RESUMEN
PURPOSE OF REVIEW: In this review, we analyze the current state of research in development of new biomarkers that may be useful in managing metastatic renal cell carcinoma (mRCC) setting. RECENT FINDINGS: Combining tumor-based biomarkers (gene expression profile) and blood-based biomarkers (ctDNA, cytokines) would be helpful in acquiring information regarding RCC and might be significant in the decision-making process. Renal cell carcinoma (RCC) is the sixth most frequently diagnosed neoplasm in men and tithe in women, making it responsible for 5% and 3% of all diagnosed cancers respectively. Metastatic stage represents a non-negligible percentage at diagnosis and is characterized by poor prognosis. Despite clinical features and prognostic score could guide clinicians in therapeutic approach of this disease, biomarkers predictive of response to treatment remain an unmet need.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Masculino , Humanos , Femenino , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/patología , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , TranscriptomaRESUMEN
Our aim was to analyse, on a population level, the year-long decline in cancer diagnoses in the region of Lombardy (Italy), and to characterise the tumours with the greatest reduction in diagnosis by patient age, sex and tumour stage at diagnosis. We used the health care utilisation databases of the Lombardy region to identify cancer patients' characteristics (eg, sex, age) and cancer-related information (eg, cancer site, stage at diagnosis). The frequency of new cancer diagnoses in 2019 and 2020 were compared in terms of percentage differences in undiagnosed cases. We observed two peaks in the decline in cancer diagnoses: March to May 2020 (-37%) and October to December 2020 (-19%). The decline persisted over the course of 2020 and was higher in males and patients aged 74+. Diagnoses of all four common cancers analysed (female breast, lung, colorectal and prostate) remained below pre-pandemic levels. For breast and colorectal cancers, the decline in diagnoses was high in the age groups targeted by population-based screening programmes. We observed a reduction in localised stage cancer diagnoses for all four cancers. Our data confirm that timely monitoring of cancer diagnoses and interventions to prevent disruption of routine diagnostic services are needed to mitigate the impact of emergencies on cancer patients.
Asunto(s)
COVID-19 , Neoplasias , COVID-19/diagnóstico , COVID-19/epidemiología , Bases de Datos Factuales , Femenino , Humanos , Masculino , Tamizaje Masivo , Neoplasias/diagnóstico , Neoplasias/epidemiología , PandemiasRESUMEN
PURPOSE: In 2003, the German Cancer Society (Deutsche Krebsgesellschaft, DKG) launched a certification program aimed at improving the quality of cancer care. The purpose of this article is to describe the experience of the Prostate Cancer Unit (PCU) at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, in the process towards DKG certification. METHODS: In 2018, PCU decided to apply for certification by adopting DKG catalogue of requirements (CoR) and quality indicators. A multiprofessional working group was established with the aim of acting the necessary steps to meet DKG standards. RESULTS: Our organizational setting (procedures, personnel) and activities were accurately analyzed, thus outlining strengths and weaknesses, and modified to comply with DKG CoR and indicators. As examples, (1) a quality management plan was developed; (2) measures were taken to strengthen the surgical expertise; (3) cases evaluated in weekly tumor boards were expanded to include surgical cases with pathological risk factors, metastatic, relapsed and castration-resistant patients; (4) a survey was added to the patient-dedicated initiatives already scheduled; (5) the TuDoc software became the tool to register all new cases of prostate cancer patients referred to PCU. CONCLUSIONS: The process of certification requires many efforts but represents a unique opportunity of improving quality of care of prostate cancer patients, making it comparable on an international scale.
Asunto(s)
Neoplasias de la Próstata/terapia , Garantía de la Calidad de Atención de Salud/normas , Anciano , Anciano de 80 o más Años , Certificación , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE OF REVIEW: The aim of this review is to sum up the state of the art of urachal carcinoma (UC) in order to easily guide clinicians. RECENT FINDINGS: UC is a rare and aggressive disease with consequent few data about diagnosis and treatment. Dates are mainly based on retrospective trial and case reports with limited prospective trial. Clinical presentation is not specific, often with urinary symptoms. Diagnosis is mainly based on CT scan and MRI, useful to evaluate local invasion and nodal status and to detect the presence of distant metastases. Therefore, biopsy is needed to obtain histological confirmation. Surgery is the gold standard for localized disease, while different chemotherapy schemes have been used in metastatic setting. Novel findings based on mutational analysis of the tumor include the use of biological treatment, such as cetuximab, and immunotherapy, such as atezolizumab, with satisfactory responses, suggesting that personalized treatment could be the most suitable option for UC.
Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia , Adenocarcinoma/patología , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Quimioterapia Adyuvante , Cistectomía/métodos , Humanos , Inmunoterapia , Terapia Molecular Dirigida , Pronóstico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Renales , Deleción Cromosómica , Cromosomas Humanos Par 9/genética , Neoplasias Renales , Células Neoplásicas Circulantes , Análisis de la Célula Individual , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologíaRESUMEN
Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.
Asunto(s)
Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Inmunoterapia , Neoplasias Renales/patología , Neoplasias Renales/terapia , Pautas de la Práctica en Medicina , Carcinoma de Células Renales/inmunología , Humanos , Neoplasias Renales/inmunología , Metástasis de la Neoplasia , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
OBJECTIVES: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting. METHODS: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m2 on days 1 and 8 every 21 days. RESULTS: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE. CONCLUSIONS: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Adulto , Anciano , Antraciclinas/uso terapéutico , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Taxoides/uso terapéutico , Resultado del TratamientoAsunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Estudios de Seguimiento , Humanos , Ipilimumab , Nivolumab , SunitinibRESUMEN
INTRODUCTION: Surveillance is the standard management in low-risk cN0 penile squamous cell carcinoma (peSCC) patients. However, no previous analysis focused on early and long-term outcomes of these patients. We report on main oncological outcomes of a large series of low-risk cN0 peSCC patients. PATIENTS AND METHODS: Between 1980 and 2017 included, 93 evaluable consecutive low-risk (ie, pT1a G1 cN0M0) peSCC patients underwent primary tumor surgery and either observation (74) or dynamic sentinel node biopsy (DSNB) (19) following a clinical diagnosis of T1 in 66 (71%), T2 in 15 (16.1%) and Tx in 12 (12.9%) patients, respectively. The statistical significance of differences in medians and proportions was tested with the Kruskal-Wallis and chi-square tests. Kaplan-Meier plots illustrated 5-year inguinal relapse (IR)-free survival rates. RESULTS: Median age was 60 years (IQR: 50-69 years). Median follow-up was 92 months (IQR 54-133 months). Surveillance was more frequently adopted in clinical (c)T1 than in cT2 tumors (79.7% vs. 36.8%). None of 19 patients who had DSNB had nodal metastasis. Overall, 7 (7.5%) out of 93 pT1aG1cN0 peSCC patients had IR after a median interval of 9 months. Of note, 1 patient only relapsed after 12 months of surveillance. After stratification according to IR, relapses occurred more frequently in younger patients (59 vs. 64 years, P < .001). The 5-year IR-free survival rates for the entire cohort was 92% (95% Confidence interval [CI] 87-98%). CONCLUSIONS: Observation is a safe and effective management for low-risk peSCC patients. Younger patients may be offered a mini-invasive staging as an alternative.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Masculino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias del Pene/patología , Carcinoma de Células Escamosas/patología , Estadificación de NeoplasiasRESUMEN
Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1-2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.
RESUMEN
INTRODUCTION: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. PATIENTS AND METHODS: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. RESULTS: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). CONCLUSION: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Sistema de Registros , Humanos , Neoplasias del Pene/patología , Neoplasias del Pene/mortalidad , Neoplasias del Pene/terapia , Masculino , Anciano , Estudios Retrospectivos , Sistema de Registros/estadística & datos numéricos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Pronóstico , Anciano de 80 o más Años , Persona de Mediana Edad , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metástasis Linfática , Resultado del TratamientoRESUMEN
Background: Immune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy. Materials and methods: This retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Among 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels <140 mE/L (18.7 vs. 12.0, p=0.04). Post-treatment sodium levels ≥140 mEq/L were associated with improved PFS (9.6 vs. 3.2 months) and OS (25.1 vs. 8.8 months) (p=0.05 and p<0.01, respectively). Patients with consistent sodium levels ≥140 mEq/L at both time points exhibited the best outcomes compared to those with lower values (PFS 11.5 vs. 3.3 months and OS 42.2 vs. 9.0 months, respectively, p<0.01). Disease control rate was significantly higher in the latter group (p<0.01). Multivariate analysis confirmed the prognostic significance of sodium levels. Conclusion: Elevated sodium levels (≥140 mEq/L) pre- and post-ICI treatment correlate with better survival outcomes in mRCC patients with BMs. This finding suggests sodium level assessment as a potential prognostic factor in these patients and warrants further investigation, particularly in combination immunotherapy settings.
Asunto(s)
Neoplasias Óseas , Carcinoma de Células Renales , Inmunoterapia , Neoplasias Renales , Sodio , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Óseas/secundario , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Anciano , Estudios Retrospectivos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/inmunología , Neoplasias Renales/patología , Neoplasias Renales/terapia , Neoplasias Renales/mortalidad , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/inmunología , Sodio/sangre , Inmunoterapia/métodos , Nivolumab/uso terapéutico , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adulto , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The BONSAI phase II trial recently demonstrated the activity of cabozantinib in metastatic collecting duct patients. The outcomes of patients in this setting treated with immunotherapy as second-line is unknown. The aim of the present report was to describe outcomes of patients enrolled in the BONSAI trial that received nivolumab as second-line treatment. MATERIAL AND METHODS: We describe the oncological outcomes in terms of overall response rate, progression-free survival, overall survival and safety. We excluded patients that did not receive any second-line treatment or were treated with agents other than nivolumab. RESULTS: We identified five patients of whom one was excluded due to lack of data. Three patients obtained clinical benefit (one partial response, two stable disease); the second-line progression-free survival (nivolumab) ranged from 2.8 to 19.9 months to and second-line overall survival ranged from 5.1 to 26.5 months. No new safety signals were observed. CONCLUSIONS: Nivolumab may be considered as second-line therapy option after cabozantinib failure in selected metastatic collecting duct carcinoma patients.
Asunto(s)
Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Nivolumab/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias Renales/patologíaRESUMEN
BACKGROUND: First-line therapies based on immune-checkpoint inhibitors (ICIs) significantly improved survival of metastatic renal cell carcinoma (mRCC) patients. Cabozantinib was shown to target kinases involved in immune-escape and to prolong survival in patients pre-treated with tyrosine-kinase-inhibitors (TKIs). The impact of ICIs combinations in first line on subsequent therapies is still unclear. METHODS: This is an open label, multicenter, single arm, phase II study designed to assess activity, safety and efficacy of cabozantinib in mRCC patients progressed after an adjuvant or first line anti-Programmed Death (PD)-1/PD-Ligand (PD-L) 1-based therapy. Primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. RESULTS: 31 patients were included in the analysis. After a median (m) follow-up of 11.9 months, mPFS was 8.3 months (90%CI 3.9-17.4) and mOS was 13.8 months (95%CI 7.7-29.0). ORR was 37.9% with an additional 13 patients achieving disease stability. Grade 3-4 adverse events occurred in 47% of patients, including more frequently creatine phosphokinase (CPK) serum level elevation, neutropenia, hyponatremia, diarrhea, hand-food syndrome, oral mucositis and hypertension. CONCLUSIONS: The BREAKPOINT trial met its primary endpoint showing that cabozantinib as second line therapy after ICIs was active in mRCC. Safety profile was manageable. TRIAL REGISTRATION NUMBER: NCT03463681 - A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma (BREAKPOINT) - https://clinicaltrials.gov/ct2/show/NCT03463681.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/patología , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
OBJECTIVES: To support laparoscopic post-chemotherapy retroperitoneal lymph-node dissection (L-PC-RPLND) as a potential new standard, we report on a large dataset of patients systematically undergoing L-PC-RPLND. PATIENTS AND METHODS: Patients with unilateral residual mass (≥1 cm), normalized markers, limited encasement (<30%) of gross retroperitoneal vessels underwent unilateral L-PC-RPLND with no adjuvant chemotherapy. Surgical performances, histology, hospital stay, complications within 30 days and follow-up visits were recorded. Multivariable linear and logistic regression models were used. RESULTS: Between February 2011 and January 2021, 151 consecutive patients underwent L-PC-RPLND. Median size of the residual mass was 25 mm (interquartile range [IQR] 20-35 mm). Overall median operative time was 208 min (IQR 177-241) and was 51 min longer (p-value <0.001) for right L-PC-RPLNDs. Eleven procedures were converted to open surgery. Median number of removed and positive nodes was 11 (IQR 8-16) and 1 (IQR 1-2), respectively. Mean hospital stay was 2 days (IQR 2-3). Nine complications (6%) occurred: two were Clavien-Dindo grade III. Definitive pathology revealed post-pubertal teratoma in 65.6%, fibro-necrotic tissue in 23.8%, teratoma with malignant somatic component in 6.6% and viable tumour in 4.0% patients. In multivariable linear regression models, fibro-necrotic tissue (32 min, CI 8.5-55.5; p < 0.01) and residual volume (1.05 min, CI 0.24-1.85; p < 0.01) achieved independent predictor status for longer operative time. All patients, but one, are alive and disease-free after a median follow-up of 22 months (IQR 10, 48). CONCLUSION: L-PC-RPLND, when adequately planned, is safe and effective for most patients with low to medium volume residual masses.
Asunto(s)
Laparoscopía , Neoplasias de Células Germinales y Embrionarias , Teratoma , Neoplasias Testiculares , Masculino , Humanos , Estudios Retrospectivos , Escisión del Ganglio Linfático/métodos , Neoplasias de Células Germinales y Embrionarias/cirugía , Teratoma/cirugía , Neoplasias Testiculares/cirugía , Neoplasias Testiculares/patología , Espacio Retroperitoneal/cirugía , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon (POLE), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.
Asunto(s)
Medicina de Precisión , Neoplasias de la Próstata , Biomarcadores , Reparación de la Incompatibilidad de ADN , Humanos , Inmunoterapia , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapiaRESUMEN
Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide. In about 55% of cases, it is diagnosed at a localised and/or locally advanced stage and therefore amenable to a curative approach. Although nephrectomy still represents the cornerstone of non-metastatic RCC (nmRCC) treatment, a relapse is observed in about 25-30% of patients undergoing curative surgery. Prognosis is drastically influenced by lymph nodal involvement. After the first disappointing results with a cytokine-based strategy, tyrosine kinase inhibitors (TKIs) were tested as adjuvant agents. Despite their efficacy in the metastatic setting, results in terms of disease-free survival (DFS) are not unequivocal and the overall survival (OS) benefit has not been demonstrated. Moreover, their toxicity profile induced a remarkable percentage of patients to discontinue the treatment. On the contrary, the KEYNOTE-564 trial showed the benefit of adjuvant pembrolizumab compared with placebo in terms of DFS with promising results in term of OS. Patients included were at intermediate or high risk of relapse, or patients with no evidence of disease after metastasectomy (M1 NED). The updated analysis presented at the American Society of Clinical Oncology Genito-Urinary (ASCO GU) 2022 confirmed the benefit of pembrolizumab versus placebo over time, although OS data are still immature. A longer follow-up and the several ongoing trials with immune checkpoint inhibitors (ICIs) will provide further data about adjuvant immuno-oncology (IO). Furthermore, the patients' selection based on clinical or biological features will be crucial in order to identify who benefits most from treatments.
RESUMEN
Importance: Metastatic collecting duct carcinoma (mCDC) is a rare type of non-clear cell renal cell carcinoma (ncRCC) with poor prognosis and no standard treatments. Despite retrospective series that have documented the benefit of cabozantinib in ncRCC, no prospective trials have evaluated this treatment in mCDC. Objective: To determine whether cabozantinib is an active treatment in patients with mCDC. Design, Setting, and Participants: The caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI) trial was an open-label, single-arm, phase 2 clinical trial carried out between January 2018 and November 2020 at a single academic center with data cut off in September 2021 on behalf of the the Italian Network for Research in Urologic-Oncology (Meet-URO 2). Eligible patients had histologic diagnosis of centrally confirmed mCDC with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). In total, 25 patients were screened. Interventions: Patients received cabozantinib, 60 mg orally once daily, until disease progression, unacceptable toxic effects, or withdrawal of consent. Main Outcomes and Measures: The primary end point was objective response rate (ORR) per RECIST, version 1.1. Results: At data cut off, of 25 patients enrolled, 23 started treatment because 2 were excluded after failing the screening process at pathologic review. The median follow-up cannot be estimated using the reverse Kaplan-Meier estimator. The median time to censoring was 11 months (95% CI, 0-22 months). Median (range) age was 66 (53-74) years. As best overall response, 3 patients presented stable disease, 1 patient achieved a complete response, and 7 a partial response. The ORR was 35% (95% CI, 16%-57%). The median progression-free survival was 4 months (95% CI, 3-13 months). The median OS was 7 months (95% CI, 3-31 months). All patients reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (14 [60%]), anorexia (9 [39%]), hand-foot syndrome (7 [30%]), hypothyroidism (7 [30%]), mucositis (7 [30%]), diarrhea (5 [22%]), and hypertension (3 [13%]). Six G3 AEs were reported: 2 arterial hyperthension, 1 pulmonary thromboembolism, 1 bleeding, and 2 fatigue. There were no permanent discontinuations from the study owing to AEs. Four patients (17%) required dose reduction to 40 mg, and 4 (17%) required a transitory interruption to manage toxic effects. Conclusions and Relevance: The study met the ORR primary end point, showing encouraging efficacy of cabozantinib in untreated patients with mCDC. Further investigations to advance the molecular understanding of this tumor are ongoing. Trial Registration: ClinicalTrials.gov Identifier: NCT03354884.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Anciano , Anilidas/efectos adversos , Carcinoma de Células Renales/patología , Fatiga , Humanos , Neoplasias Renales/patología , Piridinas , Estudios RetrospectivosRESUMEN
BACKGROUND: Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. RESULTS: We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48-0.92, p = 0.011). CONCLUSIONS: We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.