Focal Therapy of Prostate Cancer Index Lesion With Irreversible Electroporation. A Prospective Study With a Median Follow-up of 3 Years.

PURPOSE: Our aim was to assess oncologic, safety, and quality of life-related outcomes of focal therapy with irreversible electroporation in men with localized prostate cancer. MATERIALS AND METHODS: This was a single-center, phase II study. INCLUSION CRITERIA: prostate cancer International Society of Urological Pathology grade 1-2, prostate specific antigen ≤15 ng/ml, ≤cT2b. Patients were selected based on multiparametric magnetic resonance imaging and transperineal systematic and targeted magnetic resonance imaging-ultrasound fusion-guided biopsy. Ablation of index lesions with safety margin was performed. Primary end point was cancer control, defined as the absence of any biopsy-proven tumor. A control transperineal biopsy was planned at 12 months and when suspected based on prostate specific antigen and/or multiparametric magnetic resonance imaging information. Quality of life was assessed using Expanded Prostate Cancer Index Composite Urinary Continence domain, International Index of Erectile Function, and International Prostate Symptom Score. RESULTS: From November 2014 to July 2021, 41 consecutive patients were included with a median follow-up of 36 months. Thirty patients (73%) had International Society of Urological Pathology grade 1 tumors, 10 (24%) grade 2, and 1 (2.4%) grade 3. Recurrence was observed in 16 of 41 (39%) of the whole cohort, and 16 of 33 (48.4%) who underwent biopsy. In-field recurrence was detected in 5 (15%) and out-of-field in 11 (33.3%). Ten of 41 (24.6%) including 3 of 5 (60%) with in-field recurrences had significant tumors (Gleason pattern 4-5; more than 1 core or any >5 mm involved). Median recurrence-free survival was 32 months (95% CI 6.7-57.2). Twenty-six patients (63.4%) were free from salvage treatment. All patients preserved urinary continence. Potency was maintained in 91.8%. CONCLUSIONS: Irreversible electroporation can achieve satisfactory 3-year in-field tumor control with excellent quality of life results in selected patients.

[Prognostic factors and response predictors in castration resistant prostate cancer.] / Factores pronósticos y predictores de respuesta en cáncer de próstata resistente a la castración.

Prostate cancer is a health problem in many Countries worldwide. Understanding the essential function of androgens in the prostate physiology led to the development of hormonal blockade as a therapeutic option in advanced disease, with limited response with time and development of resistance. In this stage, where castration resistant prostate cancer (CRPC) is defined, it is associated with poor prognosis because survival varies between 18 and 24 months. Even with castration levels, tumors are dependent on the functional androgen receptor (AR). In this paper, we analyze pretreatment clinical parameters such as prognostic or progression-predictive biomarkers, castration resistance mechanisms, the development of new technologies for the use of the so called liquid biopsies from biological ayufluids and the identification of circulating tumor cells as CRPC response and progression biomarkers. Currently ongoing clinical trials are partially oriented to the search of new prognostic and predictive biomarkers, that will enable to open up precision medicine and so to improve oncological patient's quality of life with it.

[Immunotherapy in castration resistant prostate cancer.] / Inmunoterapia en cáncer de próstata resistente a la castración.

We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity. Generally, the objective response rate is very low, although, in patients who have response it is possible to detect a clear, long-lasting benefit. Only the autologous vaccine Sipuleucel T has demonstrated an overall survival increase in patients with good prognosis criteria. In these treatments, it is characteristic that no progression free survival increase is visible due to its action mechanism. PSA evolution may not be considered a surrogate variable of radiological response or clinical benefit in this environment either. It is necessary to identify what patient's or tumor's characteristics are able to maximize the response. An important limitation is the absence of response predictive biomarkers that serve for patient preselection. As a general rule, the best responses with isolated immunotherapeutic treatments have been observed in patients with low tumor load, which may suggest that their optimal application could be in earlier phases of the disease (high risk localized, biochemical failure, etc) Combination strategy, without doubt the one with best future, is based on additional treatments increasing cell lysis with the subsequent antigen exposure and/ or producing an immunomodulatory effect that can surmount tumor induced immunologic tolerance. The results obtained suggest that immunotherapy may be more effective in combined therapy with other active therapies (abiraterone, enzalutamide, Radium 223, docetaxel) in a fight to achieve disease chronification.

Inmunoterapia en cáncer de próstata resistente a la castración / Immunotherapy in castration resistant prostate cancer

Revisamos el papel de la inmunoterapia en el cáncer de próstata resistente a castración. Se han aplicado dos estrategias inmunoterápicas, de forma aislada o en combinación, bien entre ellas o bien con otros agentes de eficacia demostrada en este escenario y que ejercerían un papel inmunomodulador: vacunas o anticuerpos monoclonales destinados al bloqueo de puntos de control inhibidores de la respuesta inmune. Aunque a priori el CPRC presenta características que sugieren que la inmunoterapia podría jugar un papel relevante como estrategia terapéutica, su aplicación clínica ha demostrado una actividad limitada y heterogénea, en cuanto a la proporción de respondedores e intensidad de respuesta. En términos generales, la tasa de respuestas objetivas es muy baja, aunque, en los pacientes que responden, es posible detectar un beneficio claro y duradero. Sólo la vacuna autóloga Sipuleucel T ha demostrado un aumento de la supervivencia global en pacientes con criterios de buen pronóstico. Es característico en estos tratamientos que no se observe un incremento en la supervivencia libre de progresión debido a su propio mecanismo de acción. Tampoco la evolución del PSA puede considerarse una variante subrogada de respuesta radiológica o beneficio clínico en este entorno. Se hace necesario identificar qué características de los pacientes o del tumor son capaces de maximizar la respuesta. Una limitación importante es la ausencia de biomarcadores predictores de respuesta que sirvan para la preselección de pacientes. Como norma general, las mejores respuestas con tratamientos inmunoterápicos aislados se han observado en pacientes con baja carga tumoral, lo cual puede sugerir que su aplicación óptima podría ser en fases más precoces de la enfermedad (localizado de alto riesgo, fracaso bioquímico, etc.). La estrategia de combinación, sin lugar a dudas la de más futuro, se fundamenta en que los tratamientos adicionales incrementan la lisis celular con la consiguiente exposición antigénica y/o ejercen un efecto inmunomodulador capaz de vencer la tolerancia inmunológica inducida por el tumor. Los resultados obtenidos sugieren que la inmunoterapia puede ser más efectiva en modo tratamiento combinado con otros tratamientos activos (abiraterona, enzalutamida, Radio 223, docetaxel) en la lucha por lograr cronificar la enfermedad

We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity. Generally, the objective response rate is very low, although, in patients who have response it is possible to detect a clear, long-lasting benefit. Only the autologous vaccine Sipuleucel T has demonstrated an overall survival increase in patients with good prognosis criteria. In these treatments, it is characteristic that no progression free survival increase is visible due to its action mechanism. PSA evolution may not be considered a surrogate variable of radiological response or clinical benefit in this environment either. It is necessary to identify what patient`s or tumor's characteristics are able to maximize the response. An important limitation is the absence of response predictive biomarkers that serve for patient preselection. As a general rule, the best responses with isolated immunotherapeutic treatments have been observed in patients with low tumor load, which may suggest that their optimal application could be in earlier phases of the disease (high risk localized, biochemical failure, etc) Combination strategy, without doubt the one with best future, is based on additional treatments increasing cell lysis with the subsequent antigen exposure and/ or producing an immunomodulatory effect that can surmount tumor induced immunologic tolerance. The results obtained suggest that immunotherapy may be more effective in combined therapy with other active therapies (abiraterone, enzalutamide, Radium 223, docetaxel) in a fight to achieve disease chronification

Carcinoma verrucoso de pene: a propósito de dos casos / Verrucous carcinoma of the penis: report of two cases

OBJETIVO: El carcinoma verrucoso de pene es un tumor raro que supone aproximadamente el 1 por ciento de los tumores en el varón. Sus características clínicas le confieren una evolución y manejo característicos. MÉTODO Y RESULTADOS: Se presentan dos casos de pacientes de 86 y 51 años, a los que se realizó penectomía parcial y glandectomía respectivamente. Se revisan las características anatomopatológicas así como su pronóstico. CONCLUSIONES: El tumor verrucoso de pene se presenta como una lesión exofítica, (generalmente en glande o prepucio), que debe diferenciarse del carcinoma epidermoide, de peor pronóstico y de distinto manejo terapéutico. El diagnóstico diferencial se realiza mediante biopsia y estudio anatomopatológico. Es un tumor de buen pronóstico en el que se puede realizar cirugía conservadora (penectomía parcial) (AU)

Carcinoma de epidídimo. Revisión bibliográfica con motivo de un caso / Carcinoma of the epididymis : Case report and literature review

OBJETIVO: Describir un caso de carcinoma de epidídimo de crecimiento paratesticular de origen epitelial, y realizar una breve revisión de la literatura existente sobre este tipo tumoral. MÉTODO/RESULTADOS: Presentamos un caso de un varón de 69 años de edad que consultó por una masa testicular y dolor intraescrotal, junto con síntomas de irritación vesical. Poco tiempo después de realizársele orquiectomía, acude de nuevo por persistencia del cuadro vesical. Una RTU-biopsia de la pared vesical demuestra carcinoma indiferenciado de origen epididimario. Se instaura tratamiento quimioterápico, a pesar del cual desarrolla metástasis sistémica, falleciendo cuatro meses después del diagnóstico. CONCLUSIONES: El carcinoma de epidídimo es un tumor raro maligno paratesticular de origen epitelial y de muy mal pronóstico.Dada la inespecificidad del cuadro clínico, es importante conocer esta entidad para realizar un correcto diagnóstico diferencial con otras causas de masa intraescrotal. Debido a la escasa frecuencia de aparición de este tipo anatomopatológico, no se ha podido identificar un tipo de tratamiento que obtenga unas respuestas aceptables (AU)

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