How Long Can Someone Live With Untreated Womb Cancer Life Expectancy

Curvation Med Sci. 2010 Dec; 6(vi): 937–944.

Long-term survival of endometrioid endometrial cancer patients

Leszek Gottwald, ^{1, two} Piotr Pluta,³ Janusz Piekarski,³ Michał Spych,⁴ Katarzyna Hendzel,⁵ Katarzyna Topczewska-Tylinska,⁶ Dariusz Nejc,³ Robert Bibik,⁷ Jerzy Korczyński,⁸ and Aleksandra Ciałkowska-Ryszⁱ

Leszek Gottwald

¹Palliative Care Unit of measurement, Chair of Oncology, Medical University of Lodz, Poland

²Gynecological Cancer Outpatient Clinic, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, Poland

Piotr Pluta

³Department of Surgical Oncology, Chair of Oncology, Medical University of Lodz, Poland

Janusz Piekarski

³Department of Surgical Oncology, Chair of Oncology, Medical Academy of Lodz, Poland

Michał Spych

^fourDepartment of Radiotherapy, Chair of Oncology, Medical University of Lodz, Poland

Katarzyna Hendzel

⁵Section of Histopathology, Madurowicz Memorial Hospital, Lodz, Poland

Katarzyna Topczewska-Tylinska

⁶Department of Health Intendance Policy, Medical Academy of Lodz, Poland

Dariusz Nejc

³Department of Surgical Oncology, Chair of Oncology, Medical University of Lodz, Poland

Robert Bibik

⁷Department of Teleradiotherapy, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, Poland

Jerzy Korczyński

⁸Department of Fetal Medicine and Gynecology, i^st Chair of Obstetrics and Gynecology, Medical University of Lodz, Poland

Aleksandra Ciałkowska-Rysz

¹Palliative Intendance Unit of measurement, Chair of Oncology, Medical University of Lodz, Poland

Received 2009 Nov 28; Revised 2010 January 7; Accustomed 2010 Mar 23.

Abstract

Introduction

To constitute risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the report was to decide disease-gratuitous survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer.

Material and methods

A retrospective review of 142 patients with endometrioid endometrial cancer afterwards surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Middle in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival.

Results

In three patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.seven%) after primary remission, relapse was diagnosed ii-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> i), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS.

Conclusions

The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly amend. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

Keywords: endometrioid endometrial cancer, prognostic factors, affliction-costless survival, overall survival

Introduction

Endometrial cancer is the almost common gynaecological cancer, with an increasing incidence rate [1-iii]. In the Polish female population endometrial cancer is ranked quaternary in statistics of incidence of cancer, and eighth in terms of age-adjusted mortality [ii]. In the United States the lifetime risk of endometrial cancer development is evaluated at 2.7% [three]. The increased incidence of endometrial cancer is likely to result from several factors including prolonged average human lifespan, high-caloric nutrition, improved health intendance organization and living conditions [ane]. Modern diagnostic methods, advances in surgical technique and high-efficacy adjuvant therapy, and increased wellness consciousness among women take resulted in relatively early on detection of endometrial cancer (70-80% phase I), which gives patients better prognosis [4-7].

2 types of endometrial cancer are distinguished in terms of clinical and pathological features. Type I (endometrioid carcinoma) is associated with hyperoestrogenism and endometrial hyperplasia (80-90%). Blazon II (non-endometrioid carcinoma) is an oestrogen-independent malig­nancy, usually developing from atrophic endometrial tissues (x-20%) [ii, 3, 8]. Endometrioid carcinoma normally occurs in younger women, often obese or diabetic. Non-endometrioid carcinomas such equally serous papillary, clear prison cell, squamous prison cell or undifferentiated blazon in most cases touch elderly women who are neither obese nor diabetic [two, nine]. Several studies suggested more ambitious class and worse prognosis even in early on stages of non-endometrioid endometrial cancer [2, eight-11]. The 5-year overall survival rate (OS) of endometrioid endometrial cancer patients ranges from 75% to 86%. In contrast, only 35% of patients with not-endometrioid endometrial cancer survive five years from diagnosis [3, 9, 10, 12].

Several risk factors of endometrioid endometrial cancer accept been identified, merely the aetiology of the disease still remains unclear. Yet, progression from the pre-malignant form of intraendometrial neoplasia to endometrioid carcinoma seems to be well documented [i, ii, 12, 13]. To establish the chance factors of onset and progression of this disease nevertheless remains the aim of scientists. It may lead to more effective treatment in patients from the subgroup at high risk of failure and reduce the adventure of over-treatment in the low-risk group.

The aim of the study was to determine prognostic factors for Bone and illness-free survival (DFS) in women with endometrial cancer of endometrioid type.

Material and methods

Our study enrolled 142 sequent endometrioid endometrial cancer patients with median age 60.ii years (range 41-82 years), treated in the Regional Cancer Eye in Lodz between 2002 and 2004. Patients with incomplete follow-ups were excluded. All cancers were classified according to the new FIGO (International Federation of Gynecology and Obstetrics) classification 2009 [14]. Detailed clinical and pathological characteristics of the report grouping are presented in Tabular array ​ I.

Table I

Clinical and histological characteristics of the study group

Variables		n=142, n (%)
Historic period [years]	≤60	77 (54.ii)
	>sixty	65 (45.8)
History of cancer	no	109 (76.8)
	patient	5 (iii.5)
	family	28 (19.7)
Pregnancies	yes	127 (19.iv)
	no	15 (10.half dozen)
Menopausal status	premenopausal	18 (12.7)
	postmenopausal	124 (87.3)
Age at menopause [years]	≤50	61 (43.0)
	>50	81 (57.0)
Medical disease	aye	89 (62.7)
	no	53 (37.3)
Stage	I	96 (67.6)
	II	18 (12.7)
	3	26 (xviii.iii)
	Four	2 (1.4)
Depth of myometrial infiltration	≤50%	72 (50.7)
	> 50%	70 (49.iii)
Course	1	71 (50.0)
	two	54 (38.0)
	3	17 (12.0)
Surgery	no or explorative	2 (ane.4)
	cytoreductive	half-dozen (4.5)
	optimal	134 (94.1)
	TAH+BSO	xl (28.1)
	TAH+BSO+PL	100 (70.five)
Adjuvant handling	no	vi (iv.2)
	BT alone	10 (7.one)
	BT+EBRT	122(85.9)
	CT±RT	4 (ii.8)

Hundred forty one patients underwent surgical procedures outside the Regional Cancer Centre in Lodz. During surgery in 140 patients uterus and both adnexa were removed (TAH-BSO). In 99 (69.7%) cases pelvic lymphadenectomy (PL), and in 67 (47.two%) cases appendectomy were additionally performed. Para-aortic lymph node sampling was not performed in these cases. Intraoperative procedures when TAH-BSO with complete resection of all visible cancer were regarded as optimal surgery. In one adult female at phase IV no history of surgery was noted and in one patient the only explorative laparotomy was made. Afterwards adjuvant handling was conducted in the Department of Gynaecologic Radiotherapy. Most women received adjuvant vaginal brachytherapy (BT) and external axle pelvic radiotherapy (EBRT). Additionally, selected patients were treated by chemotherapy (CT) and hormonal therapy (HT) (Table ​ I). Afterwards the patients attended the Gynaecological Cancer Outpatient Clinic for follow-upwards. The clinical outcome of all patients during 5 years of observation was analysed. Personal, obstetric, oncological, clinical and pathological data were correlated with DFS and OS.

The DFS was defined equally the period from primary surgery until relapse. OS was divers as the period from primary surgery until decease or until completion of 5-year follow-upward. Complete remission (CR) was divers equally the disappearance of all signs of cancer in response to handling. Progression of neoplastic affliction was divers as the form of the illness every bit it becomes worse or spreads in the trunk. Relapse of cancer was divers as the return of signs and symptoms of cancer after a menstruation of improvement.

To assess survival parameters Kaplan-Meier analysis was used [15] and survival curves were compared using the log-rank test [sixteen]. Statistical analysis of survival was performed with the log-rank test and Cox models. A p value less than 0.05 was considered significant.

Results

Complete remission was observed in 116 out of 142 (81.7%) patients during 5 years of follow-upwards. Clinical progression or relapse was diagnosed in 26 (xviii.iii %) patients. In iii patients (2.ane%) with stage Three or IV of the illness, clinical progression during principal treatment was diagnosed. Two of them had locoregional recurrence in the pelvis pocket-size and dissemination of the affliction afterward a few months was found. In 1 example os and liver metastases were observed. These 3 patients were treated symptomatically and died during 5 months.

Relapse was observed in 23 (sixteen.2%) patients from 2 to 56 months (median 23.6, SD = 16.3) after CR accomplishment. Twenty-one out of 23 (91.three%) patients with relapse died afterwards 1 to 21 months (median 7.6) from diagnosis despite the consecutive line of handling, and but 2 (8.seven%) patients with recurrent disease survived 5 years (p< 0.001). Detailed results of treatment are shown in Table ​ II.

Table II

Relapse of the affliction

Location of relapse
only locoregional	3	13
only distant metastatic	xv	65.2
both locoregional and distant	5	21.8
total	23	100.0
Location of distant relapses at diagnosis
liver	vii	30.4
lungs	7	xxx.iv
bones	3	13.0
para-aortic and/or extraperitoneal lymph nodes	vi	26.ane
abdominopelvic layer	three	13.0
key nervous organization	2	8.seven
supraclavicular lymph nodes	1	iv.3
Treatment of relapses
simply CT	six	26.1
Southward+CT	2	eight.7
simply EBRT	2	8.7
BT+EBRT	i	iv.three
HT and symptomatically	1	4.three
only symptomatically	eleven	47.9

The DFS rate at 5 years of the unabridged grouping was 81.7%. In univariate and multivariate analyses, larger number of pregnancies (p = 0.021, p = 0.041), clinical stage I (p = 0.002, p = 0.04) and optimal surgery (p = 0.01, p = 0.028) significantly influenced DFS. In univariate and multivariate analyses, age at diagnosis, menopausal age and menopausal status, familial and patient cancer history, other diseases, pelvic lymph node dissection, depth of myometrial infiltration, course of the tumour and type of adjuvant treatment in clinical phase I (no adjuvant and/or just vaginal brachytherapy [BT] vs. BT and external-beam pelvic radiotherapy [EBRT]) did non bear upon DFS. These results are summarized in Table 3.

Table III

Disease-gratuitous survival (DFS) and 5-year overall survival (Os) − univariate and multivariate analysis

Patients	DFS				Os
		n	%	p 1	p 2	n	%	P 1	p two
TOTAL		116/142	81.vii	–	–	118/142	83.1	–
Age* [years]	≤threescore	64/77	85.vii	0.61	0.64	65/77	84.iv	0.35	0.28
	>60	52/65	80.0			53/65	81.five
History of cancer	no	91/109	83.5	0.77	0.11	92/109	83.viii	0.38	0.13
	patient	iii/5	threescore.0			three/v	60.0
	family unit	23/28	82.1			24/28	85.vii
Pregnancies*	aye	104/127	81.9	0.021	0.041	106/127	83.5	0.13	0.09
	no	12/fifteen	80.0			12/15	fourscore.0
Menopausal status	premenopausal	17/xviii	94.4	0.41	0.ninety	17/18	94.4	0.16	0.73
	postmenopausal	99/124	79.8			101/124	81.5
Age at menopause*	≤50	47/61	77.0	0.43	0.09	49/61	lxxx.3	0.25	0.58
	>50	69/81	85.two			69/81	85.2
Medical illness	yeah	75/89	84.3	0.31	0.95	76/89	85.4	0.46	0.67
	no	41/53	77.four			42/53	79.2
Phase [years]	I	ninety/96	93.8	0.002	0.040	91/96	94.eight	<0.001	0.002
	Two	thirteen/xviii	72.2			13/xviii	72.2
	III	xiii/26	l.0			14/26	53.8
	IV	0/2	0			0/2	0
Myometrial infiltration	≤fifty%	69/72	95.viii	0.09	0.38	69/72	95.viii	<0.001	0.02
	>l%	47/70	67.1			49/70	70.0
Grade	1	62/71	87.3	0.29	0.70	63/71	88.7	0.014	0.09
	2	43/53	81.1			44/53	83.0
	three	xi/18	61.1			11/18	61.ane
Surgery	no or explorative	0/2	0	0.01	0.028	0/two	0	<0.001	0.006
	cytoreductive	0/6	0			0/half-dozen	0
	optimal	116/134	86.6			118/134	88.one
	TAH+BSO	28/40	seventy.0	0.13	0.24	29/twoscore	72.5	<0.001	0.015
	TAH+BSO+PL	88/100	88.0			89/100	89.0
Adjuvant treatment	no	5/half-dozen	83.3	<0.001	0.049	5/6	83.3	0.67	0.35
	BT alone	8/10	80.0			eight/10	eighty.0
	BT+EBRT	103/122	84.4			105/122	86.1
	CT+/– RT	0/4	0			0/4	0
		FIGO I **		0.23	0.37	FIGO I**		0.eleven	0.07
		FIGO II-Three ***		–	–	FIGO II-III ***		–	–
		FIGO IV		–	–	FIGO 4		–	–

The OS rate at 5 years of the report grouping was 83.1%. In univariate analysis, clinical stage I (p < 0.001; Fig. ​ 2), optimal surgery (p < 0.001; Fig. ​ ane), pelvic lymph node autopsy (p < 0.001), depth of myometrial infiltration ≤ fifty% (p < 0.001; Fig. ​ four), and well or moderately differentiated tumour (p = 0.014; Fig. ​ iii) significantly influenced OS. Clinical stage I (p = 0.002), optimal surgery (p = 0.006), pelvic lymph node dissection (p = 0.015), and depth of myometrial infiltration ≤ 50% (p = 0.02) were independent prognostic factors for OS in multivariate analysis. In univariate and multivariate analyses, age at diagnosis, larger number of pregnancies, menopausal age and menopausal status, familial and patient cancer history, con­comitant diseases, and blazon of adjuvant treatment in clinical phase I (no adjuvant or merely BT vs. BT and EBRT) were not significantly related to OS (Tabular array Iii).

Os and radicality of surgery in endometrioid endometrial cancer.

Bone and staging of endometrioid endometrial cancer.

OS and grading of endometrioid endometrial cancer.

Bone and myometrial infiltration in endometrioid endometrial cancer.

Discussion

In our study DFS and OS rates at 5 years were similar to data published by Hirai et al. [thirteen], and were 81.7% and 83.1% respectively. In the last years there have been published numerous studies addressing the furnishings of different independent variables on the risk of evolution and prognosis of endometrioid endometrial cancer [1, four-vi, xi, 13, 17-23]. Age at diagnosis, age at menarche, parity, menopausal age, menstrual condition, hormonal contraception, and hormone replacement therapy are well known gamble factors for developing the cancer [two, 3, 11, 13, 17, 18], just as in our study, their role every bit prognostic factors predicting survival remains controversial. Just higher number of pregnancies was correlated with improve DFS, and our results match well with those of Alkbretsen et al. [xix] reporting the relationship between obstetric history and prognosis in endometrioid endometrial cancer patients. They institute better survival in parous than nulliparous women, and in the study the improved result was strongest for women with the shortest fourth dimension interval since the final childbirth. This interesting pattern may be a issue of high progesterone levels, and interruption of the continued stimulation from oestrogen during pregnancy [3].

When planning the treatment of endometrioid endometrial cancer, complete pathological and clinical data predicting the course of the disease should be taken into consideration. It is generally known and confirmed in our results that the nigh important factor affecting survival is clinical stage [12, 13, 24, 25], which determines the style of treatment, significantly predicting DFS and Os. As an example, Hirai et al. [thirteen] in 286 patients reported the overall 5-year recurrence-gratis survival in stage I – 94%, phase Ii – 71% and stage III – 38%.

The treatment of choice in operable endometrial cancer is surgery including minimally: TAH-BSO, sampling of peritoneal fluid and resection of all visible extra-uterine metastatic lesions, followed by adjuvant treatment [12, 26]. Previous studies showed that autopsy of pelvic and para-aortal lymph nodes in all patients with endometrioid endometrial cancer remains controversial, because this procedure did non influence survival in clinical stage I [4, 12]. Ayhan et al. suggest instead performing pelvic lymphadenectomy in all patients because the most of import prognostic factor in endometrial cancer is nodal involvement. Results of pelvic lymphadenectomy all-time determine the exact phase of patients, and allow tailoring of adjuvant therapy, and pelvic lymphadenectomy itself provides survival benefit and does not increase morbidity significantly [21]. In our study pelvic lymph node dissection correlated with longer OS in the whole group of patients as well. We conclude that, when technically viable, pelvic lymph node dissection should be recommended in phase I-3 illness. According to para-aortic lymphadenectomy, many authors have described para-aortic node biopsy every bit a non-therapeutic procedure [27], merely Mariani et al. postulated its possible therapeutic role based on a selected group of 137 high-hazard patients with endometrial cancer [28]. Equally para-aortic lymph node autopsy is not routinely performed in all centres of gynaecological oncology, and this procedure is noted every bit technically demanding surgery, in our textile information technology was not performed even in high-risk patients.

Although many studies have reported a significant negative correlation betwixt grade of neoplasm and outcome [8, 9, 29], our findings match well with those of Zaino et al. [xxx] and demonstrated neoplasm class to be a less significant predictor of survival, with myometrial infiltration more of import [24]. The results exercise not match well with those of Ayhan et al. [four], who in a group of 48 patients with endometrioid endometrial cancer in clinical stage 2 found high form (G3) of the neoplasm to be a significant predictor of poor survival, and depth of myometrial infiltration was non related significantly to either DFS or Bone. Interestingly, in the Gynecologic Oncology Group (GOG) study on 895 cases of endometrioid and adenosquamous carcinoma by Marrow et al., both depth of myometrial infiltration more than 1-tertiary and neoplasm grade three were demonstrated to be strong predictors of prognosis, actress-uterine disease and distant relapses in patients with stage I or 2 endometrial cancer [24]. Cirisano et al. [10] assessed the hazard of positive pelvic nodes from i% for tumours bars to the endometrium upwardly to 25% for those with deep (> 50%) myometrial infiltration. In our stance the need of adjuvant treatment should exist based on risk of relapse determined not but by stage, class of tumour, and lymph vascular infinite involvement (LVSI), simply in patients staged I additionally depth of myometrial infiltration as well.

Despite endometrial carcinoma being the well-nigh mutual gynaecological cancer in Poland, controversy exists regarding the indications for adjuvant radiotherapy, especially in clinical stage I [31]. Using surgical staging data according to the GOG [24] and the new FIGO classification from 2009 [14], in low-risk (IA Yard 1-2) endometrioid endometrial cancer adjuvant treatment is not necessary, because of the low recurrence charge per unit calculated equally 1-5% [5, 21, 22, 26]. Our results match well with the above cited recommendations, showing that radiotherapy did not improve DFS or OS in stage I illness. We also confirmed a positive correlation of adjuvant radiotherapy administered to patients with clinical phase 2-3 disease with DFS and Os. This matches well with the GOG recommendation [24] that when intermediate-risk (stage IA Grand 3, stage IB/2 Grand one-3) or loftier-risk (stage Iii) endometrioid endometrial cancer is diagnosed, with calculated hazard for relapse 10% and 14-42% respectively [5, xx, 26], adjuvant therapy is recommended [4, five, xx, 25, 31, 32]. The National Comprehensive Cancer Network (NCCN) Exercise Guidelines [33] recommend vaginal brachytherapy (BT) and/or external-axle pelvic radiotherapy (EBRT) in intermediate-chance endometrial cancer patients, and BT and/or chemotherapy (CT) in patients with FIGO IB G3 and unfavourable risk factors (age > 60 years, positive LVSI, tumour size, lower uterine interest) and 2 G3. Additionally, EBRT and/or CT is widely used as an adjuvant for intermediate-run a risk endometrial cancer, giving well-nigh 10% survival improvement, high locoregional control rates and adequate toxicity. Although in the GOG122 trial [34] a superior effect on DFS of chemotherapy compared to whole intestinal irradiation for loftier-risk patients in stage III or Iv with abdominal disease and residual nodules ≤ 2 cm was confirmed, dissimilar treatment schemes (EBRT and/or CT) in these patients are used worldwide [12, xiii]. Recurrent or metastatic endometrial tumours oft respond to salvage treatment with cytotoxic agents, and nowadays systemic CAP (cisplatin-adriablastin-endoxane) therapy as a mail service-surgical adjuvant handling for high-run a risk endometrial cancer patients instead of radiotherapy is often used [35]. In our center during 2002-2004 systemic CAP therapy was used mainly in relapses, and just in selected cases as primary adjuvant treatment.

Although the bulk of patients with endometrial cancer are diagnosed with no show of extra-uterine spread [6], fifty-fifty in low-risk patients local relapses may develop. In our report, cancer progression during handling or relapse occurred in 18.3% of patients. Local recurrences of endometrial cancer, similarly to cervical cancer, frequently occur early with axiomatic symptoms but development of distant metastatic disease may cause difficulties in prompt diagnosis [23, 26, 36]. The previous report showed that in these patients survival rate is thought to exist related to site of relapse equally the almost important factor, but also disease-free interval, and postoperative treatment equally contained prognostic variables [23, 26]. The response rates to systemic therapy reported in the literature in the range 10-78% are generally better than in our study, but this may exist due to differences in the studied patient populations [half-dozen, 7]. The results of further treatment in our patients were similar to data published by Carey et al. [seven], who found that median survival in patients with advanced endometrial cancer or afar recurrent disease rarely exceeds i yr, despite systemic therapy.

Finally, the chief goal of a surveillance strategy in patients who have been treated for endometrial cancer is to facilitate the early detection of recurrent illness, but even in such cases the prognosis for patients should be assessed very carefully.

The results of our report provided significant testify that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the affliction, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although of import, are less meaning. Further prospective, randomized studies are necessary to analyze the part of these factors.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302708/

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