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Pathology: Seminoma Pure seminoma accounts for 47% of all testis cancer patients (50% of patients with cryptorchidism have seminoma). More than 90% of the cases of pure seminoma are of the subtype called classic. These patients usually present with disease in the fourth or fifth decade. Approximately 75% of them present with stage I disease. Such patients may have modest elevations of serum beta -human chorionic gonadotropin (beta -HCG). It is worth noting that any elevation of alpha-fetoprotein connotes the presence of nonseminomatous germ cell tumor. Spermatocytic seminoma accounts for 7% of all seminomas. The median age of presentation is in the sixth and seventh decade of life. Because metastases are extraordinarily rare, orchiectomy is the only required treatment.
Pathology: Non seminomatous Germ Cell Tumors Embryonal carcinoma Yolk sac carcinoma Choriocarcinoma Teratoma
Staging of GCTs • Stage I – Testis only, T1 • Stage II – T2-4, vascular or lymphatic invasion present • Stage IIA – nodes <2 cm • Stage IIB – nodes 2-5 cm • Stage IIC – nodes >5 cm • Stage III – Distant metastases
Primary Germ Cell Tumors of the testis • Usually present with painless testicular mass • Retroperitoneal mets can cause back pain • Pulmonary mets can cause dyspnea • Initial test if suspicious for malignancy - testicular ultrasound • Staging CT of abd/pelvis, chest if X-ray abnormal
Diagnosis- Ultrasound. Most patients with testicular cancer present with a painless scrotal mass. This mass may be confused with epididymitis, particularly when pain is noted. Careful attention on physical examination, should generally discern a testicular mass from epididymitis. Testicular ultrasound will confirm the findings. Translumination of the testis may determine if the patient has a hydrocele; however, about 20% of patients with germ cell tumors of the testis will have a hydrocele. Testicular ultrasound is one of the most useful tools to evaluate a testicular mass. Findings reveal solitary or multiple hyperechoic lesions. Small areas of speckled calcifications suggest carcinoma in situ. Over 95% of patients with testicular mass will have malignant pathology.
Presenting signs of testicular cancer. Patients with retroperitoneal spread of tumor may present with back pain, usually in the lumbar region. Further lymphatic spread to supraclavicular lymph nodes (Virchow’s node) have also be seen. Patients with advanced pulmonary disease may have cough, shortness of breath, and hemoptysis. Disease spread to the central nervous system and bone is rare; thus, routine screening by radiograph or radionuclide scans is unnecessary in the absence of symptoms. Some patients present with gynecomastia. Although common in adolescents, new onset of gynecomastia in young adults should suggest germ cell malignancy or other endocrine abnormalities
Diagnosis and treatment are closely tied. The preferred approach in a patient with a testicular mass is a radical orchiectomy using the inguinal approach. Fine-needle aspiration or trans-scrotal biopsy is contraindicated because they can cause aberrant spread of tumor to inguinal and iliac lymph node chains. Chest radiography should be performed to rule out the possibility of pulmonary disease. If negative, CT of the chest should be performed. An abdominal CT scan should be done to evaluate the retroperitoneal lymph nodes.
Serum beta -human chorionic gonadotropin ( beta-HCG) and alpha-fetoprotein (AFP) levels are elevated in about 85% of the patients with disseminated germ cell tumor. These markers are useful diagnostically and therapeutically. In a patient with pathologic stage I testicular cancer, an orchiectomy should result in the reduction of serum HCG and AFP levels according to their half lives (1 day and 5 days, respectively). During treatment with chemotherapy, at least a one log reduction of serum beta-HCG should occur every 3 weeks. Patients with elevated AFP have a less predictable decline.
EARLY STAGE DISEASE Radiation therapy Radiation therapy is usually used in patients with seminoma who have stage I or early stage II disease. Most patients with stage I seminoma can be successfully treated with the total dose of 2500 to 3500 cGy to a target area, which includes the periaortic region from approximately the 11th thoracic vertebrae to the lumbar region and extends to the ipsilateral hemipelvis to include external iliac lymph nodes. Routine radiation to the orchiectomy scar or to the testis is not routinely performed. Bulky stage II disease is usually treated with moderately higher dosages of 35 to 40 cGy or alternatively with systemic chemotherapy.
EARLY STAGE DISEASE Surgery Retroperitoneal lymphadenectomy. Retroperitoneal surgery for metastatic testis cancer consists of two primary operations. In low stage disease, a modified template of dissection is used contingent upon the side of the primary tumor. Hence, the field of dissection for a right-sided testicular tumor includes the right paracaval and interaortocaval regions. For a left testicular primary, the field includes the left periaortic and preaortic lymphatics. The ipsilateral sympathetics are preserved to guarantee maintenance of emission and ejaculation postoperatively
EARLY STAGE DISEASE Surgery For early-stage (clinical stage I, IIa or IIb) nonseminomatous germ cell tumor, retroperitoneal lymphadenectomy has been the mainstay of treatment for most of the past century. The success of surgery has been predicated on the observation that testis cancer travels at a predictable pattern from the testis to the retroperitoneum before developing systemic metastases. Surgical operations have evolved from a variety of templates to minimize complications of retrograde ejaculation.
For patients with low-volume disease (3 cm in cross-sectional diameter) and normal (or within predicted half life) serum markers, the primary retroperitoneal lymph node dissection (RPLND) is preferred treatment. In such patients, RPLND will result in cures of approximately 70%, without additional therapy. In patients with completely resected disease but with metastasis to lymph nodes, adjuvant chemotherapy can be considered. Two cycles of BEP (bleomycin, etoposide, Platinol) in such patients should reduce the relapse rate to around 1%. If observed without adjuvant therapy, approximately 30% of patients have recurrence, but three cycles of BEP should produce virtually a 100% cure rate for those with relapsing disease. For patients with rising markers following orchiectomy or with retroperitoneal disease greater than 3 cm in cross-sectional diameter (clinical stage B2 disease), primary chemotherapy is indicated. In the absence of disease above the diaphragm and with serum beta-human chorionic gonadotropin and alpha-fetoprotein below 5000 IU/L and 1000 ng/mL, respectively, three cycles of BEP or four cycles of EP (etoposide, Platinol) are standard therapy.
BEP (bleomycin, etoposide, Platinol) for treatment of stage C disease Patients withdisseminated disease are treated with cisplatin-based combination chemotherapy. As mentioned earlier, various staging systems have been used over the years to categorize patients with disseminated germ cell tumors. Patients with good-risk disease can be treated with three cycles of BEP or four cycles of EP (etoposide, Platinol). In a recent randomized, prospective trial, no therapeutic differences were observed between the two regimens, with slightly greater hematologic toxicity associated with the four cycles of EP. For patients with intermediate and advanced disease, the cure rate is lower. As such, these patients are candidates for potentially more aggressive therapy. The standard treatment approach is four cycles of BEP. For patients with underlying pulmonary disease, substitution of ifosfamide for bleomycin (VIP) is reasonable. VIP therapy has an equivalent therapeutic outcome to BEP, but has slightly greater hematologic toxicity.
Postchemotherapy retroperitoneal lymph node dissection (RPLND). RPLND is another operation for metastatic testicular tumors. This procedure is performed for residual retroperitoneal tumor after administration of chemotherapy for metastatic testis cancer. The metastatic tumor can be very adherent to the great vessels and other structures; thus, proper tissue planes are difficult to determine. Specialized vascular techniques are sometimes necessary to completely resect the retroperitoneal tumor, but complete resection of all tumor is essential to ensure a good outcome.
Results of studies on salvage therapy Salvage therapy is indicated for patients who relapse from complete remission or who have an incomplete partial response to primary chemotherapy. Ifosfamide salvage therapy. VeIP (vinblastine, ifosfamide, and cisplatin) produces durable complete remissions in about 25% to 30% of patients with recurrent nonseminomatous germ cell tumor (NSGCT) treated with second-line therapy. In patients with recurrent seminoma, VeIP chemotherapy will produce durable complete remissions in approximately 50% of patients. High-dose chemotherapy with carboplatin and etoposide with peripheral stem cell rescue will produce durable complete remissions in approximately 50% of patients as second-line therapy. For patients with relapsing NSGCT, this is preferred in salvage therapy. Patients who are candidates for salvage therapy have mixed prognostic factors. Patients with pure seminoma or longer relapse-free intervals (but < 2 years) have better prognosis than those patients whose tumors progress on cisplatin, multiple regimens, or mediastinal primary tumors.
