Non-seminoma Testicular Cancer - Treatment Protocols

What Is Testicular Cancer?

The most prevalent solid organ malignancy in males between the ages of 15 and 35 is testicular cancer. There are three types of primary testicular cancer:

• Tumors of germ cells.

• Tumors of the sex cord-stroma.

• Tumors outside the gonads (extragonadal).

They are divided into two categories histologically:

1. Seminomas testicular cancer.

2. Non-seminomas testicular cancer.

What Are Non-seminomatous Germ Cell Tumors (NSGCT)?

Non-seminomatous germ cell tumors (NSGCT) are the most common testicular cancer metastasis, affecting the lungs, liver, central nervous system, and bones. At initial presentation and diagnosis, approximately one-third of the patients with non-seminomatous germ cell tumors (NSGCT) will have dispersed or distant metastasis.

The subtypes of non-seminomatous germ cell tumors are:

• Yolk sac tumors.

• Embryonal cell carcinomas.

• Choriocarcinomas.

• Teratomas.

What Are the Clinical Features of Non-seminoma Testicular Cancer?

If there is no other evidence, a solid, firm testicular mass felt during the physical examination should be assumed to be a testicular tumor. A thorough general physical examination is required to detect any signs of systemic spread.

Non-seminoma testicular cancer is associated with the following:

• Male impotence as a result of low sperm count.

• Decreased sperm motility.

• Higher levels of abnormal morphology.

Patients with the localized disease commonly present with,

• Painless nodule.

• An enlarged testis is present.

• Scrotal or testicular dull pain.

• Epididymo-orchitis- If the testicle is swollen, red, or painful, it is probably an infection. Antibiotic-resistant or painless epididymo-orchitis that does not improve after treatment should be diagnosed as testicular cancer.

• Systemic symptoms include lethargy and weight loss.

• Patients suffering from pulmonary spread may exhibit coughing blood or shortness of breath.

• Cervical or supraclavicular lymphadenopathy.

• Patients with retroperitoneal spread frequently experience back pain, varicocele, or lower limb edema because of the testicular vasculature's constriction.

• The symptoms of retro-duodenal spread include nausea, vomiting, and gastrointestinal bleeding.

How to Differentiate Intra-Testicular From Extra-Testicular Lesions?

• A thorough testicular examination will reveal the presence of a solid intra-testicular lesion.

• Gently hold and roll each testis between the fingers to distinguish intra-testicular from extra-testicular lesions.

• It is critical to thoroughly examine the contralateral testis for the presence of a hydrocele.

• The presence of a testicular lesion should be confirmed using ultrasonography.

What Is the Treatment for Non-seminoma Testicular Cancer?

The histopathology and stage of the disease determine the treatment for non-seminoma testicular cancer. Testicular cancer is responsible for 11 % of deaths in men aged 25 to 34, with a five-year survival rate of only 64%. However, the current prognosis after excision and chemotherapy is excellent, with a five-year overall survival rate of approximately 96 percent.

Treatment of the Primary Tumor:

• The conventional surgical treatment for testicular cancer is radical orchiectomy through the inguinal approach. In 75 percent of cases, orchiectomy is the stage I disease curative treatment.

• When there is a possibility of cancer, only an inguinal approach should be used for testicular surgery.

• Since lymphatic drainage from the scrotum differs from the testis, scrotal lymph channels should not be exposed to potential tumor cell contamination.

• In testicular cancer, non-absorbable sutures with a long tail are recommended for tying off the spermatic cord.

• This is to make it easier to locate if a retroperitoneal lymph node dissection is needed.

• When necessary, the patient should be advised to undergo a biopsy of the contralateral testes. Intra-testicular lesions necessitate careful examination, and the diagnosis should be made using both imaging and histopathological techniques.

• In benign conditions, orchiectomy is overtreatment. Low-volume malignant lesions can frequently be treated with organ-sparing surgery. Before any chemotherapy, sperm banking should be encouraged.

Active Surveillance:

Surveillance is aimed at avoiding radio-chemotherapy toxic effects in patients with restricted diseases. Active management entails postponing treatment for relapse after orchiectomy. Relapse occurs in over 35 % of patients, typically caused by undetectable metastases to regional retroperitoneal lymph nodes at the time of orchiectomy.

Following a radical orchiectomy, active surveillance entails a series of:

• Clinical examinations.

• Blood tests.

• Radiological imaging.

• Neoadjuvant Chemotherapy:

• Non-seminomatous testicular cancers are the most vulnerable to cisplatin-based chemotherapy.

• Patients with increased markers are usually treated with three to four cycles of the following agents of chemotherapy:

  1. Bleomycin.

  2. Cisplatin.

  3. Etoposide.

• Following the completion of chemotherapy, tumor markers are retested to see if the values have decreased. In addition, a contrast-enhanced CT scan is taken to look for any residual mass.

• If a mass with regular tumor markers is present, it indicates retroperitoneal lymph node dissection.

• If the markers remain elevated, second-line chemotherapy should be considered with the following:

  1. Vincristine.

  2. Ifosfamide.

  3. Cisplatin.

  4. Gemcitabine.

  5. Etoposide.

  6. Paclitaxel.

  7. Oxaliplatin.

Primary Retroperitoneal Lymphadenectomy-

• The primary treatment for low-stage non-seminoma testicular cancer is retroperitoneal lymph node dissection (RPLND) with adjuvant chemotherapy.

• It is a procedure to stage, diagnose, and treat patients with testicular cancer.

• One of the advantages of retroperitoneal lymph node dissection (RPLND) surgery is that it aids in the identification of patients who may benefit from postoperative chemotherapy.

• Patients with residual lymph nodes one centimeter or larger residual lymph nodes after definitive chemotherapy are generally candidates for retroperitoneal lymph node dissection (RPLND).

• The primary lymph nodes involved in the spread of non-seminoma testicular cancer are the retroperitoneal lymph nodes.

• Removing these draining lymph nodes cures most testicular tumors with retroperitoneal lymph node dissection (RPLND) alone. The cure rate for stage I non-seminoma testicular cancer is approximately 93 to 95 percent. Thus, it is the gold standard for the location of non-seminoma testicular cancer staging and treatment.

• It usually takes three to four hours of surgery and has a mortality rate of less than one percent. However, it entails the dissection of the retroperitoneal lymph nodes, which may result in retrogressive ejaculation, loss of sperm count, and bladder problems due to pelvic nerve disruption during the dissection.

What Is the Treatment Protocol for Non-seminoma Testicular Cancer?

Clinical Stage I -

• This stage accounts for roughly 70 % of all non-seminoma testicular cancer cases. It includes issues where serum markers are regular or returns to their original level after radical orchiectomy.

• The CT scans are negative for lymphatic or organ spread of disease.

• It should be noted that approximately 30 % of these patients will have undetected micrometastases at the time of their orchiectomy. Therefore, radical orchiectomy is curative for the vast majority of patients with stage I disease.

• Optional adjuvant chemotherapy with one to two cycles of chemotherapy lowers the recurrence rate, but it also has toxic side effects.

• Patients with primary testicular tumors with a high percentage of teratoma may benefit the most from retroperitoneal lymph node dissection (RPLND).

Clinical Stage IA -

• Primary tumor - Less than three centimeters in diameter and confined to the testis.

• Active surveillance is a reasonable and recommended option.

Clinical Stage IB -

• Primary tumor - Greater than three centimeters.

• Retroperitoneal lymph node dissection (RPLND) is recommended.

Clinical Stage IIA -

• This stage includes patients whose CT scans show expanded retroperitoneal lymph nodes less than 2 cm in diameter.

Clinical Stage IIB -

• The lymph nodes range in size from two to five centimeters.

• Treatment usually begins with RPLND or primary chemotherapy.

Clinical Stage IIC -

• The initial recommended treatment for this stage is chemotherapy. In such cases, the initial RPLND has a very high relapse rate. However, RPLND can be performed following chemotherapy for any residual retroperitoneal lymphatic tissue.

Clinical Stage III-

• In this stage, the metastatic disease has advanced above the diaphragm.

• Patients are typically classified as low, intermediate, or high risk.

• The risk level is determined by tumor marker levels, the size of metastatic deposits, histology, the size and number of pulmonary metastases, and the presence of cervical lymph node enlargement.

What Are the Side Effects of Chemotherapy in Non-seminoma Testicular Cancer?

Most patients experience azoospermia (no sperm during ejaculation) for at least two to three years after treatment. Cisplatin and other alkylating agents are the most harmful to spermatogenesis, with Sertoli cells being the most sensitive.

Chemotherapy may also cause other side effects, such as:

• Peripheral neuropathy (nerve damage).

• Kidney failure.

• Myelosuppression (bone marrow suppression).

• Hearing loss.

• Increased heart diseases.

• Hypogonadism (decreased function of gonads).

Conclusion

Testicular non-seminomatous germ cell tumor (NSGCT) is a malignancy that can be cured. It is best managed if medical health providers understand its pathogenesis and transmission route. It is a malignant yet treatable tumor if correctly detected and managed. Early detection and treatment are critical because testicular cancer has a high cure rate due to its sensitivity to cisplatin-based chemotherapy and radiation combined with orchiectomy or retroperitoneal lymph node dissection.