Martina Ondrušová

Testosterone Deficiency and Bone Metabolism Damage in Testicular Cancer Survivors

The aim of the study was to investigate the influence of therapeutic modalities and sexual hormone levels on changes in bone mineral density (BMD) in testicular cancer (TC) survivors. In a cross-sectional descriptive, long-term follow-up study, a total of 1,249 long-term TC survivors were evaluated according to treatment modality: orchiectomy (OE) only, OE + chemotherapy (CT), or OE + radiotherapy (RT). Luteinizing hormone (LH), total testosterone (TST), marker of bone resorption (β-carboxyl-terminal cross-linking telopeptide of type I collagen—CTx), and BMD were evaluated. Standard statistical techniques were used to test the differences between groups of patients. TST decrease was observed in 46/313 TC survivors after OE alone, in 103/665 after OE + CT, and in 66/271 after OE + RT. LH increase was observed in 23/313 TC survivors after OE alone, in 154/665 after OE + CT, and in 43/271 after OE + RT. CTx increase was observed in 116/313 TC survivors after OE alone, in 324/665 after OE + CT, and in 82/271 after OE + RT. Osteopenia/osteoporosis occurred in 136/313 TC survivors after OE alone, in 298/665 after OE + CT, and in 139/271 after OE + RT. TC survivors after RT have statistically significant decreased TST levels, increased LH and nonsignificant worse BMD (osteopenia/osteoporosis) in comparison with TC survivors after OE alone or CT. TST decrease and LH increase were statistically significant, more frequently observed in patients with osteopenia/osteoporosis. Examination of TST is an important part of follow-up in TC survivors with bilateral as well as unilateral disease. The important part of standard examination algorithm should be also the osteological examination of TC survivors mainly in patients with androgen deficiency.

Recent patterns in cutaneous melanoma descriptive epidemiology in the Slovak Republic.

An increase in melanoma incidence in the Slovak Republic (SR) is evident during approximately the same time and maybe caused by changes in socio-economic status. The paper analyses national trends in incidence, mortality, survival and clinical stages of invasive cutaneous melanoma in the SR from 1968-2007. The trends in incidence and mortality have been extracted between 1968-2007 period by the joinpoint regression analysis, clinical stages were analysed in 1978-2003. Survival data were extracted from the national database resources. Socio-economic changes, which reflected in increase in the number of holiday makers to seaside and mountainous destinations happened in the country in the y.1989. Subsequently, according to joinpoint in 1997, acceleration of increment of the incidence values of melanoma was recorded in both sexes. Mortality was increasing in males continuously, in females the stabilization was registered after the year 1999. Lower rates of relative survival might be influenced by delayed accessibility to adjuvant treatment. The number of cases diagnosed in clinical stage I increased significantly. The changes in the intensity and excessive sunbathing during vacations might be one of many factors that participate in subsequent acceleration of the increment of incidence not only in the SR.

Trends in prostate cancer incidence and mortality before and after the introduction of PSA testing in the Slovak and Czech Republics

AIMS AND BACKGROUND As two neighboring countries in central Europe with national cancer registries, the Slovak (SR) and Czech Republics (CR) are countries with a medium global rate in the occurrence of prostate cancer. This paper analyzes the incidence of prostate cancer and mortality before and after the introduction of PSA testing in the two Republics and the possible reasons for any differences discovered and compares the results with selected regions and countries of the world. STUDY DESIGN AND RESULTS In the Slovak Republic, prostate cancer incidence (age-adjusted to the world standard population) has risen from 14.6/100,000 in 1968 (95% CI, ±1.5772) to 36.2/100,000 in 2005 (95% CI, ±2.0678). The estimated annual increase in the incidence during the period 1968-1991 (before nationwide PSA testing) was 0.421; from 1991 (when nationwide PSA testing began) to up to 2003 it was 0.941. Mortality rates grew from 7.3/100,000 in 1968 to 14.9/100,000 in 2005. In spite of the geographic proximity of the two countries, the increase in incidence occurred faster in the Czech than in the Slovak Republic, from 15.8/100,000 in 1977 (95% CI, ±0.9748) to 59.5/100,000 in 2005 (95% CI, ±1.7187). The estimated annual increase in incidence in the Czech Republic for the period of 1977-1991 was 0.581. From 1991 (when national PSA testing began) until 2003, it was 1.981. In the period before 1991, mortality rose more sharply in the Czech than in the Slovak Republic, whereas after the introduction of PSA testing mortality stabilized more quickly in the Czech than in the Slovak Republic. In the Slovak Republic, a significant reduction in mortality was observed after 2002 and has continued to the present and probably is not affected only by the results connected with the increase in PSA testing. CONCLUSIONS The difference in the incidence and mortality of prostate cancer in the Slovak and the Czech Republics results from a difference in the intensity of PSA testing as well as from the introduction of complex, more effective treatment in advanced clinical stages.

Controversies in the management of clinical stage I testicular seminoma.

Introduction Following orchiectomy patients with clinical stage I (CSI) testicular seminoma may be managed by active surveillance (AS) or adjuvant treatment (radiotherapy or chemotherapy). In view of the published data on long-term toxicity, mainly second malignant neoplasms (SMNs), adjuvant radiotherapy (ART) is currently no longer recommended as adjuvant therapy for these patients. The purpose of our recent study was to compare the impact of two selected treatment approaches – AS versus adjuvant chemotherapy (ACT) on survival in patients with CSI testicular seminoma. Material and methods The cross-sectional study analyzed a total of 106 patients collected at a single centre between 4/2008–8/2015, with CSI testicular seminoma, stratified into two groups according to risk-adapted therapeutic approaches. Results In group A (low-risk), consisting of 84 patients, who underwent AS, relapse occurred in 10 (11.9%) patients after a mean follow-up of 13.8 months. In group B (high-risk), consisting of 22 patients, who were treated with ACT, relapse occurred in two (9.1%) patients after a mean follow-up of 13.8 months. Overall survival of patients in both groups was 100% with a mean follow-up of 25.3 months. The statistically significant difference in progression-free survival (PFS) between these two groups was not found. Conclusions ACT seems to be adequate treatment for patients with high-risk of relapse, as well as AS for those with low-risk of relapse. Despite its excellent prognosis, optimal management of CSI testicular seminoma remains controversial, with variations in expert opinion and international guidelines.

Recent patterns in testicular cancer incidence, mortality and survival in the Slovak Republic with reference to international comparisons.

Incidence of testicular cancer in the Slovak Republic (SR) sharply increased in 1968–2006 (annual change 0.195/100,000, 95% CI = −0.178–0.212, p < .0001). Mortality was stabilized in 1968–2006 (−0.005/100,000/year, 95% CI = −0.011–0.001, p = .148), however, from 1990, it had a mildly significant decreasing trend. The 5-year relative survival for patients from the cohort 1993–1997 reached 91.7% (95% CI = 87.5–94.7), for the cohort 1998–2002, it was 93.2% (95% CI = 89.5–95.8). The average age of patients with seminomas was 30–41 years (25–75% quantile), for nonseminomas 23–34 years (25–75% quantile).

Recent Trends in Survival of Testicular Cancer Patients – Nation-wide Population Based Study

INTRODUCTION AND AIM Survival of germ cell testicular cancer (TC) patients is better than for other malignancies and has not yet been exactly studied in the Slovak Republic. The aim of the study, based on the analyses of epidemiological data over time, was to present 5-year survival trends for germ cell TC patients. PATIENTS AND METHODS Survival is assessed within the framework of a nation-wide retroprospective study among TC patients newly diagnosed between 1993-2007 (divided to three 5-year periods according the time of diagnosis - 1993-1997, 1998-2002 and 2003-2007). Standardized 5-year survival rates were calculated and compared between the periods using a widely accepted methodology. TC patients were divided into two groups (seminomas and non-seminomas histopathologically) and to two groups according the age at diagnosis (< 40 vs. 40 years). The demographic characteristics of TC patients were analyzed using descriptive statistics. Statistical analysis was carried out using Microsoft Excel 2013, statistical software STATISTICA and Joinpoint Regression Programe, Version 4.3.1.0. RESULTS Five-year survival of TC patients (n = 2.748) diagnosed from 1993 to 2007 was 92.21%. TC patients diagnosed between 1993 and 1997 (n = 810) reached 5-year survival at 91.23%, between years 1998 and 2002 (n = 916) at 92.14% and between years 2003 and 2007 (n = 1.022) at 93.05%. There was not a statistically significant difference in survival among these three 5-year periods. Significant difference in 5-year survival was observed between seminomas and non-seminomas in each 5-year period. Compared with younger patients (age < 40 years), there was a significantly worse survival for TC patients (age 40 years) in all groups. CONCLUSION Moderate improvement in survival for TC patients in the Slovak Republic is probably influenced by diagnostic and therapeutic progress, including multidisciplinary care and patients concentration in specialized centers. The long-term follow-up of TC survivors can also help to prevent late side effects of the treatment modalities and to detect second malignancies.Key words: testicular cancer - seminoma - non-seminoma - age at diagnosis - survival.

Recent Overview of Kidney Cancer Diagnostics and Treatment

The incidence of kidney cancer has increased in the majority of countries worldwide, and this disease has relatively high lethality. For many years, the Slovak Republic has been among the countries with the highest kidney cancer incidence, in particular in 2012 (according to global estimated values) in both genders, although mainly in females. In the last few years, the Czech Republic has had the highest incidence of kidney cancer worldwide. The use of imaging techniques such as ultrasound and computerized tomography has increased the detection of asymptomatic renal cell cancer. Etiological factors include lifestyle factors such as smoking, obesity, and hypertension. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged by pharmacotherapy with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain or osseal metastases that are painful or increase the risk of fracture. Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.Key words: kidney cancer - epidemiology - risk factors - pathology - diagnosis - therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 2. 12. 2016Accepted: 3. 1. 2017.

Trends in Prostate Cancer Epidemiology in Slovakia – an International Comparison

INTRODUCTION According to worldwide estimates, Slovakia is classed as a country with a medium-high incidence of prostate cancer. Current predictions indicate that in the near future prostate cancer will become the most frequent cancer among males in Slovakia. AIMS The aims of the study presented in this paper were to analyse trends in the incidence and mortality of prostate cancer in Slovakia and compare these trends with those in other countries and regions of the world, predict epidemiological indicators of prostate cancer in Slovakia, and provide relevant and updated data for the purposes of further analyses and evaluation of the impacts of interventions. MATERIAL AND METHODS National data were analysed for the period 1968-2009. Trends in prostate cancer incidence and mortality were extracted using the joinpoint regression model and are presented with correspoding 95% CI and p values. Predictions of incidence and prevalence were calculated for the years 2014 and 2015, resp. RESULTS A significant increase in standardized incidence was observed in Slovakia (from 14.5/100,000 in 1980 to 49.0/100,000 in 2009), representing as much as a 6.7% annual percentage change in recent years. The mortality values showed a slower rate of increase, from 9.4/100,000 in 1980 to 13.3/100,000 in 2009, while national mortality of prostate cancer decreased in recent years. These facts have made prostate cancer the most prevalent malignant tumor in males in Slovakia. CONCLUSION Unlike in other countries, in Slovakia, no peak in prostate cancer incidence with a subsequent drop is observed. Mortality values reveal a favorable trend in the current national data.Key words: prostate cancer - incidence - mortality - prevalence - clinical stages The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 14. 12. 2016Accepted: 25. 1. 2017.

Management of Clinical Stage I Nonseminomatous Germ Cell Testicular Tumors: A 25-year Single-Center Experience

Micro‐Abstract Efforts to identify patients at high risk of disease progression led to a search for risk factors in clinical stage I‐nonseminomatous germ cell testicular tumors. This study analysed a 25 year single‐center experience with risk‐adapted therapeutic approaches–active surveillance versus adjuvant chemotherapy. According to the results of this study, policy of active surveillance is recommended only in low‐risk patients. Background: Surveillance after orchiectomy alone has become popular in the management of clinical stage I nonseminomatous germ cell testicular tumors (CSI NSGCTT). Efforts to identify patients at high risk of disease progression led to a search for risk factors in CSI NSGCTT. The aim of this study was to analyze a 25‐year single‐center experience with risk‐adapted therapeutic approaches—active surveillance (AS) versus adjuvant chemotherapy (ACT). Patients and Methods: From January 1992 to January 2017, a total of 485 patients with CSI NSGCTT were stratified into the AS group (low‐risk patients) and the ACT group (high‐risk patients). Differences between relapse rates and overall survival rates in these groups were statistically analyzed. Results: In the AS group, relapse occurred in 52 (17.3%) of 301 patients with a median follow‐up of 7.2 months (range, 2‐86 months). Six (2.0%) patients of this group died, with a median follow‐up of 34.3 months (range, 11‐102 months). In the ACT group, relapse occurred in 2 (1.1%) of 184 patients with a median follow‐up of 56.2 months (range, 42‐70 months). One (0.54%) patient died at 139.4 months following orchiectomy. The relapse rate for the AS group was 16.7 times higher than that for the ACT group. The groups did not differ in overall survival. The 3‐year overall survival of all patients with CSI NSGCTT was 99.1% (95% confidence interval, 97.7%‐99.7%). Three of a total of 7 deaths occurred thereafter. Conclusions: The policy of AS is recommended only in patients with low‐risk CSI NSGCTT.

Management of patients with clinical stage I nonseminomatous germ cell testicular cancer: Active surveillance versus adjuvant chemotherapy - single-centre experience.

UNLABELLED Surveillance after orchiectomy alone has become popular in the management of clinical stage I nonseminomatous germ cell testicular tumors (CSI NSGCTT). Efforts to identify patients at high risk of disease progression led to a search for risk factors in CSI NSGCTT. The aim of the present study was to analyse single-centre experience with risk-adapted therapeutic approaches (active surveillance versus adjuvant chemotherapy). From 1/1992 to 12/2013 a total of 431 CSI NSGCTT patients were included in the study and stratified into two groups according to risk-adapted therapeutic approaches. Group A (low-risk CSI NSGCTT) consisted of 276 patients who underwent active surveillance, progression of disease occurred in 46 (16.7%) patients with a median follow-up of 7.2 months. Six patients (2.2 %) of this group died with a median follow-up of 34.3 months. Group B (high-risk CSI NSGCTT) consisted of 155 patients who were treated with adjuvant chemotherapy, disease progression occurred in two (1.3 %) of them with a median follow-up of 56.2 months. One patient (0.6 %) died 139.4 months following orchiectomy. Overall survival rate of all CSI NSGCTT patients in both groups was 424/431 (98.4 %) with median follow-up of 130.4 months following orchiectomy. Surveillance policy is recommended only in patients with low-risk CSI NSGCTT. KEYWORDS testicular cancer, surveillance, adjuvant chemotherapy, disease progression.