Abstract
Surveillance, Epidemiology, and End Results (SEER) multiple myeloma (MM) survival statistics (https://seer.cancer.gov/statfacts/html/mulmy.html) that have been used to guide MM management and control have been systematically overestimated due to the inclusion of smoldering multiple myeloma (SMM), a premalignant condition of MM. Using the latest SEER release, we estimated the extent of such overestimation in the survival statistics. In 2016, 77.9% out of 5,495 patients reported as overall MM were symptomatic MM and 10.9% were SMM. Median survival was 65.8 months for overall MM versus 56.8 months for symptomatic MM (p<0.001). Inclusion of SMM overestimated MM survival by 9 months. Five-year relative survival estimates from 2015–2021 were 61.6% for overall MM, 57.9% for symptomatic MM, and 88.3% for SMM, versus SEER’s reported 62.4%. Survival statistics for symptomatic MM and SMM should be reported separately to guide MM management and prevention at the population level.
Multiple myeloma (MM) is a common plasma cell disorder accounting for approximately 10% of hematological malignancies in the United States. In 2025, there have been an estimated 36,110 patients diagnosed with MM and 12,030 deaths resulting from MM.1 Although not as prevalent as many other cancers, MM is associated with substantial health and economic burdens,2,3 and the prognosis of MM remains poor.
Data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program estimate a 5-year relative survival of 62.4% for MM during 2015–2021.1 These survival statistics from the SEER website (https://seer.cancer.gov/statfacts/html/mulmy.html) are the foremost resource to track, evaluate, and guide MM prevention and control in the United States. Moreover, SEER survival statistics are frequently used in clinical research and epidemiological studies to understand survival outcomes and trends in patients diagnosed with MM.5–11 SEER’s Annual Usage Metric reported that, in 2024, more than 126,000 publications referenced SEER data and approximately 25,000 relied on SEER data for primary analyses.12 Furthermore, the SEER website had over 22 million page views in 2024.12
Despite being the most representative and reliable cancer data in the United States that is extensively cited and used as a benchmark to guide MM prevention and control efforts, the reported statistics on SEER website can be impacted by numerous factors, such as change in diagnostic criteria, variable diagnosis documentation, and reporting. In particular, MM is consistently preceded by an asymptomatic precursor condition – smoldering multiple myeloma (SMM).13 The management of SMM has evolved over time from active monitoring for disease progression to active management using treatments for MM; however, there is no administrative code (e.g., International Classification of Diseases or International Classification of Diseases for Oncology) that distinguishes MM from SMM, thus contributing to variable reporting in cancer registries.
Consequently, SEER survival statistics have been calculated based on the cohort of all patients recorded as MM (hereafter, overall MM), which encompasses symptomatic MM (i.e., active malignancy), SMM (i.e., premalignant disease), other/unknown, and missing. As a result, we hypothesize that MM survival has been overestimated due to the inclusion of patients with SMM in SEER registries.
In April 2025, SEER published a site-specific variable for MM in SEER 17 based upon pathology reports and clinician statements that distinguishes symptomatic MM from SMM among reported diagnoses from 2012–2022 with survival follow-up until the end of 2022.14 SEER 17 includes 17 cancer registries and covers 26.5% of the U.S. population.15 Data description of the SEER Research data and dictionary of SEER variables can be found in SEER’s official website: https://seer.cancer.gov/data-software/documentation/seerstat/nov2024/.
We used data from the SEER 17 to estimate median overall survival and 5-year observed survival for symptomatic/active MM and compare them with those reported on the SEER website. For median survival, we used the cohort of patients that were diagnosed and recorded as MM (International Classification of Diseases for Oncology, 3rd edition, code 9732) in 2016. This represents the most recent cohort of patients for which median survival was reached for both overall MM and symptomatic MM, but not SMM. For assessing the trend in 5-year observed survival, we restricted our analysis to 2015–2017. We chose this time period because 2015–2017 were 1) the three most recent years for which this data was available as the survival data were followed until December 2022; and 2) the three most recent years after the change to the SLiM-CRAB diagnostic criteria for MM was implemented in 2014,16 so our analysis would not be impacted by this change.
Using the site-specific variable in SEER17, we stratified patients recorded as MM into four sub-categories: (1) symptomatic MM; (2) SMM; (3) other/unknown; and (4) missing. Among the selected patients, we pulled data on observed and relative survival for MM. Kaplan-Meier analyses were performed for observed overall survival (i.e., from the month of diagnosis to death or censoring on 12/31/2022) for overall MM (as reported on the SEER website) and stratified by SMM and symptomatic MM. Median survival was obtained from these analyses. Log-rank tests were performed to assess for statistically significant differences across groups.
Based on this cohort, we compared 5-year observed overall survival rates for overall MM, SMM, and symptomatic MM. Furthermore, the observed survival for overall MM, symptomatic MM, and SMM was stratified by treatment status. The chemotherapy variable in SEER is dichotomized into “Yes” or “No/Unknown.” Studies have shown that chemotherapy data in SEER has moderate sensitivity (approximately 68%), but high specificity, leading to a high positive predictive value.17 As such, patients in SEER for whom chemotherapy data is available are likely to have received therapy, but the absence of chemotherapy data does not imply the absence of treatment. Due to the potential for bias that may determine which patients receive treatment and/or have their treatment data recorded, we refrain from comparing survival across treatment groups. Rather, stratifying by treatment status, we aimed to quantify how survival among a given treatment group was affected by the cohort of patients analyzed (e.g., symptomatic MM vs. overall MM).
Finally, we replicated the reported 5-year relative survival estimate during 2015–2021 for overall MM on https://seer.cancer.gov/statfacts/html/mulmy.html and on SEER*Explorer and compared it with the respective estimates for symptomatic MM and SMM using SEER17. Similar to data available on SEER*Explorer, we obtained estimates of 5-year relative survival pooled during 2015–2021.18 In SEER*Explorer, data for MM is estimated from SEER21, which includes 21 cancer registries and covers 45.8% of the U.S. population4. However, the site-specific variable that distinguishes SMM from symptomatic MM was only available in SEER17, so we restricted our analysis to data from SEER17. Nevertheless, estimates of 5-year relative survival for overall MM were comparable between SEER17 (61.6%) and SEER21 (62.4%), suggesting that our results would likely be robust to the specific database used.
All analyses were conducted using SEER*Stat (v8.4.5)19 and R statistical software (v4.3.1).
Using data from SEER17, we included 5,495 newly diagnosed patients recorded as MM during 2016. Of those, 4,282 (77.9%) were symptomatic MM, 599 (10.9%) were SMM, 373 (6.8%) were other/unknown, and 241 (4.4%) were missing. Median survival for all patients recorded as MM was 65.8 months, compared to 56.8 months for patients with symptomatic MM (P <0.001; Fig. 1A). Median survival was not reached for patients with SMM by December 31st, 2022. The 5-year survival for overall MM consistently exceeded that of symptomatic MM for each diagnosis year during 2015–2017 (Fig. 1B).
Figure 1. Observed and 5-year relative survival from SEER 17.
(A) Observed survival for patients diagnosed in 2016 is shown as a function of time for overall MM (gray), symptomatic MM (orange), and SMM (blue). The shaded regions represent the 95% confidence intervals. Points and vertical line segments denote the median observed survival in months. (B) 5-year relative survival is shown as a function of the year of diagnosis. Vertical line segments denote the 95% confidence intervals. (C) Pooled 5-year relative survival for patients diagnosed during 2015–2021 is shown. Vertical line segments denote the 95% confidence intervals.
Among patients receiving treatment, observed survival for overall MM and symptomatic MM was similar (P=0.45; Table 1). However, among patients with no or unknown treatment, 5-year observed survival was 51.0% (95% CI: 48.8–53.2%) for overall MM as compared to 38.7% (95% CI: 36.0–41.5%) for symptomatic MM (P <0.001; Table 1).
Table 1.
Observed survival by treatment status for patients diagnosed in 2016
| Years | Observed Survival (%) (Standard Error) |
||||||
|---|---|---|---|---|---|---|---|
| Received Treatment | No/Unknown Treatment | ||||||
|
| |||||||
| Overall MM | Symptomatic MM | SMM | Overall MM | Symptomatic MM | SMM | ||
|
| |||||||
| 0 | 100 | 100 | 100 | 100 | 100 | 100 | |
| 1 | 84.4 (0.62) | 84.1 (0.66) | 95.5 (2.20) | 76.7 (0.92) | 68.0 (1.35) | 96.8 (0.78) | |
| 2 | 74.6 (0.75) | 73.9 (0.79) | 89.9 (3.20) | 68.3 (1.02) | 58.1 (1.43) | 92.9 (1.15) | |
| 3 | 66.6 (0.81) | 65.6 (0.86) | 83.2 (3.97) | 62.1 (1.06) | 50.5 (1.45%) | 88.6 (1.42) | |
| 4 | 59.9 (0.84) | 58.8 (0.89) | 80.9 (4.17) | 56.8 (1.09) | 44.8 (1.44) | 82.8 (1.69) | |
| 5 | 53.4 (0.86) | 52.3 (0.91) | 76.4 (4.50) | 51.0 (1.10) | 38.7 (1.42) | 78.2 (1.86) | |
| 6 | 47.7 (0.86) | 46.9 (0.91) | 68.5 (4.92) | 46.7 (1.10) | 34.2 (1.39) | 73.2 (2.00) | |
Using SEER17 data from 2015–2021 to replicate the reported 5-year relative survival estimate for overall MM on https://seer.cancer.gov/statfacts/html/mulmy.html, we obtained 61.6% (95% CI: 60.9–62.3%) for overall MM (similar to the reported 62.4% in the same time period based on SEER21), compared to 57.9% (95% CI: 57.1–58.6%) for symptomatic MM and 88.3% (95% CI: 86.1–90.1%) for SMM (Fig. 1C).
In summary, our analysis revealed a consistent overestimation in MM survival on the SEER website. By differentiating symptomatic MM from SMM using the newly released SEER17 site-specific variable, we demonstrated that the median observed MM survival was overestimated by 9 months in 2016 due to the inclusion of SMM patients. This overestimation may lead to an overly optimistic attribution of changes in MM survival to evolving management strategies in recent years. As such, the interpretation of the MM survival statistics on the SEER website should be interpreted with caution. More refined estimates of symptomatic MM survival should be used to enhance the assessment of MM management at the population level and guide MM prevention and treatment.
We acknowledge that cancer registries must provide timely data, which may preclude the time-intensive endeavor of abstracting information from pathology reports and clinician statements. Additionally, although this site-specific variable is available through SEER17, distinguishing SMM from symptomatic MM remains challenging due to the lack of clinical data on specific biomarkers and evidence of end-organ damage used to make these diagnoses16. Consequently, further work is needed to facilitate the availability and timely release of such data that would be necessary to generate unbiased estimates fundamental to guiding MM prevention and control policies.
The substantial difference in overall survival between SMM and symptomatic MM highlights the need for targeted research into SMM. The longer survival of SMM patients reinforces that it is a pre-malignant condition distinct from MM. As intensive monitoring and treatment of SMM in high-risk patients for progression becomes more available in clinical practice, monitoring trends in SMM survival using SEER’s new site-specific variable will help assess progress and inform management strategies.
Our study underscores the necessity for cancer registry databases to distinguish between premalignant and malignant stages to provide precise survival estimates when possible. MM management stakeholders—including researchers, clinicians, and policymakers—must consider these nuances to optimize patient care and resource allocation. Future research should focus on the clinical implications of these findings and explore the progression, management, and outcomes of SMM to develop targeted prevention strategies.
Acknowledgements:
We thank Ms. Jennifer Ruhl in the Quality Control section of the Surveillance, Epidemiology, and End Results (SEER) program for helpful comments on this manuscript. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; or the writing of the manuscript and decision to submit it for publication.
Funding:
This work was supported by the Foundation for Barnes-Jewish Hospital; the Siteman Cancer Center; the National Institutes of Health Grants R01 CA253475 and U01 CA265735.
Footnotes
Conflict of Interest:
All the authors of this manuscript do not have any conflict of interest to report.
Data Availability Statement:
All data for the Surveillance, Epidemiology, and End Results (SEER) database may be accessed publicly through the National Cancer Institute Surveillance, Epidemiology, and End Results Program website (https://seer.cancer.gov/data/access.html). Data description of the SEER Research data, dictionary of SEER variables, and cancer registries included are publicly available in SEER’s official website (https://seer.cancer.gov/data-software/documentation/seerstat/nov2024/).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data for the Surveillance, Epidemiology, and End Results (SEER) database may be accessed publicly through the National Cancer Institute Surveillance, Epidemiology, and End Results Program website (https://seer.cancer.gov/data/access.html). Data description of the SEER Research data, dictionary of SEER variables, and cancer registries included are publicly available in SEER’s official website (https://seer.cancer.gov/data-software/documentation/seerstat/nov2024/).