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Epidemiology and burden of uterine adenosarcoma

TL;DR — Adenosarcoma is rare enough that almost every incidence figure is a share of something else, not a population rate. Reviews place it at ~5% of uterine sarcomas (Nathenson 2016, PMID 27718181; Friedlander 2014, PMID 25341585); NCDB 1998–2011 found Müllerian adenosarcoma in 0.43% of uterine, 0.16% of cervical and 0.04% of ovarian cancers (Seagle 2016, PMID 27771166). SEER 1988–2006 contained 544 adenosarcomas among 5,496 uterine “sarcoma” registrations that included carcinosarcoma (Arend 2010, PMID 20688363). Median age is late 50s in classic series (Clement 1990, PMID 2156771) and younger in some surgical series (Yuan 2019, PMID 31139558; Li 2022, PMID 35005157). No study reports a true population incidence of uterine adenosarcoma with central pathology review. Conflicting age and stage mixes between series are expected and should not be averaged.

Share of uterine cancer and of uterine sarcoma

Uterine sarcomas themselves are uncommon: D’Angelo and Prat’s review states they account for 3% of uterine cancers (D’Angelo 2010, PMID 19853898). Within that group, adenosarcoma is the small remainder after leiomyosarcoma and endometrial stromal sarcoma, once carcinosarcoma is reclassified as a metaplastic carcinoma (D’Angelo 2010, PMID 19853898; McCluggage 2016, PMID 26715175).

Quantity Estimate Population / method Source
Share of uterine sarcomas ~5% Review synthesis of published series Nathenson 2016, PMID 27718181; Friedlander 2014, PMID 25341585
Share of uterine sarcomas 5–8% Review introducing a fertility-sparing case L'Heveder 2019, PMID 31584132
Share of uterine cancers in NCDB 0.43% (1,884 / uterine cancers in the extract) NCDB 1998–2011, uterus primary Seagle 2016, PMID 27771166
Share of cervical cancers in NCDB 0.16% (229 cases) NCDB 1998–2011 Seagle 2016, PMID 27771166
Share of ovarian cancers in NCDB 0.04% (92 cases) NCDB 1998–2011 Seagle 2016, PMID 27771166
SEER adenosarcomas 1988–2006 544 of 5,496 (10%) of a sarcoma-including-carcinosarcoma extract SEER; carcinosarcoma is the majority of that denominator Arend 2010, PMID 20688363
SEER uterine adenosarcoma 1973–2013 994 SEER extract used for nodal analysis Machida 2017, PMID 28109626
SEER for a survival model 797 SEER; no central review Qu 2020, PMID 33680946
Japan 2017 new diagnoses 41 uterine adenosarcomas vs 366 uterine sarcoma JSOG annual tumour registry, 2017 treatment-start Nagase 2021, PMID 33631867
Japan 2017 adenosarcoma / sarcoma 41/366 ≈ 11% of registered uterine sarcoma that year Same registry; one year Nagase 2021, PMID 33631867

The 5% and 10–11% figures are not directly comparable. Arend’s 10% is the observed proportion in a SEER extract whose denominator included carcinosarcoma (544/5,496), whereas the ~5% figure is a review synthesis assembled under different case definitions and eras; the sources do not establish why the estimates differ (Arend 2010, PMID 20688363; Nathenson 2016, PMID 27718181). JSOG’s 41 adenosarcomas versus 366 uterine sarcomas in 2017 is a one-year hospital-registry snapshot, not a national incidence (Nagase 2021, PMID 33631867). Brooks’ SEER analysis of 2,677 uterine sarcomas 1989–1999 included adenosarcoma in the case definition but did not report a histology-specific incidence in the abstract; overall age-adjusted uterine sarcoma incidence was 7/100,000 in Black women versus 3.6 in White and 2.7 in other races, driven by leiomyosarcoma and carcinosarcoma, not adenosarcoma (Brooks 2004, PMID 15047237).

No paper in the PubMed incidence search rerun 2026-09-01 reported an age-adjusted population incidence of uterine adenosarcoma per 100,000 women with central pathology review. The newer SEER epidemiology paper reports registry counts rather than a centrally reviewed incidence rate.

Age and site

Clement’s 100 cases: age 14–89, median 58; most presented with abnormal vaginal bleeding; enlarged uterus and tissue protruding from the external os were the common pelvic-exam findings (Clement 1990, PMID 2156771). Gallardo: mean age 50 (range 13–83); 37 corpus, 11 cervix, 4 ovary, 1 each tube, vagina, pouch of Douglas (Gallardo 2009, PMID 18941402). Yuan: median 47.5 (19–75); 19/49 (38.9%) cervical, 30/49 (61.2%) corpus (Yuan 2019, PMID 31139558). Li: median 51 (IQR 41–68); 23/31 (74.2%) corpus, 7/31 (22.6%) cervix, 1 ovary (Li 2022, PMID 35005157). Seagle NCDB: uterus 1,884, cervix 229, ovary 92 (Seagle 2016, PMID 27771166).

Younger medians in recent surgical series versus Clement’s 58 may reflect referral and the inclusion of more cervical primaries, but that is an inference from case mix rather than a tested explanation (Yuan 2019, PMID 31139558). The data do not demonstrate a falling age of incidence.

Stage mix

The majority present with stage I disease. Arend SEER: patients with adenosarcoma were younger and more often early-stage than patients with carcinosarcoma (p<0.0001) (Arend 2010, PMID 20688363). Gallardo: of 30 uterine-corpus tumours with known stage, 17 IA, 11 IB, 1 IC, 1 IIIC (Gallardo 2009, PMID 18941402). Carroll restricted the prognostic analysis to 74 of 100 identified patients; among stage I, 22 had SO and 37 did not (Carroll 2014, PMID 25449308). Registry stage mix cannot be compared with surgically staged institutional mix: SEER/NCDB lack sarcomatous overgrowth and have incomplete FIGO 2009 recoding.

Survival at population scale

Endpoint Estimate Population Source
5-year survival, stage I adenosarcoma 79% (95% CI 75–84%) SEER 1988–2006 Arend 2010, PMID 20688363
5-year survival, stage III adenosarcoma 48% (95% CI 29–65%) SEER 1988–2006 Arend 2010, PMID 20688363
Hazard of death vs carcinosarcoma HR 0.35 (95% CI 0.28–0.45) SEER, multivariable Arend 2010, PMID 20688363
Survival with uterine-wall invasion 63–69% SEER; “invade into the wall of the uterus” Arend 2010, PMID 20688363
Survival with extra-uterine disease <50% SEER Arend 2010, PMID 20688363
Stage I 5-year OS without SO up to 80% Guideline synthesis Karabajakian 2023, PMID 37202293; Ulrich 2018, PMID 30326467
Stage I 5-year OS overall 60–80% Review Nathenson 2016, PMID 27718181
Disease-specific death 34% (29/86) Japanese literature-assembled series Tate 2018, PMID 29441675
Stage IA recurrence / mortality 13% (4/30) recurrence; 3.3% (1/30) death Same Japanese series Tate 2018, PMID 29441675
NCDB: independent OS detriments Distant metastasis, positive margin, older age, higher comorbidity, adjuvant radiotherapy n=2,205 Müllerian adenosarcoma Seagle 2016, PMID 27771166

Arend’s comparison with carcinosarcoma is the cleanest relative-survival statement in the registry literature (65% lower hazard of death) and still treats two histologies coded in the same era, one of which has since been reclassified as carcinoma (Arend 2010, PMID 20688363). Tate’s 34% disease-specific death is from a series assembled mostly from published case reports and is biased toward remarkable outcomes in both directions (Tate 2018, PMID 29441675). Qu’s deep-learning c-index of 0.774 on 797 SEER patients is a discrimination statistic for a model, not a survival rate (Qu 2020, PMID 33680946).

Seagle found adjuvant radiotherapy independently associated with decreased OS (Seagle 2016, PMID 27771166). That is confounding by indication until proven otherwise: radiation is given to worse tumours. Nathenson’s institutional series found no OS difference for adjuvant radiation (Nathenson 2018, PMID 30044322). Do not average these.

Why case-mix differs

Institutional series enrich for SO, heterologous elements, and referral-stage disease (Kaku 55% SO in a GOG staging protocol, PMID 1316323; Carroll’s SO-stratified stage I split). Registries enrich for coded stage and age and are blind to SO and LVSI (Qu 2020, PMID 33680946; Machida 2017, PMID 28109626). Literature-assembled series enrich for published recurrence and death (Tate 2018, PMID 29441675). Cervical-primary series are younger (Yuan 2019, PMID 31139558). None of these is the population.

Open questions

  • What is the population incidence of uterine adenosarcoma under current WHO criteria with pathology review? Not reported in the papers retrieved this session.
  • How much do registry 5-year survival figures (Arend stage I 79%) overstate outcome for SO-positive disease and understate it for SO-negative disease? Registries cannot answer; a linked pathology-registry study would.

References

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  2. Friedlander ML, et al. GCIG consensus review for mullerian adenosarcoma of the female genital tract. Int J Gynecol Cancer. 2014;24:S78-82. PMID 25341585
  3. Seagle BL, et al. Survival of women with Mullerian adenosarcoma: A National Cancer Data Base study. Gynecol Oncol. 2016;143:636-641. PMID 27771166
  4. Arend R, et al. Long-term outcome and natural history of uterine adenosarcomas. Gynecol Oncol. 2010;119:305-8. PMID 20688363
  5. Machida H, et al. Significance of lymph node metastasis on survival of women with uterine adenosarcoma. Gynecol Oncol. 2017;144:524-530. PMID 28109626
  6. Qu W, et al. Development and Validation of a Personalized Survival Prediction Model for Uterine Adenosarcoma. Front Oncol. 2020;10:623818. PMID 33680946
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  10. Gallardo A, Prat J. Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases. Am J Surg Pathol. 2009;33:278-88. PMID 18941402
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  19. L'Heveder A, et al. Conservative management of uterine adenosarcoma: lessons learned from 20 years of follow-up. Arch Gynecol Obstet. 2019;300:1383-1389. PMID 31584132
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