próstata - un enfoque holístico a la gestión / Diet and prostate cancer - a holistic approach to management

Existen cada vez más pruebas de las encuestas epidemiológicas y de los estudios de laboratorio, la intervención y de control de casos, de que la dieta y el estilo de vida juegan un papel fundamental en la biología del cáncer de próstata y la génesis tumoral. Esto se aplica a ambos desarrollo y progresión del cáncer de próstata, aunque en muchos casos los factores iniciales específicos en la dieta son poco conocidos. Por el contrario, muchos nutrientes y hierbas también muestran una promesa significativa para ayudar a tratar el cáncer de próstata al disminuir la progresión y reducir la recurrencia, en última instancia, reduciendo el riesgo de morbilidad y mortalidad de la enfermedad. Además en todos los grados del cáncer de próstata, los controles nutricionales complementan el tratamiento convencional para mejorar la respuesta y la calidad de vida. Frenar o incluso revertir la progresión de la neoplasia intraepitelial prostática de alto grado [HGPIN]), con agentes de quimioterapia preventiva podrían ser la mejor defensa primaria contra el cáncer de próstata, evitando que se produzca en primer lugar. La información contenida en esta revisión sobre la quimio-prevención del cáncer de próstata resume la evidencia clave del papel de los diferentes componentes de la dieta y su efecto en la prevención y progresión del cáncer de próstata. La mayoría de los agentes nutricionales quimio-preventivos también poseen la ventaja añadida de ser beneficiosos para el sistema cardiovascular, salud de los huesos y para la prevención de otros tipos de cáncer(AU)

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers(AU)