Analysis of Factors Contributing to Adverse Events and Evaluation of Their Impact on Prognosis in Metastatic Renal Cell Carcinoma Patients-Real-World Experience in a Single-Center Retrospective Study and Narrative Review.

Background and Objectives: More than 430,000 new cases of renal cell carcinoma (RCC) were reported in 2020. Clear cell RCC, which occurs in 80% of cases, is often associated with mutations in the VHL gene, leading to dysregulation of hypoxia-induced transcription factors pathways and carcinogenesis. The purpose of this study is to examine the adverse events (AEs) of cabozantinib treatment and the relationship between individual patient factors and the frequency of their occurrence in detail. Materials and Methods: Seventy-one patients with metastatic RCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. Comprehensive data, including demographics, clinicopathological factors, and AEs, were collected from January 2017 to June 2021. This study evaluated the impact of various patient-related factors on the rate of adverse events and treatment tolerance using a Cox proportional hazards model. Results: Cabozantinib-induced AEs were significantly associated with body mass index (BMI), body surface area (BSA), IMDC prognostic score, and treatment line. Notably, patients receiving cabozantinib post-tyrosine kinase inhibitors reported fewer AEs. Dose reduction was unrelated to adverse event frequency, but patients requiring dose reduction were characterized with lower body mass and BSA but not BMI. Conclusions: The factors described make it possible to predict the incidence of AEs, which allows for faster detection and easier management, especially in the high-risk group. AEs should be reported in detail in real-world studies, as their occurrence has a significant impact on prognosis.

Adverse Events of Cabozantinib as a Potential Prognostic Factor in Metastatic Renal Cell Carcinoma Patients: Real-World Experience in a Single-Center Retrospective Study.

Cabozantinib, an oral inhibitor targeting MET, AXL, and VEGF receptors, has become a key component of a sequential treatment strategy for clear cell renal cell carcinoma (ccRCC). The purpose of this work is to show that effective management of adverse events (AEs) during cabozantinib treatment and achieving a balance between AEs and treatment efficacy is crucial to achieving therapeutic goals. In this retrospective study, involving seventy-one metastatic RCC (mRCC) patients receiving second or subsequent lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, we explored the impact of AEs on overall survival (OS) and progression-free survival (PFS). AEs were observed in 92% of patients. Hypothyroidism during treatment was significantly associated with prolonged OS and PFS (HR: 0.31; p < 0.001 and HR: 0.34; p < 0.001, respectively). The occurrence of hand-foot syndrome (HFS) was also linked to improved OS (HR: 0.46; p = 0.021). Patients experiencing multiple AEs demonstrated superior OS and PFS compared to those with one or no AEs (HR: 0.36; p < 0.001 and HR: 0.30; p < 0.001, respectively). Hypothyroidism and HFS serve as valuable predictive factors during cabozantinib treatment in ccRCC patients, indicating a more favorable prognosis.

Simple yet (more?) effective. Venous thromboembolism risk assessment model for germ cell tumour patients receiving first-line chemotherapy.

BACKGROUND: Germ cell tumours (GCT) are highly curable malignancies. Venous thromboembolism (VTE) is a serious complication, needing better risk assessment models (RAM). AIM: Identification of VTE incidence and risk factors in metastatic GCT patients starting first-line chemotherapy. Developing a RAM and comparing it to Khorana risk score (KRS) and Padua Prediction Score (PPS). MATERIAL AND METHODS: We retrospectively analysed GCT patients staged IS-IIIC. VTE risk factors were identified with logistic regression. Area under curve of receiver operating characteristic (AUC-ROC), Akaike and Bayesian Information Criteria (AIC, BIC) were calculated for the developed RAM, KRS and PPS. RESULTS: Among 495 eligible patients, VTE occurred in 69 (13.9%), including 40 prior to chemotherapy. Vein compression (OR: 8.96; 95% CI: 2.85-28.13; p < 0.001), clinical stage IIIB-IIIC (OR: 5.68; 95% CI: 1.82-17.70; p = 0.003) and haemoglobin concentration (OR for 1 g/dL decrease: 1.32; 95% CI: 1.03-1.67; p = 0.026) were significant in our RAM. KRS ≥ 3 (OR: 3.31; 95% CI: 1.77-6.20; p < 0.001), PPS 4-5 (OR: 3.06; 95% CI: 1.49-6.29; p = 0.002) and PPS > 5 (OR 8.05; 95% CI 3.79-17.13; p < 0.001) correlated with VTE risk. Diagnostic criteria (AUC-ROC, AIC, BIC) for the developed RAM, KRS and PPS were (0.885; 0.567; -1641), (0.588; 0.839; -1576) and (0.700; 0.799; -1585), respectively. In the numerical score, the optimal cut-off point for high-risk was ≥9, with sensitivity, specificity, positive and negative predictive value of 0.78, 0.77, 0.35 and 0.96, respectively. CONCLUSIONS: Our RAM, based on vein compression, clinical stage and haemoglobin concentration proved superior to both KRS and PPS. VTE is frequent in GCT patients.

Incidental Diagnosis of Urothelial Bladder Cancer: Associations with Overall Survival.

BACKGROUND: We investigated whether an incidental diagnosis (ID) of bladder cancer (BC) was associated with improved survival. METHODS: We retrospectively reviewed data of consecutive patients with no prior diagnosis of urothelial cancer who underwent a primary transurethral resection of bladder tumor (pTURBT) between January 2013 and February 2021 and were subsequently diagnosed with urothelial BC. The type of diagnosis (incidental or non-incidental) was identified. Overall, relative, recurrence-free, and progression-free survival rates (OS, RS, RFS, and PFS) after pTURBT were evaluated using the Kaplan-Meier curves and long-rank tests. A multivariable Cox regression model for the overall mortality was developed. RESULTS: A total of 435 patients were enrolled. The median follow-up was 2.7 years. ID cases were more likely to be low-grade (LG) and non-muscle-invasive. ID vs. non-ID was associated with a trend toward an improved 7-year OS (66% vs. 49%, p = 0.092) and a significantly improved 7-year OS, if incidental cases were limited to ultrasound-detected tumors (75% vs. 49%, p = 0.013). ID was associated with improved survival among muscle-invasive BC (MIBC) patients (3-year RS: 97% vs. 23%, p < 0.001), but not among other subgroups stratified according to disease stage or grade. In multivariable analysis, only age, MIBC, and high-grade (HG) cancer demonstrated an association with mortality. PFS and RFS among non-MIBC patients did not differ in regard to the type of diagnosis. CONCLUSIONS: Incidental diagnosis may contribute to an improved survival in BC patients, most probably in the mechanism of the relative downgrading of the disease, including the possible overdiagnosis of LG tumors. Nevertheless, in the subgroup analyses, we noted marked survival benefits in MIBC cases. Further prospective studies are warranted to gain a deeper understanding of the observed associations.

Mixed epithelial and stromal tumor of the kidney: A case report.

Mixed epithelial and stromal tumor (MEST) is a rare neoplasm of the kidney, affecting mostly women at menopausal age. While few cases of malignant transformation have been described in the literature, MEST is usually considered a benign tumor with minimal risk of local recurrence or distance metastases. The current study presents a case of a 18-year old male patient with a cystic tumor of the left kidney incidentally diagnosed on magnetic resonance imaging of the heart performed for other reasons. The patient underwent a partial nephrectomy, with perioperative course being uneventful. The pathology report revealed MEST of the kidney. No local recurrence nor disease progression have been observed in the patient during the one-year follow-up period. The present case report is evidence that may help in developing guidelines on the management of patients with benign renal masses.

Prognostic value of pan-immune-inflammation value and body mass index in geriatric patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors as first line treatment. A single-center retrospective study.

Introduction: Geriatric patients with metastatic renal cell carcinoma (mRCC) are underrepresented in clinical trials. Evaluation of the efficacy of the treatment and assignation of individuals to proper prognostic groups is an absolute necessity to guarantee them the best possible care. Material and methods: A total of 138 geriatric patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) at the Maria Sklodowska-Curie National Research Institute of Oncology were retrospectively analyzed to determine whether the body mass index (BMI) and pan-immune-inflammation value (PIV) are prognostic values for overall survival (OS) and progression-free survival (PFS) in this type of cancer. For this purpose, Cox's proportional hazard model was used. Results: The median duration of follow-up for surviving patients was 46.6 (95% CI: 17.4-75.8) months. The median OS and PFS were respectively 33.8 months (95% CI: 23.8-47.8) and 19.1 months (95% CI: 15.0-23.3). BMI (p = 0.034) and PIV (p < 0.001) were statistically significantly associated with OS, and PIV (p = 0.001) was statistically significantly associated with PFS. The risk of death for patients from the high-PIV group (cut-off point: 548) was 3.4 times higher than for those with lower PIV values. The corresponding risk of progression for patients from the high-PIV group was 2.2 times higher. The G8 geriatric screening tool was not identified as a prognostic factor. Conclusions: Lower PIV and obesity are associated with longer OS in geriatric mRCC patients treated with TKIs in the first line. These factors may be considered while making treatment decisions if further studies show the same results.

First experience in treating advanced urothelial cancer with enfortumab vedotin. Single-centre retrospective study of patients qualified for a rescue access procedure.

Introduction: Urothelial carcinoma is the most common type of urinary tract malignancy. Current treatment options, including platinum-based chemotherapy or immunotherapy, present significant challenges, ranging from limited efficacy to severe toxicities. Recent developments in antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), promise to significantly improve overall survival. The study aims to evaluate the efficacy and tolerability of EV. In addition, we highlight the observed benefits of next-line treatment after progression. Material and methods: This retrospective study involved 16 patients with advanced urothelial cancer treated with EV at the Department of Genitourinary Oncology, Maria Sklodowska- Curie National Research Institute of Oncology between November 2022 and November 2023. The study evaluated patients' medical history, response to EV treatment, and side effects. Notably, the study included patients who had already exhausted standard treatment options and who were treated with EV through a rescue access procedure. Results: Partial response was observed in 4 out of 9 (44%) patients with available imaging. Common terminology criteria for adverse events (AE) grade 3 and 4 were observed in 3 out of 16 patients, which subsequently required dose reduction. Conclusions: Enfortumab vedotin demonstrates effectiveness in real-world settings in treating advanced urothelial cancer. Proper management of AE in experienced centres may further prolong survival. Personalized treatment and the development of new ADC represent the future for improved patient outcomes.

Activity of cabozantinib in further line treatment of metastatic clear cell renal cell carcinoma. Real-world experience in a single-center retrospective study.

Introduction: Cabozantinib is an oral inhibitor of MET, AXL, and vascular endothelial growth factor receptors. It has an immunomodulatory effect and may influence the tumor's microenvironment and make mutated cells more sensitive to immune-mediated killing. These properties have made cabozantinib an effective drug for first-line or subsequent-line treatment after progression of metastatic renal cell carcinoma (mRCC), even after immunotherapy. Material and methods: Seventy-one patients with mRCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. This study retrospectively evaluated the effectiveness of cabozantinib in subsequent lines of treatment. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The best overall response (BOR) to cabozantinib was the secondary endpoint. For this purpose, Cox's proportional hazard model was used. Results: The median PFS was 11 months (5; 23) and the median OS was 16 months (10; 42) and differed significantly in the second and further lines of treatment. Progression in the second and further lines was observed in 28 (93%) and 27 (66%) patients, respectively (p = 0.006). Partial response as the BOR was observed in one patient (3%) in the second line and 13 patients (32%) in the further lines (p = 0.012). Conclusions: Cabozantinib has antitumor effects in the second and further lines of treatment. In this study we observed high efficiency of cabozantinib in further lines of treatment.

The Clinical Features of Incidentally Diagnosed Urothelial Bladder Cancer: A Retrospective Data Analysis.

INTRODUCTION: The aim of this study was to evaluate the prevalence and clinical features of incidental bladder cancer (BC) diagnosis, with special emphasis on possible associations between incidental diagnosis and primary disease stage or grade. METHODS: We retrospectively included 501 consecutive patients who underwent transurethral resection of bladder tumor and were diagnosed with primary urothelial carcinoma of the bladder between January 2013 and February 2021 in a university hospital. The type of diagnosis (incidental or nonincidental), patient baseline characteristics and primary stage and grade were studied for interdependencies. RESULTS: 28.5% of all patients and 19.8% of high grade (HG) BC patients had been diagnosed incidentally, most commonly with ultrasound. Incidental diagnosis was associated with lower primary stage and grade of the disease. Most importantly, on multivariable analysis, which included baseline patient characteristics and type of diagnosis, in the subgroup of HG BC patients, muscle-invasive BC (MIBC) or metastatic disease was three times less likely to be diagnosed incidentally than non-MIBC (odds ratio: 0.31, 95% confidence interval: 0.14-0.71, p = 0.006). CONCLUSIONS: The study is first to demonstrate that incidental diagnosis of HG BC may be surprisingly prevalent and associated with lower rates of muscle invasion or metastatic disease.

Alternative tobacco products use and its impact on urologic health - will the lesser evil still be evil? A commentary and review of literature.

INTRODUCTION: Alternative tobacco products, including electronic cigarettes (e-cigarettes) and non-combustible tobacco products or heat-not-burn (HNB) products, are substitutes to conventional combustible cigarettes with the potential to impact urologic health, similar to traditional smoking. Most urologists, however, have limited knowledge of these products and are unfamiliar with their potential health implications. We conducted a review to assess the impact of e-cigarettes and HNB products on urologic health. MATERIAL AND METHODS: A bibliographic search covering the period up to April, 2021 was conducted using MEDLINE®/PubMed® and Google Scholar. Articles were reviewed and categorized based on the potential impact on erectile dysfunction, semen quality, lower urinary tract symptoms, genitourinary malignancies, and smoking cessation. Data were extracted, analyzed and summarized. RESULTS: Mature data on the long-term impact of e-cigarette and HNB product use on urologic health are lacking. E-cigarette and HNB vapors appear to contain decreased concentrations of chemicals responsible for erectile dysfunction compared to tobacco smoke but may play a role through endothelial damage. Use of e-cigarettes is associated with lower sperm counts. No definitive data has shown a link between e-cigarette or HNB product use and lower urinary tract symptoms. Multiple carcinogens including those specifically linked to bladder cancer have been identified in the urine of e-cigarette and HNB product users. Limited data suggest e-cigarettes may aid in smoking cessation. CONCLUSIONS: Urologists may benefit from understanding the urologic health concerns surrounding e-cigarettes and HNB product use and patients may benefit from being properly educated.

Succinate Dehydrogenase-Deficient Renal Cancer Featuring Fructose-1,6-Biphosphatase Loss, Pyruvate Kinase M2 Overexpression, and SWI/SNF Chromatin Remodeling Complex Aberrations: A Rare Case Report.

Succinate dehydrogenase (SDH)-deficient renal cancer is a rare renal cancer subtype recently accepted by the World Health Organization as a unique subtype of renal cell carcinoma (RCC). Here we report a case of 17-year-old man. The detailed evaluation indicated occurrence of the SDHB-deficient RCC. The genetic testing revealed no germline mutation in SDH genes. Immunohistochemistry showed SDHB deficiency, overexpression of pyruvate kinase M2 and dramatic downregulation of fructose-1,6-bisphosphatase metabolic enzymes, and unaltered levels of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin. Strong upregulation of INI1 and BRG1 and overexpression of BAF180, subunits of SWI/SNF ATP-dependent chromatin remodeling complex, were also found. The identified tumor pathologically did not resemble clear cell renal cell carcinoma (ccRCC), but some metabolic alterations are common for both cancer types. Thus, we postulate that the phenotypical differences between ccRCC and SDHB-deficient RCC may be related to distinct molecular and metabolic alterations. IMPLICATIONS FOR PRACTICE: Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare renal tumor occurring even in young patients. Until now, in all described and genetically tested cases, mutations and deletions in SDH genes have been found. This article describes SDHB-deficient RCC without any germline mutations in SDH genes. Therefore, genetic analysis for germline mutations in SDH genes in SDH-deficient RCC, especially in young individuals, should be strongly recommended, although as of now it is not obligatory. This knowledge will allow improvement of patient monitoring including both disease recurrence and new cancer appearance.

What is the damage? Testicular germ cell tumour survivors deficient in testosterone at risk of metabolic syndrome and a need for medical intervention.

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.

SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer.

Bladder cancer (BC) is a frequently diagnosed malignancy affecting predominantly adult and elderly populations. It is expected that due to the longer life time, BC will become even more frequent in the future; thus in consequence, it will represent serious health problem of older society part. The treatment of advanced BC is mostly ineffective due to its very aggressive behavior. So far, no effective targeted therapy is used for BC treatment. Here, we found that BC is characterized by lower protein levels of BRM, INI1, and BAF155 main subunits of SWI/SNF chromatin remodeling complex (CRC) which is involved in global control of gene expression and influences various important cellular processes like: cell cycle control, apoptosis, DNA repair, etc. Moreover, the expression of SMARCA2, a BRM encoding gene, strongly correlated with BC metastasis and expression of such metabolic genes as PKM2 and PRKAA1. Furthermore, the analysis of T24 and 5637 commonly used BC cell lines revealed different expression levels of metabolic genes including FBP1 gene encoding Frutose-1,6-Bisphosphatase, an enzyme controlling glycolysis flux and gluconeogenesis. The tested BC cell lines exhibited various molecular and metabolic alterations as well as differential glucose uptake, growth rate, and migration potential. We have shown that BRM subunit is involved in the transcriptional control of genes encoding metabolic enzymes. Moreover, we found that the FBP1 expression level and the SWI/SNF CRCs may serve as markers of molecular subtypes of BC. Collectively, this study may provide a new knowledge about the molecular and metabolic BC subtypes which likely will be of high importance for the clinic in the future.

Venous thromboprophylaxis in urological cancer surgery.

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.

Radiological Response and Neutrophil-to-Lymphocyte Ratio as Predictive Factors for Progression-Free and Overall Survival in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib.

Renal cell carcinoma (RCC) represents 2-3% of all malignancies. Most RCC-related deaths are caused by metastases of the disease. Studies suggest that inflammation-related parameters are of prognostic significance in metastatic renal cell carcinoma (mRCC) patients. Neutrophilia and thrombocytosis are markers of systemic inflammation that accompanies cancer, while lymphopenia is related to dysfunctions of the immune system. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) thus seem particularly interesting from a clinical perspective. The goal of this study was to determine if the response to therapy, consisting of reductions in radiologically assessed tumor burden and in inflammation-related parameters after 12 weeks of treatment with sunitinib, has a predictive value for outcome. One hundred thirty-one mRCC patients treated with the first-line sunitinib were evaluated. Inflammation-related parameters and radiologic response were correlated with treatment outcomes, progression-free, and overall survival. We found that the longest median progression-free survival of 37 months (Q1; Q3-15; not reached) and overall survival of 40 months (Q1; Q3-26; not reached) were achieved by patients who had either partial or complete response according to RECIST 1.1 and NLR lower than 1.64. In conclusion, the study confirmed that both objective response and lower grade of inflammation during treatment are predictive of better outcomes in mRCC patients treated with sunitinib.

Hand-Foot Syndrome and Progression-Free Survival in Patients Treated with Sunitinib for Metastatic Clear Cell Renal Cell Carcinoma.

Patients with metastatic clear cell renal cell carcinoma (mRCC) typically receive systemic treatment with tyrosine kinase inhibitors (TKI). Side effects include the hand-foot syndrome (HFS), tiredness, nausea, decreased appetite, diarrhea, myelosuppression, and hypertension. This study seeks to define the relationship between the incidence of HFS after the first cycle of treatment with sunitinib as the first-line treatment for mRCC (50 mg/day, 6-week schedule: 4 weeks on and 2 weeks off) and progression-free survival. We found that patients, treated with sunitinib for mRCC, who did not experience HFS had the median progression-free survival of 9.8 months. HFS symptoms appeared in 20% of patients after the first treatment cycle. The appearance of HFS was a predictor of a longer progression-free survival. In fact, progression-free survival was elongated in the HFS group over and beyond the observation period of 60 months, which rendered the median progression-free survival calculation impossible. These findings reaffirm the importance of monitoring skin toxicity during treatment with TKI. We conclude that the appearance of adverse skin symptoms presages better outcomes in patients treated with sunitinib for mRCC.

The correlation between the incidence of adverse events and progression-free survival in patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC).

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.

Assessment of selected quality of life domains in patients who have undergone conservative or radical surgical treatment for penile cancer: an observational study.

Background Surgery is the standard treatment for organ-restricted penile cancer, but it is also a disfiguring procedure that can profoundly affect quality of life. Using a survey, in this study we assessed the effect of different surgical invasiveness on satisfaction in selected life domains of patients who underwent penile-sparing surgery and partial penectomy. METHODS: Forty patients who underwent penile-sparing surgery (n=13) or partial penectomy (n=27) were enrolled in the study. The response rate was 71%. Information was obtained after surgery on sexuality, self-esteem, masculinity and partner relationships using the International Index of Erectile Function, the Self-Esteem Scale and the Conformity to Masculinity Norms Inventory questionnaires. We evaluated the effect of primary surgery type on selected domains of quality of life and correlations between study variables after surgery. RESULTS: High self-esteem, satisfactory erectile function and masculinity results in both groups were comparable to those in the published literature. Men who underwent less disfiguring treatment had a significantly higher sense of masculinity than those who underwent partial penectomy (P=0.05). No significant differences were observed in erectile dysfunction and self-esteem. The level of aggressiveness of a surgical procedure was a predictor of sense of masculinity (P=0.01), but was not associated with self-esteem and sexual dysfunction (P=0.28 and P=0.55 respectively); 83% of patients were able to satisfactorily maintain partner relationships. CONCLUSIONS: Disfiguring treatments for penile cancer significantly interfere with the sense of masculinity, but sexual functioning and self-esteem do not differ according to the type of surgical procedure. Most men maintained stable partner relationships after surgery, regardless of surgery type.

Randomised phase II study of second-line olaratumab with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer.

INTRODUCTION: Platelet-derived growth factor receptor-α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel. METHODS: Patients were randomised to receive 21-d cycles of olaratumab (15 mg/kg, Days 1 and 8) plus mitoxantrone (12 mg/m2, Day 1) and prednisone (5 mg, twice daily) or M/P alone. Progression-free survival (PFS) was the primary end-point. Secondary end-points included overall survival (OS), safety, and circulating tumour cell (CTC) counts. RESULTS: A total of 123 patients were randomised, 63 to olaratumab + M/P and 60 to M/P. Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.87-1.90). Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P (HR = 1.08; 95% CI = 0.72-1.61). Both treatment arms had similar toxicity profiles; neutropenia (24% versus 15%), anaemia (13% versus 14%) and fatigue (11% versus 9%) (olaratumab + M/P versus M/P, respectively) were the most common grade ≥3 events. High CTC count was associated with poorer OS in both arms. Patients with very high cell counts (>37 cells/7.5 ml) exhibited improved OS with olaratumab + M/P (interaction P = 0.043). CONCLUSIONS: Olaratumab + M/P had an acceptable safety profile but did not improve the efficacy of M/P chemotherapy. Further study with selected patient populations and earlier in the disease course might be considered.

Testicular teratomas: a growing problem?

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.