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]
Introduction
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%.[3] 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.
Natural History of Testicular Cancer
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.
Lymphatic Drainage
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).[7] 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!
Nodal Metastases
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[8] 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.[9] 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.[10] 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.[11] However, Capelouto et al[12] 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.[13]
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.
Prediction of Metastatic Potential
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.[16] 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.[17]
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[18] showed that the high- risk group constituted fewer than 25% of patients with testicular cancer and accounted for less than half of the relapses.
