Serum Tumour Markers in Testicular Germ Cell Tumours: Frequencies of Elevated Levels and Extents of Marker Elevation Are Significantly Associated with Clinical Parameters and with Response to Treatment.

INTRODUCTION: Although serum tumor markers beta human chorionic gonadotropin (bHCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are well-established tools for the management of testicular germ cell tumours (GCTs), there are only few data from contemporary cohorts of primary GCT patients regarding these biomarkers. Our aim was to evaluate marker elevations in testicular GCTs and to document their associations with various clinical characteristics. PATIENTS AND METHODS: A total of 422 consecutive patients with GCTs were retrospectively analysed regarding serum levels of bHCG, AFP, and LDH during the course of treatment. Additionally, the following characteristics were recorded: histology, age, laterality, clinical stage (CS), pT-stage, and tumour size. Marker elevations were first tabulated in dichotomized way (elevated: yes/no) in various subgroups and second as continuous measured serum values. Descriptive statistical methods were employed to look for differences among subgroups and for associations of elevations with clinical parameters. RESULTS: In all GCT patients, the frequencies of elevated levels of bHCG, AFP, LDH, and bHCG or AFP were 37.9%, 25.6%, 32.9%, and 47.6%; in pure seminomas 28%, 2.8%, 29.1%, and 30.3%; and in nonseminoma 53.0%, 60.1%, 38.7%, and 73.8%. Significant associations were noted with pT-stages >pT1, clinical stages >CS1, tumour size, and younger age. Frequencies of marker elevations dropped significantly after treatment, but LDH levels remained elevated in 30.5%-34.1%. Relapsing patients (n=27) had elevated levels of bHCG, AFP, and LDH in 25.9%, 22.2%, and 29.6%, respectively, thirteen of whom with a changed marker pattern. CONCLUSIONS: The classical GCT-biomarkers correlate with treatment success. Clinical utility is limited due to proportions of < 50% of patients with elevated levels and the low specificity of LDH. The elevation rates are significantly associated with histology, clinical and pT-stages, tumour size, and younger age. Individual marker patterns may change upon relapse. Clinically, ideal biomarkers are yet to be found.

Testicular Germ-Cell Tumours: A Descriptive Analysis of Clinical Characteristics at First Presentation.

INTRODUCTION: Clinical characteristics of testicular germ cell tumours (GCTs) apparently change over time, and some vary geographically. The aim of this study is to document the clinical profile of contemporary GCT patients. PATIENTS AND METHODS: Four hundred twenty-two Caucasian GCT-patients treated in one German centre during 2000-2017, were analysed in terms of patient-age, laterality, histology, tumour-size, clinical stages (CS), pathological (pT)-stages and serum biomarker expression. The results were analysed descriptively and compared with the literature. RESULTS: Median age was 36 years and 60.2% had seminoma. Βeta-human chorionic gonadotropin was expressed in 37.9% and alpha Fetoprotein in 25.6%. CS1 presenting stage was 66.6% of all GCT patients, 79.1% in seminoma, and 47.6% in nonseminoma. Tumour size was significantly associated with pT-stages and CS. Patients >50 years had significantly more seminoma (77.6%) than younger ones (57.9%). Comparison with literature data revealed a shifting towards higher age, lower CS, higher proportion of seminoma and striking differences of characteristics among geographic regions. CONCLUSIONS: A typical contemporary clinical profile of testicular GCTs is presented in this study. Median age, relative incidence of seminoma and proportion of CS1 appear to be increasing over time. Striking differences among ethnic groups regarding the characteristics of GCT require further investigation.

Spermatogenesis in the contralateral testis of patients with testicular germ cell cancer: histological evaluation of testicular biopsies and a comparison with healthy males.

OBJECTIVE: To assess histologically signs of testicular dysgenesis (TD) in the contralateral testes of patients with testicular germ cell tumours (GCTs) and to compare these findings with the spermatogenetic quality in healthy men, as the contralateral testis is considered to be involved with dysgenetic features such as poor sperm production, and accordingly, GCTs are hypothesized to be part of the 'TD syndrome' (TDS). One testicular biopsy is thought to represent spermatogenesis in the entire testis. We evaluated this view by using testicular two-site biopsies. PATIENTS AND METHODS: 2318 patients with testicular GCT had a contralateral testicular two-site biopsy. Testicular biopsies taken on forensic autopsy from 1388 presumably healthy men served as controls. Spermatogenesis was rated histologically according to a modified Johnsen score. Clinical factors were recorded to explore associations with reduced spermatogenesis. Differences in spermatogenesis scoring results among two-site biopsies were noted. Statistical analysis involved Wilcoxon-Mann-Whitney and Jonckheere-Terpstra tests for comparing patients and controls, and for studying associations with clinical factors. Classification and regression-tree analysis was used to explore multivariate associations. RESULTS: Histologically, patients had significantly poorer spermatogenesis than healthy men. Clinically, hypospermatogenesis was significantly associated with testicular atrophy, undescended testes, male infertility, and advanced clinical stage; 5.4% of cases (95% confidence interval 4.43-6.27) had discordant findings of >2 points on double biopsy and 9.8% had differences of 1 point. Discordance was significantly associated with poor spermatogenesis and testicular atrophy. CONCLUSIONS: We confirmed histologically that there is markedly reduced spermatogenesis in the contralateral testes of patients with GCT. This result lends credence to the view that GCT is part of the so-called TDS. But as hypospermatogenesis is associated with advanced clinical stage, impairment of sperm production might at least partly be acquired secondary to the endocrine activity of GCT. There were clinically relevant discordant results on double biopsy in 5.4%, predominantly in infertile patients and in atrophic testes. Thus the histological evaluation of male infertility is best done by multiple biopsies.

Diagnosis of contralateral testicular intraepithelial neoplasia (TIN) in patients with testicular germ cell cancer: systematic two-site biopsies are more sensitive than a single random biopsy.

OBJECTIVES: Searching for testicular intraepithelial neoplasia (TIN; carcinoma in situ) in the contralateral testis of patients with germ cell tumour (GCT) may early disclose contralateral GCT. A single biopsy of the testis is thought to accurately detect TIN. Reports on false-negative biopsies have challenged this view. We investigated whether systematic two-site biopsies are more sensitive than single biopsies. We also studied the prevalence of contralateral TIN in a large patient sample. METHODS: A total of 2318 patients with testicular GCT underwent contralateral double biopsy. All of the biopsy pairs were examined histologically for spermatogenesis and for presence of TIN. Statistical analysis involved first, overall prevalence of contralateral TIN; second, associations of clinical factors with TIN; third, frequency of discordant findings regarding TIN among biopsy pairs; and finally, associations of discordance with clinical factors. RESULTS: A total of 119 patients (5.13%; 95% confidence interval [CI], 4.27-6.11) had contralateral TIN. TIN is associated with poor spermatogenesis (relative risk [RR] 15.74; 95%CI, 10.38-23.86) and with testicular atrophy (RR 3.78). According to TIN, 31.1% of biopsy pairs were discordant. Discordance was significantly less frequent in atrophic testes and in patients with poor spermatogenesis. CONCLUSIONS: We confirmed the prevalence of contralateral TIN to be about 5%. TIN is significantly associated with poor spermatogenesis and with testicular atrophy. The diagnostic extra yield imparted by double biopsies is 18%. Discordant results regarding TIN are predominantly encountered in normal-sized testicles. The new standard in diagnosing TIN is two-site biopsy.