1. Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer:
a multicentre MITO retrospective study.
Falcone F., Scambia G., Benedetti Panici P., Signorelli M., Cormio G., Giorda G., Bogliolo S., Marinaccio M., Ghezzi F., Rabaiotti E., Breda E., Casella G., Fanfani F., Di Donato V., Leone Roberti Maggiore U., Greggi S.
Submitted to Gynecologic Oncology on June 16, 2017

2. Background
The role of secondary/tertiary cytoreductive surgery has not been yet clearly defined. In particular, data on tertiary cytoreductive surgery (TCS) are even more limited than those in the secondary setting
Whether the complete cytoreduction is the primary objective of TCS must be still confirmed, and the factors predicting no postoperative residual tumor identified
Given the high technical difficulty associated with repetitive surgery, accurate patient selection is mandatory
The MITO Group endorsed a project among its surgical membership with the aim to retrospectively evaluate EOC patients undergoing TCS.

3. Methods Exclusion criteria
The primary endpoints for this study were to evaluate the impact of TCS on the overall survival and to determine predictors of complete surgical cytoreduction
The secondary endpoint was to assess the value of a potential score predicting a complete cytoreduction.
A total of 103 recurrent EOC patients, undergoing TCS within a 5-year observation period, were included in the present analysis
Aged >75 years
PS according to ECOG >1
Serological recurrence only
Non-epithelial or borderline tumors
TFI <6 months after completion of 1st-/2nd-/3rd-line therapy
Patients operated on for strictly palliative purposes
Patients with second malignancies
Exclusion criteria

4. BEFORE Results tertiary cytoreduction
Variable
Age, median [range], years
55 [20 – 71]
Origin of disease, n (%)
Ovary
Fallopian tube
Peritoneum
98 (95.1)
1 (1.0)
4 (3.9)
FIGO stage at initial diagnosis, n (%) I II
III IV
Missing
12 (11.7)
2 (1.9)
80 (77.7)
3 (2.9)
6 (5.8)
Tumor grade, n (%) 1 2 3
8 (7.8)
86 (83.5)
Histology, n (%)
Adenoca, NOS
Clear cell
Endometrioid
Mixed
Mucinous
Serous
Undifferentiated
83 (80.6)
Clinico-pathologic characteristics
BEFORE
tertiary cytoreduction
Completeness of primary cytoreduction, n (%)
0 (no visible residual tumor)
1 (residual nodules ≤0.25 cm)
2 (residual nodules >0.25 cm and ≤2.5 cm)
3 (residual nodules >2.5 cm)
Missing
67 (65.0)
12 (11.7)
11 (10.7)
6 (5.8)
7 (6.8)
Completeness of secondary cytoreduction, n (%)
83 (80.6)
9 (8.7)
3 (2.9)
1 (1.0)
Time from the end of initial treatment to first relapse (months), median [range]
21.5 [6 – 115]

5. Results AT THE TIME OF tertiary cytoreduction
Variable
Age, median [range], years
60 [23 – 75]
Years after primary diagnosis, n (%)
<2
≥2 and <3 ≥3
5 (4.8)
13 (12.6)
85 (82.5)
Last TFI, n (%)
6 – 12 months
≥12 months
65 (63.1)
38 (36.9)
ECOG performance status, n (%) 1
76 (73.8)
27 (26.2)
ASA, n (%)
1 – 2
3 – 4
90 (87.4)
CA 125 (U/mL) serum levels, n (%)
<35
35 – 500
>500
43 (41.7)
52 (50.5)
8 (7.8)
Intraoperative ascites, n (%)
≤500 mL
>500 mL
101 (98)
2 (2)
Sites of recurrence, n (%)
Abdominal
Distant
Both
86 (83.5)
9 (8.7)
Abdominal tumor involvement, n (%)
Intraperitoneal
Retroperitoneal
55 (58.5)
21 (22.3)
18 (19.1)
Clinico-pathologic characteristics
AT THE TIME OF
tertiary cytoreduction
Lesion number, n (%)
Single
Multiple
45 (43.7)
58 (56.3)
Size (mm) of largest recurrence, median [range]
25 [5 – 120]
Completeness of tertiary cytoreduction, n (%)
0 (no visible residual tumor)
1 (residual nodules ≤0.25 cm)
2 (residual nodules >0.25 cm and ≤2.5 cm)
3 (residual nodules >2.5 cm)
71 (68.9)
13 (12.6)
4 (3.9)
15 (14.6)
Post-operative complications, n (%)
G 1 – 2
G 3 – 4
G 5
3 (2.9)
10 (9.7)
0 (0)
Adjuvant therapy after tertiary cytoreduction, n (%)
Platinum-based
Non-platinum based
54 (52.4)
36 (34.9)
Follow-up (months) after TCS, median [range]
39.5 [1 – 138]
Status at last follow-up, n (%)
NED
AWD
DOD
DID
Missing
26 (25.2)
25 (24.3)
40 (38.8)
5 (4.9)
7 (6.8)

6. Results
Significant predictors of mortality and complete tumor resection
Significant predictors of mortality
Complete tertiary cytoreduction (yes* vs no)
FIGO stage at initial diagnosis (I-II* vs III-IV)
Site of abdominal recurrence (retroperitoneal only* vs other)
Interval from primary diagnosis (>3* vs <3yrs)
Hazard ratio
10.7
4.5 4
3.5
95% CI
4.3 – 26.2
1.3 – 15.6
1.1 – 14.5
1 – 12.8
p-value
<0.001
0.01
0.03
0.04
Significant predictors of complete tumor resection
Single lesion
ECOG performance status 0
Odds ratio
14.2
4.6
4 – 50.6
1.4 – 14.9
0.009
*Protective

7. prognostic factors for survival
Results
Kaplan–Meier curves
according to
significant
prognostic factors for survival

8. Results … in our study Single lesion + PS ECOG 0 PPV =94.6% NPV =45.5%
AGO score
PPV =75.8%
NPV =43.2%
The observed PPV was very consistent with that recently reported in secondary cytoreduction (72.5%)
DESKTOP III

9. Conclusions
Our study demonstrates the achievement of postoperative no residual disease as the primary objective of TCS, confirming the prognostic impact of complete surgical cytoreduction even in a tertiary setting.
Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction although the value of the clinical scores could be affected by the intrinsic nature of a tumor usually seen in long surviving patients.
In this perspective, TCS could be offered to all patients with good clinical conditions for whom a complete surgical cytoreduction is judged reasonably feasible in a high volume gynecologic oncology referral centre.