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Background: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy. Objective: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study. Patients and Methods: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan–Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Results: Median OS and PFS were 12.7 (95% CI 10.2–14.1) and 7.9 (95% CI 6.4–9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1–11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia. Conclusions: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab. [ABSTRACT FROM AUTHOR]

Background: Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, "primary refractory" (Pref), face dismal outcomes. Objective: Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients. Methods: This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve. Results: In our study, the Pref rate was 19%. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-Pref patients (55.7 months), p < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for Pref patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of Pref. This study presents limitations, mainly because of its retrospective design. Conclusions: The ARON-1 study provides valuable insights into Pref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. Method: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. Results: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7–44.2) in the overall study population: 40.0 months (95% CI 32.7–51.6) in males and 38.7 months (95% CI 26.4–41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0–51.6, vs. 24.8 months, 95% CI 16.8–40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8–55.7, vs. 38.7 months, 95% CI 26.0–41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4–59.0, vs. 15.3 months, 95% CI 8.9–41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 − 2.57, p = 0.008). Conclusions: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males. [ABSTRACT FROM AUTHOR]

Background: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. Objective: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. Methods: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan–Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Results: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9–71.3) versus 20.8 (95% CI 12.6–24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31−0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1–40.5) and 13.0 months (95% CI 6.6–23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3–22.4) and 4.9 months (95% CI 3.0–8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). Conclusions: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management. [ABSTRACT FROM AUTHOR]

The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Immuno-oncology combinations have achieved survival benefits in patients with metastatic renal cell carcinoma (mRCC). Objective: The ARON-1 study (NCT05287464) was designed to globally collect real-world data on the use of immuno-combinations as first-line therapy for mRCC patients. Patients and Methods: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of mRCC treated with first-line immuno-combination therapies were retrospectively included from 47 International Institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB). Results: A total of 729 patients were included; tumor histology was clear-cell RCC in 86% of cases; 313 patients received dual immuno-oncology (IO + IO) therapy while 416 were treated with IO-tyrosine kinase inhibitor (IO + TKI) combinations. In the overall study population, the median OS and PFS were 36.5 and 15.0 months, respectively. The median OS was longer with IO+TKI compared with IO+IO therapy in the 616 patients with intermediate/poor International mRCC Database Consortium (IMDC) risk criteria (55.7 vs 29.7 months; p = 0.045). OCB was 84% for IO+TKI and 72% for IO + IO combination (p < 0.001). Conclusions: Our study may suggest that immuno-oncology combinations are effective as first-line therapy in the mRCC real-world context, showing outcome differences between IO + IO and IO + TKI combinations in mRCC subpopulations. Clinical Trial Registration: NCT05287464. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has determined unprecedented long-term responses in several hematological and solid tumors. In the MOUSEION-03 study, we conducted a meta-analysis to determine the possibility of achieving complete remissions (CR) with immunotherapy or immuno-oncology combinations in cancer patients. Methods: The primary endpoint was to assess the incidence of CR in cancer patients receiving immune checkpoint inhibitors (ICIs) alone or in combination with other agents versus control treatments. The pooled odds ratio (OR) and 95% confidence interval (CI) for CR rate were extracted. Results: A total of 12,130 potentially relevant trials were identified; 5 phase II and 80 phase III randomized studies (37 monotherapies and 48 combinations) and 49,425 cancer patients were included. The most frequent types of malignancies were non-small cell lung cancer (n = 14,249; 29%), urothelial cancer (n = 6536; 13%), renal cell carcinoma (n = 5743; 12%), and melanoma (n = 2904; 6%). In patients treated with immunotherapy (as monotherapy or in combination with other anticancer agents), the pooled OR was 1.67 (1.52–1.84). The highest OR was registered by immune-based combinations with two ICIs (3.56, 95% CI 1.28–9.90). Conclusions: To the best of the authors' knowledge, no comprehensive meta-analysis on the use of ICIs and ICI-based combinations in solid tumors to systematically investigate the probability to achieve CR has been published so far. Although CR is not a common event in several cancer patients receiving immunotherapy, the MOUSEION-03 suggests that the use of ICIs may significantly increase the chance of achieving CR in comparison with control treatments. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging (MRI) is routinely used for locoregional staging of rectal cancer and offers promise for the prediction of hematologic toxicity. The present study compares the clinical utility of MRI-based active bone marrow (BMact) delineation with that of CT-based bone marrow total (BMtot) delineation for predicting hematologic toxicity. Methods: A prospective cohort study was performed. Eligible patients had stage II/III rectal cancer and qualified for preoperative chemoradiotherapy. The BMact areas on T1-weighted MRI were contoured. The impact of the dose–volume parameters of BMact/BMtot and clinical data on hematologic toxicity were assessed. Basic endpoints were the occurrence of grade 3/4 hematologic toxicity and peripheral blood parameters reaching a nadir. Linear regression models were generated for the nadirs and receiver operating characteristic (ROC) curves for the occurrence of grade 3/4 hematologic toxicity. Results: Thirty-five patients were enrolled. Women presented higher dose–volume parameters of BMact, BMtot, and lymphocyte nadir (ALCnadir%) than men. Models for the prediction of ALCnadir% (V5-V20BMtot, V5-V30BMact) and platelet nadir (PLTnadir%; V5-V10BMtot, V5-V20BMact) were statistically significant. In the ROC curves, a baseline lymphocyte level of 1.81 × 103/ml was adopted as the cutoff for predicting grade 3/4 lymphopenia, with specificity of 77.8% and sensitivity of 73.1%. The multivariate linear regression model for ALCnadir% had R2 = 0.53, p = 0.038. In the tenth step of selection, V5BMact (p = 0.002) and gender (p = 0.019) remained. The multivariate linear regression model for PLTnadir% had R2 = 0.20, p = 0.34. In the sixth step of selection, V15BMact remained (p = 0.026). Conclusion: The dose–volume parameters of BMact serve as better predictors of ALCnadir% and PLTnadir% than BMtot. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumours (TGCT) survivors are coping with late treatment sequelae. Testosterone deficiency may contribute to earlier onset of metabolic syndrome. The study aimed to assess connections between serum testosterone concentrations and metabolic disorders as well as body composition in TGCT survivors. 336 TGCT patients with over two years of complete post-treatment remission were divided into three groups: definite testosterone deficiency (< 8 nmol/L), 'grey zone' (8-12 nmol/L) and normal testosterone (> 12 nmol/L; control group) to assess differences in metabolism. Univariate and multivariate analyses were performed. The multivariate analysis assessed the risk of metabolic disorders and changes in body composition with regard to testosterone concentrations adjusted for age, smoking history, clinical stage, type of treatment and follow-up period. 14% of patients presented with definite testosterone deficiency; 46% were in the 'grey zone'. On multivariate analysis, low testosterone levels were related to hyperglycemia, hypercholesterolemia, hypertriglyceridemia, inflammatory processes, procoagulant state and obesity. The odds ratio (OR) for the onset of metabolic syndrome was 2.87 (95% CI 1.74-4.73, p < 0.001) for the 'grey zone' patients and 7.92 (95% CI 3.76-16.70, p < 0.001) for those with definite testosterone deficiency. Testosterone concentrations were independently associated with metabolic disorders in TGCT survivors. Testicular cancer survivors often have lower testosterone and metabolic disorders. Apart from recurrence, follow-up should focus on promoting a healthy lifestyle, preventing and managing late effects. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) represents a major complication of cancer and its treatment, contributing to increased morbidity and mortality. The appropriate choice of thromboprophylaxis method and duration is, therefore, of utmost importance. We conducted an extensive review of the literature concerning VTE in patients undergoing surgery for urological cancers. Special attention was paid to risk factors, different types of surgery (transurethral, pelvic, abdominal-open, laparoscopic and robot-assisted) and different medications used (heparins, vitamin K antagonists and new oral anticoagulants). Original papers, reviews and guidelines were identified in Medline database. The available data were then summarised for the purpose of this article. Venous thromboprophylaxis is obligatory in urological cancer patients undergoing surgical treatment. Unless individual contraindications are recognised, the available guidelines should be followed. The variety of clinical scenarios and patients' comorbidities necessitate cooperation with other specialists (cardiologists, neurologists, etc.) in choosing the optimal management. Thrombosis risk must be carefully weighed against bleeding risk. [ABSTRACT FROM AUTHOR]

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m2. Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction. [ABSTRACT FROM AUTHOR]

Cancer and its treatment can lead in men to testosterone deficiency, accompanied by somatic and mental symptoms. Germ cell tumours and their treatment may disturb the pituitary-gonadal axis, hence leading to significant clinical abnormalities. In some prostate cancer patients, castration, temporary or permanent, is a desired therapeutic condition. Yet, it is burdened with various side effects of complex intensity and significance. Last but not least, patients in the terminal stage of a malignancy present with low testosterone concentrations as a part of anorexia-cachexia syndrome. Oncological management of such patients disturbs their homeostasis, androgen metabolism included, which results in numerous complications and worsens their quality of life. In the present paper, we analysed the frequency and sequelae of testosterone deficiency in some clinical scenarios, on the basis of original papers, meta-analyses and reviews available in PubMed. Androgen secretion disorders in male cancer patients depend on a cancer type, stage and methods of treatment. Number of testicular cancer survivors is increasing, and as a consequence, more patients cope with late complications, testosterone deficiency included. Hormone therapy in prostate cancer patients significantly prolongs survival, and then numerous men experience long-term adverse effects of androgen deficiency. Those, in turn, particularly the metabolic syndrome, may contribute to increased mortality. Androgen deficiency is a part of cancer anorexia-cachexia syndrome. The role of androgen deficiency in cancer patients is still under debate, and further studies are urgently needed to establish appropriate clinical guidelines. [ABSTRACT FROM AUTHOR]

Testicular tumors and their treatment interfere with homeostasis, hormonal status included. The aim of the study was to evaluate hormonal disorders of the pituitary-gonadal axis in men treated for testicular tumors. One hundred twenty-eight men treated for a unilateral testicular tumor at our institution were included. The hormonal status was prospectively evaluated in 62 patients before orchiectomy, 120 patients 1 month after orchiectomy and 110 patients at least 1 year after the treatment. The concentrations of human chorionic gonadotropin (hCG), testosterone (T), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured. The clinically significant testosterone deficiency was defined either as testosterone <2.31 ng/mL or testosterone within the range of 2.31-3.46 ng/mL but simultaneous with T/LH ratio ≤1. Changes in hormone levels were significant: LH and FSH rose in the course of observation, and the concentration of hCG, testosterone, estradiol decreased. PRL concentration was the lowest at 1 month after orchiectomy. In multivariate analysis, the risk of the clinically significant testosterone deficiency was 0.2107 (95% CI 0.1206-0.3419) prior to orchiectomy, 0.3894 (95% CI 0.2983-0.4889) 1 month after surgery and 0.4972 (95% CI 0.3951-0.5995) 1 year after the treatment. The estradiol concentration was elevated in 40% of patients with recently diagnosed testicular cancer and that was correlated with a higher risk of testosterone deficiency after the treatment completion. Hormonal disorders of the pituitary-gonadal axis in men treated for testicular tumors are frequent. The malignant tissue triggers paraneoplastic disorders that additionally disturb the hormonal equilibrium. [ABSTRACT FROM AUTHOR]

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly. [ABSTRACT FROM AUTHOR]

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in 'low' and 'intermediate' Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81-0.99) and 0.76 (0.65-0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib's inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential. [ABSTRACT FROM AUTHOR]

Clinical practice shows significant differences in treatment outcomes across patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC). It is not known whether cabozantinib-induced adverse events are predictive factors of survival as in case of drugs such as sunitinib or axitinib. The study participants were 30 adult patients with mRCC treated with cabozantinib as a second- or further line setting. All adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Progression-free survival (PFS) values were calculated by taking the beginning of cabozantinib treatment as the start date and either disease progression or death as the end date. PFS were estimated using the Kaplan-Meier method, and compared using the log-rank test. We identified independent PFS predictors using multiple Cox proportional hazards models and reported hazard ratios (HR) with 95% confidence intervals. The median observation time cabozantinib treatment was 7.5 months, with a range of 2-15 months. During that time, 11 (37%) of the patients had mRCC progression. Median PFS on cabozantinib was not reached, and lower quartile was 6 months. All patients developed at least one adverse event in the course of cabozantinib therapy. Hypertension, hypothyroidism and HFS were observed most frequently, in about two-thirds of the patients. The co-incidence of multiple adverse events was common. Hypertension, hypothyroidism, diarrhea and liver toxicity were significantly associated with longer PFS values. Patients with three or more side effects had significantly longer PFS than those with two or fewer. Even though this study was conducted in a small patient sample and the observation time was relatively short our results confirm the predictive value of the incidence of adverse events during cabozantinib treatment in mRCC patients. To the best of our knowledge, this is the first study of this kind conducted in this group of patients. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma is the 14th most common cancer worldwide. It is a heterogeneous group of histopathological entities, of which the most common is clear cell renal cell carcinoma. Approximately 20-30% of patients present initially with metastatic disease and an additional 20% will progress after radical surgical treatment. Metastatic disease that is non-feasible for surgical treatment remains incurable. Numerous studies have demonstrated that-with the introduction of new drugs-the treatment outcomes of metastatic disease have improved. The development of new therapies as well as the optimization and individualization of procedures allow us to hope for further progress in this area. [ABSTRACT FROM AUTHOR]

Testicular teratomas represent a specific entity within the group of germ-cell tumours. They may comprise elements of all three germ layers. In contrast to prepubertal benign teratomas observed in infants and adolescents, postpubertal teratomas originate from the malignant germ-cell precursor. Given the good prognosis and curability of most patients with germ-cell tumour, medical oncologists and urological surgeons must be well acquainted with the principles of teratomas management. Surgery plays the decisive part in teratomas treatment, as these tumours are resistant to radio- and, to some extent, chemotherapy. In this article we concentrate on the management of post-chemotherapy resection of teratomatous masses, with special attention to the phenomenon of 'growing teratoma syndrome' and somatic-type transformation of teratomas. To understand the nature of teratomas better, we begin with a glimpse of their biological, molecular and immunohistochemical features. Managing germ-cell tumours, teratomas in particular, in high-volume reference centres is of utmost importance to maintain and increase the survivorship rate in these patients. [ABSTRACT FROM AUTHOR]