Chapter 092. Testicular Cancer (Part 4) ppsx

Chapter 092. Testicular Cancer (Part 4) Stages I and II Seminoma Inguinal orchiectomy followed by retroperitoneal radiation therapy cures ~98% of patients with stage I seminoma. The dose of radiation therapy (2500– 3000 cGy) is low and well tolerated, and the in-field recurrence rate is negligible. About 2% of patients relapse with supradiaphragmatic or systemic disease. Surveillance has been proposed as an option, and studies have shown that about 15% of patients relapse. The median time to relapse is 12–15 months, and late relapses (>5 years) may be more frequent than with nonseminoma. The relapse is usually treated with chemotherapy. Surveillance for clinical stage I seminoma is not recommended. Nonbulky retroperitoneal disease (stage IIA and IIB) is also treated with radiation therapy. Prophylactic supradiaphragmatic fields are not used. Relapses in the anterior mediastinum are unusual. Approximately 90% of patients achieve relapse-free survival with retroperitoneal masses <5 cm in diameter. Because at least one-third of patients with bulkier disease relapse, initial chemotherapy is preferred for stage IIC disease. Chemotherapy for Advanced GCT Regardless of histology, patients with stage IIC and stage III GCT are treated with chemotherapy. Combination chemotherapy programs based on cisplatin at doses of 100 mg/m 2 plus etoposide at doses of 500 mg/m 2 per cycle cure 70–80% of such patients, with or without bleomycin, depending on risk stratification (see below). A complete response (the complete disappearance of all clinical evidence of tumor on physical examination and radiography plus normal serum levels of AFP and hCG for ≥1 month) occurs after chemotherapy alone in ~60% of patients, and another 10–20% become disease-free with surgical resection of residual masses containing viable GCT. Lower doses of cisplatin result in inferior survival rates. The toxicity of four cycles of the cisplatin/bleomycin/etoposide (BEP) regimen is substantial. Nausea, vomiting, and hair loss occur in most patients, although nausea and vomiting have been markedly ameliorated by modern antiemetic regimens. Myelosuppression is frequent, and symptomatic bleomycin pulmonary toxicity occurs in ~5% of patients. Treatment-induced mortality due to neutropenia with septicemia or bleomycin-induced pulmonary failure occurs in 1– 3% of patients. Dose reductions for myelosuppression are rarely indicated. Long- term permanent toxicities include nephrotoxicity (reduced glomerular filtration and persistent magnesium wasting), ototoxicity, and peripheral neuropathy. When bleomycin is administered by weekly bolus injection, Raynaud's phenomenon appears in 5–10% of patients. Other evidence of small blood vessel damage is seen less often, including transient ischemic attacks and myocardial infarction. Risk-Directed Chemotherapy Because not all patients are cured and treatment may cause significant toxicities, patients are stratified into "good-risk" and "poor-risk" groups according to pretreatment clinical features. For good-risk patients, the goal is to achieve maximum efficacy with minimal toxicity. For poor-risk patients, the goal is to identify more effective therapy with tolerable toxicity. The International Germ Cell Cancer Consensus Group developed criteria to assign patients to three risk groups (good, intermediate, poor) (Table 92-2). The marker cut-offs have been incorporated into the revised TNM (primary tumor, regional nodes, metastasis) staging of GCT. Hence, TNM stage groupings are now based on both anatomy (site and extent of disease) and biology (marker status and histology). Seminoma is either good or intermediate risk, based on the absence or presence of nonpulmonary visceral metastases. No poor-risk category exists for seminoma. Marker levels play no role in defining risk for seminoma. Nonseminomas have good-, intermediate-, and poor-risk categories based on the site of the primary tumor, the presence or absence of nonpulmonary visceral metastases, and marker levels. Table 92- 2 IGCCCG Risk Classification for Advanced Germ Cell Tumors Risk Nonseminoma Seminoma Good Gonadal or retroperitoneal primary site Any primary site Absent nonpulmonary visceral metastases AFP < 1000 ng/mL Beta- hCG < 5000 mIU/mL LDH < 1.5 x upper limit Absent nonpulmonary visceral metastases Any LDH, hCG or normal (ULN) Intermediate Gonadal or retroperitoneal primary site Any primary site Absent nonpulmonary visceral metastases AFP 1000–10,000 ng/mL Beta-hCG 5000– 50,000 mIU/mL LDH 1.5–10 x ULN Presence of nonpulmonary visceral metastases Any LDH, hCG Poor Mediastinal primary site Presence of nonpulmonary visceral metastases AFP ≥10,000 ng/ML Beta-hCG > 50,000 No patients classified as poor prognosis mIU/mL LDH > 10 x ULN Note: AFP, αfetoprotein; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase. Source: From International Germ Cell Cancer Consensus Group. For ~90% of patients with good-risk GCTs, four cycles of etoposide plus cisplatin (EP) or three cycles of BEP produce durable complete responses, with minimal acute and chronic toxicity. Pulmonary toxicity is absent when bleomycin is not used and is rare when therapy is limited to 9 weeks; myelosuppression with neutropenic fever is less frequent; and the treatment mortality rate is negligible. About 75% of intermediate-risk patients and 45% of poor-risk patients achieve durable complete remission with four cycles of BEP, and no regimen has proved superior. More effective therapy is needed. . Chapter 092. Testicular Cancer (Part 4) Stages I and II Seminoma Inguinal orchiectomy followed by retroperitoneal. goal is to identify more effective therapy with tolerable toxicity. The International Germ Cell Cancer Consensus Group developed criteria to assign patients to three risk groups (good, intermediate,. human chorionic gonadotropin; LDH, lactate dehydrogenase. Source: From International Germ Cell Cancer Consensus Group. For ~90% of patients with good-risk GCTs, four cycles of etoposide plus