RESUMO
BACKGROUND: The primary objective is to determine the proportion of men with suspected prostate cancer (PCA) in whom the management plans are changed by additive gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) guided prostate biopsy (PET-TB) in combination with standard of care (SOC) using systematic (SB) and multiparametric magnetic resonance imaging-guided biopsy (MR-TB) compared with SOC alone. The major secondary objectives are to determine the additive value of the combined approach of SB + MR-TB + PET-TB (PET/MR-TB) for detecting clinically significant PCA (csPCA) compared to SOC; to determine sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of imaging techniques, respective imaging classification systems, and each biopsy method; and to compare preoperatively defined tumor burden and biomarker expression and pathological tumor extent in prostate specimens. METHODS: The DEPROMP study is a prospective, open-label, interventional investigator-initiated trial. Risk stratification and management plans after PET/MR-TB are conducted randomized and blinded by different evaluation teams of experienced urologists based on histopathological analysis and imaging information: one including all results of the PET/MR-TB and one excluding the additional information gained by PSMA-PET/CT guided biopsy. The power calculation was centered on pilot data, and we will recruit up to 230 biopsy-naïve men who will undergo PET/MR-TB for suspected PCA. Conduct and reporting of MRI and PSMA-PET/CT will be performed in a blinded fashion. DISCUSSION: The DEPROMP Trial will be the first to evaluate the clinically relevant effects of the use of PSMA-PET/CT in patients with suspected PCA compared to current SOC. The study will provide prospective data to determine the diagnostic yields of additional PET-TB in men with suspected PCA and the impact on treatment plans in terms of intra- and intermodal changes. The results will allow a comparative analysis of risk stratification by each biopsy method, including a performance analysis of the corresponding rating systems. This will reveal potential intermethod and pre- and postoperative discordances of tumor stage and grading, providing the opportunity to critically assess the need for multiple biopsies. TRIAL REGISTRATION: German Clinical Study Register DRKS 00024134. Registered on 26 January 2021.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Biópsia Guiada por Imagem , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The S3-guideline on bladder cancer recommends radical cystectomy and cisplatin-based perioperative chemotherapy (POC) for muscle-invasive bladder cancer (MIBC). Recommendation for metastatic urothelial cancer (mUC) is cisplatin-based or immuno-oncological (IO) treatment in platinum-ineligible patients (pts) or as 2nd-line therapy. OBJECTIVES: Aim of the study was to obtain representative data on clinical routine treatment of MIBC and mUC in Germany. MATERIALS AND METHODS: A nationwide survey was performed to obtain data on stage-related patient volume in hospitals and office-based physicians. Based on these results, a representative sample of treatment data was collected retrospectively from pts with MIBC and mUC. RESULTS: Data from 956 pts (MIBC 576; mUC: 380) were collected. Of the MIBC pts, 49.8% received a systemic therapy (80.4% of them received cisplatin/gemcitabine) and 50.2% were treated with a cystectomy without POC. Significant factors for cystectomy without POC were higher age >â¯75 years (odds ratio [OR] 4.91, 95% confidence interval [CI] 3.01-8.11, pâ¯< 0.001) and platinum-ineligible pts (OR 2.15, 95% CI 1.30-3.59; pâ¯= 0.003). Treatment decision without interdisciplinary tumor board was also correlated with no POC (OR 2.43, 95% CI 1.65-3.61, pâ¯< 0.001). In mUC platinum-pretreated pts generally receive IO therapy (OR 12.07, 95% CI 6.94-21.82, pâ¯< 0.001). Other significant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71, pâ¯< 0.001), higher age >â¯75 years (OR 2.83, 95% CI 1.43-5.73, pâ¯= 0.003) and platinum-ineligible pts (OR 2.57, 95% CI 1.30-5.71, pâ¯= 0.007). CONCLUSIONS: The "gold standard" cisplatin/gemcitabine is established in Germany if pts are treated with POC. Nonetheless half of the MIBC pts did not receive a POC, especially if the treatment decision is not discussed in a tumor board. In mUC IO therapy is established as 2nd-line therapy after a platinum-based treatment. Although the guideline recommendations are largely implemented, there is potential for optimization, especially in the establishment of interdisciplinary tumor boards.
Assuntos
Carcinoma , Neoplasias da Bexiga Urinária , Humanos , Idoso , Bexiga Urinária , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , MúsculosRESUMO
Systemic therapy in uro-oncology is currently undergoing major changes. In the past, drug therapies only showed good treatment results in metastasized testicular tumors. New developments indicate that an improved understanding of tumor biology will lead to targeted treatment strategies for metastatic prostate, urothelial and renal cell carcinoma. In the following article, we summarize the practice-relevant innovations in systemic therapy in the guidelines on prostate cancer, transitional cell carcinoma of the bladder and renal cell carcinoma.
Assuntos
Carcinoma de Células Renais/terapia , Carcinoma de Células de Transição/terapia , Neoplasias Renais/terapia , Neoplasias da Próstata/terapia , Algoritmos , Carcinoma de Células Renais/patologia , Carcinoma de Células de Transição/patologia , Humanos , Neoplasias Renais/patologia , Masculino , Neoplasias da Próstata/patologiaRESUMO
Novel combination therapies are currently the standard systemic treatment for metastatic hormone-sensitive prostate cancer. As a result, the overall survival of patients can be extended by approximately 1.5 years. The taxane docetaxel, the CYP17 inhibitor abiraterone and the second generation antiandrogen apalutamide can currently be used as a combination partner for classic androgen deprivation. While the de novo synthesis of testosterone is the rationale for abiraterone or apalutamide combination, taxanes offer a promising approach in the presence of primarily androgen-independent prostate cancer cells. Due to the increased rate of side effects caused by combination therapy, it is important to clarify in daily clinical practice which patient group benefits in particular from the respective combination therapy. Hereby, the metastatic pattern, general condition and age play an important role. While there is good evidence of the use of docetaxel or abiraterone in visceral metastasis, apalutamide offers a very wide range of uses. Ultimately, the recommendation for combination therapy is always an individual decision that needs to be discussed with the patient, considering the benefits and risks.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Docetaxel/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/patologia , Tioidantoínas , Resultado do TratamentoRESUMO
BACKGROUND: Does the dogma of nephron sparing surgery (NSS) still stand for large renal masses? Available studies dealing with that issue are considerably biased often mixing imperative with elective indications for NSS and also including less malignant variants or even benign renal tumors. Here, we analyzed the oncological long-term outcomes of patients undergoing elective NSS or radical tumor nephrectomy (RN) for non-endophytic, large (≥7cm) clear cell renal carcinoma (ccRCC). METHODS: Prospectively acquired, clinical databases from two academic high-volume centers were screened for patients from 1980 to 2010. The query was strictly limited to patients with elective indications. Surgical complications were retrospectively assessed and classified using the Clavien-Dindo-classification system (CDS). Overall survival (OS) and cancer specific survival (CSS) were analyzed using the Kaplan-Meier-method and the log-rank test. RESULTS: Out of in total 8664 patients in the databases, 123 patients were identified (elective NSS (n = 18) or elective RN (n = 105)) for ≥7cm ccRCC. The median follow-up over all was 102 months (range 3-367 months). Compared to the RN group, the NSS group had a significantly longer median OS (p = 0.014) and median CSS (p = 0.04). CONCLUSIONS: In large renal masses, NSS can be performed safely with acceptable complication rates. In terms of long-term OS and CSS, NSS was at least not inferior to RN. Our findings suggest that NSS should also be performed in patients presenting with renal tumors ≥7cm whenever technically feasible. Limitations include its retrospective nature and the limited availability of data concerning long-term development of renal function in the two groups.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Estudos de Coortes , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrectomia/mortalidade , Néfrons/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: To analyze the feasibility and perioperative results of patients undergoing robot-assisted cystectomy with intracorporeal urinary diversion and robot-sewn ileoileal anastomosis. METHODS: This is a mono-centric analysis of perioperative data from 48 consecutive patients undergoing robot-assisted cystectomy with intracorporeal urinary diversion and robot-sewn ileoileal anastomosis. Data include the preoperative variables, operative and postoperative course and complication rates related to bowel anastomosis. End points were time spent for anastomosis and intra- and postoperative complication rates. RESULTS: Median operating time was 23.0 (13-60) min for the ileoileal anastomosis. Median overall operating time was 295 (200-780) min, with a median of 282 (200-418) min and 414.0 (225-780) min for the ileum conduit (N = 35) and ileal neobladder (N = 13). Two patients developed paralytic ileus; in another patient acute peritonitis occurred, but was caused by urinary leakage and therefore unrelated to the bowel anastomosis. No anastomotic leakage was noticed. Costs for the robot-sewn anastomosis was 8 compared to 1250 for a stapled anastomosis which was performed in previous cases. Limitations are the non-comparative nature of the analysis and the limited number of patients. CONCLUSIONS: Robot-sewn ileoileal anastomosis is feasible with low complication rates. Compared to the stapled anastomosis, a robot-sewn ileoileal anastomosis may serve as an alternative and cost-saving approach.
Assuntos
Cistectomia/métodos , Íleo/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Técnicas de Sutura , Resultado do Tratamento , Neoplasias da Bexiga Urinária , Derivação Urinária/métodosRESUMO
The standard treatment for patients with metastatic, hormone-sensitive prostate cancer (mCSPC) has so far consisted of medical or surgical castration. However, two published clinical trials using docetaxel in combination with castration (CHAARTED and STAMPEDE) recently provided evidence for a substantial improvement in overall survival. The survival benefit was 14 and 22 months, respectively, in the two trials. In addition, the CHAARTED trial showed that patients with high-volume disease may benefit most from chemohormonal treatment. According to the current available evidence, the new standard of treatment for patients therefore consists of castration in combination with docetaxel-based chemotherapy, which should be offered to all patients who are fit to receive chemotherapy. With the results of the LATITUDE and a further study-arm of the STAMPEDE trial, the combination of androgen-deprivation therapy (ADT) plus abiraterone/prednisone has recently become an alternative treatment to chemohormonal treatment. This combination leads to an identical survival benefit compared to chemohormonal treatment and is recommended by expert panels. Based on the current evidence, it is not possible to decide which patient may benefit from chemohormonal treatment and who will benefit from the combination of ADT plus abiraterone/prednisone.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias Hormônio-Dependentes/terapia , Orquiectomia , Neoplasias da Próstata/terapia , Taxoides/uso terapêutico , Terapia Combinada , Progressão da Doença , Docetaxel , Seguimentos , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Masculino , Metástase Neoplásica/patologia , Neoplasias Hormônio-Dependentes/mortalidade , Neoplasias Hormônio-Dependentes/patologia , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de SobrevidaAssuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Músculo Liso/patologia , Metástase Neoplásica/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/patologia , Método Duplo-Cego , Humanos , Invasividade Neoplásica , Metástase Neoplásica/patologia , Resultado do Tratamento , Neoplasias Urológicas/patologiaRESUMO
BACKGROUND: Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE: This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS: A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS: In the current treatment of hormone-naïve mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Taxoides/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Intervenção Médica Precoce , Medicina Baseada em Evidências , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Próstata/mortalidade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Taxoides/efeitos adversosAssuntos
Antagonistas de Androgênios/uso terapêutico , Androstenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Oncologia/normas , Prednisona/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Humanos , Masculino , Guias de Prática Clínica como Assunto , Resultado do Tratamento , Urologia/normasRESUMO
Androgen deprivation is still standard therapy for prostate cancer, either as primary androgen deprivation therapy or with the use of secondary hormonal drugs including abiraterone and enzalutamide. However, especially the clinically occult side effects like metabolic changes or cardiovascular complications and effects on the psyche of the patient are often not recognized in daily practice. Active monitoring of such side effects is essential for prevention and early intervention. In addition, the efficacy of androgen deprivation therapies is limited by primary and secondary resistance. The underlying molecular mechanism including splice variants of the androgen receptor in contrast to mutations are usually reversible and should be regarded as a sign of efficacy of the current treatment. Therefore, the clever, timely use of androgen deprivation or even the use of a bipolar androgen therapy should enable reversal of resistance to again render tumor cells sensitive to androgen-deprivation therapy.
Assuntos
Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Metabólicas/induzido quimicamente , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Relação Dose-Resposta a Droga , Interações Medicamentosas , Resistencia a Medicamentos Antineoplásicos , Medicina Baseada em Evidências , Humanos , Masculino , Doenças Metabólicas/prevenção & controle , Neoplasias de Próstata Resistentes à Castração , Resultado do TratamentoAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Platina/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Urotélio/efeitos dos fármacos , Antineoplásicos/efeitos adversos , Carcinoma de Células de Transição , Quimioterapia Combinada , Humanos , Resultado do Tratamento , Neoplasias Urológicas/patologia , Urotélio/patologiaRESUMO
BACKGROUND: The standard treatment of patients with metastatic, hormone-sensitive prostate cancer (mCSPC) currently consists of medical or surgical castration. The addition of a cytotoxic chemotherapy was unable to provide a survival benefit over castration alone in several clinical trials using different chemotherapy regimens. RESULTS: Even a preliminary clinical trial using a docetaxel-based chemohormonal combination did not show a survival benefit. In contrast, two more recently published clinical trials (CHAARTED and STAMPEDE) using docetaxel in combination with castration provided evidence for a substantial improvement in overall survival. The survival benefit was 14 and 22 months in the two trials. In addition, the CHAARTED trial showed that patients with high volume disease may benefit most from chemohormonal treatment. CONCLUSION: According to the current available evidence, the new standard of treatment for patients therefore consists of castration in combination with docetaxel-based chemotherapy and should be offered to all patients who are fit to receive chemotherapy.
Assuntos
Antagonistas de Androgênios/administração & dosagem , Castração/mortalidade , Guias de Prática Clínica como Assunto , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada/métodos , Docetaxel , Medicina Baseada em Evidências , Alemanha , Humanos , Masculino , Oncologia/normas , Pessoa de Meia-Idade , Metástase Neoplásica , Taxa de Sobrevida , Resultado do Tratamento , Urologia/normasRESUMO
BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. RESULTS: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. CONCLUSION: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. CLINICAL TRIALS NUMBER: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).