IMPACT OF TUMOR MORCELLATION
ON THE NATURAL HISTORY OF
UTERINE LEIOMYOSARCOMA
César Serrano, Titilope Oduyebo, Judith Manola,
Yang Feng, Michael G. Muto, Suzanne George
Dana-Farber Cancer Institute , Brigham and Women’s Hospital;
Harvard Medical School, Boston, USA
CTOS 18th Annual Meeting
Oct 30 - Nov 2, 2013
New York
Paper 011
Background
•
Uterine leiomyosarcoma (ULMS) accounts for about
1.5% of all uterine malignancies and 30% of uterine
sarcomas.
•
Complete surgical excision is the only established
curative treatment modality for localized disease.
•
Minimally invasive techniques are increasingly used
in the surgical treatment of uterine leiomyoma.
•
No specific symptoms/signs or diagnostic imaging
can reliably differentiate ULMS from leiomyoma
preoperatively. Because of this, inadvertent
morcellation of ULMS is increasingly seen in clinical
practice.
Background (con’t)
• Historically, ~50% of localized ULMS recurs
following resection.
• Lungs are the most common site of recurrence.
Pautier P, et al. 2000
Major FJ, et al. 1993
Kapp DS, et al. 2008
Uterine morcellation
•
Tumor morcellation involves fragmenting of lesions in
the abdominal cavity such that they can pass
through the laparoscopic ports.
•
Tumor morcellation has been associated with
dispersal of microscopic tumor fragments, which
entails potential seeding in the peritoneum.
•
One retrospective study observed that tumor
morcellation is an adverse prognosis factor
associated with shorter disease-free survival and
overall survival.
Seidman MA et al. 2012
Park JY et al. 2011
Aims of the study
To retrospectively assess the impact of tumor
morcellation on the natural history and outcomes of
patients with ULMS when compared to patients
who underwent total abdominal hysterectomy (TAH)
as the primary procedure.
Methods
• Patients with ULMS seen at Dana-Farber Cancer
Institute and Brigham and Woman’s Hospital from
2007-2012 were reviewed.
• Patients with surgically resectable disease confined
to the uterus at presentation and adequate follow-up
were included.
• Morcellation cohort included only those cases with
intra-peritoneal morcellation
 Cases which underwent morcellation in a bag intraoperatively were excluded
• TAH cohort included cases who underwent complete
hysterectomy without tumor disruption.
Patients characteristics (n=68)
Total
(n=68)
Total Abdominal
Hysterectomy (n=52)
Morcellation
(n=16)
p-value
Age (mean)
53.5
55.3
47.8
0.0187
Size - image
9.9
10.1
9.5
0.9848
Mitosis (10hpf)
25.7
27.2
21.7
0.2131
1
4 (6.5)
4 (8.3)
0 (0.0)
2
11 (17.7)
10 (20.8)
1 (7.1)
3
47 (75.8)
34 (70.8)
13 (92.9)
I
37 (77.1)
37 (77.1)
N.A.
II
3 (6.3)
3 (6.3)
N.A.
III
8 (16.7)
8 (16.7)
N.A.
Grade [n(%)]
0.295
FIGO Stage
N.A.
Patients characteristics (n=68)
Total
(n=68)
Total Abdominal
Hysterectomy (n=52)
Morcellation
(n=16)
p-value
Age (mean)
53.5
55.3
47.8
0.0187
Size - image
9.9
10.1
9.5
0.9848
Mitosis (10hpf)
25.7
27.2
21.7
0.2131
1
4 (6.5)
4 (8.3)
0 (0.0)
2
11 (17.7)
10 (20.8)
1 (7.1)
3
47 (75.8)
34 (70.8)
13 (92.9)
I
37 (77.1)
37 (77.1)
N.A.
II
3 (6.3)
3 (6.3)
N.A.
III
8 (16.7)
8 (16.7)
N.A.
Grade [n(%)]
0.295
FIGO Stage
N.A.
Patients characteristics (con’t)
Total
(n=68)
Total Abdominal
Hysterectomy (n=52)
Morcellation
(n=16)
no
28 (41.2)
13 (25.0)
15 (93.8)
yes
40 (58.8)
38 (75.0)
1 (6.3)
none
41 (60.3)
29 (55.8)
12 (75.0)
chemotherapy
19 (27.9)
16 (30.8)
3 (18.8)
6 (8.8)
5 (9.6)
1 (6.3)
p-value
Oophorectomy
[n(%)]
<0.001
Adjuvant
therapy [n (%)]
radiotherapy
0.703
Morcellation is associated with a significantly
increased rate of LMS recurrence
When adjusting for differences in follow-up between the two
cohorts, the incidence rate of recurrence among pts who
underwent morcellation is more than two times the rate of
those who had tumor removed by TAH.
Failure
Time (months)
Incidence Rate
(person months)
Morcellation
(n=16)
TAH
(n=52)
Total
(n=68)
10
26
36
216.115
1240.575
1456.69
0.046
0.021
0.025
p-value
0.023
Time to Recurrence by Type of Surgery
0.00
0.25
0.50
0.75
1.00
Tumor morcellation led to a decrease in
Recurrence Free Survival (RFS)
0
12
24
36
Time (Months)
48
60
Number at risk
surgtype = TAH 52
surgtype = Morcellation 16
38
6
22
2
7
1
1
0
TAH
11
2
Morcellation
Higher incidence of peritoneal recurrence
after tumor morcellation
Total Abdominal
Hysterectomy
(n=52)
Morcellation
(n=16)
p-value
Abdomen/pelvis 16 (44.4)
6 (23.1)
10 (100.0)
<0.001
Other 16 (44.4)
16 (61.5)
0 (0.0)
4 (15.4)
0 (0.0)
Site of
first recurrence
Both
Total
(n=68)
4 (11.1)
Tumor morcellation is an independent risk
factor for recurrence
We investigated the relationship between each covariant
and RFS. Only morcellation, size and mitosis were found
significant in the statistical model.
TAH
Morcellation
Size (image)
Mitosis
UNIVARIATE
HR
p-value
1
2.175
0.039
MULTIVARIATE
HR
p-value
1
2.757
0.033
1.127
1.021
0.005
0.011
Conclusions
•
Uterine morcellation of presumed leiomyomas
inadvertently result in an increase in morcellated
ULMS.
•
Morcellation alters the natural course of ULMS
leading to an increased incidence and earlier
recurrences.
•
Recurrences following tumor morcellation are
significantly more likely to occur in the peritoneum.
•
Additional studies are needed to identify patients at
high risk for ULMS prior to presumed leiomyoma
resection in order to reduce the risk of inadvertent
tumor morcellation.
Co-authors / Acknowledgments
Dana-Farber Cancer Institute
Center for Sarcoma and Bone Oncology
George D. Demetri
James E. Butrynski
David R. D’Adamo
Suzanne George
Jeffrey A. Morgan
Andrew J. Wagner
Department of Biostatistics and
Computational Biology
Constance Barysauskas
Yang Feng
Judith Manola
Brigham and Women’s Hospital
Pathology Department
Christopher P. Crum
Marisa R. Nucci
Division of Obstetrics and Gynecology
Michael M. Muto
Titilope Oduyebo
ASCO Young Investigator Award
Spanish Society of Medical Oncology Translational Award
Driscoll Family Leiomyosarcoma Fund