Carboplatin for Stage I Seminoma and the Sword of Damocles

Abstract

Damocles lived on the island of Sicily approximately 400 BC and served in the court of Dionysius II of Syracuse. As told by Cicero in the Tusculan disputations, Damocles was extremely effusive of the tyrant Dionysius and continuously told him how fortunate he was to have great power and riches. Growing weary of these comments, Dionysius one day asked Damocles if he would like to sample his lifestyle. Damocles happily agreed and was subsequently treated to a bountiful banquet that included the finest foods, wines, flowers, and music. At the end of the meal he glanced up and saw a sharp sword dangling by a single horsehair above his head. Damocles quickly left the banquet, suddenly quite content with his former life. “The Sword of Damocles” has grown to describe the feeling of impending doom. In this issue of the Journal of Clinical Oncology, Aparicio et al have used this metaphor for the stress of the long follow-up experienced by patients during surveillance for clinical stage I seminoma. In their article, the authors report their well-conducted phase II study of a so-called riskadapted strategy in which patients with clinical stage I (a tumor that is apparently confined to the testicle, with normal serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein and normal computed tomography of the chest, abdomen, and pelvis) seminoma were assigned to either surveillance or chemotherapy with carboplatin. Recently, the management of clinical stage I seminoma has become controversial. Is the stress of long follow-up and good compliance eliminated by this approach? In our opinion, the answer is no, as relapses still occur at a rate that may be worse than that observed with standard radiation therapy (RT) and at sites that are different. RT has been the standard primary treatment for clinical stage I seminoma for several decades. After approximately 20 to 25 Gy administered to the retroperitoneal and ipsilateral pelvic lymph nodes (the so-called dog-leg port), the overall recurrence rate is approximately 3% to 5%, and virtually all relapses occur outside the RT portal. The 5-year overall survival rate for patients with stage I seminoma after RT is nearly 100%. Late complications from RT, such as nontesticular second malignancies and cardiovascular disease, have been well described. In the past two decades, surveillance alone has been studied as an alternative approach to the management of patients with clinical stage I seminoma. The relapse rate after orchiectomy alone is approximately 15% to 20%. Investigators at the Princess Margaret Hospital (Toronto, Canada) led the efforts. In a series of 471 patients seen between 1981 and 1994, relapses occurred in 37 patients (16%) on surveillance and in 14 patients (5.7%) treated with RT, with a 5-year actuarial survival rate of 97% and a cause-specific survival rate of 99.8% for those managed with RT (n 245) or surveillance (n 226), respectively. Because most patients on surveillance experienced relapse in the retroperitoneum and received therapeutic RT, only 13 patients (5.7%) on surveillance and 10 patients receiving prophylactic RT required subsequent chemotherapy. Hence all of the patients who experienced relapse were cured with either subsequent RT or chemotherapy. With the success of chemotherapy in patients with disseminated germ cell tumors (GCTs), the role of systemic chemotherapy has been studied in seminomas. Noting that seminoma may be more chemotherapy sensitive than its nonseminomatous counterpart, some investigators have advocated single-agent carboplatin over combination therapy. The report by Aparicio et al from the Spanish Germ Cell Cancer Cooperative Group is one such study. An interesting feature of this article is the investigation of not only the assignment of two cycles of carboplatin as adjuvant therapy for a high-risk and surveillance for a lowrisk group of patients with clinical stage I seminoma, but also the prospective use of a risk algorithm to assign highrisk or low-risk status to this patient population. These risk JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 34 DECEMBER 1 2005