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Redefining the Refined Retroperitoneal Lymph Node Dissection in Testis Cancer: A SWOT Analysis of Nonrandomized Data

Department of Medicine, Division of Genitourinary Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

A SWOT analysis, generally used in a business sense, comprises of a strategic evaluation that includes strengths, weaknesses, opportunities and threats. Here, it is applied to a body of nonrandomized clinical and scientific data.

The historical significance of using a multimodality treatment approach to metastatic cancer is best exemplified by nonseminomatous germ cell tumors of the testis (NSGCTT). The high, durable, and meaningful remission rates achieved in the cisplatin-based era in patients with both retroperitoneal disease and more distant metastases have improved continually with the evolution of combination programs. These include cisplatin with vinblastine and bleomycin; the evolution to etoposide replacement of vinblastine, with associated decrements in significant toxicities; elimination of bleomycin for certain risk categories; and lessening the duration of treatments. These advances have fuelled great optimism in developing strategic treatments that enhance cure and minimize toxicity.

Accompanying the refinements of curative chemotherapy programs have been evolutionary developments in the surgical management of NSGCTT. Once the mainstay of treatment for NSGCTT that had metastasized to the retroperitoneum, the retroperitoneal lymph node dissection (RPLND) has also undergone extraordinary improvements in operative technique, patient selection, approach (open v laparoscopic), anatomic understanding of disease landing zones, and refinements to minimize ejaculatory disturbances (both retrograde ejaculation and failure to ejaculate) that have led to nerve-sparing approaches. These are all welcome advances to the teams of physicians who care for the young and otherwise healthy men with stage II NSGCTT.

In this issue of the Journal of Clinical Oncology, Carver et al,¹ representing the disciplines of Urologic Surgery and Medical Oncology from Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY), provide masterly analyses that redefine the already established refinements of RPLND. Such an analysis is especially appropriate to emanate from MSKCC, given that institution's incredible contributions to the field that have been so important in providing advances embraced by physicians worldwide.

The issue at hand relates to the appropriate extent of RPLND for patients with retroperitoneal NSGCTT after chemotherapy (postchemotherapy [PC] -RPLND). Given the correlation of greater ejaculatory morbidity associated with more extensive bilateral infrahilar RPLND for stage I NSGCTT and a more refined (but still incomplete) understanding of nodal landing sites for metastases, the concept of modified dissection templates emerged that limited surgical boundaries to the areas most likely to contain microscopic metastases or disease below the detection of radiographic tests, and thereby minimize postoperative ejaculatory dysfunction. Although no fewer than five modified dissection templates have been described, and are now often applied to the stage II patient, the authors point out that none have undergone rigorous follow-up when applied to stage II disease in the PC setting. In other words, is the performance of a template-modified RPLND correct in the setting of patients with stage II disease of varying tumor burdens? Such an analysis would provide the much-needed comfort that less (surgery) is better or equivalent (in oncologic efficacy). Unfortunately, the results of the current study cast serious doubt on this optimistic assumption.

Short of performing a randomized study that compares both the safety and oncologic efficacy of a modified template to the more extensive bilateral infrahilar dissection in the PC setting, the authors analyzed (deduced and imputed) the nature and extent of retroperitoneal disease (teratoma or viable germ cell tumor GCT) PC. Their results include the nature of disease that would have persisted had a template RPLND been performed instead of a more extensive bilateral dissection. Given the poorer prognosis of late and uncontrolled retroperitoneal relapses, and the treacherous and wildly uncertain natural history of unresected teratoma, they argue further that the 7% to 32% of patients who would have had extratemplate disease would not have been well served by a more limited template RPLND. Can the informed reader arrive at the same conclusion?

To answer that, let us evaluate the strengths, weaknesses, opportunities, and threats of the data interpretation presented by Carver et al.¹

What are the strengths of the article? First, by any standard of NSGCTT patient experience, the database is huge. In a 14-year period at MSKCC, 532 stage II patients underwent a PC-RPLND, of whom 269 had evidence of either teratoma or viable GCT; of these, 7% to 32% (depending on the template selected) would have had evidence of extratemplate disease had a template RPLND been performed.

Second, there was a disturbing 14% incidence of extratemplate disease in the setting of normal PC computed tomography imaging of the retroperitoneum. (This number is likely to be even higher in centers that do not have the same level of experience as MSKCC.)

Third, the incidence of extratemplate disease (with no radiographic evidence of abnormalities) in those with in-template radiographic disease ranged from 8% when in-template disease was less than 1 cm to 29% when the in-template disease measured 2 to 5 cm. (Again, this incidence is likely to be higher in lower volume centers.)

Fourth, the authors cite compelling data about the ravages of uncontrolled retroperitoneal disease in diminishing the overall cure rates for NSGCTT.

The study has its share of weaknesses, too. First, it is a compilation of nonrandomized imputed data, with no long-term patient outcomes of any kind—the same criticism Carver et al¹ raise about studies that evaluated template dissections.

Second, not all patients in the database underwent a full bilateral dissection; only 76% had a bilateral dissection and 24% had a modified template—the very dissection the authors argue against.

Third, 45 patients underwent PC-RPLND with elevated tumor markers, a clinical situation that is highly likely to be associated with malignant disease. Would the exclusion of these patients and those undergoing a modified template have altered the results?

Fourth, the authors provide their beliefs (without data) that the institution of a nerve-sparing bilateral RPLND in the postchemotherapy patient can preserve ejaculatory function and maximize oncologic efficacy. I hope they are correct!

What opportunities for improved care should the reader take away from this important study? First, an understanding of the anatomic nuances of retroperitoneal template anatomy needs to be fully appreciated by the medical oncologist, as it is by the urologist, given that it is likely that the medical oncologist will be intimately involved in the treatment of the patient who experiences relapse.

Second, the increasing popularity of template RPLND in the PC stage II patient should be questioned. Until more definitive data emerge, a frank discussion between the medical oncologist and urologist should take place and the type of dissection performed should be a joint decision, and not left exclusively to the urologist.

Third, a detailed review of the retroperitoneal radiographic evaluations (with films on the screen) presurgery needs to be discussed in person with a medical oncologist, urologist, and radiologist in attendance. A full understanding of the false-negative rate of computed tomography scans in extratemplate anatomic areas, as reported in this article, is mandatory for all involved in formulating treatment decisions.

Finally, are there any threats (the risk-benefit ratio) that should be considered in interpreting or employing the findings as enumerated by Carver et al?¹ First, there are always threats involved with instituting treatments based on nonrandomized or level B and level C data. I would pose the following hypothetical question: on the basis of the data presented by Carver et al, would a regulatory body, such as US Food and Drug Administration, approve bilateral infrahilar PC-RPLND as safe and effective for use in all stage II NSGCTT patients, and if not, how should we proceed? Although the data presented are provocative, and it is hoped that the predicted benefit will be established with additional follow-up and study, the unanswered questions and somewhat heterogenous patient sample do not yet provide unequivocal support for reversion to a bilateral infrahilar dissection in all PC stage II patients. Physicians who are now confronted with a patient needing a PC-RPLND, and who have available a radiologist expert in reading PC retroperitoneal anatomy and a urologic surgeon expert in retroperitoneal dissection and nerve-sparing techniques, will serve their patients well by embracing the recommendations of this important article.

Finally, the leadership of international testis cancer consortiums should determine urgently the optimal strategies for subsequent study designs to answer definitively the weighty question posed by the premise of the findings at MSKCC.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCE

1. Carver BS, Shayegan B, Eggener S, et al: The incidence of metastatic nonseminomatous germ cell tumor outside the boundaries of a modified postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol 25: 4365-4369, 2007[Abstract/Free Full Text]

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• Incidence of Metastatic Nonseminomatous Germ Cell Tumor Outside the Boundaries of a Modified Postchemotherapy Retroperitoneal Lymph Node Dissection
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