ABSTRACT
ABSTRACT: A 76-year-old man undergoing hormone therapy for prostate cancer was referred for 68 Ga-PSMA-11-PET (PSMA PET) due to persistently detectable PSA level. No PSMA-positive tumor lesions were detected, so a delayed phase imaging was performed, which revealed focal PSMA uptake in the right seminal vesicle together with contrast accumulation on excretory phase contrast-enhanced CT. These findings were finally determined to be secondary to urinary reflux as a consequence of a prostatic enucleation he had undergone 5 months earlier following an episode of acute urinary retention.
Subject(s)
Antigens, Surface , Gallium Isotopes , Gallium Radioisotopes , Positron-Emission Tomography , Seminal Vesicles , Humans , Male , Aged , Seminal Vesicles/diagnostic imaging , Edetic Acid/analogs & derivatives , Prostatic Neoplasms/diagnostic imaging , Oligopeptides , Glutamate Carboxypeptidase II/metabolismABSTRACT
The standard of care for the first-line management of metastatic urothelial carcinoma has been recently challenged, with the combination of pembrolizumab and enfortumab vedotin (P-EV) strongly arising as a practice-changing option from classical platinum-based chemotherapies. With this paradigm shift on the horizon new questions, including the most suitable second line of treatment for these patients, and the role that the molecular characterization of these tumours will have when selecting these therapies will inevitably arise. Furthermore, after the negative results of the Keynote 361 and IMvigor 130 trials, the combination of nivolumab with platinum-based chemotherapy followed by nivolumab maintenance (Nivo GC-Nivo) has also shown positive results when compared with chemotherapy alone. Translational studies at a molecular, cellular, and functional level will be key to better explain these discordant results. In this Current Perspective, we discuss the potential impact of these results in clinical practice and propose specific guidance for prospective translational research.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Nivolumab/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/secondary , Prospective Studies , Urinary Bladder Neoplasms/drug therapyABSTRACT
INTRODUCTION: Bladder cancer (BC) is a common malignancy in Spain. The aims of this study were: to identify the proportion of patients diagnosed with BC incidentally or after symptomatic presentation in a contemporary period in Spain; to compare demographic, clinical, and pathologic characteristics between these groups. METHODS: This was a retrospective analysis of a multi-centre observational study of 26 hospitals in the Spanish National Health System of all BCs newly diagnosed in 2011. The study represented 21.5% of the Spanish population and hospitals were selected in proportion to Spain's regions to ensure a representative sample. Patients were categorized by whether the cancer was diagnosed incidentally or after symptomatic presentation and baseline demographic, pathologic, and clinical characteristics were analyzed. RESULTS: 2472 were newly diagnosed with BC at the 26 participating Spanish hospitals with 308 (12.5%) of cases diagnosed incidentally and 2164 (87.5%) diagnosed after symptomatic presentation. No differences were observed between patients diagnosed incidentally vs. symptomatically in terms of demographics or measured co-morbidities. Compared to symptomatically diagnosed bladder tumours, those diagnosed incidentally were more likely to have a papillary appearance, to be significantly smaller, and less likely to have positive/suspicious cytology. Additionally, incidentally diagnosed bladder tumours were less likely to be muscle-invasive (11.7% vs. 25.0%, pâ¯<â¯0.01) nor aggressive at pathology, with 33.6% Grade 3 compared to 50.1%, (pâ¯<â¯0.01). CONCLUSIONS: We identified a significant percentage (12.5%) of new bladder cancer diagnosis made incidentally in a representative sample of the Spanish population. These tumours exhibited less aggressive pathologic characteristics than their symptomatic counterparts.
Subject(s)
Urinary Bladder Neoplasms , Humans , Retrospective Studies , Spain/epidemiology , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. METHODS: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. RESULTS: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. CONCLUSIONS: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.
Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Electrons , Feasibility Studies , Neoplasm Recurrence, Local/surgery , Rectal Neoplasms/therapyABSTRACT
OBJECTIVES: This study aimed to describe the real-world therapeutic management of patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) (LUTS/BPH) attending primary care and urology clinics in Spain. METHODS: This observational, retrospective, multicentre study included men ≥50 years of age diagnosed with LUTS/BPH (≤8 years prior to study visit) (N = 670). Therapeutic management according to healthcare service (primary care vs. urology clinics) or progression criteria, proportion of patients with treatment change, patient profile according to therapy and evolution of LUTS severity were assessed. RESULTS: Overall differences were noticed in the management of patients between healthcare service (P < .001) and with or without progression criteria (P < .05). Most patients received pharmacological treatment at diagnosis (70.7%; 474/670), which increased at study visit (81.6%; 547/670) with overall similar profiles between primary care and urology clinics for each therapy. α1-Blockers were the most used pharmacological treatment across healthcare settings at diagnosis (61.8%; 293/474) and study visit (51%; 279/547). Only 27.1% (57/210) of patients with progression criteria at diagnosis and 35.6% (99/278) at study visit received 5α-reductase inhibitor (5ARI) alone or in combination with a α1-blocker. Overall, most patients did not change treatment (60%; 402/670) with a trend of more patients worsening in symptoms when not receiving α1-blocker plus 5ARI combination therapy. CONCLUSION: Most patients with LUTS/BPH received pharmacological treatment; however, most men with progression criteria did not receive a 5ARI alone or in combination. These results support the need to reinforce both primary care and urologists existing clinical guideline recommendations for the appropriate medical management of patients with LUTS/BPH.
Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Urology , Child , Humans , Lower Urinary Tract Symptoms/drug therapy , Lower Urinary Tract Symptoms/etiology , Male , Primary Health Care , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/drug therapy , Retrospective Studies , SpainABSTRACT
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are relevant in prostate cancer microenvironment collaborating in tumor development. The main tumor marker used in this disease, prostate-specific antigen (PSA), does not provide information related to this tumor microenvironment. Cancer cells secrete exosomes carrying bioactive molecules contributing to MDSCs recruitment and induction. The aim of this study was to characterize the perioperative changes of exosomal cytokines relevant in MDSCs recruitment induced by prostatectomy in prostate cancer patients. METHODS: Blood was drawn from 26 early-stage prostate cancer patients before and after radical prostatectomy and from 16 healthy volunteers. Serum exosomes were separated by precipitation. Cytokines related with MDSC cell recruitment and activation CCL2, CXCL2, CXCL5, CXCL8, CXCL12, MIF, S100A9 and TGF-ß were measured in serum and serum-derived exosomes using immunometric assays. RESULTS: All cytokines were detected both in serum and exosomes, except for CXCL12, which was detected only in serum. Exosomes were enriched specially in MIF, TGF-ß and CXCL2. Presurgical MIF levels in exosomes correlated negatively with serum PSA. Also, presurgical TGF-ß decreased both in serum and exosomes as Gleason score rises. Patients presurgical exosomes had increased CCL2, CXCL5 and TGF-ß levels than exosomes from healthy controls. These differences were not observed when cytokines were analyzed in serum, except for TGF-ß. Cytokine levels of CCL2, CXCL5 decreased in patients' postsurgical exosomes, while TGF-ß further increased. On the contrary, S100A9 levels were lower in patients presurgical exosomes but increased after radical prostatectomy. CONCLUSIONS: Blood exosomal content in cytokines constitute an attractive source to evaluate MDSCs immunomodulators providing additional information related to tumor microenvironment in prostate cancer.
Subject(s)
Chemokines/immunology , Exosomes/immunology , Myeloid-Derived Suppressor Cells/immunology , Neoplasm Proteins/immunology , Prostatectomy , Prostatic Neoplasms , Tumor Microenvironment/immunology , Adult , Aged , Humans , Male , Middle Aged , Neoplasm Staging , Perioperative Period , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgeryABSTRACT
OBJECTIVES: To describe the real-world demographic and clinical characteristics of patients with lower urinary tract symptoms (LUTS) as a result of benign prostatic hyperplasia (BPH) in Spain. METHODOLOGY: This observational, retrospective, multicentre study conducted in primary care and urology clinics in Spain included men aged ≥50 years diagnosed (≤8 years prior to study visit) with LUTS caused by BPH. The primary endpoint was demographic and clinical characteristics; secondary endpoints included disease progression and diagnostic tests across both healthcare settings. RESULTS: A total of 670 patients were included (primary care: n = 435; urology: n = 235). Most patients had moderate/severe LUTS (74.6%) and prostate volume >30 cc (81.7%), with no differences between settings. More patients had prostate-specific antigen (PSA) ≥1.5 ng/mL in primary care (74.5%) versus urology (67.7%). Progression criteria were prevalent (48.9%). Clinical criteria were more commonly used than the International Prostate Symptom Score (IPSS) to evaluate LUTS at diagnosis (primary care: clinical criteria 73.0%; IPSS: 26.9%; urology: clinical criteria 76.5%; IPSS: 23.4%). Proportion of patients with moderate/severe LUTS at diagnosis was lower using clinical criteria than IPSS, and the proportion of patients with 'worsening' LUTS (diagnosis to study visit) was higher when using clinical criteria versus IPSS. In both healthcare settings, the most commonly used diagnostic tests were general and urological clinical history and PSA. CONCLUSION: Demographic and clinical characteristics of patients with BPH in Spain were similar in primary care and urology; however, assessment criteria to evaluate LUTS severity differ and are not completely aligned with clinical guideline recommendations. Increased use of recommended assessments may enhance optimal BPH management.
Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Urology , Humans , Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/epidemiology , Lower Urinary Tract Symptoms/etiology , Male , Middle Aged , Primary Health Care , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/epidemiology , Retrospective Studies , Spain/epidemiologyABSTRACT
Sunitinib is one of the most widely used targeted therapeutics for renal cell carcinoma (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in RCC, we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and after development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in silico prediction models, six predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1, and DCC. Consistently, immunoblotting analysis of lysates derived from sunitinib-desensitized RCC cells and their parental counterparts showed marked differences in the levels and expression pattern of the proteins encoded by these genes. Our further analysis demonstrates essential roles for these proteins in mediating sunitinib cytotoxicity and shows that their loss of function renders tumor cells resistant to sunitinib in vitro and in vivo. Finally, sunitinib resistance induced by continuous exposure or by inhibition of the six proteins was overcome by treatment with cabozantinib or a low-dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Drug Resistance, Neoplasm , Kidney Neoplasms/genetics , Mutation , Animals , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Exons , Female , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/metabolism , Mice , Neoplasm Transplantation , Sequence Analysis, DNA , SunitinibABSTRACT
OBJECTIVES: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain. METHODS: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing. RESULTS: A bone scan (BS) is recommended at diagnosis, at the onset of bone pain, and depending on PSA levels, but it is not sensitive enough to confirm or exclude bone metastases if there is bone pain. Whole-body MRI and axial MRI are more sensitive than BS and plain X-rays, but more expensive, so they have to be used in certain situations. There is CRPC progression when there is radiologic, clinical or confirmed PSA progression. Flare phenomenon appears in treatment with taxanes and abiraterone. It was agreed that in M0 CRPC patients no drug treatment is currently recommended, although in M1 CRPC patients the first-line therapy would be mainly enzalutamide/abiraterone and/or docetaxel, depending on the symptom burden. CONCLUSION: After the consensus, we provide a series of recommendations for Spanish physicians treating CRPC to address the disease characteristics,how to tailor patient management decisions, the use of imaging techniques, and how to handle disease progression appropriately to improve patients' quality of life.
Subject(s)
Prostatic Neoplasms, Castration-Resistant/diagnosis , Prostatic Neoplasms, Castration-Resistant/therapy , Humans , Male , Practice Guidelines as Topic , SpainABSTRACT
OBJETIVOS: Establecer recomendaciones sobre la práctica clínica habitual del manejo del cáncer de próstata resistente a la castración (CPRC) en España. MÉTODOS: Un panel de 18 expertos en Urología con experiencia en el manejo del CPRC participaron en un proceso Delphi modificado a dos rondas con una reunión final presencial. El panel consideró un total de 106 cuestiones clínicas divididas en las siguientes secciones: definición del CPRC, diagnóstico de metástasis por técnicas de imagen, síntomatología, progresión, manejo de M0 y M1 y secuenciación terapéutica. RESULTADOS: Se recomienda realizar una gammagrafía ósea (GO) en el diagnóstico, al comienzo del dolor óseo y dependiendo de los niveles de PSA. La resonancia magnética de cuerpo entero y la axial son más sensibles que la GO y la radiografía, pero más caras, por lo que se reservan para ciertas situaciones. Existe progresión del CPRC cuando se confirma la progresión radiológica, clínica o por PSA. El fenómeno "flare" aparece en el tratamiento con taxanos y abiraterona. En pacientes M0 no se recomienda tratamiento farmacológico actualmente, y el tratamiento en primera línea para los pacientes M1 incluiría principalmente enzalutamida/ abiraterona y/o docetaxel, según los síntomas. CONCLUSIÓN: Se proponen recomendaciones para personalizar la toma de decisiones ante cada paciente, el uso de técnicas de imagen y cómo abordar la progresión de la enfermedad para mejorar la calidad de vida de los pacientes
OBJECTIVES: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain. METHODS: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing. RESULTS: A bone scan (BS) is recommended at diagnosis, at the onset of bone pain, and depending on PSA levels, but it is not sensitive enough to confirm or exclude bone metastases if there is bone pain. Whole-body MRI and axial MRI are more sensitive than BS and plain X-rays, but more expensive, so they have to be used in certain situations. There is CRPC progression when there is radiologic, clinical or confirmed PSA progression. Flare phenomenon appears in treatment with taxanes and abiraterone. It was agreed that in M0 CRPC patients no drug treatment is currently recommended, although in M1 CRPC patients the first-line therapy would be mainly enzalutamide/abiraterone and/or docetaxel, depending on the symptom burden. CONCLUSION: After the consensus, we provide a series of recommendations for Spanish physicians treating CRPC to address the disease characteristics how to tailor patient management decisions, the use of imaging techniques, and how to handle disease progression appropriately to improve patients' quality of life
Subject(s)
Humans , Male , Prostatic Neoplasms, Castration-Resistant/therapy , Abiraterone Acetate/therapeutic use , Prostate-Specific Antigen/analysis , Neoplasm Staging/methods , Antineoplastic Agents/therapeutic use , Androgen Antagonists/therapeutic useABSTRACT
UNLABELLED: What's known on the subject? and What does the study add? Prostate cancer (PCa) accounts for 12% of newly diagnosed cases of cancer in Europe. It is one of the most frequently diagnosed tumours in the developed world. Since the introduction of prostate specific antigen as a test for early detection of PCa, the rate of diagnosis has increased significantly and specific mortality has reduced in most western countries. Most of the data on the incidence of PCa are obtained from population-based cancer registries which frequently do not cover the whole population. This first national hospital-based PCa registry aims not only to estimate the incidence of the disease but to ascertain the clinical profile of newly diagnosed PCa patients, a useful tool for evaluating the impact of the disease and its socio-health management. OBJECTIVES: ⢠To estimate the 2010 incidence of prostate cancer (PCa) in Spain. ⢠To describe the clinical profile of newly diagnosed cases using a nationwide hospital-based registry. PATIENTS AND METHODS: ⢠This was a national epidemiological observational study in 25 public hospitals with a specific reference population according to the National Health System. ⢠Sociodemographic and clinical variables of all newly diagnosed, histopathologically confirmed PCa cases were collected in 2010, in the area of influence of each centre. Cases diagnosed in private practice were not collected (estimated nearly 10% in Spain). ⢠Data monitoring was external to guarantee quality and homogeneity. ⢠The age-standardized PCa incidence was determined based on the age distribution of the European standard population. RESULTS: ⢠In all, 4087 new cases of PCa were diagnosed for a reference population of 4933940 men (21.8% of the Spanish male population). ⢠The estimated age-standardized PCa incidence was 70.75 cases per 100000 men. ⢠Mean age at diagnosis was 69 years; 11.6% of patients presented with tumour-related symptoms and 39.5% with LUTS. Median PSA was 8 ng/mL. Gleason score was ≤ 6 in 56.5%, 7 in 26.7% and >7 in 16.8% of patients. At diagnosis, 89.8% had localized, 6.4% locally advanced and 3.8% metastatic disease. CONCLUSIONS: ⢠This study on PCa incidence in Spain, a western country with intensive opportunistic PSA screening, shows that PCa is a high incidence tumour, diagnosed close to 70 years, usually asymptomatic. ⢠Almost 40% of cases have low risk disease with a risk of over-diagnosis and over-treatment. ⢠Around 55% of patients with intermediate or high risk disease are candidates for active therapy which may result in a reduction of cancer-specific mortality.
Subject(s)
Early Diagnosis , Mass Screening/methods , Prostatic Neoplasms/epidemiology , Registries , Age Distribution , Aged , Humans , Incidence , Male , Middle Aged , Neoplasm Grading , Prostatic Neoplasms/diagnosis , Retrospective Studies , Spain/epidemiology , Survival Rate/trendsABSTRACT
BACKGROUND: Knowledge of baseline factors that influence outcomes for men with benign prostatic hyperplasia (BPH) receiving medical therapy may help to improve outcomes and cost effectiveness. OBJECTIVES: To examine the influence of baseline parameters on changes in International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Q(max)) in men with BPH receiving dutasteride, tamsulosin, or a combination of the two using 2-yr Combination of Avodart and Tamsulosin (CombAT) study data. DESIGN, SETTING, AND PARTICIPANTS: CombAT is an ongoing, 4-yr, multicentre, randomised, double-blind study in 4844 men aged >or=50 yr with clinical diagnosis of BPH, IPSS >or=12, prostate volume >or=30 cm(3), prostate-specific antigen (PSA) 1.5-10 ng/ml, and Q(max) >5 and