General Medical Information

Testicular Cancer

April 21, 2007 on 9:45 pm | In Cancer |

Testicular cancer is a highly treatable, often curable cancer that usually develops in young and middle-aged men. Testicular cancer is broadly divided into seminoma and nonseminoma types for treatment planning because seminomas are more sensitive to radiation therapy. For patients with seminoma (all stages combined), the cure rate exceeds 90%. For patients with low-stage disease, the cure rate approaches 100%.[1]

Tumors which have a mixture of seminoma and nonseminoma components should be managed as nonseminoma. Nonseminoma includes embryonal carcinoma, teratoma, yolk sac carcinoma and choriocarcinoma, and various combinations of these cell types. Tumors that appear to have a seminoma histology but that have elevated serum levels of alpha fetoprotein (AFP) should be treated as nonseminomas. Elevation of the beta subunit of human chorionic gonadotropin (HCG) alone is found in approximately 10% of patients with pure seminoma.

Risk of metastases is lowest for teratoma and highest for choriocarcinoma, with the other cell types being intermediate.

A number of prognostic classification schema are in use for metastatic nonseminomatous testicular cancer and for primary extragonadal nonseminomatous germ cell cancers treated with chemotherapy.[2-4] Most incorporate some or all of the following factors which may independently predict worse prognosis:

1. presence of liver, bone, or brain metastases
2. very high serum markers
3. primary mediastinal nonseminoma
4. large number of lung metastases

It is important to note that even patients with widespread metastases at presentation, including those with brain metastases, may still be curable and should be treated with this intent.[5]

Radical inguinal orchiectomy with initial high ligation of the spermatic cord is the procedure of choice in diagnostically evaluating a testicular mass.[6] Transscrotal biopsy is not considered appropriate because of the risk of local dissemination of tumor into the scrotum or spread to inguinal lymph nodes. A retrospective analysis of reported series in which transscrotal approaches had been used showed a small but statistically significant increase in local recurrence rates compared to the inguinal approach (2.9% versus 0.4%).[7][Level of evidence: 3iiiDi] However, distant recurrence and survival rates were indistinguishable in the 2 approaches. Local recurrence was similar in patients who did not have scrotal violation, regardless of whether or not additional treatments, such as hemiscrotal radiation, hemiscrotal resection, or inguinal lymph node dissection, were used.

An important aspect of the diagnosis and follow-up of testicular cancer is the use of serum markers. Serum markers include AFP, HCG (measurement of the beta subunit reduces luteinizing hormone (LH) cross-reactivity), and lactate dehydrogenase (LDH). They may detect a tumor which is too small to be detected on physical examination or x-rays. Below the age of 15, about 90% of testicular germ cell cancers are yolk sac tumors. In virtually all of these patients, the AFP is elevated at diagnosis and is an excellent indicator of response to therapy and disease status.[8] Serum markers plus chest x-rays are important parts of the monthly checkups for patients after definitive therapy of testicular cancer as well as periodic abdominal computed tomographic (CT) scans for 2 to 3 years. The absence of markers does not mean the absence of tumor. Patients typically receive follow-up monthly for the first year and every other month for the second year after diagnosis and treatment. While the majority of tumor recurrences appear within 2 years, late relapse has been reported and lifelong marker, radiologic, and physical examination is recommended.[9]

Evaluation of the retroperitoneal lymph nodes is an important aspect of treatment planning in adults with testicular cancer. These nodes are usually evaluated by CT scanning.[10,11] However, patients with a negative result have a 25% to 30% chance of having microscopic involvement of the lymph nodes. For seminoma, some physicians think that knowing the results of both the lymphangiogram and the CT scan is important for treatment planning. However, for nonseminoma, the inaccuracy of both is a problem and frequently surgical staging is required. About a quarter of patients with clinical stage I nonseminomatous testicular cancer will be upstaged to pathologic stage II with retroperitoneal lymph node dissection (RPLND), and about a quarter of clinical stage II patients will be downstaged to pathologic stage I with RPLND.[12] In children, the use of serial measurements of AFP has proven sufficient for monitoring response after initial orchiectomy. Lymphangiography and para-aortic lymph node dissection do not appear to be useful or necessary in the proper staging and management of these patients.[8]

Patients who have been cured of testicular cancer have approximately a 2% to 5% cumulative risk of developing a cancer in the opposite testicle over the 25 years after initial diagnosis.[13,14] However, in a single series, the risk of a second cancer in the opposite testicle was not increased in patients who had been treated with chemotherapy for their original tumor.[15] There have been reports that HIV-infected men are at increased risk of developing testicular germ cell cancer.[16] Depending on co-morbid conditions such as active infection, these men are generally managed similarly to non-HIV-infected patients.

Since the majority of testis cancer patients who receive chemotherapy are curable, it is important to be aware of possible long-term effects of platinum-based treatment:

1. Fertility: Many patients have oligospermia or sperm abnormalities prior to therapy. Virtually all become oligospermic during chemotherapy. However, many recover sperm production and can father children. The children do not appear to have an increased risk of congenital malformations.[17-20]

2. Secondary leukemias: Several reports of elevated risk of secondary acute leukemia, primarily non-lymphocytic, have appeared.[21] In some cases, they were associated with the prolonged use of alkylating agents or with the use of radiation.[22,23] Etoposide-containing regimens are also associated with a risk of secondary acute leukemias, usually in the myeloid lineage, and with a characteristic 11q23 translocation.[24-27] Etoposide-associated leukemias typically occur earlier after therapy than alkylating agent-associated leukemias and often show balanced chromosomal translocations on the long arm of chromosome 11.[24] Standard etoposide dosages (<2 grams per square meter cumulative dose) are associated with a relative risk of 15 to 25, but this translates into a cumulative incidence of leukemia of less than 0.5% at 5 years. Preliminary data suggest that cumulative doses of greater than 2 grams per square meter of etoposide may confer higher risk.

3. Renal function: Minor decreases in creatinine clearance occur (about a 15% decrease, on average) during platinum-based therapy, but these appear to remain stable in the long term, without significant deterioration.[28]

4. Hearing: Bilateral hearing deficits occur with cisplatin-based chemotherapy, but they generally occur at sound frequencies of 4 to 8 kilohertz, outside the range of conversational tones.[28] Therefore, hearing aids are rarely required at standard doses of cisplatin.

Although bleomycin pulmonary toxic effects may occur, it is rarely fatal at total cumulative doses below 400 units. However, because life-threatening pulmonary toxic effects can occur, the drug should be discontinued if early signs of pulmonary toxic effects develop. Although decreases in pulmonary function are frequent, they are rarely symptomatic and are reversible after the completion of chemotherapy. There has been a report that men treated curatively for germ cell tumors with cisplatin-based regimens have had elevations in total serum cholesterol.[29] However, this could not be confirmed in another study.[30] No clear long-term effects on coronary artery disease have been shown.

Radiation therapy, often used in the management of pure seminomatous germ cell cancers, has been linked to the development of secondary cancers, especially solid tumors in the radiation portal, usually after a latency period of a decade or more.[21,24] These include cancers of the stomach, bladder, colon, rectum, and possibly the pancreas.

Many patients have oligospermia or sperm abnormalities prior to therapy. Radiation therapy, used to treat pure seminomatous testicular cancers, can cause fertility problems due to radiation scatter to the remaining testicle during radiation to retroperitoneal lymph nodes.[31] Depending on scatter dose, sperm counts fall after radiation, but may recover over the course of 1 to 2 years. Shielding techniques can be used to decrease the radiation scatter to the remaining normal testicle. As with treatment with chemotherapy, some men have been reported to father children after radiation treatment of seminoma, and the children do not appear to have a high risk of congenital malformations.[31]

Though testicular cancer is highly curable, all newly diagnosed patients are appropriately considered candidates for clinical trials designed to decrease morbidity of treatment while further improving cure rates.

References

1. Bosl GJ, Bajorin DF, Sheinfeld J, et al.: Cancer of the testis. In: DeVita VT, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001, pp 1491-1518.

2. Bajorin DF, Bosl GJ: The use of serum tumor markers in the prognosis and treatment of germ cell tumors. Cancer: Principles and Practice of Oncology Updates 6(1): 1-11, 1992.

3. Mead GM, Stenning SP, Parkinson MC, et al.: The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party. J Clin Oncol 10 (1): 85-94, 1992.

4. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15 (2): 594-603, 1997.

5. Spears WT, Morphis JG, Lester SG, et al.: Brain metastases and testicular tumors: long-term survival. Int J Radiat Oncol Biol Phys 22 (1): 17-22, 1992.

6. Leibovitch I, Baniel J, Foster RS, et al.: The clinical implications of procedural deviations during orchiectomy for nonseminomatous testis cancer. J Urol 154 (3): 935-9, 1995.

7. Capelouto CC, Clark PE, Ransil BJ, et al.: A review of scrotal violation in testicular cancer: is adjuvant local therapy necessary? J Urol 153 (3 Pt 2): 981-5, 1995.

8. Huddart SN, Mann JR, Gornall P, et al.: The UK Children’s Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.

9. Gerl A, Clemm C, Schmeller N, et al.: Late relapse of germ cell tumors after cisplatin-based chemotherapy. Ann Oncol 8 (1): 41-7, 1997.

10. Socinski MA, Stomper PC: Radiologic evaluation of nonseminomatous germ cell tumor of the testis. Semin Urol 6 (3): 203-15, 1988.

11. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.

12. Donohue JP, Thornhill JA, Foster RS, et al.: The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 153 (1): 85-9, 1995.

13. Osterlind A, Berthelsen JG, Abildgaard N, et al.: Risk of bilateral testicular germ cell cancer in Denmark: 1960-1984. J Natl Cancer Inst 83 (19): 1391-5, 1991.

14. Colls BM, Harvey VJ, Skelton L, et al.: Bilateral germ cell testicular tumors in New Zealand: experience in Auckland and Christchurch 1978-1994. J Clin Oncol 14 (7): 2061-5, 1996.

15. van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW, et al.: Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol 11 (3): 415-24, 1993.

16. Foster RS, Donohue JP: Surgical treatment of clinical stage A nonseminomatous testis cancer. Semin Oncol 19 (2): 166-70, 1992.

17. Drasga RE, Einhorn LH, Williams SD, et al.: Fertility after chemotherapy for testicular cancer. J Clin Oncol 1 (3): 179-83, 1983.

18. Nijman JM, Schraffordt Koops H, Kremer J, et al.: Gonadal function after surgery and chemotherapy in men with stage II and III nonseminomatous testicular tumors. J Clin Oncol 5 (4): 651-6, 1987.

19. Hansen PV, Trykker H, Helkjoer PE, et al.: Testicular function in patients with testicular cancer treated with orchiectomy alone or orchiectomy plus cisplatin-based chemotherapy. J Natl Cancer Inst 81 (16): 1246-50, 1989.

20. Stephenson WT, Poirier SM, Rubin L, et al.: Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin. J Clin Oncol 13 (9): 2278-80, 1995.

21. Travis LB, Curtis RE, Storm H, et al.: Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst 89 (19): 1429-39, 1997.

22. Redman JR, Vugrin D, Arlin ZA, et al.: Leukemia following treatment of germ cell tumors in men. J Clin Oncol 2 (10): 1080-7, 1984.

23. Travis LB, Andersson M, Gospodarowicz M, et al.: Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 92 (14): 1165-71, 2000.

24. Bokemeyer C, Schmoll HJ: Treatment of testicular cancer and the development of secondary malignancies. J Clin Oncol 13 (1): 283-92, 1995.

25. Pedersen-Bjergaard J, Daugaard G, Hansen SW, et al.: Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 338 (8763): 359-63, 1991.

26. Nichols CR, Breeden ES, Loehrer PJ, et al.: Secondary leukemia associated with a conventional dose of etoposide: review of serial germ cell tumor protocols. J Natl Cancer Inst 85 (1): 36-40, 1993.

27. Bajorin DF, Motzer RJ, Rodriguez E, et al.: Acute nonlymphocytic leukemia in germ cell tumor patients treated with etoposide-containing chemotherapy. J Natl Cancer Inst 85 (1): 60-2, 1993.

28. Osanto S, Bukman A, Van Hoek F, et al.: Long-term effects of chemotherapy in patients with testicular cancer. J Clin Oncol 10 (4): 574-9, 1992.

29. Raghavan D, Cox K, Childs A, et al.: Hypercholesterolemia after chemotherapy for testis cancer. J Clin Oncol 10 (9): 1386-9, 1992.

30. Ellis PA, Fitzharris BM, George PM, et al.: Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors. J Clin Oncol 10 (10): 1609-14, 1992.

31. Gordon W, Siegmund K, Stanisic TH, et al.: A study of reproductive function in patients with seminoma treated with radiotherapy and orchidectomy: (SWOG-8711). Southwest Oncology Group. Int J Radiat Oncol Biol Phys 38 (1): 83-94, 1997.