The present and future of serum diagnostic tests for testicular germ cell tumours.

Testicular germ cell tumours (GCTs) are the most common malignancy occurring in young adult men and the incidence of these tumours is increasing. Current research priorities in this field include improving overall survival for patients classified as being 'poor-risk' and reducing late effects of treatment for patients classified as 'good-risk'. Testicular GCTs are broadly classified into seminomas and nonseminomatous GCTs (NSGCTs). The conventional serum protein tumour markers α-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and lactate dehydrogenase (LDH) show some utility in the management of testicular malignant GCT. However, AFP and hCG display limited sensitivity and specificity, being indicative of yolk sac tumour (AFP) and choriocarcinoma or syncytiotrophoblast (hCG) subtypes. Furthermore, LDH is a very nonspecific biomarker. Consequently, seminomas and NSGCTs comprising a pure embryonal carcinoma subtype are generally negative for these conventional markers. As a result, novel universal biomarkers for testicular malignant GCTs are required. MicroRNAs are short, non-protein-coding RNAs that show much general promise as biomarkers. MicroRNAs from two 'clusters', miR-371-373 and miR-302-367, are overexpressed in all malignant GCTs, regardless of age (adult or paediatric), site (gonadal or extragonadal) and subtype (seminomas, yolk sac tumours or embryonal carcinomas). A panel of four circulating microRNAs from these two clusters (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p) is highly sensitive and specific for the diagnosis of malignant GCT, including seminoma and embryonal carcinoma. In the future, circulating microRNAs might be useful in diagnosis, disease monitoring and prognostication of malignant testicular GCTs, which might also reduce reliance on serial CT scanning. For translation into clinical practice, important practical considerations now need addressing.The authors would like to acknowledge grant funding from CwCUK/GOSHCC (M.J.M. N.C. grant W1058), SPARKS (M.J.M. N.C. grant 11CAM01), CRUK (N.C. grant A13080) MRC (M.J.M. grant MC_EX_G0800464) and National Health Service funding to the Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre for Cancer (R.A.H.). The authors also thank the Max Williamson Fund, the Josh Carrick Foundation and The Perse Preparatory School, Cambridge for support.This is the author accepted manuscript. The final version is available fromNature Publishing Group via https://doi.org/10.1038/nrurol.2016.17

Evaluation of sub-acute changes in cardiac function after cisplatin-based combination chemotherapy for testicular cancer

Long-term cardiovascular morbidity is increasingly observed in chemotherapy-treated testicular cancer survivors, but little is known of early sub-clinical changes in cardiac function. We prospectively evaluated cardiac function in testicular cancer patients by echocardiography. Systolic (Wall Motion Score Index) and diastolic (E/A-ratio and Tissue Velocity Imaging (TVI)) parameters, and serum levels of N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) were assessed before the start of chemotherapy and 1 year later. Echocardiography data were compared with an age-matched group of healthy controls. Forty-two patients treated with bleomycin, etoposide and cisplatin were evaluated (median age 27 years, range 18–50). Systolic function and E/A-ratio did not change, whereas the median TVI decreased (12.0 vs 10.0 cms−1; P=0.002). Median levels of NT-proBNP increased (5 vs 18 pmoll−1, P=0.034). Compared with controls, TVI before the start of chemotherapy was not significantly different. In conclusion, we found that at a median of 10 months after cisplatin-based treatment for testicular cancer, TVI decreased significantly, indicating a deterioration of diastolic cardiac function. Serum levels of NT-proBNP increased. The prognostic significance of these changes for future cardiovascular morbidity is not clear

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK

Bleomycin, a cytotoxic chemotherapy agent, forms a key component of curative regimens for lymphoma and germ cell tumours. It can be associated with severe toxicity, long-term complications and even death in extreme cases. There is a lack of evidence or consensus on how to prevent and monitor bleomycin toxicity. We surveyed 63 germ cell cancer physicians from 32 cancer centres across the UK to understand their approach to using bleomycin. Subsequent guideline development was based upon current practice, best available published evidence and expert consensus. We observed heterogeneity in practice in the following areas: monitoring; route of administration; contraindications to use; baseline and follow-up investigations performed, and advice given to patients. A best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours has been developed and includes recommendations regarding baseline investigations, the use of pulmonary function tests, route of administration, monitoring and patient advice. It is likely that existing heterogeneity in clinical practice of bleomycin prescribing has significant economic, safety and patient experience implications. The development of an evidence-based consensus guideline was supported by 93% of survey participants and aims to address these issues and homogenise practice across the UK

Pure seminoma: A review and update

Pure seminoma is a rare pathology of the young adult, often discovered in the early stages. Its prognosis is generally excellent and many therapeutic options are available, especially in stage I tumors. High cure rates can be achieved in several ways: standard treatment with radiotherapy is challenged by surveillance and chemotherapy. Toxicity issues and the patients' preferences should be considered when management decisions are made. This paper describes firstly the management of primary seminoma and its nodal involvement and, secondly, the various therapeutic options according to stage

Clinical outcomes in patients with stage I non-seminomatous germ cell cancer

This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer (CSI NSGCT) treated with surveillance, retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months (range: 6–149 months). Thirteen of the 89 patients (14.6%) had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China

Risk of diabetes after para-aortic radiation for testicular cancer

Background: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated. Methods: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case–cohort design. Results: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7–1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05–2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11–0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI: −0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose. Conclusion: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors