ABSTRACT
The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy (AU)
Subject(s)
Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Neoplasm Staging , Biomarkers, Tumor , Genetic Markers , Societies, Medical , SpainABSTRACT
The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents/therapeutic use , Prostatic Neoplasms/therapy , Androstenes/therapeutic use , Benzamides/therapeutic use , Combined Modality Therapy/methods , Docetaxel/therapeutic use , Genes, BRCA1 , Genes, BRCA2 , Genetic Testing/methods , Humans , Male , Medical Oncology , Nitriles/therapeutic use , Orchiectomy , Phenylthiohydantoin/therapeutic use , Phthalazines/therapeutic use , Piperazines/therapeutic use , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms, Castration-Resistant/diagnosis , Prostatic Neoplasms, Castration-Resistant/therapy , Radiotherapy/methods , Randomized Controlled Trials as Topic , Societies, Medical , Spain , Thiohydantoins/therapeutic useABSTRACT
The management of genitourinary cancer, including bladder, prostate, renal and testicular cancer, has evolved dramatically in recent years due to a better understanding of tumour genetic mutations, alterations in molecular pathways, and to the development of new kinds of drugs such as targeted therapies and immunotherapies. In the field of immunotherapy, new drugs focused on stimulating, enhancing and modulating the immune system to detect and destroy cancer, have been recently discovered. Research in oncology moves quickly and new data of great relevance for clinical practice are communicated every year. For this reason, a group of experts, focused exclusively on the treatment of genitourinary tumours and who get together every year in the BestGU conference to assess the latest progress in this field have summarized the most important advances in a single review, along with a critical assessment of whether these results should alter daily clinical practice.
Subject(s)
Urogenital Neoplasms/genetics , Urogenital Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Cystectomy , Drugs, Investigational/therapeutic use , Female , Humans , Immunotherapy/methods , Immunotherapy/trends , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Male , Molecular Targeted Therapy/methods , Mutation , Neoadjuvant Therapy , Neoplasm Recurrence, Local/therapy , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/therapy , Nephrectomy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapyABSTRACT
BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.
Subject(s)
Brain Neoplasms/secondary , Neoplasms, Germ Cell and Embryonal/secondary , Testicular Neoplasms/pathology , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Humans , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/mortality , Survival Analysis , Testicular Neoplasms/drug therapy , Testicular Neoplasms/mortality , Young AdultABSTRACT
BACKGROUND: Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need. METHODS: The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II-III trials. Inclusion criteria in all trials required a TL of <50 ng dl(-1). RESULTS: Median age: 70 years; visceral metastases: 19.8%; median prostate-specific antigen (PSA): 50.7 ng ml(-1); median TL: 11.5 ng dl(-1). Median overall survival (OS; 24.5 months) was significantly longer if baseline TL was above (High TL; n=52) than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively; P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01-3.48)). Patients presenting both anaemia and low testosterone had a worse outcome compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1 months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs 21.7%) in 41 patients receiving SHT. CONCLUSION: Testosterone level under castration range was a prognostic factor for survival mCRPC patients. The PSA response to SHT differed depending on TLs. Testosterone levels might help in treatment decision.
Subject(s)
Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/mortality , Testosterone/blood , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Metastasis , Predictive Value of Tests , Prognosis , Prostatic Neoplasms, Castration-Resistant/drug therapyABSTRACT
PURPOSE: Immunotherapy (IL-2 and INF-α) was the treatment of choice for advanced renal cell carcinoma (RCC) until antiangiogenic therapy with tyrosin kinase inhibitors was developed in the early 2000s. This clinical trial explored the efficacy and toxicity of sequential treatment of IL-2 plus INF-α followed by sorafenib. METHODS: Eligibility criteria included measurable, non-resectable, histologically confirmed predominantly clear cell RCC, no prior systemic treatment, and ECOG PS 0-2. The treatment regimen was a 6-week cycle of subcutaneous IL-2 at 9 × 10(6) IU on days 1-6 of weeks 1, 2, 4 and 5 plus s.c. INF-α at 6 × 10(6) IU on days 1, 3 and 5 of weeks 1-6. Responders received 6 additional weeks of this regimen. All patients received oral sorafenib (400 mg bid) after immunotherapy until disease progression. The primary endpoint was progression-free survival. RESULTS: Forty-one patients were enrolled, median age 57 years. ECOG was 0/1 in 17/20 patients, 35 patients had prior nephrectomy and 18 patients pure clear cell cancer. Median PFS was 7.4 months (95 % CI 6.5-13.1) and OS was 16.6 months (95 % CI not reached). In 36 patients evaluable for response, ORR was 44.4 % and control rate was 94.4 %. Most adverse events (AEs) were Grade 1 or 2 toxicities (84.7 %). During immunotherapy the most common AEs were pyrexia (82.9 %), asthenia (56.1 %) and anorexia (46.3 %), whereas during sorafenib were diarrhoea (48.8 %) and hand-foot syndrome (46.3 %). CONCLUSIONS: A sequential regimen of IL-2 and INF-α followed by sorafenib showed effectiveness and manageable toxicity in patients with advanced RCC.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Interferon-alpha/administration & dosage , Interleukin-2/administration & dosage , Kidney Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/therapy , Combined Modality Therapy/methods , Disease Progression , Disease-Free Survival , Female , Humans , Immunotherapy/methods , Kidney Neoplasms/therapy , Male , Middle Aged , Neoplasm Metastasis , Niacinamide/administration & dosage , Probability , Sorafenib , Time Factors , Treatment OutcomeABSTRACT
Contexto: En el manejo integral del cáncer de próstata avanzado resistente a la castración siguen existiendo incertidumbres y controversias, a pesar de la existencia de numerosas guías de práctica clínica basadas en la evidencia, internacionalmente consensuadas. Objetivo: Elaborar un documento en el que se revise el manejo de controversias en el cáncer de próstata avanzado resistente a la castración, con recomendaciones desde su definición hasta el manejo de maniobras hormonales y el tratamiento de primera y segunda línea con nuevos fármacos como cabazitaxel y abiraterona, así como el abordaje multidisciplinario de la patología con el objetivo de buscar la alternativa más eficiente, el mejor momento de actuar y la mayor seguridad. Adquisición de la evidencia: Se realizaron 2 reuniones de un grupo de expertos multidisciplinarios implicados en el manejo de esta enfermedad (urólogos y oncólogos) donde se pusieron en común el análisis bibliográfico de artículos originales y se consensuó este documento de recomendaciones sobre el cáncer de próstata resistente a la castración, revisando e intentando dar respuesta a las actuales controversias de la enfermedad. Síntesis de la evidencia: Este documento está avalado por las principales sociedades científicas y grupos de trabajo implicados en el manejo actual de los tumores genitourinarios: la Asociación Española de Urología (AEU), el Grupo de Urología Oncológica (GUO) y el Grupo Español de Oncología Genitourinaria (SOGUG). Conclusiones: Con la adaptación e implementación de este documento de recomendaciones a la práctica clínica se dispone, por primera vez, de una verdadera hoja de ruta de calidad, eficiencia y seguridad del manejo de los pacientes con cáncer de próstata avanzado resistente a la castración (AU)
Context: Controversies and uncertainties among integral management of advanced castration resistant prostate cancer continue to exist despite the number of evidence based clinical practice guidelines published with high international consensus. Objective: To develop a document that reviews the management of controversies in advanced castration resistant prostate cancer, with recommendations from the definition, to the management in hormonal maneuvers, first-line treatment and second-line with new treatments as cabazitaxel or abirarerone and the multidisciplinary approach of the pathology with the goal of finding the most efficient, best time to act and safety. Evidence Acquisition: Two meetings of a multidisciplinary group of experts involved in the management of this disease (Oncologist and Urologist) where pooled analysis of original literature and reached consensus document of recommendations on castration resistant prostate cancer, reviewing and attempting to address the current controversies of the disease. Evidence Synthesis: This document is endorsed by the corresponding Scientific Associations and Working Groups involved in the current management of Genitourinary Tumours: the Spanish Association of Urology (AEU) with the Uro-Oncoloy Group (GUO) and the Spanish Oncology of Genitourinary Group (SOGUG). Conclusions: With the adaptation and implementation of this Document of Recommendations for clinical practice are available for the first time, a real road map for quality, efficiency and safety in the management of patients with CRPC (AU)
Subject(s)
Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Castration/trends , Evidence-Based Medicine/methods , Evidence-Based Medicine/trends , Hormones/therapeutic use , Prostaglandins, Synthetic/therapeutic use , Prostate/pathology , Prostate , PrognosisABSTRACT
CONTEXT: Controversies and uncertainties among integral management of advanced castration resistant prostate cancer continue to exist despite the number of evidence based clinical practice guidelines published with high international consensus. OBJECTIVE: To develop a document that reviews the management of controversies in advanced castration resistant prostate cancer, with recommendations from the definition, to the management in hormonal maneuvers, first-line treatment and second-line with new treatments as cabazitaxel or abirarerone and the multidisciplinary approach of the pathology with the goal of finding the most efficient, best time to act and safety. EVIDENCE ACQUISITION: Two meetings of a multidisciplinary group of experts involved in the management of this disease (Oncologist and Urologist) where pooled analysis of original literature and reached consensus document of recommendations on castration resistant prostate cancer, reviewing and attempting to address the current controversies of the disease. EVIDENCE SYNTHESIS: This document is endorsed by the corresponding Scientific Associations and Working Groups involved in the current management of Genitourinary Tumours: the Spanish Association of Urology (AEU) with the Uro-Oncoloy Group (GUO) and the Spanish Oncology of Genitourinary Group (SOGUG). CONCLUSIONS: With the adaptation and implementation of this Document of Recommendations for clinical practice are available for the first time, a real road map for quality, efficiency and safety in the management of patients with CRPC.
Subject(s)
Prostatic Neoplasms, Castration-Resistant/drug therapy , Humans , Male , Neoplasm Staging , Prostatic Neoplasms, Castration-Resistant/pathologyABSTRACT
BACKGROUND: Treatment options remain limited for patients with castration-resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a nontaxane halichondrin B analog microtubule inhibitor, in patients with metastatic CRPC with or without previous taxane exposure. PATIENTS AND METHODS: Men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/m(2) as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. The primary efficacy end point was prostate-specific antigen (PSA) response rate. RESULTS: In total, 108 patients were assessable for safety (50 were taxane-pretreated) and 105 for efficacy in the per-protocol population. The median age of patients was 71 years and median number of cycles was 4. PSA decreases of ≥ 50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. The most common grade 3/4 adverse event was neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients. CONCLUSION: Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC.
Subject(s)
Carcinoma/drug therapy , Furans/therapeutic use , Ketones/therapeutic use , Prostatic Neoplasms/drug therapy , Taxoids/therapeutic use , Aged , Aged, 80 and over , Algorithms , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma/pathology , Carcinoma/surgery , Chemotherapy, Adjuvant , Drug Resistance, Neoplasm/drug effects , Furans/adverse effects , Humans , Ketones/adverse effects , Male , Middle Aged , Neoplasm Metastasis , Orchiectomy , Patient Selection , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Treatment Failure , Treatment OutcomeABSTRACT
With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib-sunitinib vs. sunitinib-sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib-everolimus vs. everolimus-sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Clinical Trials as Topic , Kidney Neoplasms/drug therapy , Drug Delivery Systems , HumansABSTRACT
La criptorquidia constituye un factor de riesgo para el desarrollo de un tumor testiculat: La bilateralidad sincrónica es un hecho infrecuente en los tumores testiculares. El seminoma con células sincitiotrofoblásticas es una variante de seminoma sin implicaciones pronósticas
Cryptorcbidism is a riskfactor to develop a testicular tumour. Synchronus bilateral testicular tumours are unusuaL Seminoma with syncytiotrophoblastic cells is one variant of seminoma without prognostic implications
