Completion hysterectomy after chemoradiotherapy for locally advanced adeno-type cervical carcinoma: updated survival outcomes and experience in post radiation surgery

Jie Yang; Jiaxin Yang; Dongyan Cao; Keng Shen; Fuquan Zhang; Jiabin Ma

doi:10.3802/jgo.2020.31.e16

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Yang, Yang, Cao, Shen, Zhang, and Ma: Completion hysterectomy after chemoradiotherapy for locally advanced adeno-type cervical carcinoma: updated survival outcomes and experience in post radiation surgery

Original Article

J Gynecol Oncol 2020;31(2):e16.

Published online: 4 March 2020

DOI: https://doi.org/10.3802/jgo.2020.31.e16

Completion hysterectomy after chemoradiotherapy for locally advanced adeno-type cervical carcinoma: updated survival outcomes and experience in post radiation surgery

Jie Yang¹, Jiaxin Yang^1,, Dongyan Cao¹, Keng Shen¹, Fuquan Zhang², Jiabin Ma²

¹Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China

²Department of Radiation Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China

Correspondence to Jiaxin Yang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, No. 1. Shuaifuyuan, Wangfujing, Dong Cheng District, Beijing 100730, China. E-mail: yangjiaxin007@hotmail.com

Received 25 April 2019 Revised 16 August 2019 Accepted 23 August 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT).

Methods

Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors.

Results

A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282–0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189–0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067).

Conclusion

Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.

Keywords: Hysterectomy, Chemoradiotherapy, Uterine Cervical Neoplasms, Adenocarcinoma, Survival

References

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Fig. 1.

PFS and OS between the 2 groups and subgroup analysis of patients with or without prRD. CCRT, concurrent chemoradiotherapy; CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; psRD, post-radiation residual disease.

Fig. 2.

HR of completion surgery vs. surveillance for PFS and OS in specified clinical features. CCRT, concurrent chemoradiotherapy; CI, confidence interval; HR, hazard ratio; LAN, lymphoadenopathy; LVSI, lymph-vascular space invasion; OS, overall survival; PFS, progression-free survival; RD, residual disease.

Table 1.

Patients' characteristics

Characteristics	CCRT+hysterectomy (n=78)		CCRT only (n=97)	p value
Age (yr)				0.255
Median (range)		48 (22–77)	54 (27–81)
<60		71 (91.0%)	68 (70.1%)	0.001
≥60		7 (9.0%)	29 (29.9)
Stage				0.243
IB		16 (20.5%)	12 (12.4%)
IIA		5 (6.4%)	8 (8.2%)
IIB		51 (65.4%)	62 (63.9%)
III		6 (7.7%)	15 (15.5%)
Size (cm)				0.810
<2		3 (3.8%)	4 (4.1%)
2–4		21 (26.9%)	22 (22.7%)
≥4		54 (69.2%)	71 (73.2%)
Histologic type				0.084
Adeno-		53 (67.9%)	70 (72.2%)
Adenosquamous		5 (6.4%)	13 (13.4%)
Mixed adeno-type^*		20 (25.6%)	14 (14.4%)
Grade				0.147
Well		20 (25.6%)	17 (17.5%)
Moderate		25 (32.1%)	22 (22.7%)
Poor		15 (19.2%)	28 (28.9%)
Unknown		18 (23.1%)	30 (30.9%)
Lymphadenopathy				0.948
Yes		35 (44.9%)	44 (45.4%)
No		43 (55.1%)	53 (54.6%)
CA-125 abnormal		32/68 (47.1%)	39/75 (52%)	0.672
SCC-Ag abnormal		12/60 (20%)	22/69 (31.9%)	0.184
NACT		45/78 (57.7%)	22/97 (22.7%)	<0.005
Stromal invasion	Pre-treatment^†	Pathological^‡	Pre-treatment^†	0.393
<1/2	14 (17.9%)	25 (32.1%)	12 (12.4%)
≥1/2	64 (82.1%)	25 (32.1%)	85 (87.6%)
Parametrium invasion	Pre-treatment^†	Pathological^‡	Pre-treatment^†	0.287
Yes	56 (71.8%)	6 (7.7%)	77 (79.4%)
No	22 (28.2%)	44 (56.4%)	20 (20.6%)
LVSI	Pre-treatment^†	Pathological^‡	Pre-treatment^†	0.416
Negative	54 (69.2%)	58 (74.4%)	69 (71.1%)
Positive	7 (8.9%)	10 (12.8%)	9 (9.3%)
Unknown	17 (21.8%)	10 (12.8%)	19 (19.6%)
RD	Post-radiation^§	Pathological^‡	Post-radiation^§	0.706
Yes	23 (29.5%)	50 (64.1%)	25 (25.8%)
No	55 (70.5%)	28 (35.9%)	72 (74.2%)

CA-125, cancer antigen 125; CCRT, concurrent chemoradiotherapy; LVSI, lymph-vascular space invasion; NACT, neoadjuvant chemotherapy; RD, residual disease; SCC-Ag, squamous cell carcinoma antigen.

^* Mixed adenocarcinoma includes minimal deviation adenocarcinoma, adenocarcinoma with villoglandular differentiation, adenocarcinoma with mucinous differentiation, adenocarcinoma with clear cell differentiation;

^† Pre-treatment stromal and parametrium invasion were evaluated by physical examination and imaging methods; pre-treatment LVSI was evaluated by biopsy. Pre-treatment data were used to compare between the 2 groups;

^‡ Pathological evaluation of hysterectomy specimen;

^§ RD were evaluated 3 months after completion of CCRT. Post-

Table 2.

The univariate and multivariate analysis of clinicopathological factors and survival outcomes

Factors	Univariate analysis				Multivariate analysis
	PFS		OS		PFS		OS
	HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value
Age
<60	Ref		Ref
≥60	1.4 (0.75–2.68)	0.29	1.9 (0.81–4.38)	0.14
Stage
IB	Ref		Ref		Ref		Ref
IIA	3.12 (1.06–9.04)	0.04	2.16 (0.49–9.44)	0.31	1.27 (0.64–2.48)	0.49	0.57 (0.21–1.57)	0.28
IIB	1.67 (0.79–3.53)	0.18	1.59 (0.66–3.85)	0.30
III	5.17 (1.65–16.2)	0.01	0.99 (0.22–4.48)	0.99
Size (cm)
<4	Ref		Ref		Ref		Ref
≥4	1.79 (1.07–3.03)	0.03	1.63 (0.88–3.03)	0.12	1.45 (0.73–2.87)	0.20	1.52 (0.61–3.76)	0.37
Histology
Adeno	Ref		Ref
Other	0.85 (0.47–1.57)	0.61	0.88 (0.43–1.83)	0.74
Grade
1	Ref		Ref
2	0.97 (0.49–1.92)	0.92	0.73 (0.29–1.81)	0.49
3	1.36 (0.68–2.74)	0.38	1.18 (0.47–2.92)	0.73
Stromal invasion
<1/2	Ref		Ref		Ref		Ref
≥1/2	1.79 (0.94–3.41)	0.08	2.23 (0.93–5.32)	0.07	0.84 (0.26–2.74)	0.77	3.03 (0.33–27.5)	0.33
LVSI
No	Ref		Ref		Ref		Ref
Yes	2.65 (1.16–6.08)	0.02	2.0 (0.73–5.49)	0.06	1.76 (0.88–3.50)	0.11	1.60 (0.66–3.88)	0.29
Parametrium
No	Ref		Ref		Ref		Ref
Yes	1.45 (0.83–2.51)	0.19	1.29 (0.62–2.67)	0.50	0.71 (0.27–1.84)	0.48	0.78 (0.25–2.46)	0.67
LAN
No	Ref		Ref		Ref		Ref
Yes	1.60 (0.97–2.63)	0.05	1.17 (0.62–2.21)	0.63	1.33 (0.74–2.41)	0.34	1.10 (0.50–2.34)	0.81
NACT
Yes	Ref		Ref
No	0.79 (0.48–1.30)	0.36	1.49 (0.70–3.15)	0.29
psRD
No	Ref		Ref		Ref		Ref
Yes	3.23 (1.96–5.32)	<0.01	2.87 (1.52–5.42)	<0.01	9.91 (4.63–21.1)	0.00	7.11 (2.69–18.8)	<0.01
Group
Surgery	Ref		Ref		Ref		Ref
CCRT	2.17 (1.33–3.54)	<0.01	2.77 (1.45–5.32)	<0.01	7.05 (3.42–12.5)	0.00	8.44 (3.31–21.5)	<0.01

CCRT, concurrent chemoradiotherapy; CI, confidence interval; HR, hazard ratio; LAN, lymphoadenopathy; LVSI, lymph-vascular space invasion; NACT, neoadjuvant chemotherapy; OS, overall survival; PFS, progression-free survival; psRD, post-surgery residual disease.

Table 3.

Factors related to RD

Factors	No RD (n=28)	With RD (n=50)	HR (95%CI)	p value
Size (cm)				0.480
<4	8	16	Ref
≥4	20	34	1.06 (0.75–1.50)
Parametrium				0.087
No	11	11	Ref
Yes	17	39	1.65 (0.93–2.93)
Depth				0.000
<1/2	11	11	Ref
≥1/2	17	39	3.43 (2.13–5.51)
NACT				0.131
No	9	24	Ref
Yes	19	26	0.646 (0.34–1.24)
Concurrent chemotherapy				0.427
<5 courses	16	31	Ref
≥5 courses	12	19	0.88 (0.48–1.59)
Duration (wk)				0.595
≤8	22	39	Ref
>8	6	11	1.02 (0.49–2.11)

HR, hazard ratio; NACT, neoadjuvant chemotherapy; RD, residual disease.

Table 4.

Sites of recurrence

Sites of recurrence	Surgery (n=78)	CCRT only (n=89)	p value
Vault/cervix	3 (3.85%)	6 (6.74%)	0.067*
Pelvis	1 (2.28%)	6 (6.74%)	0.067^*
Abdomen	5 (6.41%)	6 (6.74%)
Distant	11 (14.1%)	13 (14.6%)	0.926^†
Multiple	6 (7.69%)	14 (15.7%)
Total	16 (33.33%)	45 (50.56%)	0.025

CCRT, concurrent chemoradiotherapy.

^* Comparing the locoregional recurrence between surgery group and CCRT group;

^† Comparing the distant recurrence between surgery group and CCRT group.

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