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Testicular Seminoma Treatment & Management

  • Author: Michael B Williams, MD, MS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
 
Updated: Mar 03, 2016
 

Approach Considerations

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[6] :

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

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. If elevation of serum markers persists, chemotherapy is similar to that used for nonseminomatous GCTs.[6]

Preferred treatments for more advanced stages are as follows:

  • Stage IIA - Radiotherapy
  • Stage IIB - Chemotherapy
  • Stage IIC, III - 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.[6] Even before orchiectomy, however, many men with testicular GCTs have reduced sperm count and sperm motility, as well as increased abnormal sperm morphology.[25]

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Chemotherapy

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.

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.[6]

 

 

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Radiotherapy

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.[6]

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.[6]

For stage I disease, a total dose of 20 Gy is delivered in 10 fractions of external beam radiotherapy.[26] 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.

 

 

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Surgical Care

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.[16]

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 details are as follows:

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

See the list below:

  • Low-stage disease - Radiation oncologist for external beam radiotherapy
  • Advanced disease - Medical oncologist for platinum-based chemotherapy
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Long-Term Monitoring

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.[6]

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.[6]

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
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Contributor Information and Disclosures
Author

Michael B Williams, MD, MS Assistant Professor, Department of Urology, Leroy T Canoles, Jr, Cancer Research Center, Eastern Virginia Medical School

Michael B Williams, MD, MS is a member of the following medical societies: American Association for Cancer Research, American Urological Association, Society of Urologic Oncology, Texas Medical Association, American Society of Clinical Oncology, American Association of Clinical Urologists

Disclosure: Nothing to disclose.

Coauthor(s)

Paul F Schellhammer, MD Professor of Urology, Eastern Virginia Medical School; Urologist, Urology of Virginia, PC

Paul F Schellhammer, MD is a member of the following medical societies: American Medical Association, American Urological Association, Society of Surgical Oncology, Society of Urologic Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

Additional Contributors

Gamal Mostafa Ghoniem, MD, FACS Professor and Vice Chair of Urology, Chief, Division of Female Urology, Pelvic Reconstructive Surgery, and Voiding Dysfunction, Department of Urology, University of California, Irvine, School of Medicine

Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American Urogynecologic Society, International Continence Society, International Urogynaecology Association, Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, American College of Surgeons, American Urological Association

Disclosure: Received honoraria from Astellas for speaking and teaching; Received grant/research funds from Uroplasty for none; Partner received honoraria from Allergan for speaking and teaching.

Acknowledgements

John W Davis, MD Assistant Professor, Department of Urology, University of Texas MD Anderson Cancer Center

John W Davis, MD is a member of the following medical societies: American College of Surgeons and American Urological Association

Disclosure: Nothing to disclose.

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

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Testicular seminoma. A 57-year-old man presents with abdominal pain of slow onset. CT scanning shows a large 25-cm retroperitoneal lesion encompassing the aorta and renal vasculature and displacing the right kidney laterally. The patient had a history of cryptorchidism repaired at age 8 years. Testes were normal and descended; however, ultrasonography showed a small 5-mm lesion on the right testis, which proved to be pure seminoma at orchiectomy. The beta-human chorionic gonadotropin level was 70 mIU/mL (reference range, &lt; 5 mIU/mL), and the alpha-fetoprotein level was within the reference range; no metastatic lesions were observed above the diaphragm, indicating stage IIb (bulky), T1N3M0. The patient was referred for 4 cycles of cisplatin-based chemotherapy.
Testicular seminoma. This scrotal ultrasound of a 37-year-old man with a painless mass in his right testis shows a right testis with hypoechoic solid masses compared to the homogeneous, more hyperechoic, healthy left testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free.
Testicular seminoma. This is a classic seminoma at low power. Uniform tumor cells are observed with mild inflammatory response (lymphocytes). Other seminoma findings not seen could include a fibrovascular stroma, syncytiotrophoblastic cells, and multinucleated histiocytes.
This is a classic testicular seminoma, high-power view, from a 37-year-old man with a painless mass in his right testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free. See related image for a scrotal sonogram of this patient. Note here that tumor cells are uniform, have abundant clear cytoplasm, a large centrally located nucleus, and a variable mitotic pattern.
Table 1. Primary Tumor (T)
pTx Primary tumor cannot be assessed
p0 No evidence of primary tumor
pTis Intratubular germ cell neoplasia
pT1 Tumor limited to the testis and epididymis
No vascular/lymphatic invasion
May invade the tunica albuginea
No invasion of the tunica vaginalis
pT2 Tumor limited to the testis and epididymis
Vascular/lymphatic invasion or tumor extending through the tunica albuginea with involvement of the tunica vaginalis
Invades beyond the tunica albuginea or into the epididymis
pT3 Tumor invades the spermatic cord with or without vascular/lymphatic invasion
pT4 Tumor invades the scrotum with or without vascular/lymphatic invasion
Table 2A. Regional Lymph Nodes (N): Clinical
Nx Nodes not assessed
N0 No regional lymph node metastasis
N1 Lymph node mass or multiple lymph node masses ≤ 2 cm in greatest dimension
N2 Lymph node mass or multiple lymph node masses >2 cm but ≤ 5 cm in greatest dimension
N3 Lymph node mass >5 cm in greatest dimension
Table 2B. Regional Lymph Nodes (N): Pathologic
pN0 No evidence of tumor in lymph nodes
pN1 Lymph node mass ≤ 2 cm in greatest dimension
≤ 5 nodes positive
pN2 Lymph node mass >2 cm but < 5 cm in greatest dimension
>5 nodes positive
Evidence of extranodal extension of tumor
pN3 Lymph node mass >5 cm in greatest dimension
Table 3. Distant Metastases (M)
M0 No evidence of distant metastases
M1a Nonregional nodal or pulmonary metastases
M2b Nonpulmonary visceral metastases
Table 4. Serum Tumor Markers (S)
S LDH hCG† (mIU/mL) AFP (ng/mL)
Sx Not assessed Not assessed Not assessed
S0 ≤ N and Normal and Normal
S1 < 1.5 x N and < 5,000 and < 1,000
S2 1.5-10 x N or 5,000-50,000 or 1,000-10,000
S3 >10 x N or >50,000 or >10,000
Table 5. Stage Grouping
Stage grouping T N M S
Stage 0 pTis N0 M0 S0
Stage I T1-T4 N0 M0 Sx
Stage IA T1 N0 M0 S0
Stage IB T2-4 N0 M0 S0
Stage IS Any T N0 M0 S1-S3
Stage II Any T Any N M0 Sx
Stage IIA Any T N1 M0 S0-S1
Stage IIB Any T N2 M0 S0-S1
Stage IIC Any T N3 M0 S0-S1
Stage III Any T Any N M1 Sx
Stage IIIA Any T Any N M1a S0-S1
Stage IIIB Any T Any N M0-M1a S2
Stage IIIC Any T Any N M0-M1a S3
Any T Any N M1b Any S
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