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.

Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial.

PURPOSE: The purpose of the study was to compare the outcomes of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) patients treated with BCG vs recirculating hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C (MMC). METHODS: A pilot phase II randomized clinical trial was conducted including HR-NMIBC patients, excluding carcinoma in situ. Patients were randomized 1:1 to receive intravesical BCG for 1 year (once weekly for 6 weeks plus subsequent maintenance) or HIVEC with 40 mg MMC, administered using the Combat BRS system (once weekly instillations were given for 6 weeks, followed by once monthly instillation for 6 months). Total recirculating dwell time for HIVEC was 60 min at a target temperature of 43° ± 0.5 °C. Primary endpoint was recurrence-free survival. Secondary endpoints were time to recurrence, progression-free survival, cancer-specific survival, and overall survival at 24 months. Adverse events were routinely assessed. RESULTS: Fifty patients were enrolled. Mean age was 73.5 years. Median follow-up was 33.7 months. Recurrence-free survival at 24 months was 86.5% for HIVEC and 71.8% for BCG (p = 0.184) in the intention-to-treat analysis and 95.0% for HIVEC and 75.1% for BCG (p = 0.064) in the per protocol analysis. Time to recurrence was 21.5 and 16.1 months for HIVEC and BCG, respectively. Progression-free survival for HIVEC vs BCG was 95.7% vs 71.8% (p = 0.043) in the intention-to-treat analysis and 100% vs 75.1% (p = 0.018) in the per protocol analysis, respectively. Cancer-specific survival at 24 months was 100% for both groups and overall survival was 91.5% for HIVEC vs 81.8% for BCG. CONCLUSION: HIVEC provides comparable safety and efficacy to BCG and is a reasonable alternative during BCG shortages. TRIAL REGISTRATION: EudraCT 2016-001186-85. Date of registration: 17 March 2016.

What is the impact of post-radical prostatectomy urinary incontinence on everyday quality of life? Linking Pad usage and International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) for a COMBined definition (PICOMB definition).

AIMS: To identify the definition for urinary continence (UC) after radical prostatectomy (RP) which reflects best patients' perception of quality of life (QoL). METHODS: Continence was prospectively assessed in 634 patients, 12 months after RP using the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) and the number of pads employed in a 24-hour period (pad usage). We used the one-way ANOVA technique with posthoc pairwise comparisons according to Scheffé's method (homogeneous subsets) for assessing the degree of QoL deficit related to urinary incontinence (UI). RESULTS: The continence prevalence is 64.4%, 74.1%, 88.3%, and 35.8% using "0 pads," "1 safety pad," "1 pad," and "ICIQ score 0" definitions, respectively. Pad usage is moderately strongly associated with ICIQ 1, 2, and 3 (ρ = 0.744, 0.677, and 0.711, respectively; p < 0.001). Concordance between classical UC definitions is acceptable between "0 pads-ICIQ score 0" (K = 0.466), but poor for "1 safety pad" and "1 pad" (K = 0.326 and 0.137, respectively). Patients with "0 pad usage" have better QoL related to urine leakage than patients with "1 safety pad" or "1 pad" (1.41 vs. 2.44 and 3.11, respectively; p < 0.05). There were no significant differences found regarding QoL between patients with ICIQ score 0 and ICIQ score 2 (1.01 vs. 1.63; p = 0.63). CONCLUSIONS: Pad usage and the ICIQ-SF's answers provide useful information. We propose a combined definition (0 pads and ICIQ score ≤2) as it is the definition with the least impact on daily QoL.

Implementing an action protocol on prostatic disease in primary care and impact on referrals to urology.

OBJECTIVES: To determine the impact of implementing a joint action protocol on prostatic disease on the referrals to Urology from Primary Care in a health care area. METHODS: We drafted a protocol for managing patients consulting for clinical signs and symptoms associated to benign prostatic hyperplasia (BPH) and to test PSA in asymptomatic males. At the same time, three e-mail addresses were opened for consultations generated from Primary Care, and joint sessions were carried out in the primary health care centers. We measured the impact of the protocol by assessing the adequacy of prostatic disease referrals to Urology, as well as by determining the course of the total number of referrals in three peripheral specialized health care centers (PSHCC). RESULTS: From January 2011, a better compliance to the referrals to Urology protocol for prostatic disease has been produced, going from 47% (assessment prior to implementing the protocol) to 64%. These results are especially good when we consider referrals associated to PSA, which went from a compliance of 33% to 84%. Regarding the course of the referrals to Urology, the referral rate (referrals per 1000 inhabitants) has decreased by 15% (from 13,8 to 11,7). CONCLUSIONS: The collaboration between Urology and Primary health care, by means of implementing joint protocols, and also by establishing new communication channels (e-mail, joint sessions), achieves a better adequacy of patients referred for prostatic disease, as well as a reduction in the total number of referrals.

Can partial nephrectomy preserve renal function and modify survival in comparison with radical nephrectomy?

OBJECTIVE: To investigate whether radical nephrectomy (RN) and nephron-sparing surgery (NSS) for T1 renal cell carcinoma influence renal function, oncological outcome or survival rate. MATERIAL AND METHODS: A retrospective study was performed, including 290 nephrectomies for tumours of a diameter of less than 7 cm; 174 radical nephrectomies were compared to 116 nephron-sparing surgeries. Preoperative and pathological data were compared between the two groups. The glomerular filtration rate was estimated using the abbreviated Modification of Diet and Renal Disease (MDRD4) study equation. The evolution of renal function was analysed from 6 months to 4 years after surgery, and the oncological outcomes were evaluated by means of cancer and non-cancer survival curves. RESULTS: The results showed a major impairment in renal function in the RN group compared to those who underwent NSS (25 vs 7 ml/min/1.73 m², 6 months after surgery), a difference that was maintained over time. Moreover, patients undergoing RN had a greater chance of developing renal failure. Overall, the survival curves showed a higher mortality rate for the RN group (p = 0.034), although the cancer-specific mortality rate did not show any statistically significant differences (p = 0.079). CONCLUSIONS: For stage T1 renal cortical tumours, NSS should, whenever possible, be regarded as the primary therapeutic option, given that it obtains similar oncological outcomes to RN and preserves renal function, which seems to translate into a lower overall mortality rate.

Testicular tumors: residual retroperitoneal mass surgery after chemotherapy;Is it possible to predict their histology?

OBJECTIVES: We present our series of residual retroperitoneal mass surgery after chemotherapy. We evaluate possible preoperative parameters that can predict the retroperitoneal mass histology. Survival and relapse rates were also evaluated. METHODS: We reviewed sixty resections of residual retroperitoneal masses of testicular tumours after chemotherapy performed at our department between 1995 and 2007. We evaluate the relationship between histology of the retroperitoneal mass and possible risk factors, such as outcomes after chemotherapy, which was evaluated as changes in the size of the retroperitoneal mass, and negativization of serum tumor markers. We also evaluate histology and size of the primary testicular cancer. RESULTS: The histology of retroperitoneal mass was necrosis or fibrosis in 25 (42%) cases, teratoma in 29 (48%) and viable tumor in 6 (10%). The size of the retroperitoneal mass decreased after the chemotherapy in 62% cases; moreover negative serum tumor markers were found in 87%. Elevated values of human chorionic gonadotropin were associated with viable cells in the retroperitoneal mass (p=0.014) and, the presence of teratoma in the primary tumor may be associated with teratoma in the retroperitoneal mass histology (p=0.002). However, no other preoperative factors that predict the residual mass histology were found. Repeated resections of retroperitoneal masses were required in four patients and 9 patients died during follow-up. CONCLUSIONS: We cannot determine preoperative parameters that accurately predict the histology of retroperitoneal masses. Therefore, resection of residual retroperitoneal masses after chemotherapy in non-seminomatous germ cell tumours must be performed.

Quality of life and adverse events in patients with nonmuscle invasive bladder cancer receiving adjuvant treatment with BCG, MMC, or chemohyperthermia.

INTRODUCTION: Chemohyperthermia (CHT) with mitomycin C (MMC) is together with Bacillus Calmette-Guérin (BCG), and passive MMC, a treatment option for patients with non muscle-invasive bladder cancer. There are no data published about the impact of CHT in quality of life (QoL). We evaluated QoL and adverse events (AE) in this 3-arm observational study. PATIENTS AND METHODS: Prospective observational study from September 2016 to March 2017, we recruited consecutive patients that received adjuvant treatment after transurethral resection of bladder tumor. Patients received induction courses of either BCG, CHT, or passive MMC. Patients filled the questionnaires Functional assessment of cancer therapy for bladder cancer patients (FACT-Bl) and International prostate symptom score (IPSS) before, during, and after the induction course. A urologist documented AE using Common Terminology Criteria for AE (CTCAE criteria). RESULTS: A total of 56 patients, receiving a total of 296 bladder instillations (BCG n = 27, CHT n = 14 and MMC n = 15). FACT-Bl showed statistically significant differences in the fourth week in favor of CHT versus BCG, IPSS did not show statistically significant differences before, during, and after induction course in all 3 arms. All patients recovered their baseline QoL at the end of the induction treatment. Overall 55.5%, 50% and 20% of patients presented any grade of AE in the BCG, CHT and MMC groups respectively. About 7% of patients in BCG and CHT arms had to discontinue treatment due to AE. BCG and CHT showed a similar rate of AE but in CHT were mostly grade I and BCG had grade I, II, and IV. Passive MMC had the safest profile. CONCLUSION: There are no clinically significant differences between BCG, CHT, and passive MMC regarding QoL and lower urinary tract symptoms during the induction course. CHT has a more favorable AE profile when compared with BCG.

Cystoscopy Real-Time Self-Visualization and Its Impact in Patient's Pain Perception.

OBJECTIVES: To determine if self-visualization of ambulatory cystoscopy provides a decrease in pain perception in male and female patients. METHODS: A quasi-randomized controlled trial involving patients scheduled for ambulatory cystoscopy from August to November 2017. The indications were: hematuria, bladder cancer surveillance, lower urinary tract symptoms, and incontinence. The patients were quasi-randomized into two groups by scheduled date. Both groups received the same explanation before and during cystoscopy. The variables analyzed were gender, age, Visual Analog Scale (VAS) score, number of previous cystoscopies, and indication and positivity of the test for bladder neoplasia. All patients were analyzed by group and gender separately. The statistical tests used were: Wilcoxon rank-sum, Kruskal-Wallis, Mann-Whitney U test, Pearson correlation, and linear regression. RESULTS: Four hundred four patients were included (318 males and 86 females) and divided into two groups, group A (no self-visualization, n = 239) and group B (self-visualization, n = 165). In males, mean VAS score was 2.6 for group A and 2.5 for group B (p = 0.276); in females, VAS score was 2.78 for group A and 1.64 for group B (p = 0.008). Regarding the remaining variables analyzed, neither positivity of the test for neoplasia (p = 0.14) nor cystoscopy indication (p = 0.597) had any influence. In patients with two or more previous cystoscopies, a reduction in mean VAS score was seen in both genders. In males having their first cystoscopy the mean VAS score was 3.1 and decreased to 2.1 for the third or more (p = 0.001); in females the mean VAS score was 2.89 for the first and 1.56 for the third or more (p = 0.02), although this benefit tended to disappear when the number of previous cystoscopies was taken into account. CONCLUSION: In male patients, self-visualization of cystoscopy did not impact pain perception, while in female patients, it seemed to provide a benefit. The number of previous cystoscopies had an influence, diminishing the perception of pain, regardless of whether the patient visualized the procedure or not.

[Mitomycin C HIVEC. Update and results in high risk patients.] / HIVEC con mitomicina C. Actualización y resultados en pacientes de alto riesgo.

Adjuvant endovesical treatment is a research field in constant exploration with the aim to minimize the risk of recurrence and progression of non muscle invasive bladder tumors. Over the last years, the administration of chemotherapy in a chemo hyperthermia regimen has been added to the existing regimens. There are various systems for its administration, but this article focus on HIVEC (Hyperthermic IntraVEsical Chemotherapy) and its current status. In this review article we update the results of this system in the case-scenarios it has been used (preoperative with ablative intention and as adjuvant therapy with prophylactic purposes), tolerance and security issues, on-going clinical trials and future perspectives.

[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.

Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex.

Renal angiomyolipomas are found in up to 80% of tuberous sclerosis complex (TSC) patients. Although these tumours are usually asymptomatic, lesions >3 cm in diameter are prone to bleeding and up to 10% of TSC patients may experience a massive and potentially fatal retroperitoneal haemorrhage. Diagnosis can be complicated because of the initial lack of symptoms and the fat-poor content of atypical renal angiomyolipomas. After diagnosis, tumour growth and the emergence of new tumours must be monitored. Treatment with mammalian target of rapamycin (mTOR) inhibitors can reduce tumour size and is indicated in patients with TSC-associated renal angiomyolipomas >3 cm in diameter. Imaging-based assessment of kidney disease is essential to the diagnosis and management of patients with TSC. The aims of imaging studies in this context are to detect and characterize tumours, assess and detect the risk of complications and evaluate the response to treatment, especially in patients treated with mTOR inhibitors. A multidisciplinary expert panel developed a series of recommendations based on current evidence and professional experience for imaging studies in adults and children with TSC-associated renal angiomyolipoma. The recommendations cover radiological diagnosis and follow-up of the classic and atypical or fat-poor TSC-associated renal angiomyolipomas, biopsy indications, minimal requirements for radiological requests and reports and recommended technical features and protocols for computed tomography and magnetic resonance imaging.

[Spanish cultural adaptation and psychometrical validation of the Treatment Benefit Scale (TBS) in the symptomatic treatment of overactive bladder]. / Adaptación cultural al Español y validación psicométrica de la Escala de Beneficio del Tratamiento (Treatment Benefit Scale -TBS) en el tratamiento sintomático de la vejiga hiperactiva.

BACKGROUND AND OBJECTIVE: Psychometric validation of the Spanish version of the Treatment Benefit Scale (TBS) scale for assessing the patient's treatment benefit on symptoms associated to overactive bladder. PATIENTS AND METHODS: The Spanish version of the TBS was administered in the final visit of a prospective observational clinic study, after 3 months of a clinical intervention. Overactive bladder patients, above 18 years old, of both genders, with an OAB-V8 score ≥8, and able to understand health questionnaires in Spanish were recruited. RESULTS: A total of 246 patients (57.7 years, 76% women) were included. The scale was not completed by 1.7% of patients. Extreme improvement was experienced by 30% of patients, 58% improved, 11% did not change, and 2% worsened after medical intervention. The TBS significantly correlated with the clinical criterion of change; (r=0.743; P<.001). A linear association was observed with changes in both OABq-SF scale domains; severity: F(linear)=33.89, P<.001 and health related quality of life: F(linear)=41.69, P<.001. The TBS was able to distinguish between groups of patients by severity and quality of life, F=11.17, P<.001 and F=13.95, P<.001. CONCLUSION: The Spanish version of the TBS scale has shown good validity psychometric properties in Spanish overactive bladder patients, supporting its use in routinely clinical practice for assessing subjective outputs related to overactive bladder treatment.

Use of onabotulinum toxin A in patients with idiopathic overactive bladder and a lack of efficacy, intolerance or contraindication with anticholinergics / Uso de la onabotulinumtoxina A en pacientes con vejiga hiperactiva idiopática con falta de eficacia, intolerancia o contraindicación para los anticolinérgicos

Objective To assess the efficacy and safety of onabotulinum toxin A in patients with idiopathic overactive bladder inadequately managed with anticholinergics. Materials and Methods A prospective, open-label, single centre, and interventional study was conducted, from 2008 to 2013, on consecutive patients with idiophatic overactive bladder that showed lack of efficacy or intolerance to anticholinergic agents. Results The study included 73 female patients aged 58.9 ± 12.9 years. A dose of 100 and 200 units of toxin were administered in 89 and 5 cases, respectively. Nineteen patients received a second injection, 8 patients received 3, and one patient was treated 4 times. Clinically, it was observed that 98% patients had urge urinary incontinence at baseline, as compared with 42% under treatment. Similar results were obtained regarding the number of pads used per day, from 2.8 at baseline to 0.5 after treatment as regards the urodynamic parameters, the first desire to void volume improved from 97 ± 63 mL to 139 ± 81 mL. Similar results were obtained as regards cystometric capacity and the volume of the first involuntary detrusor contraction. One patient had a positive urine culture resolved using a conventional oral antibiotic regimen. Intermittent catheterisation was required in 5 patients during the first week. Conclusions Onabotulinum toxin A injections significantly improved, not only the clinical symptoms, but also the urodynamic parameters in patients with idiopathic overactive bladder inadequately managed with anticholinergic drugs. This is a simple technique with minimal adverse effects and generally well tolerated.

Objetivo Evaluar la eficacia y seguridad de onabotulinumtoxina A en pacientes con vejiga hiperactiva idiopática con falta de eficacia, intolerancia o contraindicación para el uso de anticolinérgicos. Material and Métodos Se realizó un estudio observacional, prospectivo, abierto en un único centro entre 2008 y 2013, en pacientes consecutivos con vejiga hiperactiva idiopática con falta de eficacia o intolerancia a los anticolinérgicos. Resultados Las 73 pacientes fueron mujeres con edad de 58,9 ± 12,9 años. Se administraron 100 y 200 unidades de toxina en 89 y 5 casos, respectivamente. Diecinueve pacientes recibieron una segunda inyección, 8 pacientes 3 inyecciones y un paciente 4. Clínicamente se observó que inicialmente un 98% de las pacientes tenían incontinencia urinaria de urgencia y después del tratamiento solo un 42%; el número de absorbentes por día, pasó de 2,8 al inicio a 0,5 después del tratamiento. Respecto a los parámetros urodinámicos, el volumen del primer deseo miccional mejoró de 97 ± 63 mL a 139 ± 81 mL. Se obtuvieron resultados similares en capacidad cistométrica y el volumen de la primera contracción involuntaria del detrusor. Una paciente tuvo urocultivo positivo, resolviéndose con un régimen de antibiótico oral convencional. El cateterismo intermitente fue necesario en 5 pacientes durante la primera semana. Conclusiones Las inyecciones de onabotulinumtoxina A mejoraron significativamente no solo los síntomas clínicos, sino también los parámetros urodinámicos en pacientes con vejiga hiperactiva idiopática inadecuadamente manejados con anticolinérgicos. Esta es una técnica simple, con efectos adversos mínimos y generalmente bien tolerada.

HIVEC con mitomicina C. Actualización y resultados en pacientes de alto riesgo / Mitomycin C HIVEC. Update and results in high risk patients

Los tratamientos endovesicales adyuvantes son un campo de investigación en constante exploración con el objeto de minimizar el riesgo de recurrencia y progresión de los tumores de vejiga no músculo invasivos. En los últimos años, a los ya existentes se ha añadido la administración de quimioterapia en régimen de quimiohipertermia. Hay diversos sistemas de administración de ésta, centrándonos en este artículo en HIVEC (Hyperthermic IntraVEsical Chemotherapy) y su situación actual. En esta revisión, ponemos al día los resultados de este sistema en los escenarios en que ha sido empleado (tanto de forma preoperatoria con intención ablativa como de forma adyuvante con intención profiláctica), las cuestiones relativas a tolerancia y seguridad, los ensayos que hay en marcha y las perspectivas de futuro

Adjuvant endovesical treatment is a research field in constant exploration with the aim to minimize the risk of recurrence and progression of non muscle invasive bladder tumors. Over the last years, the administration of chemotherapy in a chemo hyperthermia regimen has been added to the existing regimens.There are various systems for its administration, but this article focus on HIVEC (Hyperthermic IntraVEsical Chemotherapy) and its current status. In this review article we update the results of this system in the case-scenarios it has been used (preoperative with ablative intention and as adjuvant therapy with prophylactic purposes), tolerance and security issues, on-going clinical trials and future perspectives

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

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

El cáncer de próstata es un problema de salud en muchos países a nivel mundial. La comprensión de la función esencial que los andrógenos tienen en la fisiología de la próstata condujo al desarrollo del bloqueo hormonal como opción de tratamiento en la enfermedad avanzada, con respuesta limitada en el tiempo y desarrollo de resistencia. Es en esta etapa donde se define el cáncer de próstata resistente a la castración (CPRC) y se asocia con mal pronóstico ya que la supervivencia oscila entre 18 y 24 meses a partir de ese momento. Aún con niveles de castración, los tumores son dependientes del receptor androgénico (RA) funcional. En el presente trabajo analizamos los parámetros clínicos pre-tratamiento como biomarcadores pronósticos o predictivos de progresión, los mecanismos de resistencia a la castración, el desarrollo de nuevas tecnologías para el uso de las denominadas biopsias líquidas a partir de fluidos biológicos y la identificación de células tumorales circulantes como biomarcadores de respuesta y progresión en CPRC. Los ensayos clínicos actualmente en marcha están en parte orientados hacia la búsqueda de nuevos biomarcadores pronósticos y predictivos, lo que permitirá abrir las puertas a la medicina de precisión y con ello mejorar la calidad de vida del paciente oncológico

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

[Adenocarcinoma of the female urethra: report of two cases and bibliography review]. / Adenocarcinoma de uretra femenina: presentación de dos casos y revisión de la literatura.

OBJECTIVES: Primary adenocarcinoma of the female urethra is a rare malignancy. We report two cases and a review of the latest articles focused on classification and treatment of this kind of neoplasm. METHODS: We present two females diagnosed of urethral adenocarcinoma, describing clinic and pathological features, diagnosis and treatment. CONCLUSIONS: Female urethral adenocarcinoma is an uncommon neoplasm with a heterogeneous histogenesis. The distal urethral carcinoma is more amenable to treatment, and the prognosis is better than that of proximal or entire urethral carcinoma, which is often associated with extensive local invasion and metastasis.