- Email: [email protected]
Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy
IJG-08419; No of Pages 4 International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
1
CLINICAL ARTICLE
4Q2
Zhongyu Liu a,1, Xiuli Li b,1, Weiping Li a, Yizhuo Yang a, Ye Tao c, Yuanqing Yao a,⁎ a
8
a r t i c l e
9 10 11 12
Article history: Received 28 November 2014 Received in revised form 26 April 2015 Accepted 22 July 2015
13 14 15 16 17 18 19
Keywords: Cervical cancer Neoadjuvant chemotherapy Nerve-sparing Pelvic lymphadenectomy Radical hysterectomy Robotic surgery
i n f o
a b s t r a c t
E
D
P
Objective: To evaluate the feasibility and safety of robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer (LACC). Methods: In a retrospective study, data were analyzed for patients treated for cervical cancer at a center in Beijing, China, between December 2011 and September 2013. Patients were subdivided into those with early-stage disease (FIGO stage IA2–IB1) who were treated by robotic surgery (group 1), and those with LACC (stage IB2–IIB) who were treated by robotic surgery after neoadjuvant chemotherapy (NACT; group 2). Therapeutic outcomes and complications were compared. Results: Group 1 included 32 patients and group 2 included 22 patients. Two patients in group 2 did not respond to NACT and did not undergo surgery. The operative outcomes and incidences of complications did not differ significantly between the two groups (P N 0.05 for all). There were no differences in nodal yield, lengths of parametrium removed, or vaginal cuff length (P N 0.05 for all). During a mean follow-up of 26 months, no patient experienced recurrence. Conclusion: Robotic nerve-sparing radical hysterectomy was found to be feasible and safe for LACC after NACT. A larger case series with longer follow-up data is needed to justify its widespread application. © 2015 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.
36 34
E
35
1. Introduction
38
Despite advances in pathologic screening, cervical cancer remains a major health problem for women, especially locally advanced cervical cancer (LACC) [1]. Cisplatin-based concurrent chemotherapy and external pelvic irradiation followed by brachytherapy are the standard treatment for LACC [2]; however, some studies have indicated that neoadjuvant chemotherapy (NACT) followed by radical hysterectomy is also an effective treatment for LACC [3,4]. In particular, it has been shown that NACT combined with surgery has better outcomes than does irradiation alone in terms of overall survival rate [3]. Although radical hysterectomy is the principal surgical approach for LACC, it is associated with a high incidence of postoperative complications such as bladder and rectal dysfunction [5]. Nerve-sparing radical hysterectomy has been shown to significantly decrease the incidence of morbidity, as well as bladder and rectal dysfunction [6,7]. This laparoscopic surgery has many advantages, including shorter hospital stays, rapid return to preoperative activity, decreased postoperative pain,
45 46 47 48 49 50 51 52 53
R
N C O
43 44
U
41 42
R
37
39 40
R O
Department of Obstetrics and Gynecology, PLA General Hospital, Beijing, China Department of Obstetrics and Gynecology, Hainan Branch of PLA General Hospital, Sanya, China Department of Ophthalmology, PLA General Hospital, Beijing, China
C
c
T
b
O
5 6 7
F
3
Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy
2Q1
⁎ Corresponding author at: Department of Obstetrics and Gynecology, PLA General Hospital, Fu Xing St, Beijing 100853, China. Tel.: + 86 18010012181; fax: + 86 01066938343. E-mail address: [email protected] (Y. Yao). 1 These authors contributed equally.
20 21 22 23 24 25 26 27 28 29 30 31 32 33
well preserved immune function, decreased postoperative complications, and a reduced incidence of postoperative complications [8,9]. The use of robots in cancer surgery has also been gaining increasing attention for its many benefits over conventional laparoscopy, including shorter operative times, less estimated blood loss, fewer intraoperative transfusions, fewer conversions to traditional laparotomy, and shorter hospital stays [10]. The aim of the present study was to evaluate the feasibility and safety of robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy for the treatment of patients with LACC after NACT.
54
2. Materials and methods
64
In a retrospective analysis, data were reviewed from patients treated for cervical cancer at PLA General Hospital, Beijing, China, between December 1, 2011, and September 30, 2013. Eligible patients had no tumors besides cervical cancer and no cardiovascular, pulmonary, or endocrine disease. At enrollment, patients had to agree to postoperative follow-up. The study protocol was approved by the ethics review board of the study hospital. All patients agreed to robotic surgery and provided written inform consent. The participants were divided in two groups according to their International Federation of Gynecology and Obstetrics (FIGO) stage [11]: patients with early-stage cervical cancer (FIGO stages IA2–IB1) were included in group 1 and underwent robotic surgery as their first
65 66
http://dx.doi.org/10.1016/j.ijgo.2015.05.017 0020-7292/© 2015 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
55 56 57 58 59 60 61 62 63
67 68 69 70 71 72 73 74 75 76
100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119
LACC (n = 22)
P value
t1:3
Age, y BMI Menopausal History of pelvic surgery FIGO stage IA IB1 IB2 IIA IIB Histology Squamous cell carcinoma Adenocarcinoma
48.1 (31–63) 26.6 (17.5–40.5) 15 (47) 5 (16)
49.3 (30–65) 26.8 (17.6–36.5) 10 (45) 3 (14)
0.55b 0.12b 0.91c 0.85c b0.001c
3 (9) 29 (91) 0 0 0
0 0 16 (73) 4 (18) 2 (9)
29 (91) 3 (9)
18 (82) 4 (18)
t1:4 t1:5 t1:6 t1:7 t1:8 t1:9 t1:10 t1:11 t1:12 t1:13 t1:14 t1:15 t1:16
F
0.59c
t1:17 t1:18 t1:19 t1:20 t1:21 t1:22
as absolute number or number (percentage). The Student t test was used compared normally distributed continuous variables, and the χ2 test or Fisher exact test was used to compare categorical variables. P b 0.05 was considered significant.
120 121
O
Abbreviations: LACC, locally advanced cervical cancer; BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); FIGO, International Federation of Gynecology and Obstetrics. a Values are given as median (range) or number (percentage), unless indicated otherwise. b By Student t test. c By χ2 test.
R O
98 99
Early-stage disease (n = 32)
P
96 97
Characteristic
D
94 95
t1:1 t1:2
Table 1 Baseline characteristics.a
122 123
124
3. Results
During the study period, 54 patients with cervical cancer (FIGO 125 stages IA2–IIB) met the inclusion criteria and were included in the 126 study. Among the participants, 7 (13%) had adenocarcinoma and 127 47 (87%) had squamous cell carcinoma. Group 1 included 32 patients 128 and group 2 included 22 patients. Age, BMI, menopausal status, history 129 of pelvic surgery, and histology did not differ between groups (Table 1). 130 Overall, 20 (91%) women in group 2 showed a complete or partial 131 response after a mean of 3.5 weeks (range 2.7–4.0) after the last cycle 132 of NACT (Table 2). One (5%) patient with a stage IIA tumor and progres- 133 sive disease and 1 (5%) patient with stage IIB disease and stable disease 134 received concurrent chemoradiation and did not undergo surgery. 135 Thus, 52 patients underwent robotic nerve-sparing radical hyster- 136 ectomy and pelvic lymphadenectomy. The mean operative time 137 in group 1 was 209.2 min (range 145–400) and the mean blood loss 138 was 99.7 mL (range 30–500). Only 2 (6%) women in group 1 had an 139 operative time longer than the average (380 min for one woman with 140 previous pelvic surgery history and 400 min for another with narrow 141 pelvic space owing to a high BMI of 40.5). The operative time for all 142 other patients in group 1 was less than 240 minutes. Only 1 (3%) patient 143 in group 1 had a blood loss of 500 mL and received an intraoperative 144 blood transfusion. 145 The mean operative time in group 2 was 215.8 min (range 130–450) 146 and the mean blood loss was 100.2 mL (range 35–550). One (5%) 147
T
92 93
C
90 91
E
88 89
R
86 87
R
84 85
O
83
C
81 82
N
79 80
treatment; and patients with LACC (FIGO stages IB2–IIB) were included in group 2 and underwent robotic surgery after NACT. Patients with LACC (group 2) received two or three cycles of treatment with paclitaxel (175 mg/m2; Taxol, Corden Pharma Latina, Sermoneta, Italy) plus cisplatin (75 mg/m2; Hospira, Melbourne, Victoria) [12,13]. The tumor response was analyzed in accordance with the revised Response Evaluation Criteria in Solid Tumors (RECIST) 2009 guidelines [14]. Within 4 weeks of completing NACT, patients in group 2 were re-evaluated by imaging and physical examination. Radiotherapy or chemotherapy combined with radiotherapy was applied if the tumor was found to be insensitive to the NACT regimen. Data for age, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), FIGO stage, menopausal status, pelvic surgery history, and general medical histology were obtained before surgery. All patients underwent nerve-sparing radical hysterectomy with level 1 and level 2 pelvic lymphadenectomy [15]. The nerve-sparing radical hysterectomy technical operation was readily incorporated into the conventional robotic technique and performed with a da Vinci system (Intuitive Surgical, Sunnyvale, CA, USA) [16]. Five trocars were used. A 12-mm camera trocar was placed via the open-Hasson technique; and two 8-mm ancillary robotic trocars were placed bilaterally, approximately 8–10 cm away from the camera port and 30 degrees below it to avoid collisions between the robotic arms. In addition, there were two assistant trocars (Fig. 1). The nerve-sparing radical hysterectomy technique has been described previously [17]. All surgical specimens were retrieved through the vagina to minimize intra-abdominal tumor seeding. The catheter was removed on the seventh day after surgery if the residual urine was less than 100 mL. After pelvic lymphadenectomy, the same gynecologic pathologist (Z.L.) performed assessments. For each patient, the operative time, number of pelvic lymph nodes, blood loss, vaginal cuff length, parametrium width, indwelling bladder catheter time, follow-up time, need for further adjuvant therapy, and intraoperative or postoperative complications were recorded. Additional radiation therapy or radiotherapy chemotherapy was administered to patients with pelvic lymph node metastasis, deep stromal invasion, or parametrial invasion. The last clinical follow-up examinations took place in February 2015. Tumor status at the most recent follow-up was recorded. Statistical analyses were performed with SPSS version 16.0 (SPSS Inc, Chicago, IL, USA). Normally distributed continuous variables were expressed as mean (range), and categorical variables were expressed
U
77 78
Z. Liu et al. / International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
E
2
Table 2 t2:1 Clinical outcomes of neoadjuvant chemotherapy among patients with locally advanced t2:2 cervical cancer.a t2:3
Fig. 1. The five robotic trocars. The red circle indicates the patient’s navel. A 12-mm camera trocar was placed via the open-Hasson technique (a), two 8-mm ancillary robotic trocars were placed bilaterally (b and c), and two assistant trocars were also used (d and e).
FIGO stage
Patients (n = 22)
IB2 IIA IIB
16 4 2
Complete response
Partial response
Stable disease
Progressive disease
t2:4 t2:5 t2:6 t2:7
3 1 0
13 2 1
0 0 1
0 1 0
t2:8 t2:9 t2:10
Clinical objective tumor response
Abbreviation: FIGO, International Federation of Gynecology and Obstetrics. a Values are given as number.
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
t2:11 t2:12
Z. Liu et al. / International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182
Table 3 Operative, pathologic and follow-up outcomes among women who underwent surgery.a
t3:3
Outcome
t3:4 t3:5 t3:6 t3:7 t3:8 t3:9 t3:10 t3:11 t3:12 t3:13 t3:14 t3:15 t3:16 t3:17 t3:18 t3:19 t3:20 t3:21 t3:22 t3:23
Operative/postoperative Operative time, min Estimated blood loss, mL Indwelling bladder catheter, d Pathologic Pelvic lymph nodes, n Length of right parametrium removed, mm Length of left parametrium removed, mm Vaginal cuff, mm Follow-up Duration, mo Positive lymph nodes Recurrence Died from disease Further adjuvant therapy Chemotherapy alone Radiotherapy alone Concurrent chemoradiation
t3:24 t3:25 t3:26 t3:27 t3:28
U
N C O
Early stage disease (n = 32)
R
t3:1 t3:2
R
E
183
LACC (n = 20)
P value
209.2 (145–400) 99.7 (30–500) 8.2 (7–24)
215.8 (130–450) 100.2 (35–550) 8.1 (7–20)
0.72b 0.35b 0.90b
25 (11–45) 32.9 (20–65)
27 (12–50) 33.4 (28–65)
0.82b 0.22b
32.1 (21–60)
32.8 (25–61)
0.33b
24.7 (10–45)
25.5 (10–50)
0.61b
26 (23–41) 5 0 0
26 (20–41) 3 0 0
0 0 9 (28)
11 (55) 4 (20) 5 (25)
0.41b 0.85c N0.99d N0.99d b0.001c
Abbreviation: LACC, locally advanced cervical cancer. a Values are given as median (range) or number (percentage), unless indicated otherwise. b By Student t test. c By χ2 test. d By Fisher exact test.
0 0 0
0 0 0
1 (3) 0 0 0 0
0 0 1 (3) 2 (6) 1
1 (5) 0 0 0 0
0 0 0 1 (5) 1 (5)
t4:5 t4:6 t4:7 t4:8 t4:9 t4:10 t4:11 t4:12 t4:13
0
0
0
0
0
0
0
0
1 (5)
2 (10)
1 (3)
F
161 162
0 0 0
O
159 160
t4:4
0 0 0
4 (13)
t4:14 t4:15 t4:16 t4:17 t4:18
Abbreviation: LACC, locally advanced cervical cancer. a Values are given as number (percentage).
t4:19 t4:20
4. Discussion
184
R O
157 158
Ureteral injury Bladder/urinary Bowel injury/ obstruction Blood transfusion Hernia/dehiscence Infection Lymphedema Voiding dysfunction Conversion to laparotomy Deep venous thrombosis Total
t4:3
LACC (n = 20)
The present data suggest that robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy are technically feasible and safe for LACC after NACT. There was no difference in operative time or estimated blood loss between patients with early-stage disease and LACC. The surgical and pathologic outcomes of patients with LACC after NACT administration, including pelvic lymph node count, parametrium width, vaginal cuff length, and indwelling bladder catheter time, generally met the standards achieved by radical hysterectomy. The therapeutic effects were similar to those observed among patients with early stage cervical cancer. Since robotic surgery was first approved for gynecologic therapy in 2005, it has had a profound impact on the surgical approach to gynecologic malignancies. There are various differences between robotic and conventional surgical approaches. As compared with traditional laparoscopy, robotic surgery offers several advantages for the surgeon, such as three-dimensional stereoscopic vision. Moreover, the robotic arm can rotate 360 degrees and facilitates better dexterity and precision. Therefore, this novel system has become widely accepted by gynecologic oncologists for both the therapy and staging of gynecologic malignancies. Robotic surgery is now widely used in the treatment of early stage cervical and endometrial cancers [18]. From the patient’s standpoint, it can achieve the same clinical outcomes as laparoscopy [19]. From the surgeon’s point of view, robot-assisted surgery is superior to traditional laparoscopic surgery in terms of its higher image quality, deeper perception, dexterity, and precision and speed of motion; in addition, it is more comfortable for the surgeon and leads to less eye fatigue [20]. In 2007, Sert and Abeler [21] reported the first application of robotic and laparoscopic radical hysterectomy and showed that there was no significant difference in operative time, retrieved lymph node number, or size of parametrial tissue excised between this approach and conventional surgery. However, the average intraoperative blood loss in the robotic group was lower and the average hospital stay was shorter [21]. Nevertheless, despite its shorter operative time and length of hospital stay, robotically assisted hysterectomy is substantially more expensive as compared with laparoscopic hysterectomy [22]. Conventional radical hysterectomy can lead to several complications, such as bladder dysfunction, colorectal motility disorders, and sexual dysfunction. The nerve-sparing radical hysterectomy technique is associated with a lower incidence of bladder and rectal dysfunction as compared with conventional radical hysterectomy. To preserve bladder function, modified radical hysterectomy would be a more appropriate approach [23]. The nerve-sparing operation could be easily absorbed
P
155 156
Early stage disease (n = 32)
Intraoperative Postoperative Intraoperative Postoperative
D
154
Complication
E
152 153
t4:1 t4:2
Table 4 Intraoperative and postoperative complications.a
T
150 151
woman in group 2 had an operative time of 450 minutes, which was due to a history of pelvic surgery. One (5%) patient lost 550 mL of blood and received a blood transfusion. No difference was found in the operative time or estimated blood loss between the two groups (Table 3). There was no difference in the median lengths of the tissue removed from the right parametrium and left parametrium (Table 3). Similarly, no difference was found in nodal counts between the two groups (Table 3). The number of positive lymph nodes was similar between group 1 and group 2 (Table 3). In group 1, 26 (81%) patients had the catheter removed on time; the catheter was removed on day 11 for 5 (16%) patients and on day 24 for 1 (13%) patient. In group 2, the catheter was removed on time for 16 (80%) patients, on day 11 for 3 (15%), and on day 20 for 1 (5%). The mean indwelling time of the bladder catheter was similar between the two groups (Table 3). In group 1, 9 (28%) patients received concurrent chemoradiation: 5 (16%) patients had positive pelvic nodes, whereas 4 (13%) had deep stromal invasion. In group 2, 11 (55%) patients received two cycles of chemotherapy, 5 (25%) had concurrent chemoradiation because of poor pathologic response, and 4 (20%) had radiotherapy alone owing to a lack of response to chemotherapy. Few women experienced intraoperative complications (Table 4). No significant difference in the frequency of intraoperative complications was found between groups (P = 0.68). One woman in each group received a blood transfusion for intraoperative bleeding. No cases of ureteral injury, bladder or urinary injury, bowel injury or obstruction, hernia or dehiscence, infection, lymphedema, conversion to laparotomy, or venous thrombosis were noted intraoperatively. The incidence of postoperative complications was slightly higher than that of intraoperative complications (Table 4), but did not differ between groups (P = 0.695). No patients in either group experienced the postoperative complications of bowel trauma or obstruction, incisional hernia or dehiscence, symptomatic lymphocyst, or reoperation. There was no difference in the mean follow-up period between the two groups (Table 3). At the most recent follow-up, no patient in either group had experienced disease recurrence or had died.
C
148 149
3
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227
253 254 255 256
261 262 263 264 265 266 267 268 269 270 271 272 273 337
C
251 252
E
249 250
Conflict of interest The authors have no conflicts of interest.
R
247 248
R
245 246
References
[1] Quinn MA, Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT, et al. Carcinoma of the cervix uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynecol Obstet 2006;95(Suppl. 1):S43–S103. [2] Rose PG. Concurrent chemoradiation for locally advanced carcinoma of the cervix: where are we in 2006? Ann Oncol 2006;17(Suppl. 10):x224–9. [3] NACCCMA Collaboration. Neoadjuvant chemotherapy for locally advanced cervix cancer. Cochrane Database Syst Rev 2004(2):CD001774.
O
243 244
C
241 242
N
239 240
U
237 238
F
The study was sponsored by a grant from the Capital Civilian Health Program (Z131100006813023).
235 236
O
260
234
R O
Acknowledgments
232 233
P
259
230 231
[4] Gonzalez-Martin A, Gonzalez-Cortijo L, Carballo N, Garcia JF, Lapuente F, Rojo A, et al. The current role of neoadjuvant chemotherapy in the management of cervical carcinoma. Gynecol Oncol 2008;110(3 Suppl 2):S36–40. [5] Cibula D, Velechovska P, Slama J, Fischerova D, Pinkavova I, Pavlista D, et al. Late morbidity following nerve-sparing radical hysterectomy. Gynecol Oncol 2010; 116(3):506–11. [6] Fujii S, Takakura K, Matsumura N, Higuchi T, Yura S, Mandai M, et al. Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. Gynecol Oncol 2007;107(1):4–13. [7] van den Tillaart SA, Kenter GG, Peters AA, Dekker FW, Gaarenstroom KN, Fleuren GJ, et al. Nerve-sparing radical hysterectomy: local recurrence rate, feasibility, and safety in cervical cancer patients stage IA to IIA. Int J Gynecol Cancer 2009;19(1):39–45. [8] Barkun JS, Wexler MJ, Hinchey EJ, Thibeault D, Meakins JL. Laparoscopic versus open inguinal herniorrhaphy: preliminary results of a randomized controlled trial. Surgery 1995;118(4):703–9 discussion 9–10. [9] Gitzelmann CA, Mendoza-Sagaon M, Talamini MA, Ahmad SA, Pegoli Jr W, Paidas CN. Cell-mediated immune response is better preserved by laparoscopy than laparotomy. Surgery 2000;127(1):65–71. [10] Boggess JF, Gehrig PA, Cantrell L, Shafer A, Ridgway M, Skinner EN, et al. A comparative study of 3 surgical methods for hysterectomy with staging for endometrial cancer: robotic assistance, laparoscopy, laparotomy. Am J Obstet Gynecol 2008; 199(4):360.e1–9. [11] Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynecol Obstet 2009;105(2):107–8. [12] Angioli R, Plotti F, Montera R, Aloisi A, Luvero D, Capriglione S, et al. Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer. Gynecol Oncol 2012;127(2):290–6. [13] Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003;21(17):3194–200. [14] Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–47. [15] Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol 2008; 9(3):297–303. [16] Magrina JF, Kho R, Magtibay PM. Robotic radical hysterectomy: Technical aspects. Gynecol Oncol 2009;113(1):28–31. [17] Magrina JF, Pawlina W, Kho RM, Magtibay PM. Robotic nerve-sparing radical hysterectomy: feasibility and technique. Gynecol Oncol 2011;121(3):605–9. [18] duPont NC, Chandrasekhar R, Wilding G, Guru KA. Current trends in robot assisted surgery: a survey of gynecologic oncologists. Int J Med Robot 2010;6(4):468–72. [19] Vizza E, Pellegrino A, Milani R, Fruscio R, Baiocco E, Cognetti F, et al. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2IIB cervical cancer patients after neoadjuvant chemotherapy. Eur J Surg Oncol 2011; 37(4):364–9. [20] Van Koughnett J, Jayaraman S, Eagleson R, Quan D, van Wynsberghe A, Schlachta C. Are there advantages to robotic-assisted surgery over laparoscopy from the surgeon’s perspective? J Robotic Surg 2009;3(2):79–82. [21] Sert B, Abeler V. Robotic radical hysterectomy in early-stage cervical carcinoma patients, comparing results with total laparoscopic radical hysterectomy cases. The future is now? Int J Med Robot 2007;3(3):224–8. [22] Wright JD, Ananth CV, Tergas AI, Herzog TJ, Burke WM, Lewin SN, et al. An economic analysis of robotically assisted hysterectomy. Obstet Gynecol 2014;123(5):1038–48. [23] Landoni F, Maneo A, Cormio G, Perego P, Milani R, Caruso O, et al. Class II versus class III radical hysterectomy in stage IB-IIA cervical cancer: a prospective randomized study. Gynecol Oncol 2001;80(1):3–12. [24] Trimbos JB, Maas CP, Deruiter MC, Peters AA, Kenter GG. A nerve-sparing radical hysterectomy: guidelines and feasibility in Western patients. Int J Gynecol Cancer 2001;11(3):180–6. [25] Magrina JF, Kho RM, Weaver AL, Montero RP, Magtibay PM. Robotic radical hysterectomy: comparison with laparoscopy and laparotomy. Gynecol Oncol 2008;109(1):86–91.
T
257 258
into conventional robotic radical surgery [10]. Image amplification facilitates perception of the pelvic autonomic nerves and might be helpful to complete this type of nerve-sparing surgery [24]. In addition, the robotic instrumentation is helpful for separating and preserving the autonomic nerve fibers. An important advantage of the robotic nerve-sparing technique is that it facilitates direct visualization of the autonomic nerves during the operation when the paravaginal tissues and vagina are transected. Previous studies found no difference in recurrence rates among patients with cervical cancer who had received robotic, conventional laparoscopic, or open radical hysterectomy [25]. Furthermore, none of the present study patients had experienced disease recurrence after a mean follow up of 26 months. The role of NACT in cervical cancer has become controversial. A database review illustrated the advantages of NACT followed by radical hysterectomy, finding a 14% increase in the 5-year survival rate as compared with concurrent chemoradiation alone [3]. In the present study, the safety and feasibility of the robotic approach has been demonstrated for the treatment of patients with LACC: 20 women underwent robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy after NACT, which rendered these patients—who had initially inoperable disease—surgically amenable. In addition, the present study enabled 11 patients with LACC to avoid radiotherapy. The present study has some limitations, including its small sample size. However, clinical data from both the study group and the control group were collected consecutively at the time of treatment. Additionally, the follow-up was relatively short: the therapeutic outcome of robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy for LACC after NACT should be followed up for longer to obtain more data. In summary, the present data indicate that robotic nerve-sparing radical hysterectomy is a feasible and safe procedure for the treatment of patients with LACC after NACT.
D
228 229
Z. Liu et al. / International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
E
4
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
1
CLINICAL ARTICLE
4Q2
Zhongyu Liu a,1, Xiuli Li b,1, Weiping Li a, Yizhuo Yang a, Ye Tao c, Yuanqing Yao a,⁎ a
8
a r t i c l e
9 10 11 12
Article history: Received 28 November 2014 Received in revised form 26 April 2015 Accepted 22 July 2015
13 14 15 16 17 18 19
Keywords: Cervical cancer Neoadjuvant chemotherapy Nerve-sparing Pelvic lymphadenectomy Radical hysterectomy Robotic surgery
i n f o
a b s t r a c t
E
D
P
Objective: To evaluate the feasibility and safety of robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer (LACC). Methods: In a retrospective study, data were analyzed for patients treated for cervical cancer at a center in Beijing, China, between December 2011 and September 2013. Patients were subdivided into those with early-stage disease (FIGO stage IA2–IB1) who were treated by robotic surgery (group 1), and those with LACC (stage IB2–IIB) who were treated by robotic surgery after neoadjuvant chemotherapy (NACT; group 2). Therapeutic outcomes and complications were compared. Results: Group 1 included 32 patients and group 2 included 22 patients. Two patients in group 2 did not respond to NACT and did not undergo surgery. The operative outcomes and incidences of complications did not differ significantly between the two groups (P N 0.05 for all). There were no differences in nodal yield, lengths of parametrium removed, or vaginal cuff length (P N 0.05 for all). During a mean follow-up of 26 months, no patient experienced recurrence. Conclusion: Robotic nerve-sparing radical hysterectomy was found to be feasible and safe for LACC after NACT. A larger case series with longer follow-up data is needed to justify its widespread application. © 2015 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.
36 34
E
35
1. Introduction
38
Despite advances in pathologic screening, cervical cancer remains a major health problem for women, especially locally advanced cervical cancer (LACC) [1]. Cisplatin-based concurrent chemotherapy and external pelvic irradiation followed by brachytherapy are the standard treatment for LACC [2]; however, some studies have indicated that neoadjuvant chemotherapy (NACT) followed by radical hysterectomy is also an effective treatment for LACC [3,4]. In particular, it has been shown that NACT combined with surgery has better outcomes than does irradiation alone in terms of overall survival rate [3]. Although radical hysterectomy is the principal surgical approach for LACC, it is associated with a high incidence of postoperative complications such as bladder and rectal dysfunction [5]. Nerve-sparing radical hysterectomy has been shown to significantly decrease the incidence of morbidity, as well as bladder and rectal dysfunction [6,7]. This laparoscopic surgery has many advantages, including shorter hospital stays, rapid return to preoperative activity, decreased postoperative pain,
45 46 47 48 49 50 51 52 53
R
N C O
43 44
U
41 42
R
37
39 40
R O
Department of Obstetrics and Gynecology, PLA General Hospital, Beijing, China Department of Obstetrics and Gynecology, Hainan Branch of PLA General Hospital, Sanya, China Department of Ophthalmology, PLA General Hospital, Beijing, China
C
c
T
b
O
5 6 7
F
3
Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy
2Q1
⁎ Corresponding author at: Department of Obstetrics and Gynecology, PLA General Hospital, Fu Xing St, Beijing 100853, China. Tel.: + 86 18010012181; fax: + 86 01066938343. E-mail address: [email protected] (Y. Yao). 1 These authors contributed equally.
20 21 22 23 24 25 26 27 28 29 30 31 32 33
well preserved immune function, decreased postoperative complications, and a reduced incidence of postoperative complications [8,9]. The use of robots in cancer surgery has also been gaining increasing attention for its many benefits over conventional laparoscopy, including shorter operative times, less estimated blood loss, fewer intraoperative transfusions, fewer conversions to traditional laparotomy, and shorter hospital stays [10]. The aim of the present study was to evaluate the feasibility and safety of robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy for the treatment of patients with LACC after NACT.
54
2. Materials and methods
64
In a retrospective analysis, data were reviewed from patients treated for cervical cancer at PLA General Hospital, Beijing, China, between December 1, 2011, and September 30, 2013. Eligible patients had no tumors besides cervical cancer and no cardiovascular, pulmonary, or endocrine disease. At enrollment, patients had to agree to postoperative follow-up. The study protocol was approved by the ethics review board of the study hospital. All patients agreed to robotic surgery and provided written inform consent. The participants were divided in two groups according to their International Federation of Gynecology and Obstetrics (FIGO) stage [11]: patients with early-stage cervical cancer (FIGO stages IA2–IB1) were included in group 1 and underwent robotic surgery as their first
65 66
http://dx.doi.org/10.1016/j.ijgo.2015.05.017 0020-7292/© 2015 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
55 56 57 58 59 60 61 62 63
67 68 69 70 71 72 73 74 75 76
100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119
LACC (n = 22)
P value
t1:3
Age, y BMI Menopausal History of pelvic surgery FIGO stage IA IB1 IB2 IIA IIB Histology Squamous cell carcinoma Adenocarcinoma
48.1 (31–63) 26.6 (17.5–40.5) 15 (47) 5 (16)
49.3 (30–65) 26.8 (17.6–36.5) 10 (45) 3 (14)
0.55b 0.12b 0.91c 0.85c b0.001c
3 (9) 29 (91) 0 0 0
0 0 16 (73) 4 (18) 2 (9)
29 (91) 3 (9)
18 (82) 4 (18)
t1:4 t1:5 t1:6 t1:7 t1:8 t1:9 t1:10 t1:11 t1:12 t1:13 t1:14 t1:15 t1:16
F
0.59c
t1:17 t1:18 t1:19 t1:20 t1:21 t1:22
as absolute number or number (percentage). The Student t test was used compared normally distributed continuous variables, and the χ2 test or Fisher exact test was used to compare categorical variables. P b 0.05 was considered significant.
120 121
O
Abbreviations: LACC, locally advanced cervical cancer; BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); FIGO, International Federation of Gynecology and Obstetrics. a Values are given as median (range) or number (percentage), unless indicated otherwise. b By Student t test. c By χ2 test.
R O
98 99
Early-stage disease (n = 32)
P
96 97
Characteristic
D
94 95
t1:1 t1:2
Table 1 Baseline characteristics.a
122 123
124
3. Results
During the study period, 54 patients with cervical cancer (FIGO 125 stages IA2–IIB) met the inclusion criteria and were included in the 126 study. Among the participants, 7 (13%) had adenocarcinoma and 127 47 (87%) had squamous cell carcinoma. Group 1 included 32 patients 128 and group 2 included 22 patients. Age, BMI, menopausal status, history 129 of pelvic surgery, and histology did not differ between groups (Table 1). 130 Overall, 20 (91%) women in group 2 showed a complete or partial 131 response after a mean of 3.5 weeks (range 2.7–4.0) after the last cycle 132 of NACT (Table 2). One (5%) patient with a stage IIA tumor and progres- 133 sive disease and 1 (5%) patient with stage IIB disease and stable disease 134 received concurrent chemoradiation and did not undergo surgery. 135 Thus, 52 patients underwent robotic nerve-sparing radical hyster- 136 ectomy and pelvic lymphadenectomy. The mean operative time 137 in group 1 was 209.2 min (range 145–400) and the mean blood loss 138 was 99.7 mL (range 30–500). Only 2 (6%) women in group 1 had an 139 operative time longer than the average (380 min for one woman with 140 previous pelvic surgery history and 400 min for another with narrow 141 pelvic space owing to a high BMI of 40.5). The operative time for all 142 other patients in group 1 was less than 240 minutes. Only 1 (3%) patient 143 in group 1 had a blood loss of 500 mL and received an intraoperative 144 blood transfusion. 145 The mean operative time in group 2 was 215.8 min (range 130–450) 146 and the mean blood loss was 100.2 mL (range 35–550). One (5%) 147
T
92 93
C
90 91
E
88 89
R
86 87
R
84 85
O
83
C
81 82
N
79 80
treatment; and patients with LACC (FIGO stages IB2–IIB) were included in group 2 and underwent robotic surgery after NACT. Patients with LACC (group 2) received two or three cycles of treatment with paclitaxel (175 mg/m2; Taxol, Corden Pharma Latina, Sermoneta, Italy) plus cisplatin (75 mg/m2; Hospira, Melbourne, Victoria) [12,13]. The tumor response was analyzed in accordance with the revised Response Evaluation Criteria in Solid Tumors (RECIST) 2009 guidelines [14]. Within 4 weeks of completing NACT, patients in group 2 were re-evaluated by imaging and physical examination. Radiotherapy or chemotherapy combined with radiotherapy was applied if the tumor was found to be insensitive to the NACT regimen. Data for age, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), FIGO stage, menopausal status, pelvic surgery history, and general medical histology were obtained before surgery. All patients underwent nerve-sparing radical hysterectomy with level 1 and level 2 pelvic lymphadenectomy [15]. The nerve-sparing radical hysterectomy technical operation was readily incorporated into the conventional robotic technique and performed with a da Vinci system (Intuitive Surgical, Sunnyvale, CA, USA) [16]. Five trocars were used. A 12-mm camera trocar was placed via the open-Hasson technique; and two 8-mm ancillary robotic trocars were placed bilaterally, approximately 8–10 cm away from the camera port and 30 degrees below it to avoid collisions between the robotic arms. In addition, there were two assistant trocars (Fig. 1). The nerve-sparing radical hysterectomy technique has been described previously [17]. All surgical specimens were retrieved through the vagina to minimize intra-abdominal tumor seeding. The catheter was removed on the seventh day after surgery if the residual urine was less than 100 mL. After pelvic lymphadenectomy, the same gynecologic pathologist (Z.L.) performed assessments. For each patient, the operative time, number of pelvic lymph nodes, blood loss, vaginal cuff length, parametrium width, indwelling bladder catheter time, follow-up time, need for further adjuvant therapy, and intraoperative or postoperative complications were recorded. Additional radiation therapy or radiotherapy chemotherapy was administered to patients with pelvic lymph node metastasis, deep stromal invasion, or parametrial invasion. The last clinical follow-up examinations took place in February 2015. Tumor status at the most recent follow-up was recorded. Statistical analyses were performed with SPSS version 16.0 (SPSS Inc, Chicago, IL, USA). Normally distributed continuous variables were expressed as mean (range), and categorical variables were expressed
U
77 78
Z. Liu et al. / International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
E
2
Table 2 t2:1 Clinical outcomes of neoadjuvant chemotherapy among patients with locally advanced t2:2 cervical cancer.a t2:3
Fig. 1. The five robotic trocars. The red circle indicates the patient’s navel. A 12-mm camera trocar was placed via the open-Hasson technique (a), two 8-mm ancillary robotic trocars were placed bilaterally (b and c), and two assistant trocars were also used (d and e).
FIGO stage
Patients (n = 22)
IB2 IIA IIB
16 4 2
Complete response
Partial response
Stable disease
Progressive disease
t2:4 t2:5 t2:6 t2:7
3 1 0
13 2 1
0 0 1
0 1 0
t2:8 t2:9 t2:10
Clinical objective tumor response
Abbreviation: FIGO, International Federation of Gynecology and Obstetrics. a Values are given as number.
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
t2:11 t2:12
Z. Liu et al. / International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182
Table 3 Operative, pathologic and follow-up outcomes among women who underwent surgery.a
t3:3
Outcome
t3:4 t3:5 t3:6 t3:7 t3:8 t3:9 t3:10 t3:11 t3:12 t3:13 t3:14 t3:15 t3:16 t3:17 t3:18 t3:19 t3:20 t3:21 t3:22 t3:23
Operative/postoperative Operative time, min Estimated blood loss, mL Indwelling bladder catheter, d Pathologic Pelvic lymph nodes, n Length of right parametrium removed, mm Length of left parametrium removed, mm Vaginal cuff, mm Follow-up Duration, mo Positive lymph nodes Recurrence Died from disease Further adjuvant therapy Chemotherapy alone Radiotherapy alone Concurrent chemoradiation
t3:24 t3:25 t3:26 t3:27 t3:28
U
N C O
Early stage disease (n = 32)
R
t3:1 t3:2
R
E
183
LACC (n = 20)
P value
209.2 (145–400) 99.7 (30–500) 8.2 (7–24)
215.8 (130–450) 100.2 (35–550) 8.1 (7–20)
0.72b 0.35b 0.90b
25 (11–45) 32.9 (20–65)
27 (12–50) 33.4 (28–65)
0.82b 0.22b
32.1 (21–60)
32.8 (25–61)
0.33b
24.7 (10–45)
25.5 (10–50)
0.61b
26 (23–41) 5 0 0
26 (20–41) 3 0 0
0 0 9 (28)
11 (55) 4 (20) 5 (25)
0.41b 0.85c N0.99d N0.99d b0.001c
Abbreviation: LACC, locally advanced cervical cancer. a Values are given as median (range) or number (percentage), unless indicated otherwise. b By Student t test. c By χ2 test. d By Fisher exact test.
0 0 0
0 0 0
1 (3) 0 0 0 0
0 0 1 (3) 2 (6) 1
1 (5) 0 0 0 0
0 0 0 1 (5) 1 (5)
t4:5 t4:6 t4:7 t4:8 t4:9 t4:10 t4:11 t4:12 t4:13
0
0
0
0
0
0
0
0
1 (5)
2 (10)
1 (3)
F
161 162
0 0 0
O
159 160
t4:4
0 0 0
4 (13)
t4:14 t4:15 t4:16 t4:17 t4:18
Abbreviation: LACC, locally advanced cervical cancer. a Values are given as number (percentage).
t4:19 t4:20
4. Discussion
184
R O
157 158
Ureteral injury Bladder/urinary Bowel injury/ obstruction Blood transfusion Hernia/dehiscence Infection Lymphedema Voiding dysfunction Conversion to laparotomy Deep venous thrombosis Total
t4:3
LACC (n = 20)
The present data suggest that robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy are technically feasible and safe for LACC after NACT. There was no difference in operative time or estimated blood loss between patients with early-stage disease and LACC. The surgical and pathologic outcomes of patients with LACC after NACT administration, including pelvic lymph node count, parametrium width, vaginal cuff length, and indwelling bladder catheter time, generally met the standards achieved by radical hysterectomy. The therapeutic effects were similar to those observed among patients with early stage cervical cancer. Since robotic surgery was first approved for gynecologic therapy in 2005, it has had a profound impact on the surgical approach to gynecologic malignancies. There are various differences between robotic and conventional surgical approaches. As compared with traditional laparoscopy, robotic surgery offers several advantages for the surgeon, such as three-dimensional stereoscopic vision. Moreover, the robotic arm can rotate 360 degrees and facilitates better dexterity and precision. Therefore, this novel system has become widely accepted by gynecologic oncologists for both the therapy and staging of gynecologic malignancies. Robotic surgery is now widely used in the treatment of early stage cervical and endometrial cancers [18]. From the patient’s standpoint, it can achieve the same clinical outcomes as laparoscopy [19]. From the surgeon’s point of view, robot-assisted surgery is superior to traditional laparoscopic surgery in terms of its higher image quality, deeper perception, dexterity, and precision and speed of motion; in addition, it is more comfortable for the surgeon and leads to less eye fatigue [20]. In 2007, Sert and Abeler [21] reported the first application of robotic and laparoscopic radical hysterectomy and showed that there was no significant difference in operative time, retrieved lymph node number, or size of parametrial tissue excised between this approach and conventional surgery. However, the average intraoperative blood loss in the robotic group was lower and the average hospital stay was shorter [21]. Nevertheless, despite its shorter operative time and length of hospital stay, robotically assisted hysterectomy is substantially more expensive as compared with laparoscopic hysterectomy [22]. Conventional radical hysterectomy can lead to several complications, such as bladder dysfunction, colorectal motility disorders, and sexual dysfunction. The nerve-sparing radical hysterectomy technique is associated with a lower incidence of bladder and rectal dysfunction as compared with conventional radical hysterectomy. To preserve bladder function, modified radical hysterectomy would be a more appropriate approach [23]. The nerve-sparing operation could be easily absorbed
P
155 156
Early stage disease (n = 32)
Intraoperative Postoperative Intraoperative Postoperative
D
154
Complication
E
152 153
t4:1 t4:2
Table 4 Intraoperative and postoperative complications.a
T
150 151
woman in group 2 had an operative time of 450 minutes, which was due to a history of pelvic surgery. One (5%) patient lost 550 mL of blood and received a blood transfusion. No difference was found in the operative time or estimated blood loss between the two groups (Table 3). There was no difference in the median lengths of the tissue removed from the right parametrium and left parametrium (Table 3). Similarly, no difference was found in nodal counts between the two groups (Table 3). The number of positive lymph nodes was similar between group 1 and group 2 (Table 3). In group 1, 26 (81%) patients had the catheter removed on time; the catheter was removed on day 11 for 5 (16%) patients and on day 24 for 1 (13%) patient. In group 2, the catheter was removed on time for 16 (80%) patients, on day 11 for 3 (15%), and on day 20 for 1 (5%). The mean indwelling time of the bladder catheter was similar between the two groups (Table 3). In group 1, 9 (28%) patients received concurrent chemoradiation: 5 (16%) patients had positive pelvic nodes, whereas 4 (13%) had deep stromal invasion. In group 2, 11 (55%) patients received two cycles of chemotherapy, 5 (25%) had concurrent chemoradiation because of poor pathologic response, and 4 (20%) had radiotherapy alone owing to a lack of response to chemotherapy. Few women experienced intraoperative complications (Table 4). No significant difference in the frequency of intraoperative complications was found between groups (P = 0.68). One woman in each group received a blood transfusion for intraoperative bleeding. No cases of ureteral injury, bladder or urinary injury, bowel injury or obstruction, hernia or dehiscence, infection, lymphedema, conversion to laparotomy, or venous thrombosis were noted intraoperatively. The incidence of postoperative complications was slightly higher than that of intraoperative complications (Table 4), but did not differ between groups (P = 0.695). No patients in either group experienced the postoperative complications of bowel trauma or obstruction, incisional hernia or dehiscence, symptomatic lymphocyst, or reoperation. There was no difference in the mean follow-up period between the two groups (Table 3). At the most recent follow-up, no patient in either group had experienced disease recurrence or had died.
C
148 149
3
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227
253 254 255 256
261 262 263 264 265 266 267 268 269 270 271 272 273 337
C
251 252
E
249 250
Conflict of interest The authors have no conflicts of interest.
R
247 248
R
245 246
References
[1] Quinn MA, Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT, et al. Carcinoma of the cervix uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynecol Obstet 2006;95(Suppl. 1):S43–S103. [2] Rose PG. Concurrent chemoradiation for locally advanced carcinoma of the cervix: where are we in 2006? Ann Oncol 2006;17(Suppl. 10):x224–9. [3] NACCCMA Collaboration. Neoadjuvant chemotherapy for locally advanced cervix cancer. Cochrane Database Syst Rev 2004(2):CD001774.
O
243 244
C
241 242
N
239 240
U
237 238
F
The study was sponsored by a grant from the Capital Civilian Health Program (Z131100006813023).
235 236
O
260
234
R O
Acknowledgments
232 233
P
259
230 231
[4] Gonzalez-Martin A, Gonzalez-Cortijo L, Carballo N, Garcia JF, Lapuente F, Rojo A, et al. The current role of neoadjuvant chemotherapy in the management of cervical carcinoma. Gynecol Oncol 2008;110(3 Suppl 2):S36–40. [5] Cibula D, Velechovska P, Slama J, Fischerova D, Pinkavova I, Pavlista D, et al. Late morbidity following nerve-sparing radical hysterectomy. Gynecol Oncol 2010; 116(3):506–11. [6] Fujii S, Takakura K, Matsumura N, Higuchi T, Yura S, Mandai M, et al. Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. Gynecol Oncol 2007;107(1):4–13. [7] van den Tillaart SA, Kenter GG, Peters AA, Dekker FW, Gaarenstroom KN, Fleuren GJ, et al. Nerve-sparing radical hysterectomy: local recurrence rate, feasibility, and safety in cervical cancer patients stage IA to IIA. Int J Gynecol Cancer 2009;19(1):39–45. [8] Barkun JS, Wexler MJ, Hinchey EJ, Thibeault D, Meakins JL. Laparoscopic versus open inguinal herniorrhaphy: preliminary results of a randomized controlled trial. Surgery 1995;118(4):703–9 discussion 9–10. [9] Gitzelmann CA, Mendoza-Sagaon M, Talamini MA, Ahmad SA, Pegoli Jr W, Paidas CN. Cell-mediated immune response is better preserved by laparoscopy than laparotomy. Surgery 2000;127(1):65–71. [10] Boggess JF, Gehrig PA, Cantrell L, Shafer A, Ridgway M, Skinner EN, et al. A comparative study of 3 surgical methods for hysterectomy with staging for endometrial cancer: robotic assistance, laparoscopy, laparotomy. Am J Obstet Gynecol 2008; 199(4):360.e1–9. [11] Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynecol Obstet 2009;105(2):107–8. [12] Angioli R, Plotti F, Montera R, Aloisi A, Luvero D, Capriglione S, et al. Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer. Gynecol Oncol 2012;127(2):290–6. [13] Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003;21(17):3194–200. [14] Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–47. [15] Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol 2008; 9(3):297–303. [16] Magrina JF, Kho R, Magtibay PM. Robotic radical hysterectomy: Technical aspects. Gynecol Oncol 2009;113(1):28–31. [17] Magrina JF, Pawlina W, Kho RM, Magtibay PM. Robotic nerve-sparing radical hysterectomy: feasibility and technique. Gynecol Oncol 2011;121(3):605–9. [18] duPont NC, Chandrasekhar R, Wilding G, Guru KA. Current trends in robot assisted surgery: a survey of gynecologic oncologists. Int J Med Robot 2010;6(4):468–72. [19] Vizza E, Pellegrino A, Milani R, Fruscio R, Baiocco E, Cognetti F, et al. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2IIB cervical cancer patients after neoadjuvant chemotherapy. Eur J Surg Oncol 2011; 37(4):364–9. [20] Van Koughnett J, Jayaraman S, Eagleson R, Quan D, van Wynsberghe A, Schlachta C. Are there advantages to robotic-assisted surgery over laparoscopy from the surgeon’s perspective? J Robotic Surg 2009;3(2):79–82. [21] Sert B, Abeler V. Robotic radical hysterectomy in early-stage cervical carcinoma patients, comparing results with total laparoscopic radical hysterectomy cases. The future is now? Int J Med Robot 2007;3(3):224–8. [22] Wright JD, Ananth CV, Tergas AI, Herzog TJ, Burke WM, Lewin SN, et al. An economic analysis of robotically assisted hysterectomy. Obstet Gynecol 2014;123(5):1038–48. [23] Landoni F, Maneo A, Cormio G, Perego P, Milani R, Caruso O, et al. Class II versus class III radical hysterectomy in stage IB-IIA cervical cancer: a prospective randomized study. Gynecol Oncol 2001;80(1):3–12. [24] Trimbos JB, Maas CP, Deruiter MC, Peters AA, Kenter GG. A nerve-sparing radical hysterectomy: guidelines and feasibility in Western patients. Int J Gynecol Cancer 2001;11(3):180–6. [25] Magrina JF, Kho RM, Weaver AL, Montero RP, Magtibay PM. Robotic radical hysterectomy: comparison with laparoscopy and laparotomy. Gynecol Oncol 2008;109(1):86–91.
T
257 258
into conventional robotic radical surgery [10]. Image amplification facilitates perception of the pelvic autonomic nerves and might be helpful to complete this type of nerve-sparing surgery [24]. In addition, the robotic instrumentation is helpful for separating and preserving the autonomic nerve fibers. An important advantage of the robotic nerve-sparing technique is that it facilitates direct visualization of the autonomic nerves during the operation when the paravaginal tissues and vagina are transected. Previous studies found no difference in recurrence rates among patients with cervical cancer who had received robotic, conventional laparoscopic, or open radical hysterectomy [25]. Furthermore, none of the present study patients had experienced disease recurrence after a mean follow up of 26 months. The role of NACT in cervical cancer has become controversial. A database review illustrated the advantages of NACT followed by radical hysterectomy, finding a 14% increase in the 5-year survival rate as compared with concurrent chemoradiation alone [3]. In the present study, the safety and feasibility of the robotic approach has been demonstrated for the treatment of patients with LACC: 20 women underwent robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy after NACT, which rendered these patients—who had initially inoperable disease—surgically amenable. In addition, the present study enabled 11 patients with LACC to avoid radiotherapy. The present study has some limitations, including its small sample size. However, clinical data from both the study group and the control group were collected consecutively at the time of treatment. Additionally, the follow-up was relatively short: the therapeutic outcome of robotic nerve-sparing radical hysterectomy and pelvic lymphadenectomy for LACC after NACT should be followed up for longer to obtain more data. In summary, the present data indicate that robotic nerve-sparing radical hysterectomy is a feasible and safe procedure for the treatment of patients with LACC after NACT.
D
228 229
Z. Liu et al. / International Journal of Gynecology and Obstetrics xxx (2015) xxx–xxx
E
4
Please cite this article as: Liu Z, et al, Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neoadjuvant chemotherapy, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.05.017
274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336