Testicular Seminoma Treatment & Management

In testicular seminoma, orchiectomy provides both diagnosis and therapy (see Surgical Care). Orchiectomy alone cures most stage I seminomas.

To prevent relapse, the National Comprehensive Cancer Network (NCCN) recommends the following as standard options in stage I disease ^[1] :

• Surveillance (preferred option for pT1-pT3 tumors)
• Single-agent carboplatin (one or two cycles)
• Radiotherapy (20 Gy, preferred or 25.5 Gy)

The NCCN cautions that stage IS pure seminoma is very uncommon. Because persistent elevation of serum tumor markers usually indicates metastatic disease, the NCCN recommends performing abdominal/pelvic computed tomography (CT) to determine the extent of disease. ^[1]

Preferred treatments for more advanced stages are as follows:

• Stage IIA - Radiotherapy or chemotherapy with bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin (EP) 
• Stage IIB - Chemotherapy (preferred) with BEP or EP or radiotherapy in select non-bulky (≤3 cm) cases
• Stage IIC, III (good risk) - Chemotherapy with BEP (category 1) or EP (category 1)
• Stage IIC, III (high risk) - Chemotherapy with BEP (category 1) or etoposide, mesna, ifosfamide and cisplatin (VIP)

Retroperitoneal lymph node dissection (RPLND) without adjuvant treatment is being studied as a first-line option for testicular seminoma that has spread to retroperitoneal lymph nodes, with the goal of reducing long-term toxicity and secondary malignancies. In the PRIMETEST trial, a prospective phase II study in 33 patients with clinical stage IIA/B seminoma (unilateral retroperitoneal lymph node metastases < 5 cm and human chorionic gonadotropin levels < 5 mU/mL), the progression-free survival (PFS) rate was 70% on median follow-up of 32 months; this failed to meet the study's primary endpoint primary endpoint of PFS < 30% after 36 months, but the authors suggest that RPLND may be of interest for highly selected patients. ^[29]

Another prospective phase II study of RPLND, in 55 patients with testicular seminoma and isolated retroperitoneal lymphadenopathy (nodes 1-3 cm), reported (12.0-61.6) a 2-year recurrence-free survival rate of 81% and a recurrence rate of 22% on median follow-up of 33 months. The patients who experienced recurrence received treatment with chemotherapy or additional surgery and at last follow-up, all were disease free and the 2-year overall survival was 100%. These authors conclude that RPLND is a treatment option in this setting, with low long-term morbidity. ^[30]

An ongoing study, the Surgery in Early Metastatic Seminoma (SEMS) trial, will assess recurrence-free survival at 2 years in patients who undergo RPLND as first-line treatment for testicular seminoma with low-volume (≤2 cm) retroperitoneal disease. The trial will also assess the percent of those patients who can avoid external beam radiotherapy or systemic chemotherapy.

Sperm banking should be discussed in patients of reproductive age. The discussion should take place before the patient undergoes any procedure that may compromise fertility, including orchiectomy. If the patient desires sperm banking, it may be performed before or after surgery, but must be performed before radiation therapy or chemotherapy. ^[1] Even before orchiectomy, however, many men with testicular GCTs have reduced sperm count and sperm motility, as well as increased abnormal sperm morphology. ^[31]

Chemotherapy for stage IA and IB testicular germinoma is with single-agent carboplatin. The dosage is area under the curve (AUC)=7 for one or two cycles. ^[1]

For stage II or III disease, the recommended chemotherapy regimen is etoposide plus cisplatin (EP) for four cycles, or bleomycin, etoposide, and cisplatin (BEP) for three cycles. Radiotherapy is preferred for primary therapy in stage IIA, while chemotherapy is preferred in stage IIB and in both good-risk and intermediate-risk stage IIC and III disease. For stage IIA, the presence of multiple positive lymph nodes is an indication for BEP. ^[1]

Current radiotherapy for testicular germinoma uses smaller fields and lower doses than in the past. Radiotherapy should started once the orchiectomy wound has fully healed, and should be given five times per week. ^[1]

Short-term adverse effects of radiotherapy include fatigue, nausea, and vomiting. Antiemetic medication significantly improves nausea and should be given at least 2 hours before each radiation treatment. ^[1]

For stage I disease, a total dose of 20 Gy is delivered in 10 fractions of external beam radiotherapy. ^[32] Targets include the para-aortic and ipsilateral pelvic nodes or the para-aortic nodes alone. Radiotherapy is not preferred for stage I disease, as long-term follow-up studies indicate an increase in late toxicities.

For stage IIA disease, radiotherapy is preferred for primary therapy. The total dose is 30 Gy and the field includes the para-aortic and ipsilateral iliac lymph nodes. For stage IIB disease, chemotherapy is preferred, but radiotherapy may be indicated in select cases of non-bulky disease. The total dose is 36 Gy and the field includes the para-aortic and ipsilateral iliac lymph nodes. ^[1]

Relevant anatomy

Seminoma arises from abnormal germ cells in the seminiferous tubules. The TNM staging system (see Staging) stages the tumor based on its local, regional, and distant invasion. ^[11]

Testicular lymphatics relate to the embryonic origin of the testis. The male gonad initially forms near the kidney and descends through the inguinal canal to the scrotal sac. The right gonadal vein derives from the inferior cava, while the left gonadal vein derives from the left renal vein. Additional blood supply derives from the artery of the vas and the cremasteric arteries.

Testicular lymphatics follow the vessels of the spermatic cord through the inguinal canal and into the retroperitoneum. Testicular cancer spreads predominantly and initially through lymphatic routes. On the right, the cancer landing zone is between the aorta and the inferior vena cava; on the left, it is on top of and lateral to the aorta. Within the retroperitoneum, there can be a crossover from the lymphatics draining the right toward those of the left.

Scrotal skin lymphatics are different from testicular lymphatics and drain into the inguinal nodes. Perform all orchiectomies for solid masses through an inguinal route to avoid tumor spillage into the inguinal drainage basin. If a patient undergoes scrotal exploration, subsequent therapy may necessitate hemiscrotectomy and radiation treatment of the inguinal nodes. In patients who have undergone prior herniorrhaphy, orchiopexy, or other alteration in lymphatic drainage, extend their radiation field to include the contralateral inguinal region with contralateral testis shielding.

Radical inguinal orchiectomy

Preoperative details include the following:

• Draw serum tumor markers preoperatively because values fall rapidly after orchiectomy; other staging tests can be performed preoperatively or postoperatively.

• Because of the rapid doubling time of a potential choriocarcinoma, schedule surgery for testis tumors rapidly to avoid upstaging.

• Most patients with seminoma are young and healthy and require only routine preoperative preparation.

• Discuss semen donation for subsequent fertility if the function of the contralateral testis is in question; however, many patients have poor semen quality that improves after orchiectomy.

• Cosmetic testicular prostheses are currently available from Coloplast (formerly Mentor). The saline-filled testicular prosthesis has been FDA-approved since 2002 and can be implanted in an outpatient setting if desired by the patient.

• If a patient presents with symptomatic metastatic lesions from a testis tumor, proceed with platinum-based chemotherapy and delay radical orchiectomy. Radical orchiectomy is not a morbid procedure, but it may delay initiation of chemotherapy.

• Differentiation of seminoma versus nonseminomatous germ cell tumor (NSGCT) for advanced disease is not important at the outset of treatment because both groups receive the same regimen.

• Although chemotherapy may result in disappearance of the testicular mass, orchiectomy is always indicated.

Intraoperative details are as follows:

• Spinal, general, or (uncommonly) local anesthesia may be used

• Shave the inguinal area, and prep in a standard fashion.

• Create an inguinal incision to allow exposure of the external and internal iliac canal.

• Open the external iliac fascia, exposing the spermatic cord and internal iliac canal. Control the spermatic cord with a Penrose drain in a tourniquet fashion to stop retroperitoneal lymphatic and venous drainage of tumor cells.

• Then, deliver the testis from the scrotum and ligate separately the vas deferens and spermatic arteries.

• Leave a long nonabsorbable tie on the patient side of the spermatic cord. This is to facilitate identification if retroperitoneal lymph node dissection (RPLND) becomes necessary and the patient requires dissection of the remaining spermatic cord structures from the abdominal exposure.

• Reapproximate the external oblique fascia and close the skin in standard fashion.

Postoperative care

Radical orchiectomy is usually performed on an outpatient or 23-hour admission basis, often accompanied by the staging workup. Conduct a follow-up study by staging and referring the patient for appropriate adjuvant therapies.

This surgery is comparable to an inguinal herniorrhaphy, and the patient can expect limited physical activity for a brief period after surgery. A short course of pain management medication may be indicated postoperatively.

Complications are rare but may include wound infection, inguinal skin numbness due to injury to the genitofemoral nerve, hematoma, and standard anesthetic risks.

For low-stage disease, a radiation oncologist should be consulted for external beam radiotherapy; for advanced disease consultation with a medical oncologist for platinum-based chemotherapy is beneficial.

Males should begin monthly testicular self-examinations starting at puberty. Any abnormalities found should be reported to their physician.

After diagnosis of testicular GCT, the patient and treating physician should come to a mutual understanding regarding strict adherence to follow-up regimens to monitor for tumor recurrence.

Follow-up care for testicular seminoma depends on the pathology, as outlined in Treatment. National Comprehensive Cancer Network (NCCN) follkow-up schedules take into account that relapse in stage I seminoma occurs at a median of 14 months, with the great majority occurring within 3 years. ^[1]

Recommendations for surveillance in patients with stage I seminoma include regular history and physical examination (H&P), with testicular ultrasound for equivocal exam, along with abdominal computed tomography (CT) scans, with or without pelvic CT, and chest x-rays; serum tumor markers are optional. Chest x-rays should be performed as clinically indicated with chest CT considered in symptomatic patients. ^[1]

For patients who have undergone orchiectomy only, the schedule is as follows:

• Year 1: H&P every 3-6 mo, CT at 3, 6, and 12 mo
• Years 2 and 3: H&P and CT every 6-12 mo
• Years 4 and 5: H&P annually, C every 12-24 mo

For patients who have received adjuvant chemotherapy or radiation,  the schedule is as follows:

• Years 1 and 2: H&P every 6-12 mo, CT annually
• Year 3: H&P and CT annually
• Years 4 and 5: H&P annually

For patients with stage IIA and non-bulky IIB seminoma who have gone through chemotherapy or radiotherapy, with no residual mass or residual mess < 3 cm and normal serum tumor marker levels, surveillance consists of H&P, with testicular ultrasound for equivocal exam, abdominal CT scans with or without pelvic scans. Chest x-rays are used for routine follow-up, but chest CT is preferred if thoracic symptoms are present. Serum tumor markers are optional. The schedule is as follows:

• Year 1: H&P every 3 mo, CT at 3, 6, and 12 mo, chest x-ray every 6 mo
• Year 2: H&P every 6 mo, CT annually, chest x-ray every 6 mo
• Year 3: H&P every 6 mo, CT annually
• Years 4 and 5: H&P every 6 mo, CT as clinically indicated

For patients with bulky stage IIB, IIC, and stage III seminoma who have gone through chemotherapy and have no residual mass, or residual mass ≤3 cm and normal serum marker levels, surveillance consists of H&P, with testicular ultrasound for equivocal exam, and serum tumor marker assays. Abdominal CT scans, with or without pelvic scans, are performed at 3-6 mo, then as clinically indicated, and positron emission tomography (PET) scans are performed as clinically indicated. Chest x-rays are used for routine follow-up, but chest CT is preferred if thoracic symptoms are present. The schedule for H&P and chest x-ray is as follows:

• Year 1: H&P, markers, and chest x-ray every 2 mo
• Year 2: H&P, markers, and chest x-ray every 3 mo
• Years 3 and 4: H&P and markers every 6 mo, chest x-ray annually
• Year 5: H&P, markers, and chest x-ray annually