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Recurrence and surveillance in uterine adenosarcoma

TL;DR — Recurrence risk is strongly case-mix dependent. Clement reported 23/100 recurrences at a mean 3.4 years (range 0.5–9.5), with one third at ≥5 years; Carroll reported stage I recurrence of 77% with sarcomatous overgrowth versus 22% without (Clement 1990, PMID 2156771; Carroll 2014, PMID 25449308). Tate’s literature-assembled series found 44% of 27 recurrences were distant and 75% of those involved lung (Tate 2018, PMID 29441675). Surgery for first recurrence was associated with OS of 26.3 versus 15.1 months in a 78-patient retrospective series, with unavoidable selection bias (Nathenson 2017, PMID 29445312). A PubMed search updated 2026-09-01 found no prospective comparison of adenosarcoma surveillance schedules.

Recurrence rates and timing

Series n Recurrence Timing Pattern
Clement 1990, PMID 2156771 100 23 cases Mean 3.4 years (0.5–9.5); ≥5 years in one third Almost always vagina/pelvis/abdomen; hematogenous in 2
Zaloudek 1981, PMID 6263458 25 adenosarcomas 10 (40%) Median interval to recurrence 5 years Deep myometrial invasion the correlate
Kaku 1992, PMID 1316323 30 with follow-up 9 (30%) Mean follow-up 38.3 months 6/30 (20%) already dead of tumour
Carroll 2014, PMID 25449308 Stage I: 22 SO / 37 no SO 77% vs 22% — SO the splitter
Tanner 2013, PMID 23283300 19 up-front treated (5 SO) 5/19 (26%) overall; 2-yr PFS 20% vs 100% by SO Median follow-up 72.9 months —
Gallardo 2009, PMID 18941402 29 with follow-up 6 metastases; 5 died Follow-up 2 months–18 years, average 7.5 years 4 of 5 deaths had SO; 2 deaths were typical low-grade
Tate 2018, PMID 29441675 110 assembled; SO outcome n=20; recurrences n=27 SO: 45% recurrence, 35% death; stage IA: 13% recurrence, 3.3% death Late recurrence emphasised Distant 44% of recurrences; lung in 75% of distant
Nathenson 2016, PMID 27718181 Review synthesis 23% without SO vs 77% with SO — Review compilation, not a cohort
Nathenson 2017, PMID 29445312 78 already recurrent/metastatic — Median OS from recurrence 1.8 years Pathology on recurrence influenced OS

Clement’s late recurrences (≥5 years in a third of those who recurred) are the reason reviews warn against short follow-up (Clement 1990, PMID 2156771; Tate 2018, PMID 29441675). Zaloudek’s median 5-year interval to recurrence in a 25-case series is the same signal (Zaloudek 1981, PMID 6263458).

Patterns

Local (vagina, pelvis, abdomen) predominates in the classic series (Clement 1990, PMID 2156771). Distant recurrence, when it occurs, involves lung in Tate’s assembled cases (12/27 recurrences distant; 75% of those included lung) (Tate 2018, PMID 29441675). That 75% is 9 patients in a literature-assembled series and should not be turned into a screening recommendation by itself; it is the reason Tate suggested “optimal follow-up focusing on late recurrence and lung metastasis.” Hematogenous spread was rare in Clement (2/100) (Clement 1990, PMID 2156771) and commoner once SO is selected for (Clement 1989: 4 of 10 SO cases had hematogenous metastases, PMID 2535774).

Pathology at recurrence can differ from the primary. Nathenson 2017: OS influenced by pathology on recurrence (p=0.035) (Nathenson 2017, PMID 29445312). Momeni Boroujeni documented ATRX frameshift mutations in 2 patients with high-grade recurrences after a primary low-grade adenosarcoma (Momeni Boroujeni 2022, PMID 36138078). Recurrence is not always the same tumour the first pathologist saw.

Salvage treatment

Nathenson 2017 (n=78):

  • Median OS from diagnosis of recurrence/metastasis: 1.8 years.
  • Surgery for first recurrence: median OS 26.3 vs 15.1 months.
  • Chemotherapy, palliative radiation, hormonal therapy: no OS association (p=0.58, 0.58, 0.15).
  • First-line chemotherapy PFS favoured doxorubicin/ifosfamide (15.4 months) over gemcitabine/docetaxel (5.0 months), other doxorubicin (6.5), platinum (5.7); OS from first-line chemotherapy did not differ by regimen (Nathenson 2017, PMID 29445312).

French GSF/TMRG and ESGO both recommend attempting complete surgical resection of relapse when feasible (Karabajakian 2023, PMID 37202293; Ray-Coquard 2024, PMID 39322612). That recommendation rests on the Nathenson association plus sarcoma-general practice, not a trial of resection versus systemic therapy.

Surveillance schedules

No adenosarcoma-specific surveillance RCT or prospective cohort comparing schedules was identified in the PubMed search rerun 2026-09-01. What published papers actually say:

  • L’Heveder’s conservatively managed patient was followed with pelvic ultrasound, hysteroscopy and endometrial biopsy twice a year and annual pelvic MRI for 10 years (L’Heveder 2019, PMID 31584132). That is one patient’s protocol, not a guideline.
  • Tate recommended “optimal follow-up focusing on late recurrence and lung metastasis” without specifying an interval (Tate 2018, PMID 29441675).
  • ESMO-EURACAN-GENTURIS 2021 covers follow-up of soft-tissue and visceral sarcomas as a class, not adenosarcoma (Gronchi 2021, PMID 34303806).
  • ESGO 2024 addresses follow-up and unmet needs of long-term survivors of uterine sarcoma as a group (Ray-Coquard 2024, PMID 39322612).

Any schedule in clinical use is extrapolated from uterine-sarcoma or endometrial-cancer practice plus the Clement/Tate late-recurrence observation. Intensifying imaging in stage IA without SO, where Tate’s assembled mortality was 3.3% (1/30), has no demonstrated yield (Tate 2018, PMID 29441675).

Open questions

  • Does lung imaging at defined intervals change outcome in SO-positive disease, or only the time at which metastasis is labelled? Tate’s 75% of distant recurrences involving lung is the hypothesis (PMID 29441675); it is not a screening study.
  • Should high-grade transformation at recurrence change systemic therapy independently of the primary’s grade? n=2 ATRX observations (Momeni Boroujeni 2022, PMID 36138078) plus Nathenson’s pathology-on-recurrence OS split (PMID 29445312).

References

  1. Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases. Hum Pathol. 1990;21:363-81. PMID 2156771
  2. Clement PB. Müllerian adenosarcomas of the uterus with sarcomatous overgrowth. Am J Surg Pathol. 1989;13:28-38. PMID 2535774
  3. Zaloudek CJ, Norris HJ. Adenofibroma and adenosarcoma of the uterus: a clinicopathologic study of 35 cases. Cancer. 1981;48:354-66. PMID 6263458
  4. Kaku T, et al. Adenosarcoma of the uterus: a Gynecologic Oncology Group clinicopathologic study of 31 cases. Int J Gynecol Pathol. 1992;11:75-88. PMID 1316323
  5. Carroll A, et al. Uterine adenosarcoma: an analysis on management, outcomes, and risk factors for recurrence. Gynecol Oncol. 2014;135:455-61. PMID 25449308
  6. Tanner EJ, et al. Management of uterine adenosarcomas with and without sarcomatous overgrowth. Gynecol Oncol. 2013;129:140-4. PMID 23283300
  7. Gallardo A, Prat J. Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases. Am J Surg Pathol. 2009;33:278-88. PMID 18941402
  8. Tate K, et al. Uterine adenosarcoma in Japan. Asia Pac J Clin Oncol. 2018;14:318-325. PMID 29441675
  9. Nathenson MJ, et al. Uterine Adenosarcoma: a Review. Curr Oncol Rep. 2016;18:68. PMID 27718181
  10. Nathenson MJ, et al. Treatment of Recurrent or Metastatic Uterine Adenosarcoma. Sarcoma. 2017;2017:4680273. PMID 29445312
  11. Momeni Boroujeni A, et al. Mullerian adenosarcoma: clinicopathologic and molecular characterization highlighting recurrent BAP1 loss. Mod Pathol. 2022;35:1684-1694. PMID 36138078
  12. 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
  13. Karabajakian A, et al. Uterin adenosarcoma: French Guidelines. Bull Cancer. 2023;110:836-843. PMID 37202293
  14. Ray-Coquard I, et al. ESGO/EURACAN/GCIG guidelines for the management of patients with uterine sarcomas. Int J Gynecol Cancer. 2024;34:1499-1521. PMID 39322612
  15. Gronchi A, et al. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines. Ann Oncol. 2021;32:1348-1365. PMID 34303806