Treatment options for testicular cancer by stage

Stage 0 germ cell tumors

In this stage, the tumor in the testicle is carcinoma in situ (CIS), there is no cancer spread outside the testicle, and the levels of tumor markers (like HCG and AFP) are not elevated. If this stage was diagnosed after surgery to remove the testicle, no other treatment is needed. If the CIS was found after a testicular biopsy (like for fertility problems), the doctor may recommend that it not be treated right away. Instead, the patient may be watched closely with repeated physical exams, ultrasound of the testicle, and blood tests of tumor marker levels. Treatment may not be needed as long as there are no signs that the CIS is growing or turning into an invasive cancer. CIS can be treated with surgery (to remove the testicle) or with radiation therapy to the testicle. If tumor marker levels are high, the cancer is not really 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 IS cancers.

Stage I germ cell tumors

Stage I seminomas: These cancers are cured in more than 95% of patients. They are first treated by surgically removing the testicle and spermatic cord (radical inguinal orchiectomy). After surgery, several choices exist:

• Radiation therapy: Radiation aimed at para-aortic lymph nodes (in the back of the abdomen, around the large blood vessel called the aorta) is the most common next step. Because seminoma cells are very sensitive to radiation, low doses can be used, usually for about 10 to 15 treatments.

The doctor may recommend radiation therapy even though CT scan results do not show that the cancer has spread to the nodes. This is because in about 1 in 5 patients, cancerous cells have spread, but cannot be seen on imaging tests like CT scans. Radiation therapy is usually successful in destroying these hidden (occult) metastases.

• Chemotherapy: Another choice that works as well as radiation is to give 1 or 2 doses of chemotherapy (chemo) with the drug carboplatin after surgery.
• Careful observation (surveillance): Another approach to treating men with stage I seminomas is to not give radiation or chemo right after surgery, but instead to watch patients closely for 5 years. This means seeing the doctor and getting a physical exam and blood tests every 3 to 4 months for the first 2 years, with imaging studies (CT scans and sometimes chest x-rays) every 6 months during that time. Tests and exams are done less frequently over the next 3 years. If these tests do not find any signs that cancer has spread beyond the testicle, no additional treatment will be given. In about 15% to 20% of patients the cancer will come back as spread to lymph nodes or other organs, but if it does, radiation or chemo can still be used effectively to cure the cancer.

Some doctors decide whether or not to treat with chemo or radiation based on the size of the tumor and whether it invades nearby blood vessels. If the tumor is large or invades blood or lymph vessels, they may recommend treatment with either radiation or chemo.

Stage IS seminomas: In this stage, the level of one or more tumor markers is still high after the testicle containing the seminoma is removed. This is very rare, but is often treated with radiation.

Stage I non-seminomas: These cancers are also highly curable (about 98%), but the standard treatment is different from that of seminomas. As with seminomas, the initial treatment is surgery to remove the testicle and tumor (radical inguinal orchiectomy). Then the treatment choices depend on the stage.

For stage IA (T1) there are 2 choices:

• Retroperitoneal lymph node dissection (RPLND): This has the advantage of a high cure rate but the disadvantages of major surgery, with its complications and possibly losing the ability to ejaculate normally. After RPLND, if the nodes are found to have cancer in them, chemo may be recommended.
• Careful observation (surveillance) for several years: The advantage of surveillance is that there are no problems with surgery or chemotherapy side effects. The disadvantage is that you have to see the doctor a lot and get lots of x-rays and tests. For the first year, the doctor visits and blood tests are every 1 to 2 months, and the CT scans are every 3 to 4 months. In the second year, doctor visits and blood tests are every 2 months, with CT scans every 4 to 6 months. The length of time between visits gets longer each year. Without careful watching the cancer can come back (relapse) and can grow so large that it may not be curable. So far, this has not happened in men who saw their doctor for follow-up visits as scheduled. Most relapses occur in the first year after diagnosis, with most of the rest in the second year. Relapses are generally treated with chemo. Even though more patients will have a relapse with surveillance than with lymph node dissection, the cure rates are similar for both approaches because the relapses are usually found early enough to be cured.

For stage IB (T2, T3, or T4) there are up to 3 options:

• Retroperitoneal lymph node dissection: As in stage IA, chemo may be recommended after RPLND if cancer is found in the lymph nodes.
• Careful observation (surveillance): This requires frequent doctor visits and tests for several years. This is usually not an option if the tumor is T3 or T4 or for T2 tumors where the cancer cells were growing into blood or lymph vessels when the tumor was looked at under the microscope (called vascular invasion).
• Chemotherapy: The most common option is the BEP regimen (bleomycin, etoposide, and cisplatin) for 2 cycles. This option has a high cure rate but has the disadvantage of the side effects of chemo (mostly the short-term effects, since 2 cycles cause fewer long-term effects). This approach is more often used in Europe and less often used in the United States.

Stage IS non-seminoma: If the tumor marker levels (like AFP or HCG) are still high even after the testicle/tumor is removed, but no tumor is seen on a CT scan, chemo is recommended, either with either 3 cycles of BEP or 4 cycles of EP (etoposide and cisplatin).

Doctors have learned that certain features of the tumor mean that the cancer might come back. These depend on the blood test results and the way the cancer cells look under the microscope. If these features are present, doctors are less likely to recommend observation only.

Stage II germ cell tumors

Stage IIA seminomas: After surgery to remove the testicle (radical inguinal orchiectomy), these cancers are treated with radiation to the retroperitoneal lymph nodes. Usually higher doses of radiation are given for stage II seminomas than for stage I seminomas. If radiation can't be given for some reason, chemo may be used instead.

Stage IIB seminomas: All men will have radical inguinal orchiectomy to remove the testicle with the tumor. Treatment after surgery depends on the size of the retroperitoneal lymph nodes.

• If none of the lymph nodes are larger than 3 cm across, they are treated with radiation. (If radiation can't be given for some reason, chemo may be used instead.)
• If any of the lymph nodes are more than 3 cm across, though, chemo may be given instead. Either 4 cycles of EP (etoposide and cisplatin) or 3 cycles of BEP (bleomycin, etoposide, and cisplatin) may be used.

Stage IIc seminomas: These cancers are treated with radical inguinal orchiectomy, followed by 3 or 4 cycles of chemo with either EP or BEP. Radiotherapy is generally not used for stage IIc seminoma.

Stage II non-seminomas: Treatment for these tumors depends on the tumor markers and the retroperitoneal lymph nodes. All men will have radical inguinal orchiectomy to remove the testicle with the tumor. After surgery, there are 2 main options:

• Retroperitoneal lymph node dissection (RPLND): This may be followed by further treatment with chemo if the lymph nodes have cancer in them. Chemo is usually given for 2 cycles.
• Chemotherapy: Sometimes the doctor will recommend that the patient go straight to chemo (without doing the RPLND surgery). This is more likely to happen if the retroperitoneal lymph nodes are very large on the CT scan or if the tumor marker levels (HCG and/or AFP) are high even after the testicle with the tumor is removed. The chemo is usually given for 3 or 4 cycles.

After chemo, a CT scan is repeated to see if the retroperitoneal lymph nodes are still enlarged. If they are, they are removed by RPLND.

Stage III germ cell tumors

Both stage III seminomas and non-seminomas are treated with orchiectomy followed by chemo with a combination of drugs. The main regimens are the same as those used for stage II testicular cancers (usually BEP or EP) but at least 3 cycles of BEP or 4 cycles of EP are typically given. Patients with poor prognosis non-seminomas may receive 4 cycles of BEP. This treatment produces a cure in over 70% of cases.

Once chemo is complete, the doctor looks for any cancer that remains. Patients with normal scans and normal markers are usually watched carefully after this and may need no further treatment.

Sometimes a few tumors may remain. These are most often in the lung or in the retroperitoneal lymph nodes. Further treatment at this point depends on the type of cancer.

Seminomas: Tumors that remain after chemo but do not seem to still be growing are often observed with imaging tests. Results of the PET scan and the size of the tumor will influence the decision to continue follow-up with imaging tests and tumor markers or to consider surgery and/or radiation therapy. Chemo with different drugs may be an option if these treatments don't work.

Non-seminomas: Residual tumors are usually removed surgically, which may result in a cure. Further chemo, but with different drugs, may also be an option. Patients whose cancer has metastasized to the brain usually receive chemo plus radiation therapy aimed at the brain, but surgery for the brain tumor is another option.

If the tumor marker levels are very high or the cancer is widespread then the usual chemo treatment may not always be enough. Sometimes the doctor may recommend high-dose chemotherapy followed by a stem cell transplant if regular chemo is not working. Patients might also want to consider enrolling in a clinical trial of newer chemo regimens. (For more information, see the section called "Clinical trials for testicular cancer.”)

Recurrent germ cell tumors

If the cancer goes away with treatment and then comes back, it is said to have recurred or relapsed. Treatment of recurrent germ cell tumors depends on the initial stage and treatment. Cancer that comes back in the retroperitoneal lymph nodes can be treated by surgery (RPLND) if the recurrence is small (and if the only surgical treatment given before was orchiectomy). Depending on the results of the surgery, chemo may be recommended.

If it looks as if cancer has recurred in a lot of the retroperitoneal lymph nodes or if the cancer has returned elsewhere, then chemo is usually recommended. This may be followed by surgery.

If a man's cancer recurs after chemo or if his treatment is no longer working, he will be treated with different chemo regimens, which typically include ifosfamide, cisplatin, and either etoposide, paclitaxel, or vinblastine.

The treatment of testicular cancer that has come back after chemo is not always as effective as doctors would like. So some doctors may advise high-dose chemotherapy followed by a stem cell transplant. This may be a better option for men with recurrent disease, rather than standard chemo. (See the section called "High-dose chemotherapy and stem cell transplant for testicular cancer" for more information.)

In general, if chemo is no longer working, it is probably best to get a second opinion from a center of excellence with extensive experience in treating relapsed testicular cancer patients, before starting other treatments. Clinical trials can also be considered.

Sertoli cell and Leydig cell tumors

Radical inguinal orchiectomy is usually recommended for Sertoli cell and Leydig cell tumors. Radiation therapy and chemo are generally not effective in these rare types of testicular tumors. If the doctor suspects the tumor has metastasized beyond the testicle, the retroperitoneal lymph nodes may be surgically removed.