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Tumor depth, diameter predict SLN status, survival in Merkel cell carcinoma
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Increasing primary tumor diameter and depth independently predicted positive sentinel lymph node status and worse OS and disease-specific survival, according to study results.
Because of the rarity of Merkel cell carcinoma, data on tumor depth data with respect to the sentinel lymph node (SLN) status had been limited, according to study background. Further, unlike for melanoma, the impact of the depth of tumor invasion on SLN-status and survival for Merkel cell carcinoma had been undefined.
Vernon K. Sondak, MD, chair of the department of cutaneous oncology and director of surgical education at Moffitt Cancer Center in Tampa, Fla., a professor of surgery in the departments of oncologic sciences and surgery at the University of South Florida Morsani College of Medicine and a HemOnc Today Editorial Board member, and colleagues sought to determine the prognostic impact of primary tumor-related factors on SLN status and to identify pathological and clinical factors related to survival for Merkel cell carcinoma.
Vernon K. Sondak
“The clinicopathologic factors that predict sentinel node status and ultimate recurrence and death from Merkel cell are very poorly understood,” Sondak told HemOnc Today. “Current staging systems use tumor diameter, with a cutoff of 2 cm, to discriminate low- and high-risk patients with clinically node-negative Merkel cell carcinoma.
“There are several problems with tumor diameter as a prognosticator: First, the clinical diameter is not always measured prior to the initial biopsy because the diagnosis of Merkel cell carcinoma is rarely entertained preoperatively,” Sondak added. “Secondly, depending on the nature of the biopsy, the diameter may be difficult or impossible for the pathologist to determine histologically. Finally, even patients with relatively small Merkel cell carcinomas have a significant risk for metastasis and death. For all these reasons, new prognostic factors are needed for this increasingly prevalent disease.”
Use of SLNB
The researchers retrospectively analyzed 375 patients (median age, 75 years; range, 30-96; 70% male) with Merkel cell carcinoma treated at the Moffitt Cancer Center between 1988 and 2011. Patients had a median tumor diameter of 1.5 cm (range, 0.2-12.5) and median tumor depth of 4.8 mm (range, 0.3-45).
Patients were categorized into five groups: those with negative SLNs; those with positive SLNs; those who were clinically node negative but did not undergo a sentinel lymph node biopsy (SLNB); those with regional nodal disease without a known primary tumor; and those with Merkel cell carcinoma who concurrently had clinically evident regional nodal disease.
A total of 191 patients underwent SLNB, of whom 31% were node positive.
Ninety-one patients had both tumor depth and diameter reported. Analyses indicated that increasing diameter (P = .007) and increasing tumor depth (P = .017) were associated with SLN positivity. The odds of a positive SLN increased 1.4 times (95% CI, 1.1-1.9) as the tumor depth doubled and it increased 1.7 times (95% CI, 1.2-2.6) as the tumor diameter doubled.
There was no association between age and sex and SLN status.
Researchers also observed an association with worse OS for increasing diameter (P = .003), increasing tumor depth (P = .025), increasing age (P ˂ .0001) and immunosuppression (P = .007). The probability of death for immunosuppressed patients was 1.8 times (95% CI, 1.2-2.7) greater than those not immunosuppressed.
Increasing tumor depth and diameter also were associated with worse disease-specific survival (P ˂ .01).
Disease-specific survival also differed considerably by group. Patients who were node-negative achieved the highest rate of disease-specific survival, whereas patients with Merkel cell carcinoma with concurrent clinically evident nodal disease had the worst disease-specific survival (P = .018).
“We believe these results support the routine measurement and reporting of tumor depth in all cases of Merkel cell carcinoma,” Sondak said. “Our results also support the continued use of sentinel lymph node biopsy for the staging of the clinically negative regional node basin. Further studies are needed to determine if there are any patients with clinically node-negative Merkel cell carcinoma who have such a low risk of nodal metastasis as to not require sentinel node biopsy (akin to patients with thin melanomas < 0.76 mm), and to determine optimal strategies to manage the regional nodes in patients with microscopic metastases to the sentinel node(s).”
More validation needed
In an accompanying editorial, Dale Han, MD, an assistant professor of surgery at the Yale University School of Medicine and Jayasri G. Iyer, MD, acting instructor of the division of dermatology in the department of medicine at the University of Washington, wrote that although the results of this study are promising in finding predictive markers for Merkel cell carcinoma, more needs to be done to validate these data.
“[The study] reports that tumor thickness predicts survival, although this was shown only in univariate analysis, and this is a limitation of the study,” Han and Iyer wrote. “Another limitation of this study… is that tumor thickness was known for only 188 of 375 cases (50.1%).”
Han and Iyer also pointed out that this study was unable to assess lymphovascular invasion as a predictive biomarker because of incomplete data, and that despite the findings that tumor depth was a strong predictor of outcomes, the prognostic value of tumor thickness remains undefined.
Further, they noted that patients with Merkel cell carcinoma and nodal disease and an unknown primary tumor had improved OS when compared with patients with nodal disease and a known primary (P = .038), but the 5-year disease-specific death rate was not significantly different between these cohorts, likely because of the small number of patients (n = 28) with an unknown primary tumor.
“[This study] did show a trend (P = .14) toward an improved disease-specific death rate for patients who had an unknown primary, and this may have been due in part to differences in immune control,” Han and Iyer wrote. “Further studies with larger numbers of patients with an unknown primary are required to determine whether a significant difference in disease-specific survival is evident for this population.” – by Anthony SanFilippo
For more information:
Vernon K. Sondak, MD, can be reached at the Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612; email: vernon.sondak@moffitt.org.
Disclosure: Sondak reports consultant/advisory roles with Bristol-Myers Squibb, Merck, Navidea and Novartis. See the full study for a complete list of relevant financial disclosures for the other researchers. Han and Iyer report no relevant financial disclosures.
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