GIST: Adjuvante Studien,

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The impact of operative techniques to the onset
of peritoneal tumor dissemination in patients
with uterine leiomyosarcomas
Franka Menge, Eva Hartmann, Monika Mathew, Bernd
Kasper, Peter Hohenberger Div. of Surgical
Oncology Thoracic Surgery Interdisciplinary
Sarcoma Center Faculty of Medicine Mannheim
University of Heidelberg, Germany
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Disclosures

• No disclosures

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Introductory remarks

• Uterine sarcomas are rare, but highly malignant
  tumors
• Approximately 8-10 of all uterine cancers
• Mostly diagnosed incidentally, postresectional
• lt 2 of all hysterectomy specimens for uterine
  leiomyoma
• Historically, confusion in understanding of
  pathological subtypes
• Different pathologies often combined in clinical
  reviews

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Introductory remarks - 2
Main histologic subtypes Leiomyosarcoma
(LMS) 67 Endometrial stromal sarcoma
(ESS) 17-25 Undifferentiated sarcomas (UES,
AJSP2008) 8-17 Carcinosarcoma (former
malignant Mullerian mixed tumor)
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Surgical problems of treatment

• Sarcoma is not recognized preoperatively
• Historical and modern operative techniques
• Hooking and myoma drill of the tumor
• Intraabdominal morcellation
• Consequence intraoperative tumor cell spillage
• Inoculation of the abdominal cavity

Morice, Eur J Gynaecol Oncol 2003 Einstein, Int
J Gynaecol Cancer 2008 Perri, Int J Gynaecol
Cancer 2009Seidman, PLOS One 2012
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Courtesy Storz Co.
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Typical procedure for laparoscopic myoma removal
from the uterus
Courtesy Storz Co.
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Typical procedure for laparoscopic myoma removal
from the uterus
Courtesy Storz Co.
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What if this leiomyoma is later diagnosed as a
leiomyosarcoma ?
Typical procedure for laparoscopic myoma removal
from the uterus
Courtesy Storz Co.
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Case report Patient 43 yr Signs and
symptoms abdominal pain, dysuria Preoperative
diagnosis rapidly growing uterine
leiomyoma Therapy abdominal hysterectomy and
salpingectomy with intraabdominal morcellation
(10/Dec/2012) Histological diagnosis uterine
leiomyosarcoma FIGO IB (no grading) Course of
disease 10/Dec/12 operation and first
diagnosis 30/Jan/13 CT scan multiple
intraabdominal mets. 06/Feb/13 treatment
start with doxorubicin (trial) result PD
2nd line therapy gemcitabine/docetaxel,
result PD 3rd line therapy with pazopanib
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Case 29, 43yr this was later diagnosed as a
leiomyosarcoma !
2 month follow up
preoperative
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Trocar positioning
Courtesy Storz Co.
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Location of mets. as a consequence of trocar
positioning
2 month follow up
preoperative
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Trocar positioning
3 month follow up
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Methods

• We tried to identify the impact of intrabdominal
  fragmentation or damage to the uterus on the
  occurrence and the time interval of peritoneal
  metastases of uterine LMS.
• All female patients presenting with advanced
  sarcoma of uterine origin
• 2004 2013, negative selection, typically M1 or
  locoregionally recurrent
• Retrospectively evaluated
• EORTC example of GIST study 62024

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Quality of Surgery for Primary Gastro-Intestinal
Stromal Tumors in Patients Undergoing Adjuvant
Imatinib Treatment. Experience of the EORTC
STBSG 62024 Study
CTOS 2011

• P. Hohenberger1, S. Bonvalot2, F. van Coevorden3,
  P. Rutkowski4, E. Stoeckle5, C. Olungu6, M.
  vanGlabbeke6, A. Gronchi7, P. Casali7

Mannheim University Medical Center1 Institute
Gustave Roussy, Paris2 NKI/van Leuuvenhoek
Ziekenhuis3 Maria Sklodowska Cancer Center
Warsaw4 Bergonie, Bordeaux5 EORTC Brussels6
Istituto Nazionale dei Tumori, Milano7
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Data to be reported

• Reason for surgery, n 926
• Circumstances of resection and technique(emergenc
  y, open vs. laparoscopically)
• Extent of resection
• Concordance of preop. and intraop. findings
• Completeness of resection

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Adopted for uterine sarcoma

• The data of primary surgery were reviewed.
• Revision of all source data documents
• - operation records
• - pathology report
• - letter of discharge
• - Data from 39 (46) patients could be reviewed

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Methods

• All female patients presenting with advanced
  sarcoma of uterine origin
• 2004 2013, negative selection, typically M1 or
  locoregionally recurrent
• Retrospectively evaluated.
• We reviewed the record of the operation, the
  pathology report with special regard to
  morcellation procedures, the use of myoma drill
  and completeness of the resection specimen.
• We set this into correlation with the type of
  tumor recurrence and clinical course.

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Endpoint of the analysis
retrospective comparison of the cum survival
time without peritoneal recurrence of uterine
LMS in patients with or without
intraabdominal tumor fragmentation or
damage.
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The impact of tumor morcellation on the prognosis
of patients with uterine leiomyosarcoma
Results 1

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Clinical parameters of all patients with
peritoneal metastatic spread
No tumor violation Morcellement/ myoma drill
Age Mean (range) yr 56,5 (28-75) 49,2 (43-59)
Initial presenting symptoms Abdominal pain Vaginal bleeding Palpable mass Not done 1 2 2 4 1 3 2 0
Preoperative presumptive diagnosis Uterine leiomyoma Uterine sarcoma Other, hypermenorrhoea) 3 1 0 4 2
FIGO stage IB IIB IIIA IVA n.d. 4 1 1 0 3 2 0 0 1 3
Grading G2 G3 n.d. 5 2 2 3 3 0
Size of tumor lt 8cm gt 8cm n.d. 2 6 1 2 1 3
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The impact of tumor morcellation on the prognosis
of patients with uterine leiomyosarcoma
Results 2

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The impact of tumor morcellation on the prognosis
of patients with uterine leiomyosarcoma
Results 3

• 22/39 (58) pts. had developed peritoneal
  metastases (13 LMS, 4 ESS, 5 other histologies)
  
• LMS only two patients had M1PER at initial
  surgery.
• LMS n11, sarcoma had not being recognized at
  surgery.
• 6/11 women had a documented intrabd. morcellation
  or injured uterus due to the use of an myoma
  drill
• Time to diagnosis of the peritoneal metastases
  18,3 months (range, 2-39 mos.)
• 5/11 pts. without tumor damagetime to detection
  of peritoneal spread 33,6 months (range, 14-51
  mos.), p 0.0804

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The impact of tumor morcellation on the prognosis
of patients with uterine leiomyosarcoma
Results 4
Cumulative peritoneal recurrence-free survival
time

Cumulative Disease -free Survival
p0.0804 add 3 recent pts p0.0677
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The impact of tumor morcellation on the prognosis
of patients with uterine leiomyosarcoma
Results 5
Characteristics of patients with no tumor
recurrence
No Age (yr) LMS grading FIGO Tumor size (cm) Tumor injury Follow-up (months)
1 47 G1 IB 16 No 60
2 62 G2 IB 6 intravaginal morcellation 3
3 46 G2 IB 7 Myoma drill 18
4 51 n.d. IB 9 No 3
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Limitations of the study

• Patient selection criteria !
• Referral to tertiary center for metastatic
  disease
• Atypical history, unclear histology, unclear
  relationship to previous abdominal surgery
• Limited follow-up

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Conclusions

• Intraoperative mechanical damage such as
  morcellation and use of a myoma drill in
  unrecognized uterine leiomyosarcoma seems to
  have a (statistical) significant impact to the
  onset of intraperitoneal recurrence of the
  disease.

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Conclusions
How to influence surgical data in cancer

• Preoperative diagnosis of uterine sarcoma and
  separation from benign leiomyoma is required.
• Due to the lack of adequate preoperative
  diagnostics, surgery often performed as
  non-oncologic intended procedure
• Abandonment of techniques with tumor cell
  spillage is a must as soon as there is any hint
  for malignancy.

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Conclusions
How to influence surgical data in cancer

• A specimen extraction bag could be the easiest
  aid to avoid devastating tumor progression.
• Influencing surgery (technique indication)
  impacts the disease at the early stage
• Very much cost-effectivein comparison
  tochemotherapy for M1PER

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