- Types of second primary cancer influence overall survival in cutaneous melanoma. - Background: Favorable survival in malignant cutaneous melanoma (melanoma) has increased the likelihood of second primary cancer (SPC). - We assess the influence of patient characteristics at diagnosis of first melanoma and the type of SPC (second melanoma and other SPC) on overall survival.. - Methods: We used the Swedish Cancer Registry data to assess overall survival in melanoma for the period 1990 to 2015. - Time dependent analysis showed vastly increased HRs for cancer types that are fatal also as first cancers, but SPC-specific HRs remained relatively uniform, irrespective of SPC diagnosed soon or late after first melanoma. - In early-onset melanoma, SPC diagnosis after 10 years may not negatively influence overall survival.. - Conclusions: As the overall survival of patients with many types of SPCs is unfavorable, advice about health lifestyle should benefit smoking patients and early detection methods may be recommended for SPCs of the breast, prostate and colorectum.. - Keywords: Independent primary, Second melanoma, Prognosis, Time-dependent analysis, Overall survival. - To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.. - The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.. - Full list of author information is available at the end of the article. - melanoma patients [9]. - Here we want to characterize the relationships for overall survival depending on gender, age at diagnosis and time interval between first melanoma and common types of SPCs using data from the Swedish Cancer Registry. - Patients diagnosed with histology-verified first primary invasive melanoma between 1990 and 2015 were identified in Swedish Cancer Registry according to International Classification of Diseases 7th revision (ICD-7) and they were followed for diagnosis of any of the 35 different SPCs including second melanomas.. - The follow-up for overall survival was started after first melanoma diagnosis and terminated at the date of emigration, death, or 31st December 2015, which- ever came earliest.. - The effect of time intervals from first melanoma to SPC diagnosis (no SPC, less than 1 year, 1–5 years, 6–10 years and longer than 10 years) and age at diagnosis of first melanoma (<. - Patients were stratified based on their time from first melanoma to SPC. - HRs were esti- mated according to diagnosis of SPC (time-dependent variable). - In the model, year of diagnosis of first primary melanoma, place of residence (big cities, northern Sweden, southern Sweden and unspecific) and socio- economic status (blue-collar worker, white-collar worker, farmer, private business, professional, or other/. - Kaplan-Meier curves were generated with stratification on time intervals from first melanoma to SPC diagnosis, age at diagnosis of first melanoma and gender.. - Age at diagnosis (years old) <. - Year at diagnosis . - Second melanoma 1856 4.0. - Interval from first melanoma to SPC (yrs) SPC=Second melanoma <. - Characteristics of the melanoma cohort are described in Table 1. - SPCs were de- veloped in 15.3% of the patients, among which 1/3 were second melanomas and 2/3 other SPCs. - Additional data, not shown in Table 1: median (interquartile range, IQR) time from first melanoma to SPC was and 5 (2–10) years for any SPCs, second melanoma and other SPC, respectively. - Median (IQR) age at diagnosis of first melanoma was and years for patients with any SPCs, second melan- oma and other SPC, respectively. - Median (IQR) age at diagnosis of SPC was correspondingly 72 years and years.. - The difference of overall survival be- tween genders was even higher for patients with sec- ond melanoma (56% vs. - Table 2 displays HRs for overall survival in time-dependent analysis using mul- tivariable Cox regression. - Male and female overall survival data after second melanoma are shown on the top part of Table 2. - Advanced age at diagnosis of first melanoma was associated with increased HRs ir- respective of SPC diagnoses. - deaths (60–79 years) HRs for overall survival were quite constant, approximately 3.0–4.0 for males and 5.0–6.0 for females, irrespective of the time interval from first to second cancer. - for those diagnosed at age over 79 years, the corresponding HRs range were 10–14 and 16–22. - Although among patients whose follow-up time equal or longer than 6 years, the effect of SPCs on overall survival was stronger than those with follow- up time less than 6 years.. - 1 to 2 stratified by gender and type of SPC (melanoma, other), age at diag- nosis of first melanoma and time interval between melan- oma and SPC. - As one of the stratified variables was the time interval from first melanoma to SPC there were no deaths before the allowed follow-up started. - Other features were the generally better overall survival for young compared to old patients, patients with second melanoma compared to those with other SPC and females compared to males. - Table 2 Hazard ratio of overall survival in melanoma patients based on gender, age at diagnosis of melanoma and interval from first melanoma to SPC diagnosis. - Gender Age at diagnosis (years old). - No SPC Interval from first melanoma diagnosis to SPC. - Second melanoma. - specifically when first melanoma was diagnosed before 60 and SPC was melanoma. - The decline in overall survival became ever steeper the longer the interval to SPC was.. - In Table 3 we show overall survival for common indi- vidual cancers as in Table 2. - 1 Survival probability stratified by time intervals from first melanoma to second melanoma diagnosis, gender and age at diagnosis of first melanoma in melanoma patients with/without second melanoma diagnosis. - Strata, age at diagnosis of first melanoma. - Interval: time intervals from first melanoma to second melanoma diagnosis. - Time, survival time from first melanoma diagnosis (in years). - 2 Survival probability stratified by time intervals from first melanoma to SPC diagnosis, gender and age at diagnosis of first melanoma in melanoma patients with/without other SPC diagnosis. - Interval: time intervals from first melanoma to SPC diagnosis. - Of note, for any of the listed SPCs, the HRs were below 1.0 when the first melanoma was diagnosed before age 60 and when more than 10 years elapsed from first melanoma to diagnosis of SPC except for lung cancer.. - For treatment-specific ef- fects, disease-specific survival is of main interest but for the study of co-morbidities (such as SPCs), overall survival is of primary interest. - According to an Australian study based on 20-year survival in thin melanoma (1 mm or less, accounting for 71% of all) only 2.2% of the patients had died of Table 3 Hazard ratio of overall survival in melanoma patients based on age at diagnosis of melanoma and interval from first melanoma to specific SPC diagnosis. - Age at diagnosis (years old). - No SPC Interval to SPC from first melanoma diagnosis. - In a Swedish study covering years 1958 through 2015 and median follow-up time since melanoma of 8 years, 74.2% of patients without SPC died of melanoma while for those diagnosed with SPC, first melanoma was the cause of death only among 24.5% of the patients. - Age at diagnosis is known to influence negatively both melanoma-specific and overall survival and we showed here that it also negatively influences overall survival in patients with SPC [1, 16]. - The current data on overall survival in melanoma patients, focusing on the time interval from first melanoma to SPCs, revealed two novel features. - The second novel feature was that, overall, the HRs were relatively uniform over the time intervals for diagnostic age- and SPC-specific overall survival.. - 1 to 2, which described an ever steeper decline in overall survival when the interval time was extended. - In this model the time interval to diagnosis of SPC is treated as a time-dependent variable to avoid the immortal time bias [11]. - Time-dependent data describe the true clinical situation, i.e., the overall survival for melanoma patients diagnosed with SPC. - However, even for cancers with moderate overall survival as first cancers, such as colorectal cancer and Hodgkin lymphoma, HRs as SPC were as high as around 13 and 15, respectively, when melan- oma was diagnosed at age 60 to 79 years. - In conclusion, survival analysis on melanoma patients with SPCs showed a lower overall survival in patients with second melanoma and in particular those with other SPCs. - The overall survival in SPC followed the expected overall survival from first cancer, patients with second lung cancer and CUP showed a very poor overall survival.. - For patients with SPC, a female overall survival advantage was noted over males, in addition to a strongly worsening overall survival in older patients, both in line with survival data in primary melanoma. - Time-dependent analysis sug- gested that young melanoma patients diagnosed with SPC 6 or 10 years later may not have worse overall survival. - It further showed that for melanoma diagnosed at common age groups, overall survival was relatively constant in pa- tients with particular SPCs irrespective of the time interval between first melanoma and SPC. - For the most fatal SPCs of the lung and unknown primary smoking is an important risk factor and advice about smoking cessation may be particularly well received at diagnosis of primary cancer [25]. - For the other common SPCs of the breast, prostate and colorec- tum screening methods are available and could be recom- mended at least for elderly patients with the highest risk.. - The online version contains supplementary material available at https://doi.. - org/10.1186/s x.. - Approval of the final text: All authors.. - Survival of patients with skin melanoma in Europe increases further: results. - of the EUROCARE-5 study. - https://doi.. - org/10.1016/j.ejca . - https://doi.org/10.1111/bjd.13483.. - https://doi.org/10.1093/jnci/djx030.. - https://doi.org/10.1093/jnci/81.8.611.. - https://doi.org/10.1002/cncr.20602.. - https://doi.org/10.1001/jamadermatol.2014.4777.. - https://doi.org/10.1016/j.ejca . - https://doi.org/10.1 016/j.jaad . - Reduced disease-specific survival following a diagnosis of multiple primary cutaneous malignant melanomas- a nationwide, population-based study. - https://doi.org/10.1002/ijc.30925.. - https://doi.org/10.1200/JCO . - https://doi.org/1 0.1002/ijc.30407.. - 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