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From the Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Correspondence: Address correspondence to: Joel Sheinfeld, MD, Department of Urology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021; Fax: 212-988-0806; E-mail: sheinfej{at}mskcc.org
Although the primary focus of this article1 is the further characterization of nine patients with malignant transformation of teratoma, the data presented are provocative in that they provide further evidence that an inadequately controlled retroperitoneum is a major predisposing factor for late relapse of germ cell tumor (GCT), with potentially lethal consequences.
Of 369 consecutive patients with advanced GCT, 244 (66%) patients underwent surgery in an adjunctive setting and 37 patients for recurrent disease. It is not possible to determine the total number of local recurrences following prior surgery (except for patients 5 and 6 in Table 1), or how many additional patients with recurrence did not undergo surgery. However, the data highlight the continuing controversies regarding: (1) patient selection for adjunctive postchemotherapy surgery, and (2) the appropriate extent of surgical resection.
Current series report that necrotic debris comprise approximately 45% of resected specimens, teratoma another 40%, and viable GCT the remaining 15%.2 In an effort to safely obviate postchemotherapy surgery, investigators have sought to identify criteria that are highly predictive of necrosis in the resected specimen, i.e., patients in whom surgery is of diagnostic relevance but offers no therapeutic advantage as it does in patients with viable GCT or teratoma.3 The data suggest that no single criterion or combination of criteria predict a negative histology with sufficient accuracy to eliminate the risk of residual teratoma or viable GCT, and thus obviate postchemotherapy retroperitoneal lymph node dissection (RPLND).3,4
Observation has been recommended in patients whose tumor markers have normalized and the postchemotherapy computed tomography scan is normal. Despite strict computed tomography scan criteria, 21% to 30% of resected specimens in this setting will harbor teratoma or persistent GCT.5 Furthermore, the absence of teratomatous elements in the primary tumor does not preclude its presence in resected postchemotherapy specimens. Toner et al. noted that 25 of 75 (33%) patients without teratomatous elements in the primary tumor had teratoma resected from metastatic sites.6
Multiple sophisticated statistical models to predict necrosis in the resected specimen have been developed incorporating a number of clinicopathologic criteria, including degree of tumor shrinkage, size of residual mass, prechemotherapy tumor markers, and teratomatous components in the orchiectomy specimen. Unfortunately, the risk of a false-negative prediction remains approximately 20%,2 as noted in patients 8 and 9 in Table 1, who suffered late relapse in the retroperitoneum following observation after induction chemotherapy.
Late relapse of GCT is a distinct clinical entity characterized by chemoresistance and a relatively poor prognosis. The most common site is the retroperitoneum. The risk of late relapse for patients who initially present with advanced disease and initially undergo cisplatin-based induction chemotherapy ranges from 2% to 4%.7,8 Only 22 of 37 (59%) patients in Baniel’s series of late-relapsing patients had undergone a postchemotherapy RPLND.7 More than 50% of patients with late relapse referred to Memorial Sloan-Kettering Cancer Center after induction chemotherapy had unresected retroperitoneal mass(es).8
Patients 5 and 6 in Table 1, both of whom died of their disease after suffering late relapse in the retroperitoneum following prior resection of mature teratoma, highlight the danger of incompletely resected teratoma. Despite the histologically benign nature of teratoma, unresected teratoma many result in rapid growth, or, as in these two cases, late recurrence and malignant transformation.
In the Patients and Methods section, the authors describe "resection of residual retroperitoneal mass" in patients selected to undergo adjunctive postchemotherapy surgery. The data suggest that mass resection only, or modified RPLND templates, initially developed for patients with low-volume disease in an effort to preserve ejaculatory function and minimize morbidity, do no seem to be an acceptable alternative for patients with advanced disease because they are at higher risk for disease outside the limits of modified templates. In a study of 113 patients who underwent a postchemotherapy RPLND, viable GCT or teratoma was located outside the limits of a modified RPLND in 14 of 60 patients with non-necrotic residua, but present within a palpable mass in only 6 of these 14 cases. Furthermore, if a bilateral dissection was not performed, 9 of 113 (8%) patients would have had residual teratoma or viable GCT left in the retroperitoneum.9 Therefore, the most rigorous approach remains a bilateral dissection with nerve-sparing techniques in carefully selected patients.3
I agree with the authors that an aggressive surgical approach is necessary to achieve a favorable outcome in patients with malignant transformation of teratoma, given the chemorefractory nature of this rare clinical entity. Unfortunately, the authors appear inconsistent in their message. In the third paragraph of the discussion, the authors make a "plea for complete surgical resection of any residual tumor mass", whereas in the sixth paragraph they rationalize avoiding a complete RPLND and "performing only resection of residual retroperitoneal disease (RRRTM)" to minimize morbidity because there would only be a theoretical risk of relapse. The risk of recurrence is clearly more than "theoretical", as evidenced by their own experience and that in the published literature.10 Unfortunately, only 2 of 5 (40%) relapsing patients in this series are alive, free of disease. This series underscores the importance of careful patient selection for postchemotherapy surgery and the need for a meticulous RPLND to avoid late relapse and unfavorable outcomes.
Received for publication January 7, 2003. Accepted for publication January 14, 2003.
REFERENCES
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  J. Sheinfeld and R. J. Motzer Stage I Testicular Cancer Management and Necessity for Surgical Expertise J. Clin. Oncol., June 20, 2008; 26(18): 2934 - 2936. [Full Text] [PDF]
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A. J. Stephenson, G. J. Bosl, R. J. Motzer, D. F. Bajorin, J. P. Stasi, and J. Sheinfeld Nonrandomized Comparison of Primary Chemotherapy and Retroperitoneal Lymph Node Dissection for Clinical Stage IIA and IIB Nonseminomatous Germ Cell Testicular Cancer J. Clin. Oncol., December 10, 2007; 25(35): 5597 - 5602. [Abstract] [Full Text] [PDF]
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