Risks for noncutaneous second primary malignancy in cutaneous malignant melanoma survivors: an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) program

Abstract

Background It is known that malignant melanoma (MM) survivors are at increased risk of future primary MM. However, the risk for noncutaneous second primary malignancies (SPMs) is not as well‐understood. Methods An observational study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database was performed, assessing data from patients diagnosed with primary cutaneous MM to measure overall, as well as specific, tumor type and risk of SPM. Results Of the 132,438 patients recruited in the study population (mean age 55.5 years; 54% male), 23,794 SPMs were observed (O) (18% of patients at a mean age of 68.8 years), while 17,923 SPMs were expected (E) to occur (O : E 1.33, 95% CI 1.31–1.34). Excluding cutaneous MM occurring as a new primary malignancy, there was a significantly increased risk for SPMs among cutaneous MM survivors for each of the following tumor types: eye and orbit melanoma, tracheal, thyroid, salivary gland, retroperitoneum, small intestine, kidney, lymphoid and hematopoietic system, lymphoma overall, non‐Hodgkin lymphoma, lymphocytic leukemia overall, chronic lymphocytic leukemia, male genital system (including prostate), and breast. Certain gender‐specific trends for SPMs were also detected. Conclusions Patients with primary cutaneous MM are at increased risk for primary noncutaneous MM as well as noncutaneous SPMs that include numerous tumor types. Enhanced oncologic surveillance for a variety of tumor types in melanoma survivors is warranted.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer

“…Parameters tested were those published as risk factors for SPC, [1][2][3][4][5][6][7][8][9][10] age, sex, cancer types, metastatic disease at diagnosis as well as the application of immunotherapy and CC for the FPC. A backward selection procedure was used to determine the final model by removing non-significant variables (P > 0.05) one at a time.…”

“…The hazard ratio associated with the risk of SPC as compared with the general population are reported to range from 1.2 up to 30 depending on the FPC and its treatment. [1][2][3][4][5][6][7][8][9][10] We recently reported that the administration of ICIs, mostly PD-1/PD-L1 or CTLA4 antibodies for the FPC, was associated with a reduced risk of Time to 2nd cancer (months) A B Figure 1. Time to second primary tumor according to the treatment given for the first primary tumor.…”

“…Second primary cancers (SPCs) are increasingly diagnosed in the long term follow-up of children and adult patients cured of a first primary cancer (FPC). [1][2][3][4][5][6][7][8][9][10] In recent studies, over 10% of all incident cancers are SPCs. SPCs are among the important causes of early death in patients treated and cured of a first cancer, along with cardiovascular diseases and complications of the first cancer treatments.…”

“…SPCs are among the important causes of early death in patients treated and cured of a first cancer, along with cardiovascular diseases and complications of the first cancer treatments. [1][2][3][4][5][6][7][8][9][10] There are multiple risk factors for SPCs including genetic predispositions, carcinogens involved in the FPC (e.g. smoking, alcohol, sun exposure), lifestyle, overweight, low exercise.…”

“…The cytotoxic treatments given for the first cancer may also contribute to an excess risk of SPCs for cured patients. [1][2][3][4][5][6][7][8][9][10] This has been largely documented for secondary leukemias after alkylating agents, as well as for solid tumors in the irradiated field. 1,2,5,9 In recent years, immunotherapy for cancer using immune checkpoint inhibitors (ICIs), PD-1 or PD-L1 Ab as well as anti-CTLA-4 have transformed the management of patients with advanced cancers.…”