RISK FACTOR ANALYSIS OF RECURRENCE IN LOW RISK EARLY STAGE ENDOMETRIAL CARCINOMA: THE POTENTIAL PREDICTIVE ROLE OF THE HYPERTENSIVE COMPONENT OF THE METABOLIC SYNDROME Dr Fabrizio Romano¹, Mr Alexandros Laios¹, Dr Elsa Limura¹, Dr Ayoma D Attygalle², Dr Alexandra Taylor³, Dr Susan Lalondrelle³, Mr John Butler¹, Mr Desmond PJ Barton¹, Miss Marielle Nobbenhuis¹, Mr Thomas EJ Ind¹ ¹Department of Gynaecology, The Royal Marsden Hospital, Fulham Road, SW36JJ, London, UK ²Department of Pathology, The Royal Marsden Hospital, Fulham Road, SW36JJ, London, UK ³Department of Oncology, The Royal Marsden Hospital, Fulham Road, SW36JJ, London, UK
INTRODUCTION The risk of endometrial carcinoma (EC) recurrence ranges up to 13%. Patients at early stage low risk (stage IA G1/G2 EC) carry a 1-4% risk of recurrence but their prognosis may not be always favourable. In this group, predictors of recurrence have not been comprehensively studied. We aimed to evaluate the impact of clinical-morphological factors associated with recurrence to potentially establish a risk-adjusted treatment approach.
METHODS This was a retrospective cohort of all patients treated at our institution from January 2010 to December 2016 at stage IA G1-G2 EC. The primary outcomes were recurrence rates and predictors of recurrence. Twenty-six clinic-morphological variables, including the components of metabolic syndrome (MS), were included in a logistic regression model and were summarized as odds ratio (OR) with 95% confidence intervals (CI). A p-value < 0.05 was considered statistically significant.
Variables
Odds Ratio
95% CI
p-value
Age Age >70 BMI < 40
0.99 0.47 0.98 1.8
0.92-1.06 0.05-3.98 0.92-1.05 0.33-9.74
0.841 0.49 0.63 0.495
40 and above
1.05
0.16-6.84
0.959
Family history of cancer
0.28
0.03-2.33
0.24
Parity Nulliparity (Y/N) Caucacean (Y/N) Diabetes (Y/N) Tamoxifen (Y/N) ASA grade Menopause HRT Smoker
0.96 0.5 0.64 1.39 1 0.23 1.46 1 1
0.72-1.27 0.13-1.9 0.12-3.22 0.37-5.18 0.07-0.26 0.028-1.89 0.17-12.6 N/A N/A
0.8 0.3 0.59 0.619 0.000 0.17 0.72 N/A N/A
Previous cancer history
0.56
0.066-4.76
0.59
Comorbidities HTN Type (I/II) Grading (G1/G2) On polyp (Y/N) Tumor_size
1.2 1.3
0.68-2.12 0.75-0.95
0.51 0.004
0.47 N/A 1 1.03
0.05-3.98 N/A N/A 0.99-1.06
0.49 0.79 N/A 0.1
Tumor (categorical)
1.75
0.79-3.86
0.163
2.76 2.05
0.26-29.19 0.20-20.19
0.397 0.539
1.22
0.63-2.35
0.55
36
Melf pattern LVSI Solid component percentage Pattern features
1.18
0.44-3.12
0.73
36
Inner myometrial involvement
15.2
1.83-126.23
0.012
12.25
0.63-234.8
0.096
RESULTS 97 patients were investigated with a median follow-up time of 39 months ([IQR] 21-56 months). Ten out of 97 (10.3%) recurrences occurred with a median time to recurrence of 36 months ([IQR] 23-43 months). Central vault recurrence was identified in 80% of these patients. Involvement of myometrium was the single morphological factor associated with recurrence in the univariate analysis (OR 15.2, 95%CI 1.83-126.3, p= 0.012). Hypertension (HTN) was the single predictor in the univariate and multivariate analysis (p < 0.001, chi2 test). For every additional mm in tumour size, the risk for recurrence increased by 4% (OR 1.04, 95%CI 1.011.08, p 0.046). 5-year OS (overall survival) and 5-year RFS (recurrence-free survival) were 100% and 89.7%, respectively. Table 2: Characteristics and survival data of patients with endometrial cancer recurrence Age
BMI
Diabetes
Hypertension
Surgical Approach
Treatment
Grade
TS
ETI
Solid Tumor
FDS (mm)
Involvement structures
Site of recurrence
TTR (Months)
53
32,5
-
X
LPT
H+BSO
G1
20
-
-
12
Myometrium
Vagina
48
73 65 66 63
31,1
-
17,9
-
30,7
-
29,1
-
X X X X
LPT
H+BSO
G1
20
-
-
5
Myometrium
Vagina
21
ROBOTIC
H+BSO+ BPLND
G1
30
-
-
5
Myometrium
Vagina
43
6
Abdominal Myometrium wall
LPT LPT
H+BSO
G1
H+BSO+ BPLND
G1
50 15
X -
X -
3
Myometrium
Vagina
Table 1: Univariate analysis for recurrence
67
36
X
X
ROBOTIC
H+BSO
G1
30
-
-
14
Myometrium
Vagina
44
Adenomyosis within myometrium
58
32,1
-
X
LPT
H+BSO
G2
32
-
-
16
Myometrium
Vagina
36
Nuclear pleomorphism
0.69
0.15-3.08
0.63
59
34,4
X
-
ROBOTIC
H+BSO
G2
55
X
X
15
Myometrium
Vagina
13
Extension to isthmus
0.839
0.16-4.23
0.832
56
52
X
X
LPS
H+BSO
G2
50
-
-
10
Adenomyosis
Vagina
23
Free distance from serosa
0.93
0.84-1.03
0.2
54
44
-
X
ROBOTIC
H+BSO+ BPLND+BR
G2
50
-
X
10
Myometrium
Pelvic Nodes
24
Distance from serosa >10mm
0.64
0.18-2.26
0.49
Legend: X: Yes; - : Not; FDS: free distance to serosa; TS: Tumor Size (mm); ETI: Extension to isthmus; TTR: time to recurrence; LPT: laparotomy; LPS: laparoscopy; H+BSO: hysterectomy+ bilateral salpingoophorectomy; BPLND: bilateral pelvic lymphadenectomy; BR: brachytherapy post-surgery
Figure 1: Disease-free survival
CONCLUSION In both univariate and multivariate analysis, HTN as part of MS was the single independent predictor of recurrence. Thorough diagnosis and comprehensive treatment of MS and HTN should be considered when counselling such patients about recurrence risks. The role of morphological features needs to be further elucidated in larger cohorts.
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