Radiation Oncology/Testis/Overview

Testes Overview

Epidemiology

 * 7000 cases/yr.
 * Most common neoplasm in men ages 15-35.
 * Highest incidence among white males especially from northern Europe.
 * ~2/3 are clinical Stage I
 * Most common testicular cancer in men >50 is lymphoma
 * GCTs sometimes present in extragonadal sites: mediastinum, brain and sacrococcygeal region (often midline)

Anatomy

 * Surrounded by tunica albuginea
 * Seminiferous tubules lead to rete testis, epididymis, vas efferens and finally to urethra
 * Seminiferous tubules
 * Spermatogonia participate in sperm production (~67 days)
 * Sertoli cells are epithelial cells lining seminiferous tubules
 * Nurture and support the developing sperm cells through the stages of spermatogenesis
 * Produce several hormones, including estradiol to regulate spermatogenesis and androgen-binding protein to transport androgens
 * Form blood-testis barrier
 * Leydig cells are interstitial cells
 * Responsible for endocrine function, primarily via production of testosterone
 * Controlled by LH (testosterone synthesis) and FSH (increase in number of LH receptors)
 * Rete testis = anastamosing network of tubules in the testicular hilum; sperm are concentrated
 * Epididymis = sperm maturation and storage

Natural history
10% of germ cell tumors may arise in non-gonadal sites, in which case it is usually an anterior mediastinal mass (as opposed to a posterior mediastinal mass, which is usually metastatic) or centrally located retroperitoneal (as opposed to lateralized masses seen in metastatic disease)

Risk Factors

 * Testicular abnormalities
 * Cryptorchism
 * Testicular atrophy
 * Infertility
 * Genetic abnormalities
 * cKIT mutation is associated with bilateral testicular germ cell tumors

Pathology
95% are germ cell tumors (Percentages taken from )
 * Germ cell:
 * Seminoma (50%)
 * Non-seminoma (50%)
 * Pure (15%): Embryonal (10%), teratoma (3-5%), choriocarcinoma (<1%), yolk-sac tumor (<1%)
 * Mixed (35%)
 * Sex-cord stroma:
 * Leydig cell, Sertoli cell, granulosa cell
 * Lymphoma:
 * Common in men > 50

If the tumor has any component of a non-seminoma, it should be classified as a non-seminoma. If there is an elevated AFP even if the histology shows a pure seminoma, it should be classified as a non-seminoma.
 * Seminoma - no differentiation; retains some aspects of spermatogenesis
 * NSGCT - undergo some differentiation to totipotential cells
 * Embryonic tissue differentiation - embryonal carcinoma and teratoma
 * Extra-embryonic tissue differentiation - choriocarcinoma and yolk sac tumors


 * Teratoma is not sensitive to chemotherapy. Requires resection. Does not metastasize.
 * Choriocarcinoma is one of few tumors that metastasize more frequently hematogenously (also follicular carcinoma of the thyroid, renal cell carcinoma)

Tumor markers
Check AFP, B-HCG, and LDH.
 * AFP - yolk sac, embryonal. Half-life is 5-7 days.
 * Elevated in 70% of patients with teratocarcinomas and embryonal carcinomas.
 * Never elevated in Seminomas
 * B-HCG - choriocarcinoma, embryonal. Half-life is 18-36 hrs.
 * Elevated in 40-60% of nonseminomas and ~10% of seminomas
 * Placental Alk Phos - most sensitive for surveillance of pure seminomas with ~50% sensitivity for metastatic disease
 * LDH - Surveillance marker with slight rise in ~80% of advanced seminomas and 60% of nonseminomas

1 in 5 pts with pure seminoma will have minimal B-HCG elevation (<100 mIU/mL). Tumor markers not elevated in pure teratomas.

Prognostic factors
Risk stratification:
 * Tumors can be classified as good risk, intermediate risk, or poor risk using the IGCCCG system.
 * For details see at Seminoma or Non-seminoma

Radiation technique

 * Para-aortic field borders - Designed to cover the potential drainage areas of the para-aortic region, remember testicular vein returns at L2.
 * Top border - At or near the crura of the diaphram to cover insertions of the renal vein and antegrade flow
 * Inferior border - Bifurcation of the common iliacs
 * Lateral borders- Transverse processes of the vertebral bodies to cover LNs. Keep in mind L renal hilum.

Toxicity

 * ''For risk of second malignancies, please see the second malignancies page

Review

 * Erasmus, 2006 (Netherlands) PMID 17158533 -- "Controversies in the management of clinical stage I testis cancer." (de Wit R, J Clin Oncol. 2006 Dec 10;24(35):5482-92.)