Second Primary Cancers in Melanoma Patients Critically Shorten Survival

Abstract

Background

Survival in malignant cutaneous melanoma has improved but increasing survival will result in an increased likelihood of the occurrence of second primary cancers (SPCs). SPCs may adversely interfere with survival. We quantified survival in patients with different types of SPCs, in comparison to known poor prognostic indicators of metastatic disease.

Methods

Data for melanoma and any SPCs were obtained from the Swedish Cancer Registry for years 2003 through 2015, including clinical TNM classification. SPCs were grouped into three ‘prognostic groups’ based on 5-year relative survival of these cancers as first primary cancer. Kaplan-Meier survival curves were generated and hazard ratios were estimated using Cox regression, adjusted for a number of variables and treating diagnosis of SPC as a time-dependent variable.

Results

The total number of first melanoma patients was 28,716 followed by 3,202 (11.1%) SPCs, 1/3 of which had a second melanoma while 2/3 had other SPCs. Among men diagnosed at age over 70 years, who survived at least 10 years, 31.4% had SPC. HRs (95% CI) for survival increased systematically from the reference rate of 1.00 (no SPC) to 1.59 (1.35–1.87) with SPC of good prognosis (78.6% of SPCs) to 3.49 (2.58–4.72) of moderate prognosis (12.0%) and to 7.93 (5.50–11.44) of poor prognosis (9.4%). In patients without SPC, the HRs increased to 2.62 (2.02–3.39) with any nodal metastases and to 5.88 (4.57–7.57) with any distant metastases compared to patients without local or distant metastases.

Conclusion

The data showed that SPCs are an increasingly common negative prognostic factor for melanoma. Future attempts to improve melanoma survival need to target SPCs.

Keywords:

• melanoma
• second cancer
• metastasis
• prognosis
• survival

Data Access, Responsibility, and Analysis

KH, GZ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author Contributions

Design: KH, GZ. Acquisition of data: JS, KS. Statistical analysis and interpretation: GZ, SC, KH, AF, AH. Manuscript writing: KH and all other authors. Approval of the final text: All authors. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Disclosure

A.H. is shareholder in Targovax ASA. A.H. is an employee and shareholder in TILT Biotherapeutics Ltd. The authors report no other conflicts of interest in this work.

Additional information

Funding

G.Z is a doctoral student supported by the China Scholarship Council (201606100057). This work was supported by Deutsche Krebshilfe, Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, The Swedish Research Council, Finnish Cancer Organizations, University of Helsinki and Helsinki University Central Hospital.