Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review).

PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.

Update on the treatment of metastatic renal cell carcinoma.

Metastatic renal cell cancer (mRCC) management has undergone a paradigm shift in recent decades. The first revolution came with the emergence of vascular endothelial growth factor inhibitors; there was a second wave with the unprecedented success of checkpoint inhibitors, and then the latest approach, which is becoming the new care standard in mRCC, of combining these two strategies in different ways. Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival (PFS), overall survival (OS), and objective response rate (ORR) in intermediate and high-risk patients. However, several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place, and so far, the only one for nivolumab/ipilimumab is the frontline setting. The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembroli-zumab/axitinib over sunitinib in favorable-risk mRCC, suggesting that it should no longer be the first line of choice in low-risk patients. Finally, the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS, OS, and ORR, providing a new first-line option among all International Metastatic RCC Database Consortium risk patients. Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib, cabozantinib/atezolizumab, and lenvatinib/pembrolizumab, providing promising grounds upon which to start phase III studies. In addition, other works are using novel therapeutic agents with different mechanisms of action, including telaglenastat (a glutaminase inhibitor), entinostat [an inhibitor of histone deacetylases (HDACs)], and olaparib and talazoparib, poly(ADP-ribose) polymerase inhibitors widely used in other tumors. However, some questions regarding mRCC management still need to be addressed, such as head-to-head comparisons between the current options, treatment sequencing, non-clear cell mRCC, and the role of biomarkers to ascertain the best treatment choice.

How to obtain a 3D printed model of renal cell carcinoma (RCC) with venous tumor thrombus extension (VTE) for surgical simulation (phase I NCT03738488).

This is the phase 1 of a multicenter clinical trial (NCT03738488), which aims to assess the efficacy and efficiency of surgery planning with 3D models of renal cell carcinoma (RCC) with venous tumor thrombus extension (VTE) compared to the standard images (CT). The objective of this phase is to obtain a 3D printed model of RCC with VTE that is feasible, accurate, reproducible, suitable for surgical simulation, and affordable. A specific protocol was developed to obtain the computed tomography (CT) image: early arterial and nephrogenic phase. ITK-snap® and VirSSPA Software® were used to segment the areas of interest. The resulting 3D mesh was processed with MeshMixer® and Cura®. Ten models from seven different cases were segmented and printed using different 3D printers and materials. We evaluated the material, scale, wall thickness, anatomy printed, 3D conformation, accuracy compared to the CT, suitability to perform the surgery, material, cost, and time (segmentation + design + fabrication + finishing). The four selected models were printed with a BQ Witbox FDM printer in polyurethane filament with a 0.8 mm wall thickness and 100% scale. All the relevant anatomical structures could be correctly identified, the 3D conformation was maintained with good accuracy compared to the CT and the surgery could be performed on them. Mean design time, model cost and printing time were 8.3 h, 33.4 €, and 38.5 h respectively. Various feasible 3D models of RCC with VTE were obtained after a few attempts. The final models were proved to be reproducible, accurate compared to the CT, and suitable for surgery simulation. The printing process was standardized making it possible to manufacture affordable 3D printed models.

Manejo laparoscópico transperitoneal de la enfermedad litiásica: experiencia en un hospital de tercer nivel / Transperitoneal laparoscopic management of urinary tract stone disease: experience in a third level hospital

OBJETIVO: Analizar la relación existente entre trombocitosis y hematocrito prequirúrgicos y supervivencia en nuestra serie de pacientes tratados quirúrgicamente por adenocarcinoma renal.MÉTODO: Estudio retrospectivo con análisis descriptivo estadístico de 139 pacientes intervenidos quirúrgicamente en nuestro servicio en los últimos 4 años por adenocarcinoma renal. 116 (83,45%) presentaban al diagnóstico un estadio clínico localizado, y 23 (16,54%) un estadio localmente avanzado o metastásico. Fueron recogidos datos relativos a tiempo de seguimiento y supervivencia, características iconográficas e histológicas del tumor y parámetros analíticos. Los datos fueron analizados con estadístico SPSS.RESULTADOS: El recuento plaquetario medio previo a la intervención quirúrgica fue de 260930 cels/mm3. El hematocrito medio prequirúrgico fue de 41,10%. Se encontró una relación estadísticamente significativa (p=0,04) entre el recuento plaquetario al diagnóstico y la supervivencia. Pacientes con recuentos plaquetarios superiores a 350000/mm3 presentaban una supervivencia más baja (OR: 2,94; IC 95% 1,04- 8,27). Se objetivó una relación significativa (p=0,049) entre el hematocrito al diagnóstico y la supervivencia. A mayor hematocrito disminuyó el riesgo de muerte (OR: 0,92; IC 95% 0,85- 0,99). La supervivencia global en nuestro grupo fue del 88,4%. El análisis multivariante de la misma no arrojó datos estadísticamente significativos debido al escaso número de éxitus.CONCLUSIONES: La presencia de recuentos plaquetarios elevados o niveles de hematocrito bajos al diagnóstico se relacionan, en esta serie y de forma no independiente, con una disminución de la supervivencia en nuestro grupo de pacientes intervenidos por adenocarcinoma renal. Serían necesarios estudios con mayor seguimiento y muestras más amplias para aseverar estos hallazgos(AU)

OBJECTIVE: To examine the connection between preoperative thrombocytosis and hematocrit and survival in a group of patients operated for renal cell carcinoma.METHODS: Retrospective study with descriptive and statistical analysis of 139 patients with renal cell carcinoma treated surgically over the last 4 years in our Urology clinical unit. 116 (83,45%) were diagnosed at a localized clinical stage, whereas 23 (16,54%) presented as locally advanced or metastatic disease. We collected data about survival and time on surveillance, imaging and histological characteristics of the tumor and analytical parameters. Data were analyzed by the SPSS statistical software.RESULTS: The average platelet count and hematocrit before surgery were 260,930 cells/mm3 and 41.10%, respectively. We found a statistical correlation between platelet count at the time of diagnosis and survival. Patients with platelet counts higher than 350,000 cells/mm3 had a poor survival (OR: 2.94; CI 95% 1.04- 8.27). We also found that patients with high hematocrit at diagnosis presented a lower risk of death (OR: 0.92; CI 95% 0.85- 0.99). The global survival at the end of the study was 88.4%. Multivariate analysis did not show any significant result because of the low number of deaths.CONCLUSION: The presence of high platelet count or low hematocrit correlate with poor survival in a group of surgically treated renal cell carcinoma patients. Nevertheless more studies with longer surveillance and higher number of patients are needed(AU)

[Selective arterial embolization in the treatment of intractable hematuria]. / Embolización arterial selectiva en el tratamiento de la hematuria incoercible.

OBJECTIVES: Non tractable hematuria has a varied etiology. It may be a complication difficult to treat. We report the case treated in our hospital by selective arterial embolization. METHODS: We report the case of an 86-year-old patient who underwent radiotherapy for transitional cell carcinoma. Later on, she presented with hematuria, not responding to usual therapeutic management. Urinary diversion did not solve the problem either. We decided to proceed with selective arterial embolization of the hypogastric arteries using polyvinylalcohol microspheres and metallic coils. RESULTS: Hematuria disappeared after embolization, without the recurrence after nine months of follow-up. Immediate outcome was characterized by a post-embolization syndrome which was treated with antipyretics, antibiotic and morphine derivatives. It diminished progressively and disappeared in 48 hours. CONCLUSIONS: Arterial selective embolization is a useful therapeutic resource for the management of non tractable hematuria, mainly in cancer patients, which present a deteriorated general status.

Embolización arterial selectiva en el tratamiento de la hematuria incoercible / Selective arterial embolization in the treatment of non tractable hematuria

OBJETIVOS: La hematuria incoercible es uncuadro de etiología diversa. Puede ser una complicacióndifícil de controlar. Nos proponemos presentar un caso tratadoen nuestro hospital con embolización arterial selectiva.MÉTODOS: Comunicamos el caso de una paciente de86 años sometida a tratamiento radioterápico debido aneoplasia urotelial. Presentó posteriormente una hematuriaque no cedió a las medidas terapéuticas habituales.Tampoco la derivación urinaria solucionó el cuadro. Porello optamos por practicar una embolización arterial selectivade arterias hipogástricas, con microesferas de polivinilode alcohol y coils metálicos.RESULTADO: La hematuria desapareció desde el momentode la embolización, sin reaparecer en un tiempo deseguimiento de nueve meses. La evolución inmediata secaracterizó por un “síndrome post-embolización”, tratadocon antitérmicos, antibiótico y derivados mórficos. Cedióprogresivamente hasta desaparecer a las 48h.CONCLUSIONES: La embolización arterial selectiva esun recurso terapéutico útil para el manejo de hematuriasde difícil control, sobre todo en enfermos neoplásicos, yade por sí muy deteriorados

OBJECTIVES: Non tractable hematuria has ;;a varied etiology. It may be a complication difficult to ;;treat. We report the case treated in our hospital by selective ;;arterial embolization. ;;METHODS: We report the case of an 86-year-old patient ;;who underwent radiotherapy for transitional cell carcinoma. ;;Later on, she presented with hematuria, not responding to ;;usual therapeutic management. Urinary diversion did not ;;solve the problem either. We decided to proceed with ;;selective arterial embolization of the hypogastric arteries ;;using polyvinylalcohol microspheres and metallic coils. ;;RESULTS: Hematuria disappeared after embolization, ;;without the recurrence after nine months of follow-up. ;;Immediate outcome was characterized by a post-embolization ;;syndrome which was treated with antipyretics, antibiotic ;;and morphine derivatives. ;;It diminished progressively and disappeared in 48 hours. ;;CONCLUSIONS: Arterial selective embolization is a useful ;;therapeutic resource for the management of non tractable ;;hematuria, mainly in cancer patients, which present a ;;deteriorated general status

Cáncer renal: análisis descriptivo de una serie de 267 casos intervenidos / Renal Cancer: descriptive analysis of 267 surgically treated cases

OBJETIVO: Presentar los resultados obtenidos tras realizar el análisis descriptivo de nuestra serie de 267 tumores renales intervenidos. MÉTODO: Desde enero de 1986 a octubre de 1999 se intervinieron en nuestro Servicio 267 pacientes (153 hombres y 114 mujeres) afectos de tumor renal. La edad media fue de 60,23 años. Los datos se incluyeron en una base de datos creada en el programa Access, y posteriormente analizados mediante el paquete informático SPSS, realizándose un análisis descriptivo y calculando la expectativa de vida mediante la curva de supervivencia de Kaplan-Meier. La media de seguimiento fue de 42,72 meses. RESULTADOS: La incidencia de su localización fue del 56,4 por ciento derechos y el 43,6 por ciento restante izquierdos. El diagnóstico se realizó de forma incidental en el 41,2 por ciento de los casos. En los sintomáticos, el signo de presentación más frecuente fue la hematuria (51,8 por ciento). Se realizó nefrectomía radical en el 94,2 por ciento, parcial en el 3,1 por ciento y tumorectomía en el 2,7 por ciento. En el 75,5 por ciento de los casos la vía de abordaje fue lumbar. En cuanto a la histología, el 88,7 por ciento carcinomas. El tipo celular más frecuente resultó ser el de células claras (91,5 por ciento). El 55,8 por ciento GI, el 32,9 por ciento GII y el 11,3 por ciento GIII. En cuanto al Estadio (según la clasificación TNM de 1992): 64,3 por ciento Estadio I, 15,4 por ciento II, 17 por ciento III y 3,3 por ciento IV. El 80,5 por ciento no presentaba afectación vascular. La supervivencia global fue del 71,93 por ciento a los 5 años (media de 114 meses y mediana de 167 meses). En la actualidad el 76 por ciento de los pacientes se encuentran vivos. CONCLUSIONES: La distribución por sexos en nuestra serie difiere de lo publicado por la mayoría de los autores. El diagnóstico de forma incidental supone una proporción importante de los casos. La vía lumbar es la más empleada como acceso quirúrgico. La supervivencia global se asemeja a la comunicada por otros grupos (AU)