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. Author manuscript; available in PMC: 2019 Jun 1.
Published in final edited form as: JAMA Oncol. 2018 Jun 1;4(6):832–836. doi: 10.1001/jamaoncol.2017.3605

Prior cancer among persons newly diagnosed with cancer: An initial report from the Surveillance, Epidemiology, and End Results program

Caitlin C Murphy 1,2, David E Gerber 1,2,3, Sandi L Pruitt 1,2
PMCID: PMC6370034  NIHMSID: NIHMS1009420  PMID: 29167866

Abstract

Importance:

The U.S. cancer survivor population is rapidly growing. Cancer survivors are frequently excluded from cancer clinical trials and observational research.

Objective:

To examine prevalence of prior cancer among individuals newly diagnosed with cancer.

Design and Setting:

Linked observations across the population-based Surveillance, Epidemiology, and End Results (SEER) program of cancer registries (1975—2013) for 740,990 persons newly diagnosed with cancer from January 2009 through December 2013. Prevalence of prior cancer was estimated by age (+/− 65 years) and incident cancer type.

Main Outcome and Measure:

Prevalence of prior cancer was derived from SEER sequence numbers, which represent the order of all primary reportable tumors diagnosed in a lifetime. Incident cancers were categorized as: 1) first or only primary; 2) second order or higher primary in the same cancer site; and 3) second order or higher primary in a different cancer site.

Results:

Of 765,843 incident cancers diagnosed in 2009—2013, 141,021 (18.4%) represented a second order or higher primary cancer. Overall, one-fourth (25.2%) of older (age ≥65 years) and 11% of younger adults newly diagnosed with cancer had a history of prior cancer. Prevalence of prior cancer ranged from 3.5% to 36.9% according to incident cancer type and age, with most prior cancers diagnosed in a different cancer site.

Conclusion and Relevance:

A substantial proportion of patients diagnosed with incident cancer in the United States have survived a prior cancer. These patients may be excluded from clinical trials and underrepresented in observational research, and little is known about their treatment and survivorship needs. Understanding the nature and impact of prior cancer history is critical to improving clinical trial accrual and generalizability, disease outcomes, and patient experience.

The number of U.S. cancer survivors is rapidly growing, largely driven by the aging population, expanding cancer screening efforts, and improvements in cancer treatment. Over the past 30 years, the cancer survivor population increased four-fold to 15.5 million in 2016 and is expected to reach 26.1 million by 2040.1 Almost half of all survivors have lived 10 years after their initial diagnosis, and two-thirds have survived beyond five years.2 Survivors have complex health needs,3 including surveillance for recurrence, monitoring treatment-related toxicities, and managing emerging diagnoses, such as chronic conditions4 or new primary cancers.5

Cancer survivors are frequently excluded from cancer clinical trials. More than 80% of National Cancer Institute-affiliated lung cancer trials exclude patients with a prior cancer.6 Such restrictive eligibility criteria may exclude as many as 25% of patients newly diagnosed with lung cancer from participating trials.7 Although considerable scientific progress5 has been made understanding risk of developing a future primary cancer among specific groups of cancer survivors, this earlier work does not address how many patients diagnosed with incident cancer have survived a prior cancer. Understanding prevalence of prior cancer among patients with different types of incident cancer has important implications for both treatment and research.

Methods

We report prevalence of prior cancer among individuals newly diagnosed with cancer during 2009–2013 using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program of cancer registries. We linked observations across SEER 9 registries (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah, 1975—2013) to estimate prevalence of prior cancer by incident cancer type and age (+/− 65 years). Prevalence of prior cancer was derived from SEER sequence numbers, which represent the order of all primary reportable tumors (i.e., not metastatic or recurrent tumors) diagnosed in a lifetime. Sequence number “00” indicates an individual has only one primary cancer. For persons with multiple primaries, the sequence number for the first cancer is “01,” “02” for the second, and so forth. With few exceptions, including ovarian and prostate cancers, tumors from different anatomic sites, of different histology, or from separate organs of a pair are considered independent primaries.8

We categorized incident cancers as a: 1) first or only primary; 2) second order or higher primary in the same cancer site (e.g., two melanomas diagnosed at least one year apart); or 3) second order or higher primary in a different cancer site. Appendix 1 lists tumors classified as belonging to the same or different site. SEER collects the number but not site of cancers diagnosed outside geographically defined registry areas; therefore, some (range 1.0—14.3%) cases are categorized as having a prior cancer of an unknown site [data not shown].

For persons with more than one cancer diagnosed in the same year (n=23,150, 3.1% of total), we were unable to determine the order of diagnoses within that year; therefore, we randomly selected one cancer for analysis. The majority of persons diagnosed with more than one cancer in the same year (n=17,420, 75.2% of those with ≥ 1 cancer in same year, 2.4% of total) were diagnosed with two cancers of the same site (e.g., right and left breast cancer).

Results

There were 765,843 incident cancers diagnosed among 740,990 persons during 2009–2013, of which 141,021 (18.4%) represented a second order or higher primary cancer. Table 1 shows the proportion of incident cancers diagnosed as the first or only primary or a second order or higher primary of the same or different site. Prevalence of prior cancer differed by age: 11.0% among ages 20–64 years and 25.2% among ages ≥ 65 years (Table 1). Prevalence also differed by incident cancer type. Among persons aged 20–64 years, prior cancer was most prevalent among incident myeloid and monocytic leukemia (24.8%); anus, anal canal and rectum (18.2%); cervix and other female genital organs (e.g., vagina, vulva; 15.0%); and lung and other respiratory (14.6%) cancers. Prior cancers in this younger age group generally occurred in a different cancer site, although second order breast, cervical and other female genital, male genital, and testicular cancers were more often in the same site. For persons aged ≥ 65 years, incident cancers with highest prevalence of prior cancer were melanoma (36.9%); myeloid and monocytic leukemia (36.9%); bone and joints (34.0%); and urinary bladder and other urinary organs (32.5%). With the exception of breast cancer melanoma, most prior cancers among the older age group occurred in a different site.

Table 1:

Proportion of incident cancer cases diagnosed as a first or only primary or second order or higher primary (same or different cancer site) by incident cancer type and age (+/− 65 years), SEER 9, 2009–2013

Age <65 Years Age ≥65 Years
Total First or only primary Second order or higher primary, same site Second order or higher primary, different site Total First or only primary Second order or higher primary, same site Second order or higher primary, different site
N % n % n % n % n % n %
All cancer types 364961 324992 89.0% 12034 3.3% 18353 5.0% 400882 299830 74.8% 20736 5.2% 60712 15.1%
Anus, anal canal, anorectum 3844 3145 81.8% 215 5.6% 321 8.4% 1306 905 69.3% 53 4.1% 262 20.1%
Bone and joints (including soft tissue) 3306 2867 86.7% 84 2.5% 234 7.1% 2329 1537 66.0% 79 3.4% 547 23.5%
Brain and other nervous system 5141 4694 91.3% 79 1.5% 237 4.6% 3559 2787 78.3% 8 0.2% 587 16.5%
Breast (female)1 78163 68273 87.3% 5318 6.8% 2921 3.7% 52940 39753 75.1% 7181 13.6% 3932 7.4%
Cervix and other female genital organs 9098 7734 85.0% 775 8.5% 312 3.4% 3906 2708 69.3% 452 11.6% 533 13.6%
Colon and rectum 28040 25536 91.1% 535 1.9% 1275 4.5% 37070 27954 75.4% 1759 4.7% 5684 15.3%
Corpus and uterus 13566 12440 91.7% 19 0.1% 782 5.8% 9642 7952 82.5% 24 0.2% 1315 13.6%
Esophagus 2839 2523 88.9% 12 0.4% 226 8.0% 4101 2945 71.8% 50 1.2% 850 20.7%
Eye and orbit 679 605 89.1% 15 2.2% 38 5.6% 680 495 72.8% 13 1.9% 128 18.8%
Kaposi sarcoma2 711 682 95.9% __* __* 13 1.8% 173 135 78.0% __* __* 27 15.6%
Kidney and renal pelvis 11633 10348 89.0% 197 1.7% 716 6.2% 11343 8242 72.7% 227 2.0% 2168 19.1%
Liver and intrahepatic bile duct 9107 8382 92.0% 39 0.4% 458 5.0% 9918 7720 77.8% 41 0.4% 1684 17.0%
Lung and other respiratory 25816 22056 85.4% 559 2.2% 2233 8.6% 58477 41862 71.6% 2346 4.0% 10928 18.7%
Lymphocytic leukemia 3675 3344 91.0% 10 0.3% 206 5.6% 5660 4257 75.2% 16 0.3% 1134 20.0%
Lymphoma 16124 14598 90.5% 408 2.5% 720 4.5% 17348 12546 72.3% 635 3.7% 3251 18.7%
Melanoma3 34033 29222 85.9% 2549 7.5% 1463 4.3% 32190 20317 63.1% 5330 16.6% 5065 15.7%
Mesothelioma 313 266 85.0% __* __* 34 10.9% 1064 758 71.2% __* __* 250 23.5%
Myeloid and monocytic leukemia 4583 3448 75.2% 39 0.9% 441 9.6% 5947 3754 63.1% 75 1.3% 1481 24.9%
Myeloma 3808 3425 89.9% 61 1.6% 210 5.5% 6437 4930 76.6% 58 0.9% 1117 17.4%
Oral cavity and pharynx 13197 11466 86.9% 617 4.7% 712 5.4% 10831 7503 69.3% 965 8.9% 1797 16.6%
Ovary4 5303 4820 90.9% __* __* 341 6.4% 4631 3795 81.9% __* __* 624 13.5%
Pancreas 6491 5818 89.6% 3 0.0% 453 7.0% 13223 10090 76.3% 11 0.1% 2469 18.7%
Penis and other male genital organs 587 503 85.7% 36 6.1% 21 3.6% 649 421 64.9% 42 6.5% 151 23.3%
Prostate5 43116 40940 95.0% __* __* 1532 3.6% 54480 48701 89.4% __* __* 4284 7.9%
Stomach 4797 4253 88.7% 55 1.1% 350 7.3% 7489 5644 75.4% 115 1.5% 1335 17.8%
Testis 3942 3802 96.4% 70 1.8% 31 0.8% 90 68 75.6% 0 0.0% 18 20.0%
Thyroid and other endocrine 17773 16276 91.6% 88 0.5% 885 5.0% 4431 3222 72.7% 26 0.6% 883 19.9%
Urinary bladder and other urinary organs 8835 7607 86.1% 196 2.2% 657 7.4% 23568 15911 67.5% 1086 4.6% 4920 20.9%
Miscellaneous 6456 5653 87.6% 42 0.7% 531 8.2% 16839 12528 74.4% 115 0.7% 3288 19.5%
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SEER does not consider recurrences of tumors of the same histology reporting within 2 months as a new primary; both sides (left and right) of a paired organ site are generally considered independent primary cancers, with some exceptions: Kaposi sarcoma, mesothelioma, ovary, and prostate (described below)

Proportion of second order or higher primary cancers with unknown prior site ranges from 1.0% (testis, age≥65 years) to 14.3% (myeloid and monocytic leukemia, age <65 years), with median of 5.3% in ages <65 years and 2.9% in ages ≥65 years

1

Among breast cancer cases with a prior breast cancer in ages <65 years (n=5318), 347 (6.5%, 0.4% of total) also had a prior cancer of a different site; in ages ≥65 years (n=7181), 897 (12.5%, 1.7% of total) also had a prior cancer of a different site

2

Kaposi sarcoma (any site or sites) is always considered a single primary

3

Among melanoma cases with a prior melanoma in ages <65 years (n=2549), 199 (7.8%, 0.6% of total) also had a prior cancer of a different site; in ages ≥65 years (n=5330), 1341 (25.2%, 4.2% of total) also had a prior cancer of a different site

4

Bilateral epithelial tumors of the ovary within 60 days of diagnosis are a single primary

5

Only the first invasive adenocarcinoma of the prostate is reported to SEER

*

SEER coding rules specify that only the first of this cancer type is reportable (i.e., no subsequent primary tumors of the same site are reported to SEER)8

Discussion

Implications for Cancer Care Delivery

One quarter of older (age ≥65 years) and more than 10% of younger adults newly diagnosed with cancer have a history of prior cancer. Prevalence of prior cancer ranged from 3.5% to 36.9% according to incident cancer type and age, with most prior cancers diagnosed in a different cancer site.

Prior cancer history has important implications for cancer care delivery. Patients may have competing priorities concerning treatment decisions: a new diagnosis may interrupt management, treatment adherence, or outcomes related to a prior cancer. Differences in the prevalence of prior cancer by incident cancer type also highlight underlying or shared risk factors that may be amenable to targeted surveillance. For example, 30% or more of older persons diagnosed with cancers attributable to human papilloma virus (e.g., cervical and female genital, anal, oral cavity) or tobacco (e.g., lung, esophageal, oral cavity) had a prior cancer. An even larger proportion (36.9%) diagnosed with myeloid leukemia had a prior cancer, which may reflect leukemogenic effects of earlier cancer treatments.

Many cancer clinical trials exclude patients with a prior cancer, a practice that may exclude a substantial proportion of otherwise eligible patients. Excluding patients with a prior cancer likely arises from a long-held belief that a prior cancer diagnosis may interfere with study conduct and/or outcomes. However, this restrictive criterion limits generalizability and trial-generated knowledge to patients with a first or only primary—a slight majority of patients with certain cancer types. This is particularly concerning for older adults with uncommon cancers, where trial accrual is critical, standard therapies may be suboptimal, and prior cancer history is prevalent.

Determining the impact of prior cancer exclusion criteria on trial accrual requires disease- and protocol-specific details, including stage and timing of prior cancer diagnoses.9 In lung cancer, most trials use a 5-year exclusion window,6 prior cancers generally occur within that window, and having a prior cancer does not adversely impact survival.7,10,11 Consequently, including patients with a prior cancer in lung cancer trials could substantially improve accrual without affecting study outcomes. The sizable number of cancers newly diagnosed among cancer survivors highlights the importance of addressing similar questions for other cancer types.

Patients with prior cancer are also frequently excluded from observational research, including treatment and outcome studies using SEER-Medicare,12 Patterns of Care,13 Cancer Care Outcomes Research and Surveillance Consortium,14 and Veterans Health Administration15 data. Because observational studies often provide “real world” data to complement clinical trials, reconsidering the rationale of this eligibility criterion is important to advancing evidence-based practice.

Limitations

We could not determine order of multiple cancers diagnosed in the same year because only year of diagnosis is available in SEER data (i.e., not month or day). Prior cancers diagnosed outside of registry geographic areas are reflected in sequence number only, and there is no corresponding information on the prior cancer characteristics, including site. However, these limitations pertained to fewer than 5% of the total cancer cases diagnosed in the study period and are unlikely to impact our conclusions.

Conclusions

As the cancer survivor population continues to grow, understanding the nature and impact of a prior cancer is critical to improving trial accrual, generalizability of results from trials and observational studies, disease outcomes, and patient experience.

Key Points.

Question: How many patients diagnosed with incident cancer are cancer survivors?

Findings: Approximately 25% of older adults (age ≥65 years) and more than 10% of younger adults newly diagnosed with cancer have a history of prior cancer. Prevalence of prior cancer ranged from 4% to 37% according to age and incident cancer type, with most prior cancers diagnosed in a different cancer site.

Meaning: As the cancer survivor population continues to grow, understanding the nature and impact of a prior cancer is critical to improving clinical trial accrual, generalizability of results from trials and observational studies, disease outcomes, and patient experience.

Acknowledgements

This work was supported by the National Cancer Institute (R03CA191875 to SLP and DEG and K24CA201543 to DEG) and National Center for Advancing Translational Sciences (KL2TR001103 to CCM) at the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

The sponsor had no role in: design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Murphy had full access to all the data in the study and takes responsibility for the data and the accuracy of the data analysis.

Appendix I. Cancers considered to represent the same site

  1. Anus, anal canal, anorectum

  2. Bone and joints; soft tissue

  3. Brain and other nervous system, including cranial nerves and other nervous system

  4. Breast

  5. Cervix; vagina; vulva; other female genital organs

  6. Colon; rectum and rectosigmoid junction; small intestine

  7. Corpus and uterus

  8. Esophagus

  9. Eye and orbit

  10. Kaposi sarcoma

  11. Kidney and renal pelvis

  12. Liver and intrahepatic bile duct; gallbladder and other biliary; other digestive organs

  13. Lung and bronchus; trachea, mediastinum, and other respiratory; pleura

  14. Lymphocytic leukemia (including acute lymphocytic leukemia, chronic lymphocytic leukemia and other lymphocytic leukemia)

  15. Lymphoma (including Hodgkin and non-Hodgkin lymphoma)

  16. Melanoma of the skin; other non-epithelial skin

  17. Mesothelioma

  18. Myeloid and monocytic leukemia (including acute monocytic leukemia, acute myeloid leukemia, chronic monocytic leukemia, and other monocytic/myeloid leukemia)

  19. Myeloma

  20. Oral cavity and pharynx (lip, tongue, salivary gland, floor of mouth, gum and other mouth, nasopharynx, tonsil, oropharynx, hypopharynx, other oral cavity); nose, nasal cavity and middle ear; larynx

  21. Ovary

  22. Pancreas

  23. Penis; other male genital organs

  24. Prostate

  25. Stomach; retroperitoneum; peritoneum, omentum, and mesentery

  26. Testis

  27. Thyroid; other endocrine including thymus

  28. Urinary bladder; ureter; other urinary organs

Footnotes

The authors have no conflicts of interest to disclose.

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