Exposure to various factors in adolescence and adulthood appears linked to the development of testicular cancer. Firefighters and aircraft maintenance personnel and farmers exposed to organochloride pesticides appear to have an increased risk of developing testicular cancer. Case-control studies have revealed significant associations between seminoma and levels of cis-nonachlor, trans-nonachlor, oxychlordane, and total chlordane.

Ochratoxin A, a substance less well-studied, naturally occurs in the mold in grains, coffee, nuts, and spices that have recently been linked to testicular cancer.

Patients usually present with an asymptomatic testicular mass which may be associated with infertility. Testicular pain from malignancy is relatively rare but still should be included in the differential diagnosis.

On physical exam, there is usually a unilateral, firm to hard palpable mass in the scrotum which is localized to the testis. This may be associated with a hydrocele that would preclude palpation, so testicular ultrasonography may be needed to identify the mass. Metastatic disease, although rare, can present initially with lymphadenopathy in the retroperitoneum and the anterior mediastinum. Even massive metastatic disease can be produced from a non-palpable testicular malignancy.

Typically, testicular ultrasonography shows an intratesticular mass that is relatively hypoechoic and homogeneous. As the mass increases in size, it may become less homogeneous due to hemorrhage and necrosis.

The initial evaluation is by testicular ultrasonography. A CT scan of the abdomen and pelvis is the initial staging modality, but it may fail to identify retroperitoneal nodes in 15% to 20%. A chest CT is usually recommended only when there is an abnormal chest x-ray first. PET scanning is not usually part of the initial workup but may be useful in tracking activity and growth in residual masses following definitive chemotherapy.[9][3][10][11]

Several laboratory values may be useful in following tumor burdens. These include AFP, B-HCG, and LDH. Alpha-fetoprotein (AFP) elevation indicates at least some nonseminomatous disease and those patients are then treated as nonseminomas, germ cell patients. LDH may be used to follow the overall seminomatous tumor burden. Beta-human chorionic gonadotropin (HCG) is present in 5% to 10% of seminoma patients; these usually demonstrate the syncytial cytotrophoblastic subtype. Such elevations tend to be associated with metastatic disease, but the beta-HCG elevation by itself has no connection with overall survival. 

As noted earlier, a plain chest film may reveal metastatic disease, and chest CT is only indicated to evaluate abnormalities on the plain abnormalities. Ultrasound is the typically the most useful diagnostic method for follow-up of metastatic masses.

There are several treatment options available to these patients, but surgery, a radical orchiectomy, is almost always the primary intervention. The surgical approach usually requires an incision in the groin with the removal of the entire testicle and most of the spermatic cord. This is called a radical inguinal orchiectomy and is both therapeutic and a part of the staging procedure. A scrotal incision approach should be avoided in any orchiectomy or surgical testicular exploration where malignancy is suspected.[12][13][14]

Stage 1 disease may be offered single therapy with carboplatin and for more advanced disease Bleomycin, Etoposide, and Cisplatin (BEP) or Etoposide and Cisplatin (EP) may be used.

Most men do not have a significant decrease in testosterone or low testosterone symptoms of sexual dysfunction with the removal of a single testicle. The procedure is not usually a cause of infertility, and 25% of men with testicular malignancies are already infertile before getting a testicular cancer diagnosis.

Sperm counts may increase after removal of the cancerous testicle. Reconstructive surgery with a prosthetic testicle is an option which may be exercised with the primary operation delayed until active treatment is done or completely declined. Retroperitoneal lymph node dissection is more complex and invasive. It is used for staging and is usually open, but laparoscopic approaches are being developed. Complications include immediate problems, such as infection or bowel blockage, and loss of the ability to ejaculate. For these reasons, retroperitoneal lymph node dissections are rarely done for seminoma except possibly for growing, residual abdominal masses not responding to other treatments. Radiation or chemotherapy generally is indicated for the management of positive lymph nodes.

Other germcell tumors

Testicular Dermoid

Trauma

Metastatic Disease

NCI has a Phase III clinical trial named Retroperitoneal Lymph Node Dissection in Treating Patients with Testicular Seminoma with Lymphadenopathy or Stage I-IIB Testicular Seminoma.

Sloan Kettering has a Phase I/II Study of Topical SOROO7 in Patients with Skin Metastasis from Cancer.

Testicular seminoma is the germ cell tumor, which is very sensitive to radiation therapy. Radiation therapy planning is based on the results of a contrast-enhanced CT of the chest abdomen and pelvis.   The optimal IMRT dose has been decreased to 20–25 Gy in CS I and to 30–36 Gy in CS IIs.   Because of low pelvic relapse rates reported in stage I tumors (less than 5%), the indication for pelvic irradiation is no longer  This omission increases post-treatment fertility rates and diminished gastrointestinal toxicity.  The optimal RT dose generally recommended is between 25 and 30 Gy in 15 to 20 fractions.  Because left sided, primaries tend to relapse around the insertion of the left testicular vein the, left para-aortic region must be included in the irradiated volume.  Radiation therapy planning is based on the results of a contrast-enhanced CT of the chest abdomen and pelvis.  

Volumetric modulated arc therapy radiotherapy has been studied in which radiation is delivered in a continuous manner as the treatment gantry rotates around the patient. With this approach, there is a greater spread of low-dose radiation in healthy tissues.

Proton  (PT) pencil scanning beam therapy provides unique depth dose characteristics of protons. There is a significant reduction of doses to adjacent critical structures proximal and distal to the target volume in comparison to more traditional treatments. This therapy allows escalation of doses delivered to the tumor and normal tissue sparing reducing toxicity and improving quality of life. This is possible only if the proton machine employs the pencil scanning beam, which avoids the production of neutrons and reduces the dose delivered to the total body. Proton therapy is recommended in pediatric patients because of the tenfold decrease in radiation dose. 

The optimal IMRT dose has been decreased to 20–25 Gy in CS I and to 30–36 Gy in CS IIs.

In one study from Mass General, photon beams were weighted to yield a maximum of 26 Gy(RBE) and a minimum of 25.5 Gy(RBE) in 1.5 Gy(RBE)/fraction to the CTV. For proton plans, a 5 mm compensator expansion was added to emulate a PTV expansion in photon treatment planning. 

Proton pencil beam scanning allows more precise targeting of the tumor with a 10 fold decrease in total radion dose compared with IMRT.  

Bleomycin, Etoposide, and Cisplatin (BEP) or Etoposide and Cisplatin (EP) are the 2 most common chemotherapy regimen.  Recent studies suggest that 3 cycles are as effective as 4 with fewer side effects. 

Staging: the  TNM system:

• T stands for tumor size.
• N indicates whether nearby lymph nodes are involved.
• M denotes whether cancer has metastasized (spread).

In the numerical system:

• Stage I describes cancer confined to the testicle.
• Stage II describes cancer with metastases in the pelvis and abdomen.
• Stage III refers to cancer with metastases in the chest.

Management (National Comprehensive Cancer Network - NCCN Guidelines)

Stage 0 Seminomas: Carcinoma in situ (CIS) where the levels of tumor markers like HCG and AFP are not elevated. Treatment may not be needed as long as there are no signs that the CIS is growing or turning into invasive cancer. (The diagnosis is typically made via a biopsy.)  If CIS is treated, it is with an orchiectomy (to remove the testicle) or with testicular radiation.

If tumor marker levels are high, then the cancer is not stage 0, even when only CIS is found in the testicle, and there are no signs of cancer spread. These cases are treated like stage I cancers. CT scan of the abdomen and pelvis is required to verify the extent of the malignancy in such cases.

All of the following cancers are treated initially with initial radical orchiectomy. After surgery, there may be several treatment choices as follows:

Stage I Seminomas:

• Careful observation (surveillance over 10 years): Usually, recurrence is found in the first 2 years
• Single-agent chemotherapy with carboplatin
• Radiation therapy: Seminoma is quite radiosensitive, but the general trend is to go with chemotherapy in more advanced disease, as seminoma is also very chemosensitive and this avoids radiation-related side effects when there is extensive disease.

Stage II A:

• Radiation Therapy
• Chemotherapy with Bleomycin, Etoposide, and Cisplatin (BEP) or Etoposide and Cisplatin (EP).

Stage II B and C:

• Chemotherapy with BEP or EP is preferred
• Radiation therapy is acceptable if affected nodes are less than 3 cm.

Stage III:

• Stage III is treated with BEP or EP chemotherapy.

Small tumors are often watched with CT scans to see if they grow. If they do, further treatment is needed. If the tumors are detected on a PET scan, surgery or different chemotherapy is indicated.

Stage IV refers to cancer that has spread to any other organ.

According to the Testicular Cancer Society:   "The overall survival rate is greater than 95%. If diagnosed early, while the cancer is confined to the testicle, the survival rate is 99%. If the cancer has spread to regional lymph nodes the survival rate is 96% and even if there are distant metastases the survival rate is over 70%."

Surgery:  For all patients, orchiectomy may be complicated by retrograde ejaculation however infertility is not seen in all patients.  Sperm counts may increase after removal of the cancerous testicle.  

Complications of radiation therapy and chemotherapy may include anemia, immune compromise, and hair loss.

Incompletely treated, widespread metastasis may be complicated by extensive bleeding which may be fatal. Frequent sites of metastasis are the lungs, lymph nodes, liver, and bones

Reconstructive surgery with a prosthetic testicle is an option which may be exercised with the primary operation delayed until active treatment is done or completely declined. 

Surveillance for all stages may include interval CT. 

The Testicular Cancer Resource Center recommended follow-up: 

Princess Margaret Hospital Protocol

• Years 1-3: Tumor Markers done every 4 months (for the first 2 years only) Chest X-ray done every 8 months Physical exam and Abdominal CT scan done every 4 months
• Years 4-7: Tumor Markers optional Chest X-ray done once a year Physical exam and Abdominal CT scan done every 6 months
• Years 8-10: Tumor Markers optional Chest X-ray done once a year Physical exam and Abdominal CT scan done once a year

Nichols protocol

• Year 1: Tumor Markers and Chest X-ray done every 2 months Abdominal CT scan done every 3 months
• Year 2: Tumor Markers and Chest X-ray done every 2 months Abdominal CT scan done every 4 months
• Years 3-5: Tumor Markers and Chest X-ray done every 6 months Abdominal CT scan done every 6 months
• After Year 5: Tumor Markers and Chest X-ray done once a year

Because evidence suggests that TGCT is initiated in very early life, exposure to these persistent organic pesticides during fetal life or via breastfeeding should be avoided. 

There is no recommended protocol for screening for testicular cancer, however, it is essential that young men be taught to do testicular self-exam.  Education must include evidence of excellent prognosis of early-stage disease.  More than half of solid, palpable intratesticular masses are non-germ cell tumors.

Pelvic nodes are anatomically near to L1-L4 sympathetic roots of the superior hypogastric plexus. When oncologically possible, they should be surgically spared, at least unilaterally, to preserve ejaculatory function.

Contrary to non-seminomatous germ cell tumors, retroperitoneal lymph node dissection (RPLND) is not indicated in seminomas.

Excellent treatment survival rates have been accomplished, the focus should now be placed on identifying early-stage disease.  Patients need to be able to examine themselves and need to be educated about the successful management of the early disease. 

Primary care providers including nurse practitioners must know that urgent testicular ultrasound is indicated for a new testicular mass.  The oncology team needs to educate the patients on options for their stage of disease with continued emphasis on minimizing complications of therapy.  Further paths of inquiring may establish optimal surveillance schedules.