The Role of Sentinel Lymph Node Biopsy in Patients with Merkel Cell Carcinoma: Uncertainty Prevails

Abstract

‘‘Uncertainty is an uncomfortable position. Certainty is an absurd one.’’–Voltaire Sentinel lymph node (SLN) biopsy is a minimally invasive staging procedure that is now used in a wide range of cancer types to allow rational planning of further management. In patients with melanoma and breast cancer, the value of SLN biopsy is firmly established. It also provides useful and apparently reliable staging information for patients with other forms of cancer in which lymphatic spread to regional lymph nodes occurs. These include squamous cell carcinoma of the skin, oro-pharyngeal cancer, clear cell sarcoma, penile cancer, vulvar cancer, cervical cancer, vaginal cancer, endometrial cancer, testicular cancer, prostate cancer, esophageal cancer, gastric cancer, colorectal cancer, anal cancer, thyroid cancer, extra mammary Paget’s disease, and lung cancer. The value of SLN biopsy in patients with Merkel cell carcinoma (MCC), however, has not been clearly established, and its role in managing these patients remains unclear. The study by Kachare et al. reported in this issue of Annals of Surgical Oncology sheds some light on the matter, and its results suggest that management based on SLN status improves survival in patients with MCC. It was a large and well-conducted study, but the SEER data on which it was based were collected retrospectively, with possible biases at play, and the findings therefore should be regarded as hypothesis-generating rather than definitive. Biases may have been introduced for several reasons. Was SLN biopsy more likely to have been performed in younger, fitter patients and in those more likely to have T1 tumors managed at centers of excellence? What other investigations and treatments apart from radiation therapy (RT) might the patients have received? (And it must be noted that specific RT details are not available from the SEER database, e.g., whether it was administered to the primary tumor site, the regional lymph nodes, or both.) Could the fact that RT was more frequently given to patients who had a SLN biopsy than to those who did not (58 vs. 40 %) have been responsible, partly or wholly, for the better outcome in the SLN biopsy group? (This factor does not appear to have been included in the multivariate analysis that was performed.) Was SLN biopsy more likely to have been performed in recently treated patients compared with those treated earlier in the series? There may also have been selection bias, because although 3,118 patients with MCC were identified in the SEER database, more than half of them were excluded. The results of two other studies are pertinent to this discussion. For patients treated at the Memorial SloanKettering Cancer Center, Fields et al. reported that SLN status predicted neither recurrence nor survival. The 153 patients in this study make it the largest single-center experience of SLN biopsy in MCC reported to date. More recently, Fritsch et al. from the Medical University of South Carolina interrogated the SEER database from 1998 to 2008 to assess the role of SLN biopsy in head and neck MCC. Of 721 patients with MCC who underwent SLN biopsy, 173 (24 %) had head and neck primaries. The rate This comment refers to the article available at doi:10.1245/s10434013-3434-3.