Testicular Cancer
Summary of Key Points
Incidence
• One percent of all male malignancies, accounting for 6000 to 8000 new cases a year in the United States
• Most common malignancy among men aged 15 to 35
• Germ cell tumors: 95% of all testicular cancers
• Pure seminoma: 40% of all germ cell tumors
• Nonseminoma: 60% of all germ cell tumors, with embryonal elements most frequent
Diagnosis and Staging Evaluation
• Complete history and physical examination
• Bilateral testicular ultrasonography
• Tumor serum markers (lactate dehydrogenase [LDH], β-human chorionic gonadotropin [β-hCG], and α-fetoprotein [AFP])
• Complete blood count, chemistry studies including renal function
• Computed tomography (CT) of chest, abdomen, and pelvis
• Additional imaging studies as appropriate (e.g., imaging of brain in patient with pure choriocarcinoma)
• Radical (inguinal) orchiectomy (transscrotal biopsy or orchiectomy should be avoided)
Primary Therapy
Seminoma
• Localized disease is curable with orchiectomy alone. Both adjuvant chemotherapy and adjuvant low-dose radiotherapy to lymph nodes can reduce the risk of relapse.
• Locally advanced disease (stage IIA/IIB) is curable in more than 90% of patients with orchiectomy plus radiotherapy to involved nodal areas or with combination chemotherapy.
• Metastatic disease (stage III) or bulky locally advanced disease (stage IIB/IIC) is curable in 90% with combination chemotherapy
• Postchemotherapy retroperitoneal lymphadenectomy can prevent subsequent relapse in select patients
Nonseminoma
• Clinically localized disease is curable with orchiectomy alone in 60% to 87% of patients
• Risk of relapse is decreased with both retroperitoneal lymphadenectomy as well as with adjuvant combination chemotherapy, although in selected patients, surveillance without surgery is a possible option
• Adjuvant combination chemotherapy after lymphadenectomy may further decrease risk of relapse, but does not impact survival
• No bulky locally advanced (stage IIA) disease is cured with retroperitoneal lymphadenectomy alone in up to 65%. Adjuvant chemotherapy after surgery can reduce the risk of relapse for these patients.
• Moderate to bulky nodal disease (stage IIB/C) requires combination chemotherapy
• Metastatic disease (stage III), or bulky locally advanced disease is curable in 80% of patients with combination chemotherapy
• Postchemotherapy retroperitoneal lymphadenectomy can prevent subsequent relapse in selected patients
Effective Second- and Third-Line Therapies
• Chemotherapy salvages about 80% of patients who have failed surgical or radiation therapeutic treatments
• Second-line chemotherapy for patients who have failed prior chemotherapy curative in 20% of patients
• Subsequent high-dose therapy with autologous bone marrow transplant (ABMT)/peripheral stem cell transplant (PSCT) possibly curative in 15% to 20% of those who have failed second-line therapy
1. A 29-year-old man presents with a swollen right testicle. AFP and hCG are both slightly elevated. He undergoes an orchiectomy revealing 60% embryonal cell carcinoma and 40% teratoma. CT scan reveals a 7-cm mass in the interaortocaval space, with no other metastases. He undergoes treatment with BEP × 3 cycles. Eight weeks after the last cycle of chemotherapy when his tumor markers have normalized he undergoes a CT scan, which shows reduction in the retroperitoneal tumor to 2.5 cm. What is the next appropriate step?
A Surveillance with every 6-month abdominal CT scans, tumor markers, and chest x-rays
B Salvage chemotherapy with TIP (taxol, ifosfamide, cisplatin)
C Resection of the retroperitoneal tumor without full node dissection
D Resection of retroperitoneal tumor with full node dissection (RPLND)
2. A 31-year-old man presents with pain in the left testis for 6 months. Ultrasound reveals an 8-cm mass. Tumor markers are minimally elevated. Orchiectomy reveals a mixed NSGCT (40% embryonal cell, 30% yolk sac, 20% teratoma, 10% choriocarcinoma) with lymphovascular invasion. CT scans show no evidence of metastasis and tumor markers normalize after orchiectomy. Based on the presence of lymphovascular invasion you calculate his risk of recurrence to be close to 50%. Appropriate therapy at this point includes all of the following except:
A Active surveillance with abdominal imaging, chest x-ray, and tumor markers every 2 to 3 months initially
B Adjuvant chemotherapy with BEP × 1 cycle
3. A 19-year-old man presents to the emergency room with persistent headaches for 2 months. Examination is significant for an enlarged left testicle. While in the emergency room, he has a witnessed seizure. An MRI reveals a 2-cm left temporal mass. CT scan shows multiple lung metastases. AFP is 250 µg/L and hCG is >50,000 IU/L. A biopsy of the brain mass is most likely to reveal:
1. Answer: D. This patient has for stage II good-risk NSGCT with a large component of teratoma in the testis. Teratoma is generally insensitive to chemotherapy, and it is likely that his retroperitoneal tumor contained elements of both chemotherapy-sensitive GCT as well as chemotherapy-insensitive teratoma. Although slow growing, teratoma has the potential to transform into other more aggressive cancers. A full RPLND should be performed in this case to remove all lymph nodes that potentially contain teratoma. Although surveillance can be an option for men with residual masses less than 1 cm in size, this patient has a high likelihood of eventual progression if followed expectantly. Salvage chemotherapy might be indicated if his tumor markers were still elevated (recall that teratoma does not make AFP or hCG).
2. Answer: C. This patient has for stage I good-risk NSGCT with lymphovascular invasion. A study by the Sweden and Norway Testicular Cancer Project (SWENOTECA) showed that the administration of one cycle of BEP chemotherapy to men with stage I NSGCT with lymphovascular invasion can dramatically reduce the risk of relapse to approximately 3%. Despite the high risk of relapse, surveillance is an option for men who wish to avoid chemotherapy, recognizing that there remains a real risk of growing retroperitoneal disease that would require BEP × 3 cycles in the future. Although less favored, adjuvant RPLND still remains an option for men with stage I disease, especially for those who cannot tolerate or comply with a chemotherapy regimen. Unlike in pure seminoma, radiotherapy has no role in the modern management of NSGCT.
3. Answer: B. Choriocarcinomas and seminomas both produce hCG, however extremely elevated hCG values are less commonly seen in pure seminoma. Choriocarcinoma tends to metastasize systemically, including to the brain. Choriocarcinoma tumors also tend to bleed easily and caution should be used when removing these surgically. A brain MRI is recommended for any patient with a very elevated hCG or with a large component of choriocarcinoma. Yolk sac tumors produce AFP but do not make hCG. Teratoma produces neither AFP nor hCG.
