Chapter 092. Testicular Cancer (Part 3) Tumor Markers Careful monitoring of the serum tumor markers AFP and hCG is essential in the management of patients with GCT, as these markers are important for diagnosis, as prognostic indicators, in monitoring treatment response, and in the detection of early relapse. Approximately 70% of patients presenting with disseminated nonseminomatous GCT have increased serum concentrations of AFP and/or hCG. While hCG concentrations may be increased in patients with either nonseminoma or seminoma histology, the AFP concentration is increased only in patients with nonseminoma. The presence of an increased AFP level in a patient whose tumor shows only seminoma indicates that an occult nonseminomatous component exists and the patient should be treated for nonseminomatous GCT. LDH levels are not as specific as AFP or hCG but are increased in 50–60% patients with metastatic nonseminoma and in up to 80% of patients with advanced seminoma. AFP, hCG, and LDH levels should be determined before and after orchiectomy. Increased serum AFP and hCG concentrations decay according to first-order kinetics; the half-life is 24–36 h for hCG and 5–7 days for AFP. AFP and hCG should be assayed serially during and after treatment. The reappearance of hCG and/or AFP or the failure of these markers to decline according to the predicted half-life is an indicator of persistent or recurrent tumor. Testicular Cancer: Treatment Stage I Nonseminoma If, after an orchiectomy (for clinical stage I disease), radiographs and physical examination show no evidence of disease and serum AFP and hCG concentrations are either normal or declining to normal according to the known half-life, patients may be managed by either a nerve-sparing retroperitoneal lymph node dissection (RPLND) or surveillance. The retroperitoneal lymph nodes are involved by GCT (pathologic stage II) in 20–50% of these patients. The choice of surveillance or RPLND is based on the pathology of the primary tumor. If the primary tumor shows no evidence for lymphatic or vascular invasion and is limited to the testis (T1), then either option is reasonable. If lymphatic or vascular invasion is present or the tumor extends into the tunica, spermatic cord, or scrotum (T2 through T4), then surveillance should not be offered. Either approach should cure >95% of patients. RPLND is the standard operation for removal of the regional lymph nodes of the testis (retroperitoneal nodes). The operation removes the lymph nodes ipsilateral to the primary site and the nodal groups adjacent to the primary landing zone. The standard (modified bilateral) RPLND removes all node-bearing tissue down to the bifurcation of the great vessels, including the ipsilateral iliac nodes. The major long-term effect of this operation is retrograde ejaculation and infertility. Nerve-sparing RPLND, usually accomplished by identification and dissection of individual nerve fibers, may avoid injury to the sympathetic nerves responsible for ejaculation. Normal ejaculation is preserved in ~90% of patients. Patients with pathologic stage I disease are observed, and only the <10% who relapse require additional therapy. If retroperitoneal nodes are found to be involved at RPLND, then a decision regarding adjuvant chemotherapy is made on the basis of the extent of retroperitoneal disease (see below). Surveillance is an option in the management of clinical stage I disease when no vascular/lymphatic invasion is found (T1). Only 20–30% of patients have pathologic stage II disease, implying that most RPLNDs in this situation are not therapeutic. Surveillance and RPLND lead to equivalent long-term survival rates. Patient compliance is essential if surveillance is to be successful. Patients must be carefully followed with periodic chest radiography, physical examination, CT scan of the abdomen, and serum tumor marker determinations. The median time to relapse is about 7 months, and late relapses (>2 years) are rare. The 70–80% of patients who do not relapse require no intervention after orchiectomy; treatment is reserved for those who do relapse. When the primary tumor is classified as T2 through T4 (extension beyond testis and epididymis or lymphatic/vascular invasion is identified), nerve-sparing RPLND is preferred. About 50% of these patients have pathologic stage II disease and are destined to relapse without the RPLND. Stage II Nonseminoma Patients with limited, ipsilateral retroperitoneal adenopathy (nodes usually ≤3 cm in largest diameter) and normal levels of AFP and hCG generally undergo a modified bilateral RPLND as primary management. Increased levels of either AFP or hCG or both imply metastatic disease outside the retroperitoneum; chemotherapy is used in this setting. The local recurrence rate after a properly performed RPLND is very low. Depending on the extent of disease, the postoperative management options include either surveillance or two cycles of adjuvant chemotherapy. Surveillance is the preferred approach for patients with resected "low-volume" metastases (tumor nodes ≤2 cm in diameter and <6 nodes involved) because the probability of relapse is one-third or less. For those who relapse, risk-directed chemotherapy is indicated (see below). Because relapse occurs in ≥50% of patients with "high-volume" metastases (>6 nodes involved, or any involved node >2 cm in largest diameter, or extranodal tumor extension), two cycles of adjuvant chemotherapy should be considered, as it results in cure in ≥98% of patients. Regimens consisting of etoposide (100 mg/m 2 daily on days 1– 5) plus cisplatin (20 mg/m 2 daily on days 1–5) with or without bleomycin (30 units per day on days 2, 9, and 16) given at 3-week intervals are effective and well tolerated. . Chapter 092. Testicular Cancer (Part 3) Tumor Markers Careful monitoring of the serum tumor markers AFP and hCG. decline according to the predicted half-life is an indicator of persistent or recurrent tumor. Testicular Cancer: Treatment Stage I Nonseminoma If, after an orchiectomy (for clinical stage I disease),