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BACKGROUND: Nivolumab+ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years median follow-up from CheckMate 214. PATIENTS AND METHODS: Patients with aRCC (N=1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. Endpoints included OS, and independent radiology review committee-assessed progression-free survival (PFS) and objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients. RESULTS: With 8 years (99.1 months) median follow-up, the HR (95% CI) for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all IMDC risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). Median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1-not estimable (NE) versus 19.8-33.2; ITT], 82.8 versus 19.8 months [54.1-NE versus 16.4-26.4; I/P], and 61.5 versus 33.2 months [27.8-NE versus 24.8-51.4; FAV]). Incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, those receiving subsequent therapy based on their response status, clinical subpopulations, and adverse events over time. CONCLUSIONS: Superior survival, durable response benefits, and a manageable safety profile were maintained with NIVO+IPI versus SUN at 8 years, the longest phase III follow-up for a first-line checkpoint inhibitor combination therapy in aRCC.
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BACKGROUND: The number of cancer survivors has increased in recent decades, and the majority of them suffer from sequelae of their disease and treatment. This study, which is part of the larger research project OPTILATER, aims to explore different aspects of care services for long-term survivors (≥ 5 years after initial cancer diagnosis) in Germany. The study places an emphasis on the situation of people from different age groups, with different socio-demographic and cultural backgrounds, and sexually and gender diverse individuals. METHODS: To investigate experiences related to follow-up care, focus groups (n = 2) will be conducted with members of patient advisory councils and advocacy groups, representatives of communities, healthcare workers and networks, as well as members of Associations of Statutory Health Insurance Physicians. Guided interviews will be carried out with patients and relatives (n = 40) to investigate needs, barriers and obstacles in terms of follow-up care. On this basis, additional focus groups (n = 2) will be carried out to derive possible scenarios for improving the consideration of needs. Focus groups and interviews will follow a semi-structured format and will be analysed content-analytically. Focus groups and interviews will be conducted online, recorded, transcribed, and analysed independently by two persons. DISCUSSION: The qualitative approach is considered suitable because of the exploratory research aims. The identification of experiences and barriers can reveal disparities and optimization potential in the care of long-term cancer survivors.
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Sobreviventes de Câncer , Grupos Focais , Neoplasias , Pesquisa Qualitativa , Humanos , Sobreviventes de Câncer/psicologia , Feminino , Masculino , Neoplasias/terapia , Neoplasias/psicologia , Alemanha , Necessidades e Demandas de Serviços de Saúde , Pessoa de Meia-Idade , Adulto , IdosoAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Estadiamento de Neoplasias , Humanos , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Neoplasias Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Seguimentos , Europa (Continente)/epidemiologiaRESUMO
BACKGROUND: Renal cell carcinoma is the third most common tumor among urological tumors. In Germany more than 14,000 people are affected every year. The sex ratio is 2/3 men and 1/3 women. OBJECTIVES: The S3 guideline is intended to provide all disciplines dealing with renal cell carcinoma with the current status of diagnostics, therapy and follow-up care of the patients with this tumor. MATERIALS AND METHODS: The first version of the German guideline on renal cell carcinoma was published in 2015. The development was carried out at S3 level, which means that a structured, evidence-based literature search was carried out, recommendations and statements were developed in topic-related working groups and were approved by an interdisciplinary group of officials elected by the different medical societies. The chapters were gradually revised in 2017, 2020 and 2021 to reflect new aspects. This article provides information about the most important innovations of the most recent update from 2023. RESULTS: In the epidemiology subsection, the substance trichlorethene has been added as a risk factor for the development of renal cell carcinoma. While there were no new data on neoadjuvant therapy, the checkpoint inhibitor pembrolizumab was the first substance to demonstrate improved disease-specific and overall survival in the adjuvant situation. The combination nivolumab plus cabozantinib and lenvatinib plus pembrolizumab were included in the chapter on systemic therapy for metastatic clear cell renal cell carcinoma. New are the chapters on non-clear cell renal cell carcinoma and hereditary tumors. CONCLUSIONS: The S3 guideline provides a structured, evidence-based overview of all aspects of renal cell carcinoma.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/patologia , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico , Alemanha , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: For many years, therapy for metastatic hormone-sensitive prostate cancer (mHSPC) was dominated by monotherapy using androgen deprivation therapy (ADT). With the demonstration of survival benefit with intensified systemic therapy from the CHAARTED and STAMPEDE trials, this has fundamentally changed. We analyzed the phase III trials that led to the change in therapy in mHSPC. In addition, we summarized ongoing trials in mHSPC. OBJECTIVES: The ongoing studies and current data on systemic therapy in mHSPC were analyzed. RESULTS: Monotherapy with ADT is no longer considered the standard therapy for mHSPC. Combination therapy with ADT and novel androgen receptor targeting agents (ARTAs: abiraterone, apalutamide, enzalutamide) is now the established standard option. The added value of further intensification of therapy was demonstrated in the first trials of triple therapy with ADTâ¯+ docetaxelâ¯+ darolutamide or abiraterone in mHSPC. Current studies are also investigating new forms of therapy. Lutetium177-PSMA radioligand therapy is an established standard in metastatic castration-resistant prostate cancer (mCRPC) and is currently being evaluated in combination with ADTâ¯+ ARTA in mHSPC. The use of PARP inhibitors (PARPi) have been established in mCRPC. Current studies are showing early evidence of benefit from novel combination therapies of PARPiâ¯+ ARTA, which represent a further expansion of the therapeutic landscape. Experimental therapies are testing another combination, such as an AKT inhibitor with ARTA in patients with PTEN (phosphatase and tensin homolog) loss. Based on the proof of principle in mCRPC, this combination is now being evaluated in earlier stage mHSPC. Other experimental therapies in clinical testing include inhibitors of cyclin dependent kinases (CDK). CONCLUSIONS: Combination therapies are the current standard of care for mHSPC, with the combination of ADTâ¯+ ARTA dominating. Preliminary results underline the importance of further intensification of therapy by means of triple therapy. However, novel combinations with radioligand therapy or PARP inhibitors are also promising in the treatment of mHSPC. Preliminary results show the principle efficacy of AKT inhibitors in patients with PTEN loss, which similar to therapy with CDK4/6 inhibitors still have to prove their clinical relevance in randomized trials.
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Antagonistas de Androgênios , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , Hormônios/uso terapêuticoRESUMO
BACKGROUND: During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. METHODS: A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. RESULTS: The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. CONCLUSIONS: This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients.
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Ensaios Clínicos como Assunto , Neoplasias , Humanos , Oncologia , Neoplasias/terapiaRESUMO
PURPOSE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. CONCLUSION: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.
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Carcinoma de Células Renais , Neoplasias Renais , Axitinibe , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Ipilimumab , Neoplasias Renais/tratamento farmacológico , NivolumabeRESUMO
BACKGROUND: The treatment landscape of metastatic clear cell renal cell carcinoma (mccRCC) has been transformed by targeted therapies with tyrosine kinase inhibitors (TKI) and more recently by the incorporation of immune checkpoint inhibitors (ICI). Today, a spectrum of single agent TKI to TKI/ICI and ICI/ICI combinations can be considered and the choice of the best regimen is complex. MATERIALS AND METHODS: We performed an updated decision-making analysis among 11 international kidney cancer experts. Each expert provided their treatment strategy and relevant decision criteria in the first line treatment of mccRCC. After the collection of all input a list of unified decision criteria was determined and compatible decision trees were created. We used a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees, to determine the most common treatment recommendations as well as deviations. RESULTS: Diverse parameters were considered relevant for treatment selection, various drugs and drug combinations were recommended by the experts. The parameters, chosen by the experts, were performance status, International Metastatic renal cell carcinoma Database Consortium (IMDC) risk group, PD-L1 status, zugzwang and contraindication to immunotherapy. The systemic therapies selected for first line treatment were sunitinib, pazopanib, tivozanib, cabozantinib, ipilimumab/nivolumab or pembrolizumab/axitinib. CONCLUSION: A wide spectrum of treatment recommendations based on multiple decision criteria was demonstrated. Significant inter-expert variations were observed. This demonstrates how data from randomized trials are implemented differently when transferred into daily practice.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , SunitinibeRESUMO
OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (nâ¯=â¯95), ABI (nâ¯=â¯140), or ENZA (nâ¯=â¯85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (Pâ¯=â¯0.058 and Pâ¯=â¯0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (Pâ¯=â¯0.001) and ENZA (Pâ¯=â¯0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.
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Androstenos/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Docetaxel/uso terapêutico , Metaloproteinase 7 da Matriz/sangue , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes. The progress in translational research in recent years has led to innovations in the therapeutic environment. With the decoding of the homologous repair deficiency (HRD) machinery and its ability to be influenced by PARP inhibitors, targeted therapies moved into the therapeutic focus for selected patients. The first positive phase III study for PARP inhibitors is already available. In addition, immunotherapy for the treatment of prostate cancer, which is now widely used in oncology, is also making progress; both checkpoint inhibitors and bispecific antibodies have shown clinically useful activities. Cellular therapies such as CAR T cells, which are directed against prostate-specific membrane antigen (PSMA), are still at an early stage of development. In this review, the authors provide a summary of the basic principles and clinical development of these new therapies.
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Imunoterapia , Terapia de Alvo Molecular , Neoplasias da Próstata/terapia , Humanos , Masculino , Neoplasias da Próstata/patologiaRESUMO
Current pivotal phase 3 studies have permanently changed the first-line treatment landscape in metastatic renal cell carcinoma. These studies showed that immune checkpoint combinations were more efficacious than sunitinib, a previous standard of care. Nivolumab plus ipilimumab is characterized by a survival advantage, a high rate of complete response and durable remission in patients with intermediate and unfavorable prognosis. Despite frequent immune-mediated side effects, fewer symptoms and a better quality of life were observed compared to sunitinib. Pembrolizumab or avelumab plus axitinib were characterized by an improved PFS and a high response rate with a low rate of intrinsic resistance. In addition, a significant survival benefit was achieved with pembrolizumab plus axitinib. The side effect profile is driven by the "chronic" toxicity of axitinib, but there is additional risk of immune-mediated side effects of the PD-1/PD-L1 immune checkpoint inhibitors. The quality-of-life data published so far do not suggest any improvement compared to the previous standard sunitinib. The PD-1/PD-L1 immune-check-point inhibitors thus form the "backbone" of the first-line therapy of metastatic renal cell carcinoma. Monotherapy with VEGFR-TKI remains an option in cases with contraindications and possibly for subgroups with favorable prognosis.
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Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Imunomodulação/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/uso terapêutico , Axitinibe/administração & dosagem , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Humanos , Ipilimumab/administração & dosagem , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Metástase Neoplásica/patologia , Nivolumabe/administração & dosagem , Qualidade de Vida , Sunitinibe/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The combination of cisplatin, 5-fluorouracil (5-FU) and cetuximab (PFC) is the reference first-line treatment for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). We analysed whether treatment intensification by the addition of docetaxel to PFC improved efficacy in R/M SCCHN. METHODS: A total of 180 patients with R/M SCCHN (1:1) were assigned to receive either cisplatin (40 mg/m2), docetaxel (40 mg/m2) and 5-FU (2000 mg/m2) at days 1 and 8 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (DPFC) or standard cisplatin (100 mg/m2) at day 1, 5-FU (1000 mg/m2) at days 1-4 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (PFC). Chemotherapy was repeated every 21 days and continued for a maximum of 6 cycles in absence of disease progression or limiting toxicity, followed by cetuximab maintenance (500 mg/m2 every 2 weeks). The primary end-point was progression-free survival (PFS). RESULTS: A preplanned interim analysis for toxicity after 20 patients/arm revealed excessive grade 3 and 4 gastrointestinal (65%) and infectious toxicities (35%) in arm A, which led to dose reduction of cisplatin to 30 mg/m2 and 5-FU to 1000 mg/m2 for subsequent patients. With a median follow-up of 2 years, grade 4 toxicities were 21.3% vs. 30.8% for DPFC and PFC, respectively. More treatment-related deaths occurred with DPFC vs. PFC, with 11.2% and 6.6%, respectively. For DPFC and PFC, the median PFS was 6.3 vs. 6.4 months (hazard ratio [HR] = 0.97, p = 0.87), the median overall survival was 8.9 vs. 10.6 months (HR = 1.29 p = 0.1) and response rates were 38.2% vs. 31.9% (p = 0.9), respectively. CONCLUSIONS: DPFC failed to improve efficacy in R/M SCCHN. On the contrary, a high toxicity and mortality rate was detected in both arms, which underscores the vulnerability of patients with R/M SCCHN, and research on the need for further optimisation of the front-line chemotherapy backbone is ongoing.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The introduction of molecular targeted agents has fundamentally changed the treatment of metastatic renal cell carcinoma. A first wave of development was based on the improved understanding of tumor biology since the discovery of the importance of the von Hippel-Lindau gene as the key driver of the disease and paved the way for antiangiogenic agents. Of relevance is the overexpression of proangiogenic and proliferation-promoting factors (VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor) as well as an overactivation of the PI3K-Akt signaling pathway: the target structure is the "mammalian target of rapamycin" (mTOR) molecule, which is involved in the regulation of cell proliferative processes. VEGF-, PDGF-, and mTOR-signals and signaling pathways are central targets of current targeted substances. A second wave is certainly to be seen in the development of therapeutic approaches with the targeted activation and modulation of the immune system, which has brought "immunotherapy" back into the focus of interest. Central development is the application of immune-checkpoint inhibitors, with the help of which (re-)activation of the cellular defense, especially of T cells, takes place, which per se holds the potential of a cytoreductive therapy by killing the tumor cells. Even though the prognosis has improved significantly due to the rapid development of recent years, treatment remains challenging as most patients experience progress, and long-term survival is only achieved in about 20% of cases because some patients are primarily refractory or do not respond. The more intensive interlocking of molecular biology, pathology, clinical research, and interdisciplinary uro-oncology, as is the claim of molecular tumor boards, can contribute to the individual selection of a suitable therapy strategy and, thus, establish the latest findings and developments for the benefit of patients in the clinic.
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Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Terapia de Alvo Molecular , Neoplasias/genética , Fator A de Crescimento do Endotélio Vascular , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fosfatidilinositol 3-Quinases , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais , Serina-Treonina Quinases TOR , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Tumors of the genitourinary system are common. In recent years, our understanding of their molecular background and therefore the number of potential predictive biomarkers has massively increased. OBJECTIVES: The aim of the current work is to give an overview of recent (molecular) developments and predictive biomarkers in urologic oncology and to give a perspective of what might become relevant in the future of the field. MATERIAL AND METHODS: We considered the recent literature and study data and combined it with our own expertise in tumors of the urinary system, kidneys, and prostate. RESULTS AND CONCLUSIONS: The molecular subtypes of muscle-invasive urothelial bladder cancer (MIBC) hold a predictive and prognostic significance and correlate with clinicopathological features. Immune therapy with checkpoint inhibitors (CPI) has a major role in urothelial carcinoma (UC), but also in renal cell carcinoma and a subgroup of prostate cancers. The first-line use in UC is restricted to PD-L1-"positive" cases (≥IC2/3, CPSâ¯≥ 10). Further predictive markers are currently under evaluation, while the predictive significance of tumor mutational burden (TMB) is under debate. In addition to a subgroup of renal cell carcinomas, a subgroup of prostate carcinomas with alterations in the DNA repair system might benefit from a customized therapy approach (PARP inhibitors, platin-containing chemotherapy). The multitude of potentially therapy-relevant molecular alterations and related predictive biomarkers calls for the implementation of sophisticated molecular analyses in daily routine. This will lead to an even more rapid dynamic in the field of genitourinary pathology.