How Safe Is Sentinel Lymph Node Biopsy in Patients With Vulvar Cancer?

Abstract

In the current issue, Van der Zee et al provide important data suggesting that the sentinel lymph node (SLN) concept can be safely applied in patients with vulvar cancer. In this study, a group of 276 patients with a negative SLN biopsy (SLNB) were observed for a median of 35 months, and 202 patients had a minimum follow-up time of 2 years. Eight groin relapses (2.9%) were observed. Exclusion of patients with multifocal disease reduced the failure rate to 2.3%. The authors concluded that SLNB, when performed by a skilled multidisciplinary team, was safe for patients with early vulvar cancer. To readers who have followed the development of SLNB for patients with breast cancer or melanoma, this observation may seem obvious and slow in its development. To some gynecologic oncologists treating vulvar cancer, declaring SLNB safe will seem premature. How can these two seemingly disparate positions be true at the same time? It has been 30 years since Ramon Cabanas used lymphography in patients with penile carcinoma to describe the SLN as the first site of lymphatic drainage from a primary tumor. The SLN was not identified by location, as Gould et al suggested in patients with parotid tumors, but rather by an imaging procedure. The following year, DiSaia et al recognized the potential benefit of the SLN concept for patients with vulvar cancer and described “utilizing the superficial inguinal lymph nodes as the sentinel nodes for treatment planning.” Many gynecologic oncologists began performing superficial inguinal lymphadenectomy, which reduced the incidence of wound breakdown lymphedema compared with standard inguinal femoral lymphadenectomy. In April 1992, the Gynecologic Oncology Group (GOG) reported the results of protocol 74, which had a similar design to the study by Van der Zee et al. A total of 121 patients with negative superficial inguinal lymph nodes were observed, and nine (7.3%) had a groin relapse. This relapse rate was compared with the long-term follow-up of 81 control patients treated with complete inguinal femoral lymphadenectomy on GOG protocol 36. Among the historical controls, there were no groin relapses. The GOG properly rejected superficial inguinal lymphadenectomy, and most gynecologic oncologists resumed performing inguinal femoral lymphadenectomy. Coincidentally, in April 1992, Morton et al described the modern lymphatic mapping procedure in patients with cutaneous melanoma. In 2001, 13 cancer centers from around the world pooled their results for a total of 17,600 melanoma patients, including more than 3,000 patients who underwent SLNB. One of the important findings was the prognostic significance of detection of clinically apparent, compared with clinically occult, lymph node metastases. As a result, the nodal category for the American Joint Committee on Cancer staging for melanoma was amended to distinguish micrometastases from macrometastases, effectively establishing SLNB as a standard procedure for cutaneous melanoma patients. Around the same time, SLNB was rapidly embraced by breast cancer surgeons and patients. Just as surgical oncologists were moving toward SLNB for these two common tumors, gynecologic oncologists were moving in the other direction, toward more extensive lymphadenectomy for patients with vulvar cancer. Despite the disappointing results of GOG protocol 74, many gynecologic oncologists began performing SLNB in vulvar cancer patients. By 2000, there were enough single-institution experiences supporting SLNB for patients with vulvar cancer to mount two large multicenter trials. The GOG began a validation trial in December 1999, which is still accruing patients, to determine the sensitivity and false-negative rate of SLNB in a large community-based setting. The Dutch investigators began an observational trial in March 2000, which is reported in this issue of the Journal of Clinical Oncology. How can a new procedure be described as safe? In declaring the safety of SLNB in vulvar cancer, Van der Zee et al assumed a 2% relapse rate in patients receiving the current standard treatment. The authors’ own work suggests that the acceptable relapse rate for patients is as close to zero as possible, and patients consider lymphedema as an acceptable toxicity to achieve this degree of safety. The 2% relapse rate is high compared with the GOG historical controls. However, the historical GOG patients underwent an extensive inguinal femoral lymphadenectomy that most gynecologic oncologists no longer perform because of the associated morbidity. How does the 3% false-negative rate compare with experiences at other disease sites? Large single-institution studies report falsenegative rates of 4% to 5% in validation trials of SLNB in patients with breast cancer and melanoma. In the multi-institutional community setting, the National Surgical Adjuvant Breast and Bowel Project B-32 investigators found a false-negative rate of 9.8% in patients with early breast cancer. Despite these high numbers, isolated axillary failures are considered rare in patients with early breast cancer because the majority of SLN-negative patients receive adjuvant treatment that effectively treats microscopic metastases. This situation is different from vulvar cancer. Adjuvant therapy for vulvar cancer (regional radiotherapy) is exclusively based on lymph node status. Mortality from local relapse in the groin is high in all studies, including the study reported here. The current treatment paradigm for vulvar cancer does not leave room for error in the determination of lymph node status. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 6 FEBRUARY 2