ABSTRACT: Carcinoma of the testis is the most common malignancy in males 15 to 35 years of age. Testicular cancer has become one of the most curable solid neoplasms and, as such, serves as a paradigm for the multimodality treatment of malignancies. The cure rate for patients with clinical stage I disease is nearly 100%, and patients with advanced disease now achieve complete remission rates of over 90%. The markedly improved outlook for patients with this cancer over the past 15 years has led to a reassessment of management options, especially in patients with clinical stage I disease. The realization that platinum-based chemotherapy could cure most patients with an advanced nonseminomatous germ cell tumor (NSGCT), especially those with minimal disease, led to the introduction of various strategies to decrease the morbidity associated with surgical management. These strategies include surveillance protocols, chemotherapy for clinical stage II disease, and observation protocols for a subset of patients with advanced disease who have had a partial response to chemotherapy. Retroperitoneal lymph node dissection (RPLND) has an important place in the management of both low- and high-stage testicular cancer. It offers the patient two basic benefits: accurate staging and the possibility of a surgical cure, even in the presence of metastatic disease. [ONCOLOGY 11(5):717-729, 1997]
Despite the fact that carcinoma of the testis accounts for only 1% of all malignancies in males, it is the most common solid malignancy affecting males between the ages of 15 and 35 years. As such, testicular cancer raises significant issues pertaining to such factors as future fertility and the development of a potentially life-threatening disease in a previously healthy, productive individual. These issues need to be taken into account in overall patient management.
The incidence of testicular cancer has gradually increased over the last 25 years, from 2.3 cases per 100,000 men in 1964 to 4 per 100,000 men in 1993; this trend is due mainly to an increased incidence in white males.[1,2] Thirty years ago, testicular cancer accounted for 11.4% of all cancer deaths in the 25- to 34-year-old age group, with an overall 5-year survival rate of 64%. In 1994, the cure rate for testis cancer approached 100%. Improved diagnostic techniques and tumor markers, as well as effective platinum-based multidrug chemotherapeutic regimens, have combined to significantly reduce patient morbidity and mortality.
In addition, modifications in the surgical management of testicular cancer have significantly lowered the morbidity associated with the classic full bilateral retroperitoneal lymph node dissection (RPLND), which was routinely performed prior to the early part of the 1980s. This advance, combined with the fact that approximately 30% to 50% of patients with a clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) actually have pathologic stage II disease, has made surgery an important treatment option for both physicians and patients.
Retroperitoneal lymph node dissection not only is an important component of the management of patients with low-stage NSGCT but also has a major role in the management of residual disease following chemotherapy. Approximately 30% of patients who are initially treated with chemotherapy are found to have a residual mass at follow-up. Removing this mass restages the patient and, in cases where persistent carcinoma exists, the physician is alerted to the need for further management.
Therefore, as will be discussed below, RPLND plays a role in both low- and high-stage disease. It is a well-defined, reproducible surgical procedure with low morbidity, which benefits the patient in terms of both allowing for accurate pathologic staging and providing a surgical cure.
Clinical observation of patients with testicular cancer has led to an understanding of its local growth characteristics, as well as its patterns of spread. Following malignant transformation of the germinal epithelium, tumor growth initially tends to remain confined to the testis itself, as the tough fibrous tunica albuginea offers a degree of protection to the epididymis. The tumor gains access to the lymphatics at the testicular mediastinum.
With the notable exception of choriocarcinoma, germ cell testicular neoplasms spread in a predictable, stepwise fashion. The lymphatic drainage of the testicle has been well documented by both surgeons and anatomists.[4-6] One of the first experimental studies of testicular lymphatics was performed in 1910 by Jamieson and Dobson (Figure 1). Apart from their important contribution in defining lymphatic drainage of the testicle, these authors correctly pointed out that in order to cure testicular cancer, complete removal of the "retroperitoneal lymphatic area" was necessary; however, they felt that this procedure was exceedingly difficult and dangerous, if not impossible!
The spermatic cord contains four to eight lymphatic channels that ascend into the retroperitoneum and fan out medially into the retroperitoneal lymph node chain. The first echelon of lymph nodes draining the right testis is located within the interaortocaval nodes, at the level of the second vertebral body. The first echelon of nodes draining the left testis is located in the para-aortic region in an area bounded by the renal vein superiorly, the aorta medially, the ureter laterally, and the origin of the inferior mesenteric artery inferiorly. Following spread of germ cell neoplasms to either the left or right primary echelon of nodes, subsequent metastasis may occur in a retrograde fashion to the common external and inguinal nodes, or cephalad via the cysterna chyli, thoracic duct, and supraclavicular nodes (Figure 2).
In a review of 104 consecutive patients with stage II (B) NSGCT, Donohue et al made a number of important observations confirming the predictable lymphatic spread of testicular tumors. They reported that suprahilar lymph node spread was extremely rare in stage BI disease but was not uncommon in stage BII disease. They also confirmed the absence of contralateral node involvement in low-stage disease when the ipsilateral nodes were negative. In addition, in this series gonadal vein involvement was noted in a significant number of cases in both low- and high-stage B disease. Obviously, these observations have important implications for the surgical management of testicular cancer.
Despite the predictability of lymph node metastasis in testicular cancer, there is a 5% distant failure rate following node-negative RPLND. This is probably due to the fact that the testicular lymphatics may very occasionally bypass the retroperitoneal lymph nodes altogether and communicate directly with the thoracic duct. Lymphatics of the epididymis drain into the external iliac chain; therefore, in locally extensive disease, epididymal involvement may be associated with positive pelvic lymph nodes. Testicular cancer that involves the scrotum may result in inguinal node metastasis; in addition, prior scrotal surgery or retrograde spread from extensive retroperitoneal involvement may also cause inguinal node metastasis.
Scrotal violation in the setting of orchiectomy for testicular cancer has generally been condemned as compromising patient prognosis. As a result, inguinal orchiectomy with high ligation of the cord has been the standard of care in the initial management of testicular cancer for almost 100 years. However, Capelouto et al recently conducted a meta-analysis focusing on the implications of scrotal violation in patients with testicular cancer. Out of a total of 1,182 patients, scrotal violation had occurred in 206 patients. No statistical differences in distant recurrence or survival were found, implying that scrotal violation may not carry a significantly worse prognosis.
In summary, apart from choriocarcinoma, which undergoes both lymphatic and hematogenous spread at an early stage, germ cell testicular tumors tend to spread, in a predictable fashion, to the retroperitoneal lymph nodes. Suprahilar involvement usually develops only in higher-stage disease and, as such, occurs more frequently on the left side than on the right. If the ipsilateral nodes are negative, the contralateral nodes also are uninvolved. Cross-metastases occur more frequently with right-sided tumors.
Distant spread of testicular cancer occurs most commonly to the pulmonary region, with intraparenchymal pulmonary involvement. Subsequent spread is to the liver, viscera, brain, and, late in the disease course, bone.
This predictable pattern of spread has led to the development of new surgical techniques that provide both accurate pathologic staging and therapeutic benefit, while at the same time being associated with minimal morbidity.
Most patients with NSGCT present with clinical stage I disease. Since 30% to 50% of these patients may have clinically undetectable metastases, controversy exists as to their subsequent management.[14,15] In order to offer the patient the highest chance of cure with the lowest possible morbidity, certain parameters are used to predict the likelihood of metastasis. Factors that determine the likelihood of relapse in the retroperitoneal nodes, or of late recurrence in clinical stage I NSGCT, are: the extent of the primary tumor (ie, T-stage), lymphatic or vascular invasion, the presence of embryonal carcinoma in the primary tumor, and the absence of yolk sac tumor.
Prognostic indices using these risk factors have been developed. As a result of these indices, patients with clinical stage I NSGCT are no longer managed as a homogeneous group. Rather, treatment may now be individualized according to the likelihood of positive retroperitoneal lymph nodes. Patients who are at low risk of having positive nodes may be placed into observation protocols and thus spared the morbidity of adjuvant therapy. However, despite the prognostic criteria, it is still not possible to establish highly accurate distinctions between patients who should and should not receive adjuvant therapy. In this regard, the Medical Research Council study in the United Kingdom showed that the high- risk group constituted fewer than 25% of patients with testicular cancer and accounted for less than half of the relapses.
1. Schotterfeld D, Warshouer ME, Sherlock S, et al: The epidemiology
of testicular cancer in young adults. Am J Epidemiol 222:112, 1980.
2. Peterson GR, Lee JA: Secular trends of malignant tumors of the testes
in white men. Cancer J Clin 43:7, 1993.
3. Oliver RTD: Clues from natural history and results of treatment supporting
the monoclonal origin of germ cell tumors. Cancer Surv 9:333-368, 1990.
4. Hinman F: The operative treatment of tumors of the testicle. JAMA
5. Butt AP, Arkin A: Malignant diseases of the retained testicle. Surg
Gynecol Obstet 19:419, 1914.
6. Rouviere H; Tobias MJ, trans: Anatomy of the Human Lymphatic System.
Ann Arbor, Michigan, Edwards Bros, 1938.
7. Jamieson JK, Dobson JF: The lymphatic drainage of the testicle. Lancet
8. Donohue JP, Zackery JM, Maynard BR, et al: Distribution of nodal
metastases in nonseminomatous testis cancer. J Urol 128:315-320, 1982.
9. Ray B, Hajou SI, Whitmore WF, Jr., et al: Proceedings: distribution
of retroperitoneal lymph node metastases in testicular germinal tumors.
Cancer 33:340, 1974.
10. Whitemore WF, Jr: Germinal tumors of the testis, in Proceedings
of the Swedish National Cancer Conference, pp 485-499. Philadelphia, JB
11. Keber GM: Sarcoma of the testicle, conclusions based upon 114 cases.
Am J Med 117:535, 1899.
12. Capelouto CC, Clarke PE: A review of scrotal violation in testicular
cancer: Is adjuvant local therapy necessary? J Urol 153:981-985, 1995.
13. Johnson DE, Appele C, Samuels MC, et al: Metastases from testicular
carcinoma. Urology 8:234, 1976.
14. Rowland RC, Weissman D, et al. Accuracy of preoperative staging
in stage A and B nonseminomatus germ cell testis tumors. J Urol 127:718,
15. Duchesne GM, Monurich A, Dearnaley DP, et al: Orchiectomy alone
for stage I seminoma of the testis. Cancer 65:1155, 1990.
16. Fung CY, Kalish LA, Brodsky GL, et al: Stage I nonseminomatous germ
call testicular tumor: prediction of metastatic potential by primary pathology.
J Clin Oncol 6(9):1467-1473, 1988.
17. Levin M: Prognostic features of primary and metastatic testis germ
cell tumors. Urol Clin North Am 20(1):39-53, 1993.
18. Freedman LS, Parkinson MC: Histopathology in the prediction of relapse
of patients with stage I testicular teratoma treated by orchidectomy alone.
Cancer 2:294-297, 1987.
19. Boden G, Gibb R: Radiotherapy and testicular neoplasms. Cancer 2:1195,
20. Thomas JL, Bernardino ME, Bracken RB, et al: Staging of testicular
carcinoma: comparison of CT and lymphangiography. Am J Roentgenol 127:991-996,
21. Richie JP, Garnick MB, Finberg H, et al: Computed tomography: How
accurate for abdominal staging testis tumors? J Urol 27:715-717, 1982.
22. MacLeod DG, Weiss RB: Staging relations and outcomes in early stage
testicular cancer: A report from the testicular cancer intergroup study.
J Urol 145:1178-1183, 1991.
23. Samuelson L, Forsberg L, Olsson AM, et al: Accuracy of radiologic
staging procedures in nonseminomatous testis cancer composed with findings
from surgical exploration and histopathological studies of tissues. Br
J Radiol 59:131, 1986.
24. Ellis JM, Kopecky JR: Comparison of NMR and CT imaging in the evaluation
of metastatic retroperitoneal lymphadenopathy from testicular carcinoma.
J Comput Assist Tomogr 8:709, 1986.
25. Lee JK: Retroperitoneum, in Lee JKT, Segel SS, Stanley RJ (eds):
Computed Body Tomography with MRI Correlation, 2nd ed, chap 17, pp 740.
New York, Raven Press, 1989.
26. Sogen PC: Evolution of management of Stage I NSGCT. Urol Clin North
Am 18:561-573, 1991.
27. Foster RS, McNulty A, Rubin LR: Fertility of patients with low stage
NSGCT management with nerve sparing RPLND. J Urol 152(4):1139-1142, 1996.
28. Krarupt T: The testis after torsion. Br J Urol 50:43, 1978.
29. Guzzieri S, Lembo A, Ferro G, et al: Sperm antibodies and infertility
in patients with testis cancer. Urology 26:139, 1985.
30. Lange PH, Chang WY, Fraly EE: Fertility issues in the therapy of
nonseminomatous germ cell tumors. Urol Clin North Am 14:731, 1987.
31. Foster RS, McNulty A, Rubin LR, et al: The fertility of patients
with clinical stage I testis cancer managed by nerve sparing retroperitoneal
lymph node dissection. J Urol 152(4):1139-1142, 1994.
32. Mansen SW, Berthelsen JG, Von Der Mease H: Long term fertility and
Leydig cell function in patients treated for germ cell cancer with cisplatin,
vinblastine and bleomycin versus surveillance. J Clin Oncol 10:1695, 1990.
33. Williams SD, Btablein DM, Einhorn LH, et al: Immediate adjuvant
chemotherapy versus observation with treatment at relapse in pathological
stage II testicular cancer. N Engl J Med 317:1433, 1987.
34. Donohue JP, Thornhill JA, Foster RS: Retroperitoneal lymphadenectomy
for clinical Stage A testis cancer (1965 to 1989): Modifications of technique
and impact on ejaculation. J Urol 169:137-243., 1993.
35. Skinner DG, Lievskovsky G: Complications of thoracoabdominal retroperitoneal
lymph node dissection. J Urol 127:1107-1110, 1982.
36. Pizzocaro G, Durand JC, Fuchs WA: Staging and surgery in testicular
cancer. Eur Urol 7:1-10, 1981.
37. Richie JP: Modified retroperitoneal lymph node dissection for patients
with clinical stage 1 testicular cancer. Semin Urol 216:222, 1988.
38. Baniel J, Foster RS, Rowland RG, et al: Complications of primary
RPL. J Urol 152:424, 1994.
39. Albers P, Ulbright TM, Albers J, et al: Tumor proliferative activity
is predictive of pathological stage in clinical stage A nonseminomatous
testicular germ cell tumors. J Urol 155:579-588, 1995.
40. Peters PC: Selective for testicular cancer. Semin Oncol 15:321-323,
41. Donohue JP, Thornhill JA, Foster RS, et al: Retroperitoneal lymphadenectomy
in clinical stage A nonseminomatous germ cell tumor: Review of the Indiana
University experience. Br J Urol 71:326, 1993.
42. Baniel J, Foster RS, Einhorn L, et al: Late relapse of clinical
stage I testicular cancer. J Urol 154:1370, 1995
43. Richie JP, Kantoff PW: Is adjuvant chemotherapy necessary for patients
with stage B1 testicular cancer. J Clin Oncol 9(8):1393-1398, 1991.
44. Pizzocaro G: Monfardin: No adjuvant chemotherapy in selected patients
with pathologic stage II nonseminomatous germ cell tumors of the testis.
J Urol 131:667-680, 1983.
45. Williams SD, Stablain DM, Einhorn LM: Immediate adjuvant chemotherapy
versus observation with treatment at relapse in pathological stage II testicular
cancer. N Engl J Med 317:1433-1438, 1987.
46. Javadpour N, Young JDJ: Prognostic factors in nonseminomatous testicular
cancer. J Urol 135:497-499, 1986.
47. Weissbach L, Mamhapp JM: Adjuvant chemotherapy of metastatic stage
II nonseminomatous testis tumor. J Urol 146:1295-1298, 1991.
48. Socinski MA, Garnick MB, Stomper P, et al: Stage II nonseminomatous
germ cell tumors of the testis: An analysis of treatment options in patients
with low volume disease. J Urol 140:1437-1441, 1988.
49. Bajorin DF, Herr HW, Motzer RJ, et al: Current perspectives on the
role of adjunctive surgery in combined modality treatment of patients with
germ cell tumors. Semin Oncol 19:145:158, 1992.
50. Levitt MD, Reynolds PM, Steiner MJ, et al: Nonseminomatous germ
cell testicular tumors: residual masses after chemotherapy. Br J Surg 72:19022,
51. Fossa SD, Ous S, Lien HH, et al: Post chemotherapy lymph node histology
in radiologically normal patients with metastatic nonseminomatous testicular
cancer. J Urol 141:557-559, 1989.
52. Richie JP: The surgical management of advanced abdominal disease.
Semin Urol 2:238-243, 1986.
53. Donohue JP, Rowland R: Complications of retroperitoneal lymph node
dissection. J Urol 125:338-365, 1981.
54. Loehrer PJ, Mui S, Claik S, et al: Teratoma following cisplatin
based chemotherapy for nonseminomatous germ cell tumors: A clinicopathologic
correlation. J Urol 135-1189, 1986.
55. Ahmed T, Bosi GJ, Majdu SI: Teratoma with malignant transformation
in germ cell tumors in men. Cancer 56:860-863, 1985.
56. Sheinfeld J, Bajornin D: Management of post chemotherapy residual
mass. Urol Clin North Am 20(1):133-142, 1993.