3. EPIDEMIOLOGY AETIOLOGY PATHOLOGY
3.1. Epidemiology and Aetiology
Testicular cancer represents 1% of adult neoplasms and 5% of urological tumours, with three to ten new cases per 100,000 males/per year in Western societies [6]. The incidence of TC has increased during recent decades, predominantly in industrialised countries [7-10], and it continues to rise. At diagnosis, 1-2% are bilateral and 90-95% of cases are germ cell tumours (GCT) [6]. The peak incidence is in the third decade of life for nonseminomatous germ cell tumour (NSGCT), including mixed GCT patients, and in the fourth decade for seminomatous germ cell tumour (SGCT) patients. In 5% of GCT patients, the primary site is at an extragonadal location [11]. Although cure rates remain high, with > 95% long-term survival across different stages of disease, it is recognised that diagnosis and fear of recurrence may have a significant impact on psychological well-being, while long term toxicities can significantly reduce quality of life (QoL). It is essential to ensure that consequences of treatment are treated holistically to improve long-term survivorship. Complications of treatment and their management can be reviewed in Appendix 5, available online: https://uroweb.org/guidelines/testicular-cancer/publications-appendices.
There are two fundamental categories of TGCTs based on their development from the precursor lesion germ cell neoplasia in situ. Most malignant post-pubertal GCTs originate from germ cell neoplasia in situ (GCNIS). Histologically and clinically, these are subdivided into seminomas and non-seminomas, the latter encompassing embryonal carcinoma, extra-embryonal elements (postpubertal-type yolk sac tumour and choriocarcinoma) and somatic elements (postpubertal-type teratoma) [12].
Non-GCNIS derived tumours include prepubertal-type teratoma and prepubertal-type yolk sac tumour, which often occur in childhood, and spermatocytic tumours, which usually occur in older males (although with some exceptions). Although there is overlapping histology between the prepubertal-type teratoma/yolk sac tumour and the postpubertal-type teratoma and yolk sac tumour elements in the GCNIS-derived NSGCT, these have a separate and independent pathogenesis [12].
Risk factors for GCNIS-derived GCTs are components of the testicular dysgenesis syndrome, which encompasses cryptorchidism, hypospadias, decreased spermatogenesis, and impaired fertility [13-15] or disorders of sex development [16]. Additional risk factors include, a family history of TC among first-degree relatives and the presence of a contralateral testicular tumour or GCNIS [17-25], although the risk was lower in TC patients who previously had received platinum-based chemotherapy [26,27]. Genome-wide association studies revealed detectable susceptibility loci leading to an increased relative risk to develop TC [28].
3.2. Histological classification
The recommended pathological classification is based on the 2022 update of the World Health Organization (WHO) pathological classification [29]. This is outlined in Appendix 1, ‘Pathological classification’, available online: https://uroweb.org/guidelines/testicular-cancer/publications-appendices. Expert genitourinary pathology review of orchiectomy specimens is recommended for optimal management [30].