A single-center comparison of our initial experiences in treating penile and urethral cancer with video-endoscopic inguinal lymphadenectomy (VEIL) and later experiences in melanoma cases.

Background: Video-endoscopic inguinal lymphadenectomy (VEIL) is a minimally invasive approach that is increasingly indicated in oncological settings, with mounting evidence for its long-term oncological safety. Objectives: To present our single-center experience of treating penile and urethral cancer with VEIL, as well as its more recent application in melanoma patients. Methods: We prospectively recorded our experiences with VEIL from September 2010 to July 2018, registering the patient primary indication, surgical details, complications, and follow-up. Results: Twenty-nine patients were operated in one (24) or both (5) groins; 18 had penile cancer, 1 had urethral cancer, and 10 had melanoma. A mean 8.62 ± 4.45 lymph nodes were removed using VEIL and of these, an average of 1.00 ± 2.87 were metastatic; 16 patients developed lymphocele and 10 presented some degree of lymphedema; there were no skin or other major complications. The median follow-up was 19.35 months; there were 3 penile cancer patient recurrences in the VEIL-operated side. None of the melanoma patients presented a lymphatic inguinal recurrence. Conclusions: VEIL is a minimally invasive technique which appears to be oncologically safe showing fewer complications than open surgery. However, complications such as lymphorrhea, lymphocele, or lymphedema were not diminished by using VEIL.

Stereotactic body radiation therapy in patients with metachronous oligorecurrent prostate cancer: A single-center experience.

INTRODUCTION AND OBJECTIVE: Metachronous oligorecurrence in prostate cancer (PCa) occurs in patients with localized disease who, after failed radical treatment, develop oligometastases. Metastasis-directed stereotactic radiotherapy (SBRT) aims to delay androgen deprivation therapy. In this study, we report our experience to elucidate the role of SBRT in a selected population of patients with metachronous oligorecurrence. MATERIAL AND METHODS: Retrospective analysis of patients treated with SBRT for oligorecurrent PCa between November 2015 and December 2020. We detailed clinicopathological characteristics at disease onset (age, PSA, stage, primary treatment), clinical scenario at diagnosis of oligorecurrence (PSA, PSA velocity, metastases characteristics), progression-free survival, castration resistance-free survival, dose, and toxicity of SBRT. RESULTS: Thirty-eight SBRT treatments were applied to 13 lymph node and 25 bone metastases in a total of 28 patients. After a follow-up of 34.57 months (21.17-57.59), 17 patients had radiological progression of the disease and 11 presented castration resistant PCa. PFS and CRFS were 21.93 and 44.13 months, respectively. Only 2 patients presented grade 1 toxicity. CONCLUSIONS: In patients with metachronous oligorecurrent PCa, SBRT constitutes a safe and effective treatment that allows delaying the onset of androgen deprivation therapy and the time to castration resistance, assuming low levels of toxicity.

Microbiological assessment of arterial allografts processed in a tissue bank.

The transmission of microbial infection through tissue allografts is one of the main risks that must be controlled in tissue banks. Therefore, microbiological monitoring controls and validated protocols for the decontamination of tissues during processing have been implemented. This study is based on the evaluation of data from microbiological cultures of arteries (mainly long peripheral arteries) processed in the tissue bank of Valencia (Spain). Donors' profile, pre- and post-disinfection tissue samples were assessed. The presence of residual antibiotics in disinfected tissues was determined and the antimicrobial potential of these tissues was tested. Our overall contamination rate was 23.69%, with a disinfection rate (after antibiotic incubation) of 87.5%. Most (76.09%) of the microbial contaminants were identified as Gram positive. Arterial allografts collected from body sites affected by prior organ removal showed higher risk of contamination. Only vancomycin was detected as tissue release. The antimicrobial effect on Candida albicans was lower than that for bacterial species. Risk assessment for microbial contamination suggested the donor's skin and the environment during tissue collection as the main sources for allograft contamination. Antibiotic-disinfected arterial allografts showed antimicrobial potential.

Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer.

INTRODUCTION & OBJECTIVES: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program. MATERIALS & METHODS: Prospective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined. RESULTS: SelectMDx showed statistically significant differences related to PPFS (HR 1.035, 95%CI: 1.012-1.057) (p = 0.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805). CONCLUSIONS: In the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.

Does active surveillance avoid overtreatment in prostate cancer? Lessons learned from salvage radical prostatectomies.

OBJECTIVE: Determine whether our institution´s active surveillance (AS) protocol is a suitable strategy to minimise prostate cancer overtreatment. MATERIAL AND METHODS: Retrospective analysis of 516 patients on AS after prostate cancer diagnosis. Population divided into "per-protocol" vs "induced" AS depending on fulfilment of protocol´s inclusion criteria. Radical prostatectomies after AS were selected and stratified based on: reclassification, progression or patient anxiety. Clinicopathological features and biochemical relapse-free survival were studied. Primary endpoint was overtreatment ratio based on the presence of insignificant prostate cancer and adverse pathological features in the surgical specimen. Kaplan-Meier curves were used to estimate the biochemical relapse-free survival and compared with log-rank test. RESULTS: 304 patients fulfilled inclusion criteria; 100 proceeded to radical prostatectomy (31% "induced", 69% "per-protocol" AS). Surgery indications were reclassification, progression and anxiety in 66%, 18% and 16% of patients respectively. Rate of positive lymph nodes was higher in the progression group (11%) compared to reclassification and anxiety (5% and 0% respectively, P = .002). Positive surgical margins were more frequently reported in the progression cohort compared to reclassification (28% vs 20%). Median follow-up from diagnosis until last radical prostatectomy was 48.3 months (32.4-70). 3 year biochemical relapse-free survival in the salvage radical prostatectomy was 85.4% (95 CI 78.3-93.2). Insignificant cancer was noticed in 7% of patients (Epstein´s vs 24% Wolters´ criteria). Rate of patients with adverse pathological features was 36%. CONCLUSIONS: The majority of patients who underwent salvage surgery after AS were not overtreated. Radical prostatectomy should be considered a safe rescue treatment.

Seroconversion and Abundance of IgG Antibodies against S1-RBD of SARS-CoV-2 and Neutralizing Activity in the Chilean Population.

COVID-19 is a pandemic caused by SARS-CoV-2. In Chile, half a million people have been infected and more than 16,000 have died from COVID-19. As part of the clinical trial NCT04384588, we quantified IgG against S1-RBD of SARS-CoV-2 (anti-RBD) in recovered people in Santiago and evaluated their suitability as COVID-19 convalescent plasma donors. ELISA and a luminescent SARS-CoV-2 pseudotype were used for IgG and neutralizing antibody quantification. 72.9% of the convalescent population (468 of 639) showed seroconversion (5-55 µg/mL anti-RBD IgG) and were suitable candidates for plasma donation. Analysis by gender, age, and days after symptom offset did not show significant differences. Neutralizing activity correlated with an increased concentration of anti-RBD IgG (p < 0.0001) and showed a high variability between donors. We confirmed that the majority of the Chilean patients have developed anti-SARS-CoV-2 antibodies. The quantification of anti-RBD IgG in convalescent plasma donors is necessary to increase the detection of neutralizing antibodies.

Clinical drivers for imaging testing in non-metastatic castration-resistant prostate cancer in clinical practice: Results of the IDENTIFICA study. / Factores clínicos determinantes para la realización de pruebas de imagen en cáncer de próstata resistente a la castración no metastásico en la práctica clínica: resultados del estudio IDENTIFICA.

INTRODUCTION: The aim of the study was to describe the clinical drivers that lead physicians to perform imaging tests in search of metastasis in non-metastasic castration prostate resistant cancer (nmCRPC) patients. METHODS: Observational, cross-sectional study conducted at the Departments of Urology of 38 Spanish hospitals. The study included 188 patients diagnosed with nmCRPC who underwent an imaging test for the assessment of metástasis. In one study visit, physicians were requested to specify the clinical factors that led them to perform these tests. The results of the imaging tests and the clinical characteristics of the patients since the time of prostate cancer (PC) diagnosis, were reported. Regression analyses were used to determine predictors of imaging test results. RESULTS: Prostate-specific antigen (PSA) level was the most important driver to order imaging tests (57.1%), followed by regular follow-up (16.5%) and PSA doubling time (PSADT) (12.0%). Although these drivers were not associated to detection of metastasis, patients with PSA levels ≥20 ng/mL had a greater risk of metastasis than patients with PSA levels <4ng/mL (P=.004) and CRPC patients diagnosed with metastasis (mCRPC) had higher median PSA levels (20.9; interquartile range [IQR]: 6.7-38.6) than nmCRPC (9.1; IQR: 5.0-18.0) (P=.005). Sixty-six percent of the patients did not undergo any imaging test after CRPC diagnosis until the study visit (10.6, IQR: 4.0-19.5 months). Curative-intent treatment at PC diagnosis and Gleason score predicted longer time from PC to CRPC diagnosis. CONCLUSIONS: Physicians based their decisions to order imaging tests for metastasis detection in nmCRPC patients mainly on PSA and PSA kinetics, including the regular follow-up stated by guideline recommendations.

Update and optimization of active surveillance in prostate cancer in 2021. / Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021.

INTRODUCTION AND OBJECTIVES: Within the paradigm shift of the last decade in the management of prostate cancer (PCa), perhaps the most relevant event has been the emergence of active surveillance (AS) as a mandatory strategy in low-risk disease. We carry out a critical review of the clinical, pathological and radiological improvements that allow optimizing AS in 2021. MATERIAL AND METHODS: Critical narrative review of the literature on improvement issues and controversial aspects of AS. RESULTS: Adequate use of traditional criteria, optimized by enhanced biopsy and calculation of the prostate volume technique thanks to multiparametric magnetic resonance imaging (mpMRI) allow a better selection of patients for AS. This management should not be limited to patients under 60years of age, and patients with intermediate-risk PCa should be carefully selected to be included. Biopsies are still required in the follow-up, which can be personalized according to risk patterns. The pathologist must identify the cribriform or intraductal histology on biopsies in order to exclude these patients from AS, in the same way as with patients with alterations in DNA repair genes. CONCLUSIONS: Controversial indications such as the inclusion of patients from intermediate-risk groups, or the transition to active treatment due to exclusive progression in tumor volume, should be further optimized. It is possible that the future competition of tissue biomarkers, the refinement of objective parameters of mpMRI and the validation of PSA kinetics calculators may sub-stratify risk groups.

Assessment of Confirmed Clinical Hypersensitivity to Rituximab in Patients Affected with B-Cell Neoplasia.

Rituximab hypersensitivity reactions are rare but are one of the main causes of rituximab elimination from antilymphoma immunochemotherapy treatments. While the clinical picture may be indistinguishable from other infusion-related reactions, hypersensitivity reactions (HSR) do not disappear and instead become more intense with subsequent administrations. Objective. To describe the use of the 12-step protocol for desensitization to intravenous rituximab in clinical practice and the complementary study of a possible IgE-mediated HSR in the context of B-cell lymphoma treatment. Methods. A 12-step rituximab desensitization protocol was performed prospectively within clinical practice in 10 patients with a history of severe infusion reactions or in patients who had a repeated reaction at subsequent doses despite taking more intense preventive measures. Skin prick tests were performed at the time of reaction and at a later time to eliminate false negatives due to possible drug interference. Results. Overall, with the desensitization protocol, 70% of patients were able to complete the scheduled immunochemotherapy. Two patients had to discontinue the therapy due to clinical persistence and the third due to lymphoma progression. Intradermal tests with 0.1% rituximab were positive in only 20% of cases, demonstrating a mechanism of hypersensitivity. Conclusions. The 12-step desensitization protocol is very effective and assumable within healthcare practice. There is a need to determine the mechanism underlying the infusion reaction in a large proportion of cases due to the risk of future drug exposure.

The relationship between inguinal hernia and minimally-invasive surgery for prostate cancer: A systematic review of the literature. / La relación entre hernia inguinal y cirugía mínimamente invasiva para el cáncer de próstata: revisión sistemática de la literatura.

OBJECTIVE: We aimed to perform a systematic review about the relationship between inguinal hernia and surgery for prostate cancer. BACKGROUND: Diagnosis of abdominal wall defects and prostate cancer may be either synchronous or metachronous. The convenience and safety of combined prostatectomy and hernioplasty, the incidence of hernias after prostatectomy and the feasibility of prostatectomy in patients with previous laparoscopic hernioplasty are still debated. METHODS: PubMed and Embase were queried by dedicated search strings. Two researchers independently reviewed the pooled references and selected the articles of interest, including reviews. RESULTS: Sixty-five studies were evaluated, 22 of them analysed the feasibility and the outcomes of a combined surgery, namely one-stage radical prostatectomy and herniorrhaphy or hernioplasty. Literature evidences support the combined intervention to patients suffering from an inguinal hernia and a prostate cancer amenable of radical prostatectomy. Sixteen studies addressing the potential increase in the occurrence of inguinal hernia after radical prostatectomy were evaluated. Approximately 15% of patients who undergo retro-pubic radical prostatectomy will develop inguinal hernia. It is suggested that the incidence might be lower in laparoscopic prostatectomy series, particularly in case of transperitoneal approach. The median time to the appearance of the hernia is around 6 months. After evaluation of 14 studies, it is concluded that laparoscopic hernioplasty does not preclude prostatectomy but hinders further pelvic surgery. CONCLUSIONS: One-stage combined hernioplasty and radical prostatectomy may be accepted except in cases of lymph-nodes dissection and/or positive hydro-distress test of the urethro-vesical anastomosis. Accurate patient's counselling and dedicated consent form are mandatory, in the setting of an experienced multidisciplinary team.

Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature.

Posttransplant high-dose cyclophosphamide (PTCy) effectively prevents GvHD after haploidentical SCT. However, its use in HLA-matched SCT has been less explored. Fifty-six consecutive patients who underwent allo-SCT for hematological malignancies have been included in this prospective single-center protocol. Donors have been HLA-identical siblings, fully-matched unrelated or 1-allele-mismatched unrelated donors in 30%, 32%, and 37% of cases, respectively. Nine patients have received a TBI-containing MAC regimen, while the remaining (84%) received RIC platforms based on Fludarabine plus Busulfan/Melphalan. Due to the high graft failure (GF) rate (21%) in a preliminary analysis in the allo-RIC cohort (n = 29), protocol amendments have been implemented, with no further cases of GF after the introduction of mini-thiotepa (0/18). The overall incidence of grade II-IV acute GvHD is 24% (95% CI: 17-31%) with four steroid-refractory cases. Severe chronic GvHD has occurred in only 1 of 43 evaluable cases. The 1-year NRM and relapse are 18% (95% CI: 12-26%) and 30% (18-42%) and the OS and DFS are 78% and 64%, respectively. These outcomes support the feasibility of using PTCy as a SOC outside the haplo-setting, albeit mini-thiotepa (3 mg/kg) was incorporated in the standard allo-RIC platforms to prevent GF. Despite the limitations of a single-center experience and the short follow-up, these protocols show promising results with particular benefit in reducing the occurrence of moderate-to-severe GvHD.

Structural transition induced by compression and stretching of puckered arsenene nanotubes.

The stretching and compression effects on puckered arsenene nanotubes (AsNTs) are investigated by using density functional calculations. The atomic arrangement determines the nanotube properties and relative stability; therefore, zigzag, chiral, and armchair present different properties. Since the AsNT properties depend on the diameter, three cases are considered: (a) (0, 9) and (9, 0), (b) (0, 14) and (14, 0), and (c) (0, 19) and (19, 0) NTs. For all calculated parameters of the smallest NTs, it is found that the armchair (0, 9) nanotube is always more stable than the zigzag (9, 0) nanotube. On the other hand, for the two largest NTs, a structural transition from armchair to zigzag is found upon stretching. Phase transitions are of great interest, in part because they result in changes of the properties of the material under study, changes that can be used in many technologies. To our knowledge, this is the first time that a structural transition in a puckered nanotube has been predicted. Our results show that the electronic band gap of the AsNTs can be modulated by increasing or decreasing the axial lattice parameter. It is also found that semiconductor NTs are more stable than metallic NTs.

[Prophylactic application of medicated calcium sulphate in uncemented total hip prosthesis]. / Aplicación profiláctica de sulfato de calcio medicado en prótesis total de cadera no cementada.

The increase in total hip arthroplasty occurs by many factors, such as increasing life expectancy, improving surgical technique as well as innovating the design and implant material. However, despite technological advances, peri-prosthetic infection has remained one of the most devastating complications. This study evaluates the prophylactic application of calcium sulfate pearls medicated in the femoral canal and acetabular surface to prevent peri-prosthetic infections in patients who underwent total uncemented primary hip arthroplasty against a control group by measuring acute phase reactants. 146 patients, 67 were applied calcium sulfate pearls medicated and 79 prophylactic antibiotic intravenous in the period from 2013 to 2016. To perform the diagnosis of peri-prosthetic infection was assessed PCR associated with VSG, communication between fistula and prostheses and positive culture in 2 or more different sites. There was a decrease in the values of acute-phase reactants in patients who were given calcium sulfate pearls. 14 patients presented infection in the control group and 3 in the study group. The prophylactic use of calcium sulphate pearls within the medullary canal and acetabular surface is an option for the prophylaxis of peri-prosthetic infections, however the study deserves follow-up with more patients.

El incremento en la cirugía de artroplastía total de cadera es motivado por muchos factores, como el aumento en la expectativa de vida, mejoría continua en la técnica quirúrgica e innovaciones en el diseño y los materiales de los implantes que, sumados, han convertido a este procedimiento en una solución efectiva a la degeneración articular, con excelentes resultados. Sin embargo, a pesar de los avances tecnológicos, la infección periprotésica se ha mantenido como una de las complicaciones más devastadoras. Este estudio evalúa la aplicación profiláctica de perlas de sulfato de calcio medicadas en el canal femoral y superficie acetabular para prevenir infecciones periprotésicas en pacientes que fueron sometidos a una artroplastía total de cadera primaria no cementada contra un grupo control mediante la medición de reactantes de fase aguda y cultivo de líquido sinovial. Se sometieron al estudio 146 individuos: 67 a quienes se les aplicaron perlas de sulfato de calcio medicado y 79 a quienes se les aplicó antibiótico profiláctico intravenoso de Septiembre de 2013 a Agosto de 2016. Como método diagnóstico de infección periprotésica temprana se evaluaron la proteína C reactiva asociada a velocidad de sedimentación globular aumentada, una fístula que comunicara con la prótesis, cultivo positivo de dos o más sitios periprotésicos de líquido sinovial o tejido. Los resultados clínicos demostraron que hubo una disminución en los valores de los reactantes de fase aguda en los sujetos a quienes se les aplicaron las perlas de sulfato de calcio medicado. Se encontró que 14 personas presentaron infección en el grupo con profilaxis parenteral, comparado con tres del grupo con profilaxis local con perlas de sulfato de calcio medicado; ambos grupos con ceftriaxona. Se consideró que el uso profiláctico de perlas de sulfato de calcio dentro de canal medular y la superficie acetabular es una buena opción para prevenir infecciones periprotésicas en quienes han sido sometidos a una artroplastía total de cadera primaria no cementada; sin embargo el estudio amerita seguimiento con más pacientes para tener significancia estadística.

Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed. / Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada.

OBJECTIVES: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. MATERIALS AND METHODS: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. RESULTS: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR=5.18; IC 95%=1.16-23.11; P=.03). CONCLUSIONS: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

Variability in the multicentre National Registry in Active Surveillance; a questionnaire for urologists. / Variabilidad dentro del Registro Nacional multicéntrico en Vigilancia Activa; cuestionario a urólogos.

BACKGROUND: Our main objective was to report the current use of active surveillance in Spain and to identify areas for potential improvement. METHODS: A questionnaire generated by the Platform for Multicentre Studies of the Spanish Urology Association (AEU/PIEM/2014/0001, NCT02865330) was sent to all associate researchers from January to March 2016. The questionnaire included 7 domains covering various aspects of active surveillance. RESULTS: Thirty-three of the 41 associate researchers responded to the questionnaire. Active surveillance is mainly controlled by the urology departments (87.9%). There was considerable heterogeneity in the classical clinical-pathological variables as selection criteria. Only 36.4% of the associate researchers used prostate-specific antigen density (PSAd). Multiparametric magnetic resonance imaging (mpMRI) was clearly underused as initial staging (6%). Only 27.3% of the researchers stated that their radiology colleagues had a high level of experience in mpMRI. In terms of the confirmation biopsy, most of the centres used the transrectal pathway, and only 2 out of 33 used the transperineal pathway or fusion software. Half of the researchers interviewed applied active treatment when faced with disease progression to Gleason 7 (3+4). There was no consensus on when to transition to an observation strategy. CONCLUSIONS: The study showed the underutilisation of informed consent and quality-of-life questionnaires. PSAd was not included as a decisive element in the initial strategy for most researchers. There was a lack of confidence in the urologists' mpMRI experience and an underutilisation of the transperineal pathway. There was also no consensus on the follow-up protocols and active treatment criteria, confirming the need for prospective studies to analyse the role of mpMRI and biomarkers.

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital. / Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico.

OBJECTIVES: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. MATERIAL AND METHODS: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. RESULTS: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. CONCLUSIONS: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets.

Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies.

Radiation therapy for oligorecurrence in prostate cancer. Preliminary results of our centre. / Radioterapia para la oligorrecurrencia en cáncer de próstata. Resultados preliminares en nuestro centro.

INTRODUCTION AND OBJECTIVE: There is growing interest in the use of more aggressive therapeutic modalities for treating metastatic prostate cancer. In this study, we examine the use of stereotactic body radiation therapy (SBRT) for patients with oligorecurrent prostate cancer. We analysed the biochemical response and toxicity of patients who underwent this therapy at our centre. MATERIAL AND METHOD: We selected patients who experienced oligorecurrence between January 2015 to December 2016 and were administered SBRT. The association of androgen deprivation (AD) was left in each case to the decision of the tumour committee. We describe the clinical situation at diagnosis of oligorecurrence, the treatment administered and the biochemical response. We considered a biochemical response to be a 50% reduction in the absolute prostate-specific antigen (PSA) readings. RESULTS: SBRT was administered to 11 patients with bone (82%) and/or lymph node oligometastasis (18%). The treatment regimen for bone oligometastasis was 27Gy divided into 3 sessions, while the treatment for lymph node oligometastasis reached 70Gy. Seven patients had no treatment at the time of diagnosis, 2 were in the castration-resistant phase, 1 patient was in the off phase of intermittent AD, and 1 patient had adjuvant AD for pN1. Seven patients presented a biochemical response with a PSA reduction of 75-100%. The response was not assessable in 4 patients due to the continuing adjuvant AD. With a mean follow-up of 10.5 months, only 2 patients had progressed. Grade 1 gastrointestinal toxicity was detected in only 1 patient. CONCLUSION: Our data suggest that the use of SBRT in carefully selected patients with metastatic oligorecurrence of prostate cancer can achieve biochemical response and potentially delay progression and the use of systemic treatments.

PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme. / PCA3 como biomarcador de segunda línea en un programa de screening oportunista prospectivo, aleatorizado y controlado.

OBJECTIVES: PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). MATERIAL AND METHODS: 5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA ≥3ng/ml had a PCA3 test done. All men with PCA3 ≥35 underwent an initial biopsy (IBx) -12 cores-. Men with PCA3 <35 were randomized 1:1 to either IBx or observation. We compared them to those obtained with ERSPC RC-3. RESULTS: PCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(-) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (P<.001). In the PCA3(+) arm (n=301, 35.9%), PCa was identified in 115 men at IBx (38.2%). In the randomized arm, 256 underwent IBx and PCa was found in 46 (18.0%) (P<.001). The biopsy-sparing potential would have been 64.1% as opposed to 76.6% if we had used ERSPC RC-3. However, the estimated false negative cases for HGPCa would have been reduced by 37.1% (89 to 56 patients). Moreover, if we had applied PCA3-35 to avoid IBx, 14.7% PCa and 9.1% of clinical significant PCa patients would not have been diagnosed during this FU. CONCLUSIONS: When PCA3-35 is used as a second-line biomarker when PSA ≥3ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 <35.