Comparison of Survival Between Patients With Single vs Multiple Primary Cutaneous Melanomas

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Abstract

This cohort study evaluates incidence, time to subsequent melanomas, difference in staging, and survival among patients with single vs multiple primary melanomas in the Netherlands. Is there a difference in survival between patients with a single primary melanoma vs multiple primary melanomas? In this cohort study of 54 645 patients with a single primary melanoma and 2284 patients with multiple primary melanomas in the Netherlands, Breslow thickness was significantly decreased for second primary melanomas, but the likelihood of dying was 31% higher among patients with multiple primary melanomas, a statistically significant finding. Stricter follow-up strategies may be warranted for patients with multiple primary melanomas. Melanoma is one of the most rapidly increasing forms of cancer worldwide. Most studies about survival among patients with melanoma consider only the primary tumor and disregard the potential effect of multiple primary tumors. A better understanding of the prognosis of patients with multiple primary melanoma is important for patient counselling and follow-up strategies. To describe the epidemiologic features of multiple primary melanoma in patients from the Netherlands. This retrospective, population-based cohort study included adults with histologically proven, primary, invasive cutaneous melanoma in the Netherlands between January 1, 2000, and December 31, 2014, with a median follow-up of 75.1 months, using data from PALGA, the Dutch Nationwide Network and Registry of Histopathology and Cytopathology. Follow-up data were retrieved from the Netherlands Cancer Registry. Statistical analysis was performed from August 1, 2018, to September 3, 2018. A multivariable Cox model with a time-varying covariate was performed to assess overall survival between patients with a single primary melanoma vs those with multiple primary melanomas. Secondary outcomes included incidence of multiple primary melanoma, differences in Breslow thickness, and time between first and second multiple primary melanoma. Of the 56 929 study patients, 31 916 (56.1%) were female, with a mean (SD) age of 56.4 (16.2) years. A total of 54 645 single primary melanomas and 4967 multiple primary melanomas in 2284 patients were included. The median Breslow thickness decreased from 0.90 mm (interquartile range, 0.55-1.70 mm) for the first melanoma to 0.65 mm (interquartile range, 0.45-1.10 mm) for the second melanoma ( P < .001). For their second melanoma, 370 patients (16.2%) had a higher T stage, 1112 (48.7%) had the same T stage, and 802 (35.1%) had a lower T stage. In addition, 841 of 2284 second melanomas (36.8%) in patients with multiple primary melanomas were found during the first year of follow-up, whereas 624 of 2284 (27.3%) were found after 5 years of follow-up. These proportions did not vary when stratified for melanoma stage. Worse overall survival was seen among patients with multiple primary melanomas compared with patients with a single primary melanoma (hazard ratio, 1.31; 95% CI, 1.20-1.42; P < .001). A significant decrease in Breslow thickness between the first and second multiple primary melanoma was found, and overall survival among patients with multiple primary melanomas was significantly worse than that among patients with a single primary melanoma. These findings suggest that more strict follow-up strategies may be warranted for patients with multiple primary melanomas.

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Increased risk of second primary cancers after a diagnosis of melanoma.

Budd Tucker, Alisa M. Goldstein, Steven Freedman … (2010)

To quantify the risk of subsequent primary cancers among patients with primary cutaneous malignant melanoma. Population-based registry study. We evaluated data from 9 cancer registries of the Surveillance, Epidemiology, and End Results program from 1973-2006. We included 89 515 patients who survived at least 2 months after their initial melanoma diagnosis. Of the patients with melanoma, 10 857 (12.1%) developed 1 or more subsequent primary cancers. The overall risk of a subsequent primary cancer increased by 28% (observed to expected [O:E] ratio = 1.28). One quarter of the cancers were subsequent primary melanomas (O:E = 8.61). Women with head and neck melanoma and patients younger than 30 had markedly increased risks (O:E = 13.22 and 13.40, respectively) of developing a subsequent melanoma. Second melanomas were more likely to be thin than were the first of multiple primary melanomas (thickness at diagnosis <1.00 mm, 77.9% vs 70.3%, respectively; P < .001). Melanoma survivors had increased risk of developing several cancers; the most common cancers with elevated risks were breast, prostate, and non-Hodgkin lymphoma (O:E = 1.10, 1.15, and 1.25, respectively). Melanoma survivors have an approximately 9-fold increased risk of developing subsequent melanoma compared with the general population. The risk remains elevated more than 20 years after the initial melanoma diagnosis. This increased risk may be owing to behavioral factors, genetic susceptibility, or medical surveillance. Although the percentage of subsequent primary melanomas thicker than 1 mm is lower than for the first of multiple primary melanomas, it is still substantial. Melanoma survivors should remain under surveillance not only for recurrence but also for future primary melanomas and other cancers.

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Clinicopathological features of and risk factors for multiple primary melanomas.

Ami Patel, Leah Ben-Porat, Cristina Ferrone … (2005)

The incidence of multiple primary melanomas ranges from 1.3% to 8.0% in large retrospective reviews; however, the impact of certain risk factors is not understood. To determine the incidence of multiple primary melanomas (MPM) from a prospective, single-institution, multidisciplinary database, and to describe the clinical and pathological characteristics and risk factors specific to these patients. Review of a prospectively maintained database at Memorial Sloan-Kettering Cancer Center in New York, NY. A total of 4484 patients diagnosed with a first primary melanoma between January 1, 1996, and December 31, 2002. Incidence of and risk factors for MPM. Three hundred eighty-five patients (8.6%) had 2 or more primary melanomas, with an average of 2.3 melanomas per MPM patient. Seventy-eight percent had 2 primary melanomas. For 74% of patients, the initial melanoma was the thickest tumor. Fifty-nine percent presented with their second primary tumor within 1 year. Twenty-one percent of MPM patients had a positive family history of melanoma compared with only 12% of patients with a single primary melanoma (SPM) (P<.001). Thirty-eight percent of MPM patients had dysplastic nevi compared with 18% of SPM patients (P<.001). The estimated cumulative 5-year risk of a second primary tumor for the entire cohort was 11.4%, with almost half of that risk occurring within the first year. For patients with a positive family history or dysplastic nevi, the estimated 5-year risk of MPM was significantly higher at 19.1% and 23.7%, respectively. The most striking increase in incidence for the MPM population was seen for development of a third primary melanoma from the time of second primary melanoma, which was 15.6% at 1 year and 30.9% at 5 years. The incidence of MPM is increased in patients with a positive family history and/or dysplastic nevi. These patients should undergo intensive dermatologic screening and should consider genetic testing.