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Testicular Cancer

Testicular cancer begins as a scrotal mass, which is usually not painful. Diagnosis is by ultrasonography. Treatment is with orchiectomy and sometimes lymph node dissection, radiation therapy, chemotherapy, or a combination, depending on histology and stage.

In the US, about 9560 new cases of testicular cancer and about 410 deaths (2019 estimates) occur each year (1). Testicular cancer is the most common solid cancer in males aged 15 to 35. Incidence is 2.5 to 20 times higher in patients with cryptorchidism. This excess risk is decreased or eliminated if orchiopexy is done before 10 years of age. Cancer can also develop in the contralateral normally descended testis. The cause of testicular cancer is unknown.

Most testicular cancers originate in primordial germ cells. Germ cell tumors are categorized as seminomas (40%) or nonseminomas (tumors containing any nonseminomous elements). Nonseminomas include teratomas, embryonal carcinomas, endodermal sinus tumors (yolk sac tumors), and choriocarcinomas. Histologic combinations are common; eg, teratocarcinoma contains teratoma plus embryonal carcinoma. Functional interstitial cell carcinomas of the testis are rare.

Even patients with apparently localized tumors may have occult nodal or visceral metastases. For example, almost 30% of patients with nonseminomas will relapse with nodal or visceral metastases if they undergo no treatment after orchiectomy. Risk of metastases is highest for choriocarcinoma and lowest for teratoma.

Tumors originating in the epididymis, testicular appendages, and spermatic cord are usually benign fibromas, fibroadenomas, adenomatoid tumors, and lipomas. Sarcomas, most commonly rhabdomyosarcoma, occur occasionally, primarily in children.Testicular Cancer

Testicular Cancer

DR P. MARAZZI/SCIENCE PHOTO LIBRARY

General reference

Symptoms and Signs of Testicular Cancer

Most patients present with a scrotal mass, which is painless or sometimes associated with dull, aching pain. In a few patients, hemorrhage into the tumor may cause acute local pain and tenderness. Many patients discover the mass themselves after minor scrotal trauma.

Diagnosis of Testicular Cancer

  • Ultrasonography for scrotal masses
  • Exploration if testicular mass is present
  • Staging by abdominal, pelvic, and chest CT as well as tissue examination
  • Serum tumor markers such as alpha-fetoprotein and beta-HCG (human chorionic gonadotropin)

Many patients discover the mass themselves during self-examination. Monthly self-examination should be encouraged among young men.

The origin and nature of scrotal masses must be determined accurately because most testicular masses are malignant, but most extratesticular masses are not; distinguishing between the two during physical examination may be difficult. Scrotal ultrasonography can confirm testicular origin. If a testicular mass is confirmed, serum tumor markers alpha-fetoprotein and beta-HCG should be measured and a chest x-ray taken. Serum markers may help differentiate benign from cancerous masses but results are not definitive. Then, inguinal exploration is indicated; the spermatic cord is exposed and clamped before the abnormal testis is manipulated.

If cancer is confirmed, abdominal, pelvic, and chest CT is needed for clinical staging using the standard TNM (tumor, node, metastasis) system (see tables AJCC/TNM Staging of Testicular Cancer and TNM and Serum Marker Definitions for Testicular Cancer). Tissue obtained during treatment (usually radical inguinal orchiectomy) helps provide important histopathologic information, particularly about the proportion of histologic types and presence of intratumoral vascular or lymphatic invasion. Such information can predict the risk of occult lymph node and visceral metastases. Patients with nonseminomas have about a 30% risk of recurrence despite normal x-rays and serum markers and having what appears to be localized disease. Seminomas recur in about 15% of such patients.TABLEAJCC/TNM* Staging of Testicular Cancer

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TABLETNM and Serum Marker Definitions for Testicular Cancer

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Prognosis for Testicular Cancer

Prognosis depends on histology and extent of the tumor. The 5-year survival rate is > 95% for patients with a seminoma or nonseminoma localized to the testis or with a nonseminoma and low-volume metastases in the retroperitoneum. The 5-year survival rate for patients with extensive retroperitoneal metastases or with pulmonary or other visceral metastases ranges from 48% (for some nonseminomas) to > 80%, depending on site, volume, and histology of the metastases, but even patients with advanced disease at presentation may be cured.

Treatment of Testicular Cancer

  • Radical inguinal orchiectomy
  • Radiation or chemotherapy for seminomas
  • Chemotherapy or retroperitoneal lymph node dissection for nonseminomas

Radical inguinal orchiectomy is the cornerstone of treatment and helps provide important diagnostic information; it also helps formulate the subsequent treatment plan. A cosmetic testicular prosthesis may be placed during orchiectomy. Silicone prostheses are not widely available because of the problems with silicone breast implants. However, saline implants have been developed. For men who wish to retain reproductive capacity, sperm banking is potentially available in anticipation of radiation therapy or chemotherapy.

Radiation therapy

An option for seminoma after unilateral orchiectomy is radiation therapy, usually 20 to 40 grays (Gy; a higher dose is used for patients with a nodal mass) to the para-aortic regions up to the diaphragm. The ipsilateral ilioinguinal region is no longer routinely treated. Occasionally, the mediastinum and left supraclavicular regions are also irradiated, depending on clinical stage. However, in stage I disease, single-dose carboplatin has largely replaced radiation therapy due to concerns of long-term cardiovascular toxicity and higher incidence of secondary cancers and death with radiation. There is no role for radiation therapy in nonseminoma.

Lymph node dissection

For nonseminomas, many experts consider standard treatment to be retroperitoneal lymph node dissection. For clinical stage 1 tumors in patients who have no prognostic factors that predict relapse, an alternative is active surveillance (frequent serum marker measurements, chest x-rays, CT). Intermediate-sized retroperitoneal nodal masses may require retroperitoneal lymph node dissection and chemotherapy (eg, bleomycin, etoposide, cisplatin), but the optimal sequence is undecided.

Lymph node dissection is done laparoscopically at some centers. The most common adverse effect of lymph node dissection overall is failure to ejaculate. However, a nerve-sparing dissection is often possible, particularly for early-stage tumors, which usually preserves ejaculation.

Chemotherapy

Nodal masses > 5 cm, lymph node metastases above the diaphragm, or visceral metastases require initial platinum-based combination chemotherapy followed by surgery for residual masses. Such treatment commonly controls the tumor long term. Fertility is often impaired, but no risk to the fetus has been proved if pregnancy does occur.

Surveillance

Surveillance is appropriate for some patients, although many clinicians do not offer this option because it requires rigorous follow-up protocols and excellent patient adherence to be safe. It is more commonly offered to patients at low risk of relapse. High-risk patients usually get retroperitoneal lymph node dissections or, in some centers, 1 to 2 courses of chemotherapy after orchiectomy instead of surgery.

Recurrences

Nonseminoma recurrences are usually treated with chemotherapy, although delayed retroperitoneal lymph node dissection may be appropriate for some patients with nodal relapse and no evidence of visceral metastases. Surveillance is not used as often for seminomas because the morbidity of 2 weeks of radiation therapy is so low and the results in preventing late relapse so high that there is less reason to try to avoid treatment.

Key Points

  • Testicular cancer is the most common solid cancer in males aged 15 to 35 but is often curable, particularly seminoma.
  • Assess scrotal masses by ultrasonography and if they are testicular, do a chest x-ray and measure alpha-fetoprotein and beta-HCG.
  • Do radical inguinal orchiectomy, usually with radiation therapy (for seminomas) and retroperitoneal lymph node dissection (for nonseminomas).