RESUMEN
BACKGROUND: Great advances have been made for the treatment of urothelial carcinoma by the introduction of checkpoint inhibitors (CPI). Single-agent immunotherapy with CPIs has been approved for patients with metastatic or locally advanced inoperable urothelial carcinoma who have either progressed during or after platinum-based chemotherapy or who are cisplatin-ineligible. For cisplatin-ineligible patients, approval is restricted to patients with high programmed cell death ligand 1 (PD-L1) expression. For patients with nonmuscle invasive bladder cancer (NMIBC) or patients with muscle invasive bladder cancer (MIBC) who receive curative therapy, no CPIs have received approval in Germany. OBJECTIVES: To provide an overview of the current landscape of immunotherapy in patients with urothelial carcinoma. METHODS: Summary of the therapeutic landscape and resulting challenges based on currently published data using a PubMed search. RESULTS: In the treatment of metastatic or inoperable urothelial carcinoma, CPIs represent standard treatment. Depending on the results of currently performed trials, an extension of its use to the perioperative setting (neoadjuvant/adjuvant) and to patients with Bacillus Calmette Guérin (BCG) unresponsive NMIBC in the near future is currently being discussed. CONCLUSIONS: Immuno-oncologic treatment using CPIs has become an integral part of the management of patients with advanced bladder cancer. For biomarker-based patient selection and combination therapies, there is an urgent need for further investigations within clinical trial protocols.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígeno B7-H1/uso terapéutico , Carcinoma de Células Transicionales/terapia , Inmunoterapia/tendencias , Receptor de Muerte Celular Programada 1/uso terapéutico , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias Urológicas/terapia , Anticuerpos Monoclonales , Antígeno B7-H1/metabolismo , Carcinoma de Células Transicionales/inmunología , Carcinoma de Células Transicionales/patología , Alemania , Humanos , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Urológicas/inmunología , Neoplasias Urológicas/patologíaRESUMEN
In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.
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Costos de la Atención en Salud , Reembolso de Seguro de Salud , Seguro de Salud , Lutecio/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radioisótopos/uso terapéutico , Antígenos de Superficie , Consenso , Alemania , Hospitales Universitarios , Humanos , Ligandos , Lutecio/efectos adversos , Lutecio/economía , Masculino , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Radioisótopos/efectos adversos , Radioisótopos/economía , Resultado del TratamientoRESUMEN
AIM: Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with 177Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. METHODS: A total of 104 patients were treated with 351 cycles of 177Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle. Patients were followed-up for overall survival (OS). Any PSA decline, PSA decline ≥50%, initial PSA, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), visceral metastases and cumulative injected activity were analyzed and evaluated according to OS. Multivariable analysis with parameters with a p-value ≤0.05 in univariate analysis was performed, additionally adjusting for age and presence of visceral metastases. RESULTS: A total of 51 patients (49%) died during the observation period. The majority of patients (97%) presented with bone metastases, 77% with lymph node metastases and 32% with visceral metastases. All patients were treated with at least one line of chemotherapy. Either abiraterone or enzalutamide had been given in 100% of the patients. Any PSA decline occurred in 70 (67%) and a PSA decline ≥50% in 34 (33%) of patients after the first cycle. The median OS was 56.0 weeks (95%CI: 50.5-61.5). Initial PSA decline ≥50%, initial LDH, visceral metastases, second line chemotherapy or prior radium-223 did not have an effect on survival, whereas any initial PSA decline, initial ALP <220 U/L and cumulative injected activity ≥18.8 GBq were associated with a longer survival. A step-by-step analysis revealed a PSA decline ≥20.87% as the most noticeable cut-off prognosticating longer survival, which remained an independent prognosticator of improved OS in the multivariate analysis. CONCLUSION: 177Lu-PSMA-617 RLT is a new effective therapeutic and seems to prolong survival in patients with advanced mCRPC pretreated with chemotherapy, abiraterone and/or enzalutamide.
Asunto(s)
Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radiofármacos/uso terapéutico , Anciano , Antígenos de Superficie/sangre , Dipéptidos/administración & dosificación , Glutamato Carboxipeptidasa II/sangre , Compuestos Heterocíclicos con 1 Anillo/administración & dosificación , Humanos , Lutecio , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/patología , Radiofármacos/administración & dosificación , Análisis de SupervivenciaRESUMEN
BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES: Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS: In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS: Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC.
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Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Ensayos de Uso Compasivo , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Humanos , Lutecio , Masculino , Metástasis de la Neoplasia , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios RetrospectivosRESUMEN
What new developments in urooncology were discussed at the 2015 annual meetings of ASCO, EAU, DGU and ESMO? This review summarises news relevant to the daily diagnosis and treatment of prostate, bladder and kidney cancer. While study results seem to change paradigms in the treatment of prostate cancer, particularly in metastatic but still hormone-sensitive stages, immunotherapeutic strategies for the treatment of kidney and urothelial cancer are very promising and might expand the systemic therapeutic options in the years to come.
RESUMEN
Genitourinary neoplasms are relatively common and the frequency increases with age. Due to demographic changes more patients with inflammatory rheumatic diseases will have concomitant genitourinary tumors or they will develop them under antirheumatic therapy. In such cases, disease-modifying antirheumatic drugs (DMARD) and immunosuppressive therapy have to be carefully balanced on an individual basis. Based on the limited evidence available large increases in the risks from conventional and/or biological DMARDs for patients with genitourinary malignancies appear to be unlikely for most situations. In addition to these more common situations paraneoplastic symptoms in the musculoskeletal system can occur due to genitourinary malignancies. Moreover, novel drugs with immunostimulating activity for some genitourinary tumors may provoke autoimmune symptoms and thus present new challenges for interdisciplinary cooperation between rheumatologists and uro-oncologists. In this review, the diagnostic procedures, therapies and follow-up of cancers in the field of urology are delineated according to the current German and European guidelines. We describe the core issues that both urologists and rheumatologists should bear in mind. Direct communication, routine exchange and involvement of rheumatologists in interdisciplinary tumor boards should improve future treatment quality of our joint patients.
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Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Neoplasias Urogenitales/inducido químicamente , Neoplasias Urogenitales/prevención & control , Artritis Reumatoide/complicaciones , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Europa (Continente) , Medicina Basada en la Evidencia , Alemania , Humanos , Resultado del TratamientoRESUMEN
What is new in urooncology in the year 2014? This review gives a brief but comprehensive overview of new developments in diagnosis and treatment of localized as well as advanced prostate, bladder and kidney cancer which have been presented on the occasion of the annual meetings of the European and American urologic and oncological associations in 2014. Attention is particularly directed to those data and results from trials which might be of direct or indirect clinical relevance.