The MICA-NKG2D axis in clear cell renal cell carcinoma bolsters MICA as target in immuno-oncology.

NKG2D is a major natural killer (NK) cell-activating receptor that recognizes eight ligands (NKG2DLs), including MICA, and whose engagement triggers NK cell effector functions. As NKG2DLs are upregulated on tumor cells but tumors can subvert the NKG2D-NKG2DL axis, NKG2DLs constitute attractive targets for antibody (Ab)-based immuno-oncology therapies. However, such approaches require a deep characterization of NKG2DLs and NKG2D cell surface expression on primary tumor and immune cells. Here, using a bioinformatic analysis, we observed that MICA is overexpressed in renal cell carcinoma (RCC), and we also detected an association between the NKG2D-MICA axis and a diminished overall survival of RCC patients. Also, by flow cytometry (FC), we observed that MICA was the only NKG2DL over-expressed on clear cell renal cell carcinoma (ccRCC) tumor cells, including cancer stem cells (CSC) that also coexpressed NKG2D. Moreover, tumor-infiltrating leukocytes (TIL), but not peripheral blood lymphoid cells (PBL) from ccRCC patients, over-expressed MICA, ULBP3 and ULBP4. In addition, NKG2D was downregulated on peripheral blood NK cells (PBNK) from ccRCC patients but upregulated on tumor-infiltrating NK cells (TINK). These TINK exhibited impaired degranulation that negatively correlated with NKG2D expression, diminished IFN-γ production, upregulation of TIM-3, and an impaired glucose intake upon stimulation with cytokines, indicating that they are dysfunctional, display features of exhaustion and an altered metabolic fitness. We conclude that ccRCC patients exhibit a distorted MICA-NKG2D axis, and MICA emerges as the forefront NKG2DL for the development of targeted therapies in ccRCC.

Pelvic lymph node dissection in high-risk prostate cancer

ABSTRACT Introduction: The therapeutic role of pelvic lymph node dissection (PLND) in prostate cancer (PCa) is unknown due to absence of randomized trials. Objective: to present a critical review on the therapeutic benefits of PLND in high risk localized PCa patients. Materials and Methods: A search of the literature on PLND was performed using PubMed, Cochrane, and Medline database. Articles obtained regarding diagnostic imaging and sentinel lymph node dissection, PLND extension, impact of PLND on survival, PLND in node positive "only" disease and PLND surgical risks were critically reviewed. Results: High-risk PCa commonly develops metastases. In these patients, the possibility of presenting lymph node disease is high. Thus, extended PLND during radical prostatectomy may be recommended in selected patients with localized high-risk PCa for both accurate staging and therapeutic intent. Although recent advances in detecting patients with lymph node involvement (LNI) with novel imaging and sentinel node dissection, extended PLND continues to be the most accurate method to stage lymph node disease, which may be related to the number of nodes removed. However, extended PLND increases surgical time, with potential impact on perioperative complications, hospital length of stay, rehospitalization and healthcare costs. Controversy persists on its therapeutic benefit, particularly in patients with high node burden. Conclusion: The impact of PLND on biochemical recurrence and PCa survival is unclear yet. Selection of patients may benefit from extended PLND but the challenge remains to identify them accurately. Only prospective randomized study would answer the precise role of PLND in high-risk pelvis confined PCa patients.

Pelvic lymph node dissection in high-risk prostate cancer.

INTRODUCTION: The therapeutic role of pelvic lymph node dissection (PLND) in prostate cancer (PCa) is unknown due to absence of randomized trials. OBJECTIVE: to present a critical review on the therapeutic benefits of PLND in high risk localized PCa patients. MATERIALS AND METHODS: A search of the literature on PLND was performed using PubMed, Cochrane, and Medline database. Articles obtained regarding diagnostic imaging and sentinel lymph node dissection, PLND extension, impact of PLND on survival, PLND in node positive "only" disease and PLND surgical risks were critically reviewed. RESULTS: High-risk PCa commonly develops metastases. In these patients, the possibility of presenting lymph node disease is high. Thus, extended PLND during radical prostatectomy may be recommended in selected patients with localized high-risk PCa for both accurate staging and therapeutic intent. Although recent advances in detecting patients with lymph node involvement (LNI) with novel imaging and sentinel node dissection, extended PLND continues to be the most accurate method to stage lymph node disease, which may be related to the number of nodes removed. However, extended PLND increases surgical time, with potential impact on perioperative complications, hospital length of stay, rehospitalization and healthcare costs. Controversy persists on its therapeutic benefit, particularly in patients with high node burden. CONCLUSION: The impact of PLND on biochemical recurrence and PCa survival is unclear yet. Selection of patients may benefit from extended PLND but the challenge remains to identify them accurately. Only prospective randomized study would answer the precise role of PLND in high-risk pelvis confined PCa patients.

Circulating and Tumor-Infiltrating NK Cells From Clear Cell Renal Cell Carcinoma Patients Exhibit a Predominantly Inhibitory Phenotype Characterized by Overexpression of CD85j, CD45, CD48 and PD-1.

Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.

Prognostic Factors in De Novo Metastatic Renal Cell Carcinoma: A Report From the Latin American Renal Cancer Group.

PURPOSE: To assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries. PATIENTS AND METHODS: Of 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method. RESULTS: Of 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58). CONCLUSION: Our study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

[Epidemiology, etiology and prevention of bladder cancer.] / Epidemiología, etiología, prevención del cáncer vesical.

Bladder cancer is the seventh most frequent cancer on male population and eleventh within the whole inhabitants. Differences in incidence and mortality between countries and regions exist. Those differences depend on variables including epidemiological data, social and cultural features and economics amongst the several populations that are exposed to different risk factors and treatment approaches. Smoking is the strongest risk factor for bladder cancer, representing approximately 50% of the cases. Its alternative, the electronic cigarette does not seem to providea decrease in risk of bladder cancer. Employment exposure to aromatic amines, aromatic polycyclic hydrocarbons and chlorate hydrocarbons, are still important risk factors. Water consumption with high levels of arsenic has also shown an increased risk of bladder cancer. Fast acetylators or genetic predisposition would be tentative risk factors. Some medical treatments with chemotherapy oradiation therapy increase bladder cancer risk. Identifying all these factors allows for progress in the field of prevention and early detection. The main objective is to decrease incidence and mortality related to bladder cancer.

El cáncer de vejiga (CV) es el séptimo cáncer más frecuente en la población masculina y el undécimo en frecuencia cuando se consideran ambos sexos. Existen diferencias de incidencia y mortalidad entre los países y regiones, en relación a una serie de variables que incluyen desde la recolección de los datos epidemiológicos, las características socioculturales y económicas de las distintas poblaciones hasta diferencias en la exposición a los factores de riesgo y formas de tratamiento. El tabaquismo es el factor de riesgo mejor establecido para el CV, representando aproximadamente el 50% de los casos; su alternativa, el cigarrillo electrónico, no parece ser menos riesgoso para la aparición de este tumor. La exposición ocupacional a aminas aromáticas, hidrocarburos aromáticos policíclicos e hidrocarburos clorados, pese a la prohibición de la utilización de determinadas sustancias, sigue siendo un factor de riesgo importante para CV. La ingesta de agua con niveles elevados de trihalometanoso arsénico han demostrado tener relación a un aumento de la incidencia del CV. Los acetiladores lentos o predisposiciones genéticas podrían ser de importancia en la potenciación de los factores de riesgo. Hay tratamientos médicos con quimioterapia o radioterapia que aumentan el riesgo de CV. La importancia del reconocimiento de todos éstos factores hace posible avanzarsobre el terreno de la prevención y la detección precoz,c on la intención de disminuir de la incidencia y mortalidad por CV.

Epidemiología, etiología, prevención del cáncer vesical / Epidemiology, etiology and prevention of bladder cancer

El cáncer de vejiga (CV) es el séptimo cáncer más frecuente en la población masculina y el undécimo en frecuencia cuando se consideran ambos sexos. Existen diferencias de incidencia y mortalidad entre los países y regiones, en relación a una serie de variables que incluyen desde la recolección de los datos epidemiológicos, las características socioculturales y económicas de las distintas poblaciones hasta diferencias en la exposición a los factores de riesgo y formas de tratamiento. El tabaquismo es el factor de riesgo mejor establecido para el CV, representando aproximadamente el 50% de los casos; su alternativa, el cigarrillo electrónico, no parece ser menos riesgoso para la aparición de este tumor. La exposición ocupacional a aminas aromáticas, hidrocarburos aromáticos policíclicos e hidrocarburos clorados, pese a la prohibición de la utilización de determinadas sustancias, sigue siendo un factor de riesgo importante para CV. La ingesta de agua con niveles elevados de trihalometanos o arsénico han demostrado tener relación a un aumento de la incidencia del CV. Los acetiladores lentos o predisposiciones genéticas podrían ser de importancia en la potenciación de los factores de riesgo. Hay tratamientos médicos con quimioterapia o radioterapia que aumentan el riesgo de CV. La importancia del reconocimiento de todos éstos factores hace posible avanzar sobre el terreno de la prevención y la detección precoz, con la intención de disminuir de la incidencia y mortalidad por CV

Bladder cancer is the seventh most frequent cancer on male population and eleventh within the whole inhabitants. Differences in incidence and mortality between countries and regions exist. Those differences depend on variables including epidemiological data, social and cultural features and economics amongst the several populations that are exposed to different risk factors and treatment approaches. Smoking is the strongest risk factor for bladder cancer, representing approximately 50% of the cases. Its alternative, the electronic cigarette does not seem to provide a decrease in risk of bladder cancer. Employment exposure to aromatic amines, aromatic polycyclic hydrocarbons and chlorate hydrocarbons, are still important risk factors. Water consumption with high levels of arsenic has also shown an increased risk of bladder cancer. Fast acetylators or genetic predisposition would be tentative risk factors. Some medical treatments with chemotherapy o radiation therapy increase bladder cancer risk. Identifying all these factors allows for progress in the field of prevention and early detection. The main objective is to decrease incidence and mortality related to bladder cancer

Small renal masses in Latin-American population: characteristics and prognostic factors for survival, recurrence and metastasis - a multi-institutional study from LARCG database.

BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.

Priorities in testis cancer care during Covid-19 Pandemic

ABSTRACT Introduction: There is little information on how to prioritize testis cancer (TC) patients' care during COVID-19 pandemic in order to relieve its pressure on the health care systems. Objective: To describe the recommendations for diagnosis, treatment and follow-up of patients with TC amidst COVID- 19 pandemic. Material and Methods: Pubmed search and review of the main urological association guidelines on TC. Results: The biology of TC requires immediate care of patients during diagnosis, initial surgical therapy and management of recurrent disease. Active surveillance is the first choice of management and should be offered to all compliant clinical stage I TC patients provided they understand the need to self-isolate. Active surveillance may also help decrease the demand for intensive care unit beds, ventilators, personal protective equipment, and other critical hospital and human resources by minimizing surgeries without compromising patient outcomes. Complications of therapy and symptomatic patients represent medical emergencies and should be treated immediately. Telemedicine may be useful during follow-up periods. Conclusions: Most stages of testis cancer require urgent care; however, all recommendations must be adapted to local health care priorities considering that most of these patients are at low risk of severe COVID-19 infection.

Priorities in testis cancer care during Covid-19 Pandemic.

INTRODUCTION: There is little information on how to prioritize testis cancer (TC) patients' care during COVID-19 pandemic in order to relieve its pressure on the health care systems. OBJECTIVE: To describe the recommendations for diagnosis, treatment and follow-up of patients with TC amidst COVID- 19 pandemic. MATERIAL AND METHODS: Pubmed search and review of the main urological association guidelines on TC. RESULTS: The biology of TC requires immediate care of patients during diagnosis, initial surgical therapy and management of recurrent disease. Active surveillance is the first choice of management and should be offered to all compliant clinical stage I TC patients provided they understand the need to self-isolate. Active surveillance may also help decrease the demand for intensive care unit beds, ventilators, personal protective equipment, and other critical hospital and human resources by minimizing surgeries without compromising patient outcomes. Complications of therapy and symptomatic patients represent medical emergencies and should be treated immediately. Telemedicine may be useful during follow-up periods. CONCLUSIONS: Most stages of testis cancer require urgent care; however, all recommendations must be adapted to local health care priorities considering that most of these patients are at low risk of severe COVID-19 infection.

Biochemical recurrence-free conditional probability after radical prostatectomy: A dynamic prognosis.

OBJECTIVE: To estimate the conditional biochemical recurrence-free probability and to develop a predictive model according to the disease-free interval for men with clinically localized prostate cancer treated with minimally invasive radical prostatectomy. METHODS: The study population consisted of 3576 consecutive patients who underwent laparoscopic radical prostatectomy and 2619 men treated with robotic radical prostatectomy in the past 15 years at Institute Mutualiste Montsouris, Paris, France. Biochemical recurrence was defined as serum prostate-specific antigen ≥0.2 ng/dL. Univariable and multivariable survival analyses were carried out to identify the prognostic factors for overall free-of-biochemical recurrence probability and conditional survival with respect to the years from surgery without recurrence. A detailed nomogram for the static and dynamic prognosis of biochemical recurrence was developed and internally validated. RESULTS: The median follow-up period was 8.49 years (interquartile range 4.01-12.97), and 1148 (19%) patients experienced biochemical recurrence. Significant variables associated with biochemical recurrence in the multivariable model included preoperative prostate-specific antigen, positive surgical margins, extracapsular extension, pathological Gleason ≥4 + 3 and laparoscopic surgery (all P < 0.001). Conditional survival probability decreased with increasing time without biochemical recurrence from surgery. When stratified by prognosis factors, the 5- and 10-year conditional survival improved in all cases, especially in men with worse prognosis factors. The concordance index of the nomogram was 0.705. CONCLUSIONS: Conditional survival provides relevant information on how prognosis evolves over time. The risk of recurrence decreases with increasing number of years without disease. An easy-to-use nomogram for conditional survival estimates can be useful for patient counseling and also to optimize postoperative follow-up strategies.

Robotic surgery in public hospitals of Latin-America: a castle of sand?

INTRODUCTION: There is no information about the evolution of robotic programs in public hospitals of Latin-America. OBJECTIVE: To describe the current status and functioning of robotic programs in Latin-American public hospitals since their beginning to date. METHODS: We conducted a survey among leading urologists working at public hospitals of Latin-America who had acquired the Da Vinci laparoscopic-assisted robotic system. Questions included: date the program started, its utilization by other services, number and kind of surgeries, surgery paying system, surgery related deaths, occurrence and reasons of robotic program interruptions and its use for training purposes. Medians and 25-75 centiles (IQR) were estimated. RESULTS: Since 2009, there are ten public hospitals of four Latin-American countries that acquired the Da Vinci robotic system. The median number of months robotic programs has been functioning without considering transitory interruption: 43 (IQR 35, 55). Median number of urologic and total surgeries performed: 140 (IQR 94, 168) and 336 (IQR 292, 621), respectively. The corresponding median number of urologic and total surgeries performed per month: 3 (IQR 2, 5) and 8 (IQR 5, 11). Median number of total surgeries performed per year per institution was 94 (IQR 68,123). The median proportion of urologic cases was 40% (IQR 31, 48), ranging from 24 to 66%. Five of ten institutions had their urology programs transitory or definitively closed due to the high burden costs. CONCLUSION: Adoption and development of robotic surgery in some public hospitals of Latin-America have been hindered by high costs.

Estado actual de la formación urológica en América Latina / Current status of urological training in Latin America

Objetivo: Conseguir una formación médica de calidad para los residentes es una preocupación constante en la Confederación Americana de Urología (CAU), tercera sociedad urológica mundial. Se pretende analizar la diversidad de los programas estatales de formación, con intención de identificar oportunidades de mejora global en los mismos y analizar también la realidad profesional en los diferentes países. Métodos: Se revisan datos obtenidos en el II y III Foro Educativo CAU relacionados con la formación de postgrado e implicaciones laborales. Esta información se complementa con la opinión de representantes implicados con la formación académica en la Confederación Americana de Urología, que han analizado la realidad y estado actual de la formación urológica a través de una encuesta de 10 preguntas que describe diferentes aspectos de los programas de residencia en los países confederados en CAU. Resultados: Un total de 3.000 graduados médicos se forman como residentes en Urología en el entorno CAU. Cada año 670 residentes inician su programa de formación en America Latina, España y Portugal, un territorio que atiende casi 650 millones de habitantes, con una fuerza profesional activa de en torno a 16.800 profesionales. Se presentan datos detallados sobre la realidad formativa, laboral y acreditativa en los países que componen la CAU. También se analiza la proporción de residentes que llevan a cabo actividades de investigación y programa de doctorado durante la residencia. Finalmente se analiza la proporción de profesionales que reciben formación específica al finalizar la residencia, la importancia relativa de la misma y cuáles son los entornos más demandados para llevarla a cabo. Conclusiones: La formación postgrado actual en el entorno de la CAU es heterogénea en sus programas, así como en los modos de acreditación y de re-certificación. Las actividades académicas no parecen correctamente valoradas. Sin embargo, la formación específica sí ofrece mejores expectativas de desarrollo profesional (AU)

Objective: Achieving residents' medical training of quality is a constant concern in the Confederación Americana de Urología (CAU), the third Urological Society worldwide. We aim to analyze the diversity of state training programs, with the intention to identify opportunities for global improvement within them and also to analyse the professional reality in different countries.Methods: Data from 2nd and 3rd Foro Educativo CAU regarding postgraduate training and labour implications are reviewed. This information is complemented by the opinion of representatives involved with the academic training in Confederación Americana de Urología, who have analyzed the reality and current status of the urological training through a 10-question survey that describes different aspects of residency program in the countries confederated in CAU.Results: A total of 3,000 graduate doctors train as residents in Urology at the CAU environment. Each year 670 residents begin their training program in Latin America, Spain and Portugal, a territory that serves nearly 650 million people, with an active professional force of around 16.800 professionals. Detailed data on training, employment and supporting reality in the countries that comprise the CAU are presented. We also discuss the proportion of residents who carry out research and doctorate during the residency program. Finally, we examine the proportion of professionals who receive specific training at the end of their residence, the relative importance of this training and what are the most popular environments to carry it out. Conclusions: Current postgraduate training in CAU environment is heterogeneous in their programs, as well as in the modes of accreditation and recertification. Academic activities do not seem to be properly valued. However, specific training offers better expectations of professional development (AU)

[Current status of urological training in Latin America.] / Estado actual de la formación urológica en América Latina.

OBJECTIVE: Achieving residents' medical training of quality is a constant concern in the Confederación Americana de Urología (CAU), the third Urological Society worldwide. We aim to analyze the diversity of state training programs, with the intention to identify opportunities for global improvement within them and also to analyse the professional reality in different countries. METHODS: Data from 2nd and 3rd Foro Educativo CAU regarding postgraduate training and labour implications are reviewed. This information is complemented by the opinion of representatives involved with the academic training in Confederación Americana de Urología, who have analyzed the reality and current status of the urological training through a 10-question survey that describes different aspects of residency program in the countries confederated in CAU. RESULTS: A total of 3,000 graduate doctors train as residents in Urology at the CAU environment. Each year 670 residents begin their training program in Latin America, Spain and Portugal, a territory that serves nearly 650 million people, with an active professional force of around 16.800 professionals. Detailed data on training, employment and supporting reality in the countries that comprise the CAU are presented. We also discuss the proportion of residents who carry out research and doctorate during the residency program. Finally, we examine the proportion of professionals who receive specific training at the end of their residence, the relative importance of this training and what are the most popular environments to carry it out. CONCLUSIONS: Current postgraduate training in CAU environment is heterogeneous in their programs, as well as in the modes of accreditation and recertification. Academic activities do not seem to be properly valued. However, specific training offers better expectations of professional development.

Comparative Analysis of Partial Gland Ablation and Radical Prostatectomy to Treat Low and Intermediate Risk Prostate Cancer: Oncologic and Functional Outcomes.

PURPOSE: We analyzed the oncologic and functional outcomes of partial gland ablation compared with robot-assisted radical prostatectomy in patients with low and intermediate risk prostate cancer. MATERIALS AND METHODS: A total of 1,883 patients underwent robot-assisted radical prostatectomy and 373 underwent partial gland ablation from July 2009 to September 2015. We selected 1,458 of these participants for analysis, including 1,222 and 236 treated with robot-assisted radical prostatectomy and partial gland ablation, respectively. Patients had a Gleason score of 3 + 3 or 3 + 4, clinical stage T2b or less, prostate specific antigen 15 ng/dl or less, unilateral disease and life expectancy greater than 10 years. Propensity score matching analysis (1:2) was applied in the overall robot-assisted radical prostatectomy sample, which selected 472 patients for comparison. For partial gland ablation 188 men underwent high intensity focused ultrasound and 48 underwent cryotherapy. Oncologic outcomes were analyzed in terms of the need for salvage treatment. Partial gland ablation failure was defined as any positive control biopsy after treatment. Functional outcomes were assessed by validated questionnaires. RESULTS: Matching was successful across the 2 groups, although men treated with partial gland ablation were older (p <0.001). Mean followup in the partial gland ablation group was 38.44 months. Partial gland ablation failure was observed in 68 men (28.8%), including 53 (28.1%) treated with high intensity focused ultrasound and 15 (31.2%) treated with cryotherapy. Partial gland ablation was associated with a higher risk of salvage treatment (HR 6.06, p <0.001). Complications were comparable between the groups (p = 0.06). Robot-assisted radical prostatectomy was associated with less continence recovery and a lower potency rate 3, 6 and 12 months after surgery (p <0.001). CONCLUSIONS: In select patients with organ confined prostate cancer partial gland ablation offered good oncologic control with fewer adverse effects that required additional treatments. Potency and continence appeared to be better preserved after partial gland ablation.

Learning curve of minimally invasive radical prostatectomy: Comprehensive evaluation and cumulative summation analysis of oncological outcomes.

BACKGROUND AND OBJECTIVE: The primary objective was to evaluate the learning curve of minimally invasive radical prostatectomy (MIRP) in our institution and analyze the salient learning curve transition points regarding oncological outcomes. METHODS: Clinical, pathologic, and oncological outcome data were collected from our prospectively collected MIRP database to estimate positive surgical margin (PSM) and biochemical recurrence (BCR) trends during a 15-year period from 1998 to 2013. All the radical prostatectomies (laparoscopic prostatectomy [LRP]/robot-assisted laparoscopic radical prostatectomy [RARP]) were performed by 9 surgeons. PSM was defined as presence of cancer cells at inked margins. BCR was defined as serum prostate-specific antigen >0.2ng/ml and rising or start of secondary therapy. Surgical learning curve was assessed with the application of Kaplan-Meier curves, Cox regression model, cumulative summation, and logistic model to define the "transition point" of surgical improvement. RESULTS: We identified 5,547 patients with localized prostate cancer treated with MIRP (3,846 LRP and 1,701 RARP). Patient characteristics of LRP and RARP were similar. The overall risk of PSM in LRP was 25%, 20%, and 17% for the first 50, 50 to 350, and>350 cases, respectively. For the same population, the 5-year BCR rate decreased from 30% to 16.7%. RARP started 3 years after the LRP program (after approximately 250 LRP). The PSM rate for RARP decreased from 21.8% to 20.4% and the corresponding 5-year BCR rate decreased from 17.6% to 7.9%. The cumulative summation analysis showed significantly lower PSM and BCR at 2 years occurred at the transition point of 350 cases for LRP and 100 cases for RARP. In multivariable analysis, predictors of BCR were prostate-specific antigen, Gleason score, extraprostatic disease, seminal vesicle invasion, and number of operations (P<0.05). Patients harboring PSM showed higher BCR risk (23% vs. 8%, P< 0.05). CONCLUSIONS: Learning curve trends in our large, single-center experience show correlation between surgical experience and oncological outcomes in MIRP. Significant reduction in PSM and BCR risk at 2 years is noted after the initial 350 cases and 100 cases of LRP and RARP, respectively.

American Confederation of Urology (CAU) experience in minimally invasive partial nephrectomy.

PURPOSE: To describe the perioperative and oncology outcomes in a series of laparoscopic or robotic partial nephrectomies (PN) for renal tumors treated in diverse institutions of Hispanic America from the beginning of their minimally invasive (MI) PN experience through December 2014. METHODS: Seventeen institutions participated in the CAU generated a MI PN database. We estimated proportions, medians, 95 % confidence intervals, Kaplan-Meier curves, multivariate logistic and Cox regression analyses. Clavien-Dindo classification was used. RESULTS: We evaluated 1501 laparoscopic (98 %) or robotic (2 %) PNs. Median age: 58 years. Median surgical time, warm ischemia and intraoperative bleeding were 150, 20 min and 200 cc. 81 % of the lesions were malignant, with clear cell histology being 65 % of the total. Median maximum tumor diameter is 2.7 cm, positive margin is 8.2 %, and median hospitalization is 3 days. One or more postoperative complication was recorded in 19.8 % of the patients: Clavien 1: 5.6 %; Clavien 2: 8.4 %; Clavien 3A: 1.5 %; Clavien 3B: 3.2 %; Clavien 4A: 1 %; Clavien 4B: 0.1 %; Clavien 5: 0 %. Bleeding was the main cause of a reoperation (5.5 %), conversion to radical nephrectomy (3 %) or open partial nephrectomy (6 %). Transfusion rate is 10 %. In multivariate analysis, RENAL nephrometry score was the only variable associated with complications (OR 1.1; 95 % CI 1.02-1.2; p = 0.02). Nineteen patients presented disease progression or died of disease in a median follow-up of 1.37 years. The 5-year progression or kidney cancer mortality-free rate was 94 % (95 % CI 90, 97). Positive margins (HR 4.98; 95 % CI 1.3-19; p = 0.02) and females (HR 5.6; 95 % CI 1.7-19; p = 0.005) were associated with disease progression or kidney cancer mortality after adjusting for maximum tumor diameter. CONCLUSION: Laparoscopic PN in these centers of Hispanic America seem to have acceptable perioperative complications and short-term oncologic outcomes.

Questionable oncologic benefits of degarelix.

INTRODUCTION: Luteinizing hormone releasing hormone (LhRh) antagonist degarelix has been approved by the Food and Drug Administration (FDA) for the treatment of advanced prostate cancer in 2008. However, the studies that followed such initial approval have several limitations. OBJECTIVE: To make a critical review of those publications. METHODS: Literature search on degarelix. RESULTS: The studies supporting the use of degarelix are criticized on the basis of selection bias in regards to the heterogeneous populations described, ad hoc analyses with low statistical merit, and the presentation of selected data that would appear to be favorable to the evaluated medication. In addition, those studies still have not shown that any of the data that they point out have any association with clinical benefit. CONCLUSION: The flawed methodology of these publications makes the evidence to support the use of degarelix rather weak.

First off-time treatment prostate-specific antigen kinetics predicts survival in intermittent androgen deprivation for prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) doubling time is relying on an exponential kinetic pattern. This pattern has never been validated in the setting of intermittent androgen deprivation (IAD). Objective is to analyze the prognostic significance for PCa of recurrent patterns in PSA kinetics in patients undergoing IAD. METHODS: A retrospective study was conducted on 377 patients treated with IAD. On-treatment period (ONTP) consisted of gonadotropin-releasing hormone agonist injections combined with oral androgen receptor antagonist. Off-treatment period (OFTP) began when PSA was lower than 4 ng/ml. ONTP resumed when PSA was higher than 20 ng/ml. PSA values of each OFTP were fitted with three basic patterns: exponential (PSA(t) = λ.e(αt)), linear (PSA(t) = a.t), and power law (PSA(t) = a.t(c)). Univariate and multivariate Cox regression model analyzed predictive factors for oncologic outcomes. RESULTS: Only 45% of the analyzed OFTPs were exponential. Linear and power law PSA kinetics represented 7.5% and 7.7%, respectively. Remaining fraction of analyzed OFTPs (40%) exhibited complex kinetics. Exponential PSA kinetics during the first OFTP was significantly associated with worse oncologic outcome. The estimated 10-year cancer-specific survival (CSS) was 46% for exponential versus 80% for nonexponential PSA kinetics patterns. The corresponding 10-year probability of castration-resistant prostate cancer (CRPC) was 69% and 31% for the two patterns, respectively. Limitations include retrospective design and mixed indications for IAD. CONCLUSION: PSA kinetic fitted with exponential pattern in approximately half of the OFTPs. First OFTP exponential PSA kinetic was associated with a shorter time to CRPC and worse CSS.

The learning curve of robotic assisted laparoscopic radical prostatectomy: what is the evidence?

OBJECTIVE: The robotic technique has been associated with a decreased LC for radical prostatectomy. The objective is to review the literature in search of any evidence that the RALP is able to shorten the learning curve for radical prostatectomy compared to the open and pure laparoscopic techniques. METHODS: A Medline search of the English-language literature was performed to identify all papers published relating to RALP and LC. RESULTS: There is substantial variability in the RALP literature regarding the number of cases a surgeon needs to achieve and sustain in time acceptable operative times and reasonable outcomes. The information on RALP LC comes from isolated single institution reports with questionable methodological analyses. There are no studies comparing the LC of RALP with open or pure laparoscopic techniques. CONCLUSIONS: There is no reliable information to support the notion that RALP shortens the prostatectomy LC. The evidence is limited to case series, with a Level of Evidence 4.