Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study

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Abstract

Background

The situation of patients developing multiple primary cancers is becoming more frequent and graver. This study investigated the risks of developing second primary cancers that are related to first primary cancers, and the interval times of synchronous and metachronous multiple primary cancers.

Patients and methods

Retrospective data were retrieved from 109,054 patients aged ≥18 who were diagnosed with a first solid cancer and registered at Siriraj Cancer Center between 1991 and 2015. A two-month period between first- and second- primary cancers was used to differentiate metachronous and synchronous multiple primary cancers. The combinations of subsequent cancers and relative risks (RRs) of having multiple primary cancers versus having single primary cancer for the top-ten first and second primary cancers were examined. The RR was adjusted for age of the first primary cancer. A survival analysis of the time to second-primary-cancer development was performed.

Results

Multiple primary cancers were found in 1785 (1.63%) patients. Most (70.87%) second primary cancers occurred after 2 months of first breast, skin, colorectal, lung, head and neck, liver, male genital cancer–prostate, thyroid, and female genital cancer–non-uterine cancers, resulting in those cancers being classified as metachronous multiple primary cancer. After adjustment for age at first diagnosis, head and neck cancers had the highest metachronous association with second esophageal cancers (RR, 25.06; 95% CI, 13.41–50.77). Prostate cancer and second colorectal cancer also demonstrated a high metachronous association (RR, 2.00; 95% CI, 1.25–3.05). A strong synchronous association was found between uterine and ovarian cancers (RR, 27.77; 95% CI, 17.97–43.63). The median time from the first uterine cancer to second-cancer development was 55 days.

Conclusions

The top-ten most frequent multiple primary cancers were the following: breast; liver; head and neck; colorectal; male genital cancer–prostate; skin; female genital cancer–uterine; thyroid; lung; and female genital cancer–non-uterine. Second primary cancers showed specific associations that depended on the first primary cancer. Physicians should be cognizant of the most common combinations and the interval times of metachronous and synchronous multiple primary cancers.

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Most cited references 35

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Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

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Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors

Prashanth Rawla, Tagore Sunkara, Adam Barsouk (2019)

According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Nearly 2 million new cases and about 1 million deaths are expected in 2018. CRC incidence has been steadily rising worldwide, especially in developing countries that are adopting the “western” way of life. Obesity, sedentary lifestyle, red meat consumption, alcohol, and tobacco are considered the driving factors behind the growth of CRC. However, recent advances in early detection screenings and treatment options have reduced CRC mortality in developed nations, even in the face of growing incidence. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Meanwhile, the general population can reduce their risk by lowering their red meat, alcohol, and tobacco consumption and raising their consumption of fibre, wholesome foods, and certain vitamins and minerals.

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Multiple primary tumours: challenges and approaches, a review

Alexia Vogt, Sabine Schmid, Karl Heinimann … (2017)

When in a patient more than one tumour in the same or a different organ is diagnosed, multiple primary tumours may be present. For epidemiological studies, different definitions of multiple primaries are used with the two main definitions coming from the project Surveillance Epidemiology and End Results and the International Association of Cancer Registries and International Agency for Research on Cancer. The differences in the two definitions have to be taken into consideration when reports on multiple primaries are analysed. In this review, the literature on multiple primaries is reviewed and summarised. Overall, the frequency of multiple primaries is reported in the range of 2–17%. Aetiological factors that may predispose patients to multiple primaries can be grouped into host related, lifestyle factors and environmental influences. Some of the most common cancer predisposition syndromes based on a clinical presentation are discussed and the relevant genetic evaluation and testing are characterised. Importantly, from a clinical standpoint, clinical situations when multiple primaries should be suspected and ruled out in a patient are discussed. Furthermore, general principles and possible treatment strategies for patients with synchronous and metachronous multiple primary tumours are highlighted.

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Author and article information

Contributors

Vitoon Chinswangwatanakul: vitoon.chi@mahidol.ac.th

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 23 September 2021

Publication date PMC-release: 23 September 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 1045

Affiliations

[1 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Siriraj Cancer Center, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; 2 Wanglang Road, Bangkok Noi, Bangkok, 10700 Thailand

[2 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Surgery, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand

[3 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand

[4 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Siriraj Center of Excellent for Research in Bioinformatics and Clinical Data Management, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand

[5 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Integrative Computational Bioscience Center, , Mahidol University, ; Nakhon Pathom, Thailand

[6 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Siriraj Genomics, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand

[7 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Gynecology, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand

[8 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Transfusion Medicine, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand

Article

Publisher ID: 8766

DOI: 10.1186/s12885-021-08766-9

PMC ID: 8461969

PubMed ID: 34556087

SO-VID: 1c93c211-ec13-4eb9-b70c-65dc705f0afb

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. 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.

History

Date received : 21 May 2021

Date accepted : 6 September 2021

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer registry,metachronous,multiple primary cancers,second primary cancer,synchronous

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer registry, metachronous, multiple primary cancers, second primary cancer, synchronous

Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study

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Abstract

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Patients and methods

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Conclusions

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Karger: Oncology

Most cited references 35

Cancer statistics, 2020

Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors

Multiple primary tumours: challenges and approaches, a review

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