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

The impact of operative techniques to the onset of peritoneal tumor dissemination in patients

with uterine leiomyosarcomas

Disclosures

No disclosures

Introductory remarks

Uterine sarcomas are rare, but highly malignant tumors Approximately 8-10% of all uterine cancers Mostly diagnosed incidentally, postresectional < 2% of all hysterectomy specimens for uterine leiomyoma Historically, confusion in understanding of pathological

subtypes Different pathologies often combined in clinical reviews

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)

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

Courtesy: Storz Co.

Typical procedure for laparoscopic myoma removal from the uterus

Courtesy: Storz Co.

Typical procedure for laparoscopic myoma removal from the uterus

Courtesy: Storz Co.

Typical procedure for laparoscopic myoma removal from the uterus

Courtesy: Storz Co.

What if this leiomyoma is later diagnosed as a leiomyosarcoma ?

Case report:

Patient: 43 yrSigns and symptoms: abdominal pain, dysuria

Preoperative diagnosis: rapidly growing uterine leiomyomaTherapy: 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: PD3rd line therapy with pazopanib

Case #29, 43yr: this was later diagnosed as a leiomyosarcoma !

preoperative

2 month follow up

Trocar positioning

Courtesy: Storz Co.

preoperative

2 month follow up

Location of mets. as a consequence of trocar positioning

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

Quality of Surgery for Primary Gastro-Intestinal Stromal Tumors in Patients Undergoing Adjuvant

Imatinib Treatment. Experience of the EORTC STBSG 62024 Study

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

CTOS 2011:

Reason for surgery, n = 926 Circumstances of resection and technique

(emergency, open vs. laparoscopically) Extent of resection Concordance of preop. and intraop. findings Completeness of resection

Data to be reported :

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

Adopted for uterine sarcoma

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.

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

Results 1

Patients identified with an advanced uterine sarcoma, 2004-13 (n=46)

Leiomyosarcoma 50% (n=23)

Endometrial stroma sarcoma26% (n=12)undifferentiated endometrialsarcoma 4% (n=2)others 19% (n=9)

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 painVaginal bleedingPalpable massNot done

1224

1320

Preoperative presumptive diagnosis

Uterine leiomyomaUterine sarcomaOther, hypermenorrhoea)

310

4

2

FIGO stage IBIIBIIIAIVAn.d.

41103

20013

Grading G2G3n.d.

522

330

Size of tumor < 8cm> 8cmn.d.

261

213

Leiomyosarcoma (n= 25)

0

2

4

6

8

10

12

no metastasis 16% (n=4)

only peritoneal 12% (n= 3)

peritoneal and pulmonary40% (n=10)

primarily metastatic disease12% (n=3)

pulmonary and other site 4%(n=1)

peritoneal and other site 8%(n=2)

lost 8% (n=2)

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

Results 2

• 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 n=11, 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

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

Results 3

Cumulative peritoneal recurrence-free survival time C

umul

ativ

e D

isea

se -f

ree

Sur

viva

l

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

Results 4

p=0.0804

add 3 recent pts p=0.0677

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

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

Results 5

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

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.

Conclusions

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.

How to influence surgical data in cancer:

Conclusions

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

How to influence surgical data in cancer: