Development of castration resistance in prostate cancer patients treated with luteinizing hormone-releasing hormone analogues (LHRHa): results of the ANARESISTANCE study.

PURPOSE: Evaluate the percentage of patients with prostate cancer treated with luteinizing hormone-releasing hormone analogues (LHRHa) that develop castration resistance after a follow-up period of 3 years. The secondary objective is to evaluate the variables potentially related to the progression to castration resistant prostate cancer (CRPC). METHODS: A post-authorization, nation-wide, multicenter, prospective, observational, and longitudinal study that included 416 patients treated with LHRHa between 2012 and 2017 is presented. Patients were followed for 3 years or until development of CRPC, thus completing a per-protocol population of 350 patients. A Cox regression analysis was carried out to evaluate factors involved in progression to CRPC. RESULTS: After 3 years of treatment with LHRHa 18.2% of patients developed CRPC. In contrast, in the subgroup analysis, 39.6% of the metastatic patients developed CRPC, compared with 8.8% of the non-metastatic patients. The patients with the highest risk of developing CRPC were those with a nadir prostate-specific antigen (PSA) > 2 ng/ml (HR 21.6; 95% CI 11.7-39.8; p < 0.001) and those receiving concomitant medication, most commonly bicalutamide (HR 1.8; 95% CI 1-3.1, p = 0.0431). CONCLUSIONS: The proportion of metastatic patients developing CRPC after 3 years of treatment with LHRHa is consistent with what has been previously described in the literature. In addition, this study provides new findings on CRPC in non-metastatic patients. Concomitant medication and nadir PSA are statistically significant predictive factors for the time to diagnosis of CRPC, the nadir PSA being the strongest predictor.

Bone mass behavior after 1 year of different treatment strategies in prostate cancer patients subjected to androgen deprivation therapy.

The aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray absorptiometry was performed at baseline and after 1 year. Bone mass changes at the L2-L4 lumbar spine, femoral neck and total hip were evaluated. No differences were found at baseline. After 1 year, men receiving denosumab or alendronate (Group 1 and 2) showed a significant bone mass increase at the lumbar spine (+2.4 and +5.0 %, respectively), while no significant changes were observed in Group 3 and 4. At the femoral neck, Group 1 and 2 patients showed a significant bone mass increase (+3.7 and +3.6 %, respectively), while no significant changes were observed in Group 3 and 4. At the total hip, we observed a significant bone mass increase in Group 1 (+2.9 %) and a significant bone mass loss in Group 3 patients (-1.9 %). No significant changes were observed in Group 2 and 4. Denosumab increased significantly bone mass in all three dual X-ray absorptiometry standard sites, while alendronate did not at total hip. No benefit was observed in men previously treated with alendronate who switched to denosumab treatment.

[Priapism secondary to penis infiltration of bladder cancer]. / Priapismo secundario a infiltración peneana por contigüidad de carcinoma vesical infiltrante.

Metastasic priapism is a rare entity produced by tumor cell implantation or direct infiltration of corpora cavernousum of the penis. In up to 80% of cases the primary tumor has an urological origen like prostate or bladder cancers. Treatment depends on syntomatology and patient's prognosis. Generally, average survival in these patients is poor due to metastasic progression, among 1 to 1 and a half years. We present a case report of secondary priapism for direct invasion of the corpora cavernousum of the penis for bladder carcinoma.

Priapismo secundario a infiltración peneana por contigüidad de carcinoma vesical infiltrante / Priapism secondary to penis infiltration of bladder cancer

El priapismo de origen metastático es una entidad muy poco frecuente que se produce por implantación de células tumorales, o bien, por invasión directa por contigüidad de los cuerpos cavernosos. Hasta en un 80% de los casos el origen de los tumores primarios es genitourinario, principalmente por tumores prostáticos y vesicales. El tratamiento dependerá de la sintomatología que produzca y del pronóstico del paciente; pero generalmente, la supervivencia al año es muy pobre debido a que presentan una neoplasia en fase metastásica. Presentamos un caso de priapismo por invasión por contigüidad de los cuerpos cavernosos secundario a un carcinoma vesical (AU)

Metastasic priapism is a rare entity produced by tumor cell implantation or direct infiltration of corpora cavernousum of the penis. In up to 80% of cases the primary tumor has an urological origen like prostate or bladder cancers. Treatment depends on syntomatology and patient’s prognosis. Generally, average survival in these patients is poor due to metastasic progression, among 1 to 1 and a half years. We present a case report of secondary priapism for direct invasion of the corpora cavernousum of the penis for bladder carcinoma (AU)

[Transitional cell carcinoma relapse in uretero-ileal conduit after radical cystectomy]. / Recidiva de carcinoma transicional en conducto uretero-ileal tras cistectomía radical.

Transitional cell carcinoma relapse in ileal conduit after radical cistectomy is a rare event, especially without upper urinary tract involvement. We describe a case of uretero-ileal transitional cell tumour five years after cistectomy for invasive urothelial tumour. Patient underwent endoscopic treatment with good results after 13 months of follow-up.

Recidiva de carcinoma transicional en conducto uretero-ileal tras cistectomía radical / Transitional cell carcinoma relapse in uretero-ileal conduit after radical cistectomy

La recidiva de un tumor urotelial en el conducto uretero-ileal tras una cistectomía es poco frecuente, especialmente sin afectación del tracto urinario superior. Presentamos un caso de afectación de la unión uretero-ileal por tumor urotelial en un paciente cistectomiazado desde hacía 5 años por un tumor vesical infiltrante, al cual se le somete a un tratamiento endoscópico de su lesión con buenos resultados a los 13meses de seguimiento (AU)

Transitional cell carcinoma relapse in ileal conduit after radical cistectomy is a rare event, especially without upper urinary tract involvement. We describe a case of uretero-ileal transitional cell tumour five years after cistectomy for invasive urothelial tumour. Patient underwent endoscopic treatment with good results after 13 months of follow-up (AU)

Cistectomía radical laparoscopica en los tumores vesicales clínicamente localizados. (T2) / Laparoscopic radical cystectomy in clinically localized (T2) bladder tumors

Objetivo: La cistectomía radical laparoscópica se ha desarrollado a partir de la expansión de la prostatectomía radical laparoscópica. Esta técnica permite un abordaje poco invasivo para el tratamiento de los tumores vesicales infiltrantes de la capa muscular con disminución del sangrado y una más rápida recuperación postoperatoria. Métodos: Entre septiembre de 2004 y enero de 2007 se han realizado 54 cistectomías radicales por vía laparoscópica, 48 en estadio T2 y de estas últimas 43 (90%) eran varones y 5 (10%) mujeres. La edad media fue de 64 años (27-88a). La linfadenectomía se practicó por acceso laparoscópico en todos los casos, obteniendo una media de 13 ganglios (4-24). La derivación urinaria se realizó por la incisión de extracción del espécimen en todos los casos menos uno que se realizó completamente intracorpóreo, siendo ureteroileostomía cutánea tipo Bricker en 30 casos (62%), neovejiga ortotópica tipo Padovana en 17 casos (35%) y ureterostomía cutánea en un caso (2%). Resultados: El tiempo quirúrgico medio de todo el procedimiento fue de 287 minutos (180-480), 270 minutos para los casos con derivación tipo Bricker y de 316 para los casos con una neovejiga. El índice de transfusión fue del 25%. El tiempo medio de íleo paralítico fue de 5 días (2-10d) con un tiempo medio de ingreso para los pacientes con Bricker de 13 días (6-34) y de 16 días (8-30) para las neovejigas. El control oncológico, con un seguimiento medio de 10,8 meses (0,4-30m), presenta una supervivencia cáncer específica del 90% con un tiempo medio de supervivencia estimado de 28 meses (IC 95% 26-30). La supervivencia media global ha sido del 79% con un tiempo de supervivencia de 26 meses (IC 95% 23-29). Conclusiones: La cistectomía radical laparoscópica es una técnica factible que ofrece ventajas. Permite una exéresis con un menor sangrado y un postoperatorio más llevadero. Estudios aleatorizados deberían demostrar estas ventajas para confirmar si puede llegar a ser la técnica de elección. La realización de la derivación urinaria por la laparotomía, obligada para la extracción de la pieza quirúrgica, optimiza los resultados de la derivación y el tiempo quirúrgico total sin reducir los beneficios de la exéresis laparoscópica (AU)

Objectives: Laparoscopic radical cystectomy has been developed after the expansion of laparoscopic radical prostatectomy. This technique makes possible a minimally invasive approach to muscle-invasive bladder cancer with less blood loss and faster postoperative recovery. Methods: From September 2004 to January 2007, 54 laparoscopic radical cystectomies were performed, 48 of them in stage T2, from which 43 (90%) were male and 5 (10%) female patients. Mean age was 64 years (27-88). Lymphadenectomy was carried out by laparoscopic approach in all cases, with a mean of 13 nodes obtained (4-24). Urinary diversion was done through the incision needed to extract the specimen in all cases but one that was completed completely intracorporeally; constructing a Bricker-type ureteroileostomy in 30 (62%) cases, orthotopic neobladder (Vesica Ileale Padovana) in 17 cases (35%), and cutaneous ureterostomy in 1 case (2%). Results: Mean surgical time for the whole procedure was 287 minutes (180-480), 270 minutes for Bricker-type derivation cases and 316 minutes for neobladder cases. Blood transfusion rate was 25%. Mean ileal paralysis was 5 days (2-10) with a mean hospital stay of 13 days (6-34) for Bricker cases and 16 days (8-30) for neobladder cases. Oncological control, after a mean follow-up of 10,8 months (0,4-30), showed a cancer-specific survival of 90% with a mean survival time of 28 months (95% CI 26-30). Global mean survival was 79% with a mean survival of 26 months (95% CI 23-29). Conclusions: Laparoscopic radical cystectomy is a feasible technique that offers some advantages. It allows excision with less blood loss and an easier postoperative period. Randomized studies should demonstrate these advantages to confirm this approach as the technique of choice. Urinary diversion performed through the laparotomy incision, necessary to extract the specimen, optimizes derivation results and whole surgical time without reducing the beneficial effects of the laparoscopic exeresis (AU)

[Laparoscopic radical prostatectomy: learning curve with a mentor training program]. / Prostatectomía radical laparoscópica: la curva de aprendizaje con tutor.

INTRODUCTION: We describe and evaluate the results of our mentor training program for laparoscopic radical Prostatectomy (LRP). MATERIAL AND METHODS: From March 2004 through December 2005, we have performed 105 (LRP). Three groups have been analysed: Group 1: The mentor as the first surgeon with the trainee acting as the assistant. Group 2: The trainee as the first surgeon with the mentor acting as the assistant. Group 3: The trainee as the first surgeon with another trainee/resident as the assistant. We have evaluated operative, postoperative data and surgical/oncological control. RESULTS: There was no statistical difference in mean operative time in Groups 2 and 3 (200'-198'), but there was a difference from Group 1 (148,4') (p<0,05) we have observed a progressive operative time decrease only in Group 1. Blood loss, surgical-oncological control, pathological stage and hospital stay have been similar in the three groups. CONCLUSIONS: Skills for LRP can be effectively and safely taught by the presence of an experienced mentor. Waiting for long term results according to potency and continence, it was not associated to higher patient risk, neither to a worse surgical/oncologic outcome. We consider that this program is reproducible and allows a shorter learning curve.

[Comparison between open and laparoscopic approach in radical prostatectomy]. / Prostatectomia radical laparoscópica versus abierta.

INTRODUCTION: To evaluate the differences between laparoscopic (LRP) and open radical prostatectomy (ORP). MATERIAL AND METHODS: From 2004 to 2005 180 Radical prostatectomies (RP) were performed, 105 laparoscopical and 75 by an open approach. Different urologists have acted as first surgeon; 51% of them, fully experienced ones in OPR, and 56% in LRP. Differences in operative time, estimated blood loss (difference of pre and post operative hematocrite), and duration of hospitalization were compared. Additionally, we have also analysed surgical and oncologic control of the specimen defined by the following variables: Malignant margins (MM) (positive margin in a pT3 specimen), and benign/malign surgical incision (BSI/MSI). RESULTS: Groups were similar concerning age, clinical stage and Gleason score, and there are only differences in PSA. Mean operative time was significantly higher in LRP (172 minutes) versus ORP (145 minutes) (p < 0.001). Difference of pre and post operative hematocrite was also higher in the open group (10.7 vs 9.2) (p = 0.03), together with hospital stay, which was one day longer in the ORP group (p = 0.001). ORP group had a higher rate of benign surgical incisions (48.7% vs 26.7%) (p = 0.001). Regarding oncologic results, LRP presented a 5.4% of positive margins, which compared significantly with a 16.9% rate in the open group (p = 0.023). However, no differences concerning malignant surgical incisions were observed. CONCLUSION: With no differences in clinical and pathological stage, LRP offers a significant reduction of surgical aggressiveness on the specimen, together with a better MM control. We also observe a clear decrease in blood loss and hospital stay. Therefore, we conclude that LRP in our environment is a valid approach of surgical prostate cancer treatment in spite of a longer operative time (27 minutes) and a steep learning curve.

Prostatectomía radical laparoscópica: la curva de aprendizaje con tutor / Laparoscopic radical prostatectomy: learning curve with a mentor training program

Objetivos: Exponer con detalle el sistema de aprendizaje de la prostatectomía radical laparoscópica (PRL) con tutor llevado a cabo en nuestro centro así como los resultados. Material y métodos: Se realiza el análisis de variables intraquirúrgicas, postoperatorias y del control quirúrgico y oncológico de la pieza, de 105 PRL (marzo 2004-diciembre 2005) según los siguientes grupos: Grupo 1: tutor como primer cirujano y alumno como asistente. Grupo 2 alumno como primer cirujano y el tutor como ayudante. Grupo 3: alumno como primer cirujano y otro alumno/residente como ayudante. Resultados: No se han observado diferencias significativas en cuanto la media de tiempo quirúrgico (TQ) entre el grupo 2 y 3 (188’-170’, p=0,09). Ésta ha sido menor en el Grupo 1 (150’, p<0,05), disminuyendo con el tiempo. La pérdida sanguínea, el control quirúrgico-oncológico, el estadio patológico y el tiempo de estancia hospitalaria han sido similares en los tres grupos. Conclusiones: La presencia de un laparoscopista experto como tutor permite aprender la PRL de manera segura y efectiva. En espera de los resultados funcionales y oncológicos a largo plazo, este sistema de aprendizaje no se asocia ni con un mayor riesgo para el paciente ni con un peor control quirúrgico/oncológico. Consideramos que este método es fácilmente reproducible y permite un acortamiento de la curva de aprendizaje

Material and Methods: From March 2004 through December 2005, we have performed 105 (LRP). Three groups have been analysed: Group 1: The mentor as the first surgeon with the trainee acting as the assistant. Group 2: The trainee as the first surgeon with the mentor acting as the assistant. Group 3: The trainee as the first surgeon with another trainee/resident as the assistant. We have evaluated operative, postoperative data and surgical/oncological control. Results: There was no statistical difference in mean operative time in Groups 2 and 3 (200’-198’), but there was a difference from Group 1 (148,4’) (p<0,05) we have observed a progressive operative time decrease only in Group 1. Blood loss, surgical-oncological control, pathological stage and hospital stay have been similar in the three groups. Conclusions: Skills for LRP can be effectively and safely taught by the presence of an experienced mentor. Waiting for long term results according to potency and continence, it was not associated to higher patient risk, neither to a worse surgical/oncologic outcome. We consider that this program is reproducible and allows a shorter learning curve

Prostatectomía radical laparoscópica versus abierta / Comparison between open and laparoscopic approach in radical prostatectomy

Objetivos. Analizar las diferencias entre la prostatectomía radical abierta (PRA) y la prostatectomía radical laparoscópica (PRL). Material y métodos. Se evalúan 180 cirugías prostáticas radicales realizadas en el 2004 y 2005, de las cuales 105 (58%) fueron laparoscópicas (PRL) y 75 (42%) por vía abierta. Más de la mitad de las intervenciones se realizaron por cirujanos expertos: 51% en las PRL y 56% en las PRA. Se compararon las variables: tiempo quirúrgico, sangrado intraoperatorio (diferencia entre hematocrito prequirúrgico y postquirúrgico) y los días de ingreso. El control oncológico y quirúrgico se evaluaron mediante los parámetros: margen maligno (MM) (margen positivo en un pT3) e incisión quirúrgica benigna (IQB) y maligna (IQM). Resultados. Los dos grupos son comparables respecto a la edad, estadio clínico, Gleason de la biopsia y volumen, sólo difiriendo en el valor de PSA. La media del tiempo quirúrgico fue significativamente mayor en la PRL (172 minutos) versus la PRA (145 minutos). La diferencia del hematocrito fue mayor en la PRA (10,7 puntos) respecto a la PRL (9,2 puntos) (p=0,03), así como los días de ingreso, representando un día más en la PRA (p=0,001). Un 26,7% de las PRL han presentado IQB, frente a un 48,7 % en las PRA (p=0,001). Desde el punto de vista oncológico se han observado un 5,4% de MM en las PRL versus un 16,9% en las PRA. (p=0,023). No obstante, no se han observado diferencias respecto a las IQM. Conclusión. En la PRL, a igualdad de estadio clínico y patológico, se observa un mejor control de los márgenes junto con una menor afectación quirúrgica de la pieza. También existe una menor pérdida sanguínea así como una reducción de los días de ingreso. Por tanto, se puede concluir que la PRL es, en nuestro entorno, una técnica válida para el tratamiento del cáncer de próstata organoconfinado, a pesar de un mayor tiempo quirúrgico (27 minutos) y de la dificultad de su aprendizaje

Introduction. To evaluate the differences between laparoscopic (LRP) and open radical prostatectomy (ORP). Material and Methods. From 2004 to 2005 180 Radical prostatectomies (RP) were performed, 105 laparoscopical and 75 by an open approach. Different urologists have acted as first surgeon; 51% of them, fully experienced ones in OPR, and 56% in LRP. Differences in operative time, estimated blood loss (difference of pre and post operative hematocrite), and duration of hospitalization were compared. Additionally, we have also analysed surgical and oncologic control of the specimen defined by the following variables: Malignant margins (MM) (positive margin in a pT3 specimen), and benign/malign surgical incision (BSI/MSI). Results. Groups were similar concerning age, clinical stage and Gleason score, and there are only differences in PSA. Mean operative time was significantly higher in LRP (172 minutes) versus ORP (145 minutes) (p<0.001). Difference of pre and post operative hematocrite was also higher in the open group (10.7 vs 9,2) (p=0.03), together with hospital stay, which was one day longer in the ORP group (p=0.001). ORP group had a higher rate of benign surgical incisions (48.7% vs 26.7%) (p=0.001). Regarding oncologic results, LRP presented a 5.4 % of positive margins, which compared significantly with a 16.9% rate in the open group (p=0.023). However, no differences concerning malignant surgical incisions were observed. Conclusion. With no differences in clinical and pathological stage, LRP offers a significant reduction of surgical aggressiveness on the specimen, together with a better MM control. We also observe a clear decrease in blood loss and hospital stay. Therefore, we conclude that LRP in our environment is a valid approach of surgical prostate cancer treatment in spite of a longer operative time (27 minutes) and a steep learning curve

[Current status of radical laparoscopic prostatectomy]. / Estado actual de la prostatectomía radical laparoscópica.

Laparoscopic surgery can be said to have come of age when it was first indicated for cancer conditions. Advances in this field are largely due to the French school, which has made it a standard practise in prostate cancer. It complies with the principles required for cancer as well as conventional surgery, but it remains to be verified whether its long-term results, both from tumoral and functional perspectives, are not only similar to those of classical surgery, but even better. In fact, increasing numbers of clinical groups are incorporating this technique in their daily work.

Estado actual de la prostatectomía radical laparoscópica / Current status of radical laparoscopic prostatectomy

La cirugía laparoscópica puede considerarse que ha alcanzado la mayoría de edad al indicarse en la patología oncológica, y debe su desarrollo a las escuelas francesas que sistematizaron su empleo en el cáncer prostático. Cumple los principios que ha de seguir la cirugía oncológica, al igual que la cirugía convencional, pero queda aún por demostrar que los resultados a largo plazo, tanto desde el punto de vista tumoral como el funcional sean mejores que la cirugía clásica. Cada vez son más los grupos que están incorporando estas técnicas a su quehacer diario

Laparoscopic surgery can be said to have come of age when it was first indicated for cancer conditions. Advances in this field are largely due to the French school, which has made it a standard practise in prostate cancer. It complies with the principles required for cancer as well as conventional surgery, but it remains to be verified whether its long-term results, both from tumoral and functional perspectives, are not only similar to those of classical surgery, but even better. In fact, increasing numbers of clinical groups are incorporating this technique in their daily work

[Intraprostatic embolization of cholesterol crystals]. / Embolización intraprostática de cristales de colesterol.

The cholesterol embolism syndrome (CES) is an unusual disease that carries a high mortality rate. Finding intraprostatic cholesterol crystal embolization as the result of transrectal prostate biopsy in a patient with several risk factors for atherosclerosis, should alert the urologist to the possibility of CES existence.

Embolización intraprostática de cristales de colesterol / Intraprostatic embolization of cholesterol crystals

La Enfermedad por émbolos de colesterol (EEC) es una patología poco conocida pero con una alta mortalidad asociada. La presencia de embolias de cristales de colesterol a nivel intraprostático como hallazgo poco común en las biopsias prostáticas transrectales en un enfermo con factores de riesgo tromboembólico, debe alertarnos sobre la posible existencia de la EEC

The cholesterol embolism syndrome (CES) is an unusual disease that carries a high mortality rate. Finding intraprostatic cholesterol crystal embolization as the result of transrectal prostate biopsy in a patient with several risk factors for atherosclerosis, should alert the urologist to the possibility of CES existence