Monday, May 12, 2014

The Basics of Testis Cancer Diagnosis: Epidemiology & Presentation

Testis Cancer is a rare cancer, with approximately 9,000 boys and men being diagnosed each year.  Fortunately, the cure rates are excellent -- only 400 men will die of testis cancer each year -- leaving about 20,000 survivors with cancer and 200,000 cured of the disease in the US at any given moment.[1] Testis cancer affects mostly young men and boys, therefore the diagnosis can create tremendous anxiety and uncertainty for the patient and their family.

Here we review the Basics of Testis Cancer Diagnosis.

EPIDEMIOLOGY

As stated above, approximately 9,000 men and boys are diagnosed with testis cancer each year; 400 will die of the disease, 20,000 are surviving with the disease and 200,000 have been cured.  Testis cancer is the most common malignancy among men 20-40 years old and is the 2nd most common malignancy in young men 15-19 years old (leukemia is #1).[2]  Corresponding to these statistics, there are three, well-known age peaks for testis cancer:

  • Infancy
  • Age 30-40 years
  • Age 60

Most cases (about 70%) present as a unilateral mass confined to the testicle (a cancer in only one testicle).  Approximately 30% of men will present with metastatic disease -- the most common sites being the retroperitoneum and the lungs.[3]  Bilateral tumors (tumors in both testicles) can appear synchronously or metachronously (at the initial diagnosis or develop later), but is extremely rare, occuring in 2% or less of patients.[4]

RISK FACTORS

There are 4 risk factors for testis cancer:

  • Cryptorchidism (an undescended testicle) [5-7]
    • 4 to 6-fold risk of developing cancer in the undescended testicle
    • 2 to 3-fold risk is orchidopexy (surgical lowering of the testicle) occurs before puberty.
    • A slight increased risk also exists in the normal, descended testicle (relative risk 1.74).
  • Family history of testicular cancer [8-11]
    • 8 to 12-fold risk if a brother with testis cancer
    • 2 to 4-fold risk if father with testis cancer
    • Average age at diagnosis is 2-3 years younger than general population if a first-degree relative has testicular cancer
  • Personal history of testicular cancer [4,12]
    • Only 2% of testis cancer patients will have cancer in both testicles, but...
    • 12-fold risk if a history of testis cancer
      • higher in younger men
      • higher in seminoma
  • Intratubular germ cell neoplasia (ITGCN) [13,14]
    • Most testis cancer arise from the precursor lesion known as ITGCN (or carcinoma-in-situ, CIS)
    • ITGCN is present adjacent to testis cancer in 80-90% of patients
    • If ITGCN is present, the risk of subsequent testis cancer is:
      • 50% at 5 years
      • 70% at 7 years

CLINICAL PRESENTATION

Most testis cancers present as a mass confined to the testicle.  Therefore, the most common presentation is a painless testicular mass.  Most of these masses are palpable and of significant size (a few to several centimeters).  Small, non-palpable lesions without pain and in the absence of distant disease have a higher likelihood of being a benign tumors.  In a number of studies, upwards of 80% of non-palpable, asymptomatic masses that are 2cm or smaller will be benign tumors.[15-18]  Benign lesions may include testicular cysts, small infarcts, Leydig cell nodules, or small Leydig cell or Sertoli cell tumors.

Serious, acute pain is associated with rapidly growing tumors and associated hemorrhage or infarction (if the tumor outgrows its blood supply).  Most patients with pain complain of dull scrotal discomfort or heaviness.  Rarely trauma can lead to a diagnosis, mostly because it brings a mass or pain to the patient's awareness.  

For the upwards of 30% of men who present with metastatic cancer, symptoms of metastases can be the presenting complaint. Bulky retroperitoneal lymphadenopathy can lead to abdominal mass; abdominal, flank or back pain due to direct invasion or obstruction of muscles, blood vessels or the ureters; lower extremity swelling if the IVC is compressed or gastrointestinal symptoms if the intestines are involved.  Pulmonary metastases can present as chest pain, shortness of breath and cough.

As testis cancers can lead to diminished spermatogenesis, infertility can be the initial presentation in rare men.  

DIAGNOSIS

The mainstays of diagnosis are scrotal ultrasound and serum tumor markers.

Serum tumor markers are covered in a previous blog (click here).  

Scrotal Ultrasound

Scrotal ultrasound often demonstrates an intratesticular, hypoechoic (dark) mass.  Testis cancers are often vascular (or hypervascular), although the absence of blood flow does not rule out a testis cancer.  Even in patients with suspicion of metastatic cancer, a scrotal ultrasound should be used to identify an active primary tumor or a "burned-out" testicular mass -- which is typically a small, impalpable scar or calcification.  Radical orchiectomy should strongly be considered for any intra-testicular mass and suspicion of testis cancer.

Advanced Imaging

Abdominal and Pelvic CT scan can be performed before or after orchiectomy to evaluate the retroperitoneum.  An initial chest x-ray should be performed to rule-out involvement in the lungs.  Chest CT is only warranted if suspicion of pulmonary disease on x-ray.  Routine imaging of the brain or bones is not recommended unless specific symptoms.   

Summary

  • Testis cancer is a rare entity, affecting approximately 9,000 men and boys each year; however the cure rate is excellent, leaving approximately 200,000 survivors in the US.
  • Testis cancer is the most most common cancer in men aged 20-40, and 2nd most common in men age 15-19 years old.
  • The main risk factors for testis cancer are cryptorchidism (undescended testis), a family or personal history of testis cancer or ITGCN.
  • The most common presentation is a painless, palpable testis mass.
    • 70% of cancers are confined to the testicle.
    • Symptoms are often related to metastatic invasion in the retroperitoneum or lungs.
  • Diagnosis involves routine imaging and bloodwork involving scrotal ultrasound, serum tumor markers and abdominal imaging.

To read more about Testis Cancer follow this link.

This blog was written by Phillip M. Pierorazio, MD, Director of the Division of Testis Cancer at the Brady Urological Institute at Johns Hopkins.









[1] American Cancer Society. Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014.
[2] Horner MJ, Ries LAG, Krapcho M,et al: SEER Cancer Statistics Review, 1975–2006. Bethesda (MD): National Cancer Institute, 2009.
[3]  McGlynn KA, Devesa SS, Graubard BI,et al: Increasing incidence of testicular germ cell tumors among black men in the United States. J Clin Oncol 2005; 23: 5757-5761
[4] Fossa SD, Chen J, Schonfeld SJ,et al: Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 2005; 97: 1056-1066
[5] Dieckmann KP, Pichlmeier U: Clinical epidemiology of testicular germ cell tumors. World J Urol 2004; 22: 2-14
[6] Wood HM, Elder JS: Cryptorchidism and testicular cancer: separating fact from fiction. J Urol 2009; 181: 452-461
[7] Akre O, Pettersson A, Richiardi L,et al: Risk of contralateral testicular cancer among men with unilaterally undescended testis: a meta-analysis. Int J Cancer 2009; 124: 687-689.
[8] Hemminki K, Chen B: Familial risks in testicular cancer as aetiological clues. Int J Androl 2006; 29: 205-210.
[9] Mai PL, Chen BE, Tucker K,et al: Younger age-at-diagnosis for familial malignant testicular germ cell tumor. Fam Cancer 2009; 8: 451-456.
[10] Sonneveld DJ, Sleijfer DT, Schrafford Koops H,et al: Familial testicular cancer in a single-centre population. Eur J Cancer 1999; 35: 1368-1373
[11] Westergaard T, Olsen JH, Frisch M,et al: Cancer risk in fathers and brothers of testicular cancer patients in Denmark: a population-based study. Int J Cancer 1996; 66: 627-631.
[12] Theodore C, Terrier-Lacombe MJ, Laplanche A,et al: Bilateral germ-cell tumours: 22-year experience at the Institut Gustave Roussy. Br J Cancer 2004; 90: 55-59.
[13] Dieckmann KP, Skakkebaek NE: Carcinoma in situ of the testis: review of biological and clinical features. Int J Cancer 1999; 83: 815-822.
[14] Montironi R: Intratubular germ cell neoplasia of the testis: testicular intraepithelial neoplasia. Eur Urol 2002; 41: 651-654.
[15] Connolly SS, D’Arcy FT, Gough N,et al: Carefully selected intratesticular lesions can be safely managed with serial ultrasonography. BJU Int 2006; 98: 1005-1007, discussion 1007.
[16] Giannarini G, Dieckmann KP, Albers P, Heidenreich A, Pizzocaro G: Organ-sparing surgery for adult testicular tumours: a systematic review of the literature. Eur Urol 57(5): 780-790, 2010.
[17] Hindley RG, Chandra A, Saunders A,et al: Impalpable testis cancer. BJU Int 2003; 92: 572-574.
[18] Shilo Y, Zisman A, Raz O, Lang E, Strauss S, Sandbank J, Segal M, Siegel YI, Leibovici D: Testicular sparing surgery for small masses. Urol Oncol 30(2): 188-191, 2012.

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