Journal List > J Gynecol Oncol > v.31(2) > 1142873

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

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.

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.
jgo-31-e16f1.tif
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.
jgo-31-e16f2.tif
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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