Thick Melanomas: Assessing Prognosis
Melanoma thickness has long been recognized as a useful prognostic indicator for melanoma. While the American Joint Committee on Cancer (AJCC) staging system emphasizes a combination of factors for staging, the system recognizes that thickness of a tumor is clearly important to predicting long-term outcomes. The risk for mortality increases as the thickness of the tumor increases. One recent analysis showed that the 10-year melanoma-specific survival (MSS) rate was as high as 92 percent for patients with thin melanomas up to 0.3mm thick and as low as 32 percent for those with melanomas thicker than 0.8mm. Specifically within tumors less than or equal to 1mm in thickness, researchers found “a biologically-relevant difference in outcome above and below 0.8mm.” For tumors up to 0.8mm, the 10- and 20-year MMS rates were 93.4 percent and 85.7 percent, respectively. For tumors 0.9-1mm thick, the10- and 20-year MMS rates were 81.1 percent and 71.4 percent, respectively.1
Melanomas >4 mm are generally considered “thick” and associated with a poor prognosis. As advanced melanoma treatments become more common, there is a need to understand prognostic attributes for these lesions that may lead to specific treatment consideration.
New Findings
While it is established that survival decreases as Breslow thickness increases, researchers sought to determine the relationship between survival and ultrathick tumors defined as >15 mm.
Their analysis looked at a pooled cohort of more than 5,500 Dutch patients with melanomas >4.0 mm in thickness diagnosed from 2000-2014.2 Median follow up was a little over three years. Breslow thickness has been associated with lower survival in both thin (<1.0 mm) and intermediate thickness melanomas (<4.0 mm); its association with survival was lost in ultrathick melanomas (defined as >15 mm) in this study. Other studies have shown recurrence free survival correlation to be lost when lesions became thicker than 8mm, although overall survival was not significantly different.3
An explanation for the more favorable than expected outcomes for ultrathick melanomas includes the fact that many have polypoid architecture and that desmoplastic melanomas were overrepresented in these thick primary melanomas (which tend to have a more favorable outcome). It is not clear if tumor microenvironment features are different in these thick primary melanomas.
Even with a generally poor prognosis for thick tumors, the ability to refine the patient’s risk profile can be helpful. Therapeutic options for advanced melanoma are expanding. Although the impact of these treatments would not be reflected in the data set evaluated here, the evolving approach to patient care makes prognosis more important. Patients who are candidates for therapeutic interventions must weigh the potential benefits and risks of treatment against their prognosis without treatment.
What About Breslow Density?
Researchers recently have advocated for a renewed focus on Breslow density (BD), a potential prognostic indicator that has not been as widely acknowledged as Breslow thickness (BT).
BD is a measure of the density of melanoma cells at the position where the BT is measured. Researchers investigated whether BD has prognostic value for overall survival independent of the BT.4 They analyzed 100 cutaneous melanomas and found that BT and BD had a strong correlation but were independent prognostic factors for OS. A combined Breslow score that reflects a function of BT and BD showed a marginal improvement in predicted five-year survival as compared with the BT alone. They call for further studies to determine if the combined Breslow score could become a validated clinical tool for prognosis.
1. Lo SN, Scolyer RA, Thompson JF. Long-Term Survival of Patients with Thin (T1) Cutaneous Melanomas: A Breslow Thickness Cut Point of 0.8 mm Separates Higher-Risk and Lower-Risk Tumors. Ann Surg Oncol. 2018 Apr;25(4):894-902.
2. El Sharouni MA, Rawson RV, Sigurdsson V, Witkamp AJ, van Gils CH, Scolyer RA, Thompson JF, van Diest PJ, Lo SN. The progressive relationship between increasing Breslow thickness and decreasing survival is lost in patients with ultrathick melanomas (≥15 mm in thickness). J Am Acad Dermatol. 2022 Feb 1: S0190-9622(22)00174-8.
3. Blakely AM, Cohen JT, Commission DS, Vezeridis MP, Miner TJ. Prognosis and management of thick and ultrathick melanoma. Am J Clin Oncol. 2019;42(11):824-829
4. Rashed H, Flatman K, Bamford M, Teo KW, Saldanha G. Breslow density is a novel prognostic feature in cutaneous malignant melanoma. Histopathology. 2017 Jan;70(2):264-272.
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