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.)