Gynecologic Oncology/Sarcomas

Leiomyosarcoma (LMS)

Case 1: Leiomyosarcoma diagnosis after hysterectomy by benign gynecologist

42 yo underwent a TAH for presumed fibroid causing meno-metorrhagia. Uterus was 20 wks in size. Ovaries appeared normal according to the pathology report. Final pathology is significant for LMS. She is then sent to the gynecologic oncologist for further management.

• Investigations:CT Chest/Abdomen/Pelvis (Lung metastasis is common)
• Surgery:
  • CT negative: No further surgery recommended
    
    • Risk of ovarian metastasis is <3% PMID 14529683; Lymph node metastasis is less than 7% (Barakat, ISBN 1451176597
      Ovarian preservation recommended as worsened disease specific survival with oophorectomy PMID 12798712
  • CT positive: Poor prognosis. Not much literature available
• Adjuvant Radiation: No benefit in overall survival and progression free survival. Benefit in loco-regional failures. However in LMS increased distant failures

• EORTC 55874 (1987-2000) -- observation vs. pelvic RT
  • Randomized. 224 patients with high grade uterine sarcoma (leiomyosarcoma 46%, carcinosarcoma 41%, endometrial stromal sarcoma 13%), Stage I-II, treated with TAH/BSO + washings (75%), nodal sampling optional (25%). Arm 1) observation vs. Arm 2) pelvic RT 50.4/28 Field: top border L4/L5, lower border lower margin of obturator foramina, posterior border S2/S3
  • 2008 PMID 18378136 -- "Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)." (Reed NS, Eur J Cancer. 2008 Mar)
    • Outcome: Loco-Regional Recurrence(LRR) only observation 18% vs. RT 3%, LRR at any time 40% vs. 21% (SS); no impact on PFS or OS
    • By subset: No benefit for LMS, improved local control for Carcinosarcoma
    • Conclusion: Pelvic RT improves local control but not PFS or OS for carcinosarcoma, there is no benefit in leiomyosarcoma

• Adjuvant Chemotherapy: Phase II data shows activity of four cycles of gemcitabine and docetaxel followed by 4 cycles of doxorubicin PMID 23335221
  • FIGO stage I 81%, stage II 15%, and serosa-only stage IIIA 4%
  • 78% progression free at 2 years and 57% progression free at 3 years
  • Phase III randomized trial underway GOG 277
    • ARM 1: Gemcitabine 900 mg/m2 IV days 1 and 8 plus Docetaxel 75 mg/m2 IV day 8 (GCSF support) x 4 cycles every 21 days -->CT/MRI if disease free --> Doxorubicin 60 mg/m2 IV q 21 days x 4 cycles
    • ARM 2: Observation