Gynecol Surg (2016) 13:485–492 DOI 10.1007/s10397-016-0967-z

ORIGINAL ARTICLE

Feasibility of laparoscopic radical hysterectomy after chemoradiation therapy in persistent locally advanced cervical cancer A. Reyes Claret 1 & Á. Martín Jiménez 1 & A. Robles Gourley 1 & M. Llull Gomila 1 & M. C. Martínez Canto 1 & A. Torrent Colomer 1

Received: 4 April 2016 / Accepted: 30 June 2016 / Published online: 7 July 2016 # Springer-Verlag Berlin Heidelberg 2016

Abstract To evaluate the feasibility, the surgical outcome and oncologic results of laparoscopic radical hysterectomy (RH) in patients with suspicion of central persistent locally advanced cervical cancer (LACC) after chemoradiation therapy (CRT). Observational retrospective study including data concerning five patients between November 2005 and June 2015, with LACC and suspicion of central persistent tumour less than 2 cm. After completing treatment with CRT and brachytherapy, these patients were submitted to laparoscopic RH. Median patient age was 58.2 (45–71) years. FIGO stage at initial diagnosis was IB2: one case, IIB: three cases and IIIA: one case. Median tumour volume at diagnosis was 38 (30–42) mm. Median residual cervical tumour after treatment assessed with MRI was 14 (7–20) mm. Feasibility rate was 100 %. All cases underwent type C1 RH. The median operating time was 214 (140–360) min. Only one intraoperative complication was registered (ureteral injury). Three postoperative complications were found, two of them were grade II. However, one grade IV complication was documented: a patient with a vesicovaginal fistula who died due to long-term postoperative complications (urinary sepsis) at 1 year and 5 months after surgery. Median hospital stay was 9 days (range 4–55). Histopathological study reported tumour-free specimens in four patients with complete response after CRT, and one patient had 1-mm residual tumour. Clear surgical margins were obtained in all cases. With mean follow-up of 20.8 months (range 8–58), only one death secondary to

* A. Reyes Claret [email protected]; [email protected]

1

Department of Obstetrics and Gynecology, Son Llàtzer Hospital, Carretera de Manacor Km 4, 07198 Palma de Mallorca (Balearic Islands), Spain

urinary sepsis was registered. Secondary recurrence after RH was not documented. In experienced hands, laparoscopic RH after CRT therapy is feasible but with increased risk of severe complications due to surgery on irradiated tissues. This kind of surgery and the laparoscopic approach could be a less mutilating surgery that we can offer to our patients; however, we must improve the selection of cases who will benefit from this procedure. Keywords Cervical cancer . Chemoradiation therapy . Radical hysterectomy . Laparoscopy

Introduction Since 1999, chemoradiation therapy (CRT) has represented the standard treatment for locally advanced cervical cancer (LACC) [1, 2]. However, about 30–50 % of patients diagnosed with LACC will recur and ultimately die because of the disease [3]. Residual tumour after CRT is one of the most important prognostic factors, and reported rates of persistent disease range between 35 and 61 % [4–7]. In cases of recurrence after a disease-free period or real persistent disease (from 4 to 6 months after completion CRT), surgery will be the last chance for survival, with pelvic exenteration (PE) representing the most used option. However, in approximately one of every five cases, patients have very small central recurrences (<2 cm) limited to the cervix or vagina [8] and may be candidates for a less radical approach than PE, specifically radical hysterectomy. This intervention has received little attention in the literature [9–11], and most of the published articles are about procedures performed by laparotomy. Laparoscopic approach is even less described in this context. In our knowledge, there are only five articles employing

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minimally invasive approach to perform a radical hysterectomy [6, 12–15]. All, except one [15], are as part of systematic adjuvant surgery a few weeks after completing CRT, in cases of complete clinical and radiological response or partial response of residual cervical tumour. In this current study, we report the surgical and oncological outcomes of five patients with suspected central persistent LACC after chemoradiation therapy submitted to a laparoscopic radical hysterectomy in our institution. The aim of the study is to evaluate the feasibility and morbidity directly related to the surgical procedure.

Materials and methods This observational retrospective study included data concerning five patients with LACC with suspected central persistent tumour after completing treatment with standard concurrent CRT and brachytherapy. All patients were submitted to a laparoscopic radical hysterectomy between November 2005 and June 2015 at Son Llàtzer Hospital, Balearic Islands, Spain. Inclusion criteria were as follows: (1) biopsy-proven carcinoma of the cervix (stage FIGO IB2-IVA), (2) common histological subtype (squamous cell, adenocarcinoma or adenosquamous tumour), (3) no evidence of extrapelvic disease on conventional imaging (abdominopelvic MRI or computed tomography [CT] scan and pelvic MRI) after completion of CRT, (4) age >18 and <70 years, (5) ECOG performance status <2, (6) primary treatment using pelvic external radiation therapy (45–50 Gy) with concomitant cisplatin chemotherapy (40 mg/m2 per week) and uterovaginal brachytherapy (dose 15 Gy) following CRT. All patients were submitted to a laparoscopic para-aortic lymphadenectomy extended to the level of the left renal vein, before starting CRT. In cases of nodal involvement, the radiation field was extended to the para-aortic chain with 45 Gy. Patients in poor physical condition (ECOG performance status >2), patients with a progressive disease despite chemoradiotherapy, or with metastatic spread were not candidates for surgery and were excluded of the study. Four months after CRT was completed (or brachytherapy if administered), clinical and radiological responses were evaluated by both gynaecological examination (with digital vaginal and rectal exam) and MRI using the RECIST response criteria [16]. Patients with clinical or radiological persistent disease <2 cm (with no proven extrapelvic disease, tumour progression or extension to rectum or bladder) were included in the study. Patients with incomplete CRT treatment without brachytherapy due to toxicity were included too. Only in one case, positron emission tomography/computed tomography (PET/TC) was requested. In patients with no evidence of persistent tumour, follow-up consisted in clinical examination

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at least every 3 months during the first 2 years and then every 6 months during the next 3 years. A systematic pelvic MRI and abdominal CT scan were performed every 6 months for the first 2 years, then every year; and also a yearly chest X-ray. All included cases were exposed and approved by the local institutional review board (IRB); moreover, all patients signed a written informed consent agreeing to be submitted to all the procedures. The following data were collected: age, body mass index (BMI), histological type, previous abdominal surgery, FIGO stage, early and late postoperative complications (any adverse event occurring within and after 30 days from surgery, respectively) according to Clavien-Dindo classification [17], duration of surgery, transfusion requirement, duration of hospital stay, and oncological outcome. Patients who met the inclusion criteria were triaged to laparoscopic radical hysterectomy according to the Querleu-Morrow classification scheme [18]. Type of radicality was determined depending on the extent of the disease based on the pre-surgical imaging study and intraoperative findings. A radical hysterectomy was performed according to the surgical steps described in our previous publication [19]. First of all, a bilateral ureteral catheterization was performed with the double-J stent (Angiomed Gmbl·l & Co., Karlsruhe, Gy) through cystoscopy, which remained approximately for 2 months. In the laparoscopic time, the patient was positioned in Trendelemburg position and a 0° laparoscope was used. Three 5-mm ancillary trocars were placed in the left and right iliac fossa and upper pubic region. We highlight the greatest difficulty in dissecting the vesicouterine septum and rectovaginal space due to radiotherapy-induced fibrosis, so we recommend bowel preparation before surgery and to check the bladder integrity filled with saline + methylene blue through the bladder catheter at the end of the intervention. Dissection of avascular spaces (para-rectal and para-vesical fosa) requires more careful dissection because of the increased resistance of the irradiated tissue. The ureter is completely freed until its entry into the trigone. Pulling up bladder pillars allows exposing the dome or the ureter’s tunnel, which in these cases will be more difficult due to the post-lies fibrosis. However, thanks to the double-J stent guide, and the magnified view offered by laparoscopy, this step can be performed safely. The remaining procedure follows according to standard steps.

Results Five patients met the inclusion criteria. Clinical and pathological characteristics of patients and tumours are summarized in Table 1. Median patient age was 58.2 (range 45–71), and median BMI was 28.3 kg/m2 (range 21–40) with three patients classified as overweight/obese. All patients had previous abdominal surgery. Initial biopsy showed all cases with

Gynecol Surg (2016) 13:485–492 Table 1

487

Clinical and pathological features of the study population

Feature

Value

Table 2

Surgical results

Feature

Value

All cases, n

5

Mean operative time (min)

214 (140–360)

Age (years), median (range)

58.2 (45–71)

Conversion to laparotomy

BMI kg/m2, median (range) Histotype, n

28.3 (21–40) Squamous n = 5

Previous abdominal surgery, n

1 Surgery n = 4 ≥2 Surgeries n = 1 IB2 n = 1 IIB n = 3 IIIA n = 1

Surgical radicality type, n C1 Intraoperative transfusion

1 5

FIGO stage, n

Tumour’s size MRI, mm, median (range) Aortic LFN status at surgery, n Aortic lymph node count n (range)

38 (30–42) Negative n = 3 Positive n = 2 14.8(9–22)

Surgery indication, n

Persistence n = 4 Incomplete treatment n = 1

Residual cervical tumour at post-treatment MRI, mm, median (range)

14 (7–20)

squamous carcinoma. FIGO stage at initial diagnosis was as follows: one patient with FIGO IB2, three patients with FIGO IIB and one patient with FIGO IIIA. Median tumour volume at diagnosis was 38 mm (range 30–42 mm). All patients were submitted to laparoscopic para-aortic lymphadenectomy before beginning CRT. Two of them had para-aortic nodal involvement, and the radiation field was extended to the paraaortic chain with 45 Gy. One patient underwent bilateral pelvic lymphadenectomy at the same time; final pathologic exam showed pelvic nodal involvement. Median residual cervical tumour at post-treatment assessed with MRI was 14 mm (range 7–20). The interval time between the diagnosis of the persistence and the surgical procedure was 25 days (range 15–35 days). All patients had pathologic citologies with suspicion of persistent tumour; however, the biopsy was not conclusive in most of them. Only one patient was submitted to surgery due to incomplete CRT treatment because brachytherapy was not administered due to severe radiation toxicity. Although there was no evidence of residual tumour assessed with MRI, the oncological committee decided to schedule adjuvant surgery. Surgical results All patients were successfully operated. Surgical results and morbidity are summarized in Table 2. Feasibility rate was 100 %, and no conversion to laparotomy in relation to difficulties in dissecting irradiated tissue fibrosis was registered. All patients underwent type C1 RH. In two patients, a bilateral pelvic lymphadenectomy was added to the surgical procedure. The decision was not based on radiological findings; it was at discretion of the surgeon. The median operating time was

0

Intraoperative complications: Ureteral injury (replantation) Postoperative complications, n (Clavien-Dindo classification): All cases

1

Grade II: Febrile urinary infection

2 1

Vesical dysfunction

3

1

Grade IV: Urinary and rectovaginal fistulae

1

Postoperative reintervention, n Percutaneous nephrostomy and colostomy Postoperative transfusion, n Postoperative mortality Median hospital stay, days (range)

1 1 0 9 (4–55)

214 min (range 140–360 min) slightly higher in patients submitted to pelvic lymphadenectomy (mean 33 min in addition). One intraoperative complication was registered. It was a left ureteral injury that required conversion to laparotomy after laparoscopic radical hysterectomy was performed. Immediate reimplantation of the proximal ureter in a psoic bladder was carried out; the patient was discharged with a bladder catheter that was kept during 1 month. After that, the patient recovered normal urinary function. No blood transfusions were required during surgery. On the other hand, three patients had a postoperative complications, all related to the urinary system. All cases were late onset (>48 h after IQ), and two of them were grade II complications. There were one urinary infection that required antibiotic treatment and one vesical dysfunction with urinary retention solved with bladder catheter during 8 days. There was one grade IV complication that consisted in the vesicovaginal fistula diagnosed 14 days after surgery that required percutaneous nephrostomy. The patient was diagnosed 3 days after RH of active infection for tuberculosis. Twenty-six days after surgery, the evolution was torpid. A definitive colostomy was necessary due to pelvic septic necrosis and rectovaginal fistulae. The patient was discharged after 55 days and finally died a year and 5 months after surgery due to urologic sepsis caused by multiresistent Pseudomona. No cases of operative mortality and within the first 30 days after surgery were recorded. Only one case of postoperative transfusion was necessary. The median hospital stay was 9 days (range 4–55).

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Oncological results (summarized in Table 3) Histopathological study reported tumour-free specimens in four patients with complete response after CRT. One patient had 1-mm residual tumour, and clear surgical margins were obtained in all cases. During a mean follow-up of 20.8 months (range 8–58), only one death secondary to urinary sepsis was registered. Secondary recurrence after RH was not documented. Finally, four patients are alive and disease-free.

Discussion According to the literature, in LACC, complete response after concurrent CRT and stage are the two most important prognostic factors. The rate of residual disease after primary treatment increases in relation to the FIGO stage: 41–52 % in stage IB2 [20–22], 41–56 % in bulky stage IIA and IIB, 51.6–68 % in stage III and 72.7–73.7 % in stage IVA tumours [20, 21]. These percentages refer to the histological response, after a hysterectomy is performed a few weeks after primary treatment (4–8 weeks), the so-called completion surgery. The role of this adjuvant surgery and the radicality (simple or radical hysterectomy) that must be entailed remain controversial [23, 24]. The benefit of completion surgery to overall or diseasefree survival rates has never been demonstrated [25]. It is accepted that surgery is the only curative treatment for patients with recurrent or persistent pelvic cancer after chemoradiation therapy. Currently, there is no accurate method of detecting residual or recurrent disease after CRT, which makes it difficult to determine population of women who needs salvage surgery. Physical examination is the most often used method for diagnosis. In a retrospective study with 102 patients, the sensitivity of clinical examination for residual disease was 51 % and the specificity was 62 % [26].

Table 3

Histological confirmation prior to surgery is difficult to achieve. It is well known that radiation-induced morphologic changes continue also after finishing CRT with a risk of false positive findings in biopsies or cytology. Sensitivity of vaginal cytology is poor, probably due to radiation-induced dysmorphia [27]. Our patients had pathologic cytologies with suspicion of persistent tumour. However, the biopsy was not conclusive in the majority of them. Imaging techniques have been included to improve the diagnosis of residual/persistent disease. The MRI is the standard imaging technique used. However, its accuracy in predicting response after CRT still is under debate because of the high risk of false positive results. Studies show sensitivities of 80 %, specificities of 55 % and positive and negative predictive values of 50 and 83 %, respectively [28]. All of our MRI explorations were suggestive of residual cervical tumour with a median diameter of 14 mm (range 7–20). In the other hand, over the last few years, there has been an increase in the use of positron emission tomography/ computed tomography (PET/TC) to detect residual or recurrent disease. Meta-analysis showed that the sensitivity and specificity of PET-CT for local regional recurrence were 0.82 (95 % CI: 0.72–0.90) and 0.98 % (95 % CI: 0.96– 0.99), respectively [29]. Curiously, in our series, the only patient who had a PET-TC and was suggestive of persistence in the left parametrium showed no residual tumour in the pathological analysis. So, the use of PET-CT in local regional recurrent/persistent cervical cancer is not currently supported by published literature [30]. Our study reports tumour-free specimens in four patients (80 % of cases), three with suspected persistent disease by MRI and one case submitted to surgery due to incomplete CRT treatment and no radiological disease suspected. These results confirm the need to find more effective diagnostic methods to select better those patients who will benefit from surgery. Although exenteration is the common surgical approach in post-radiation patients with isolated pelvic relapse, radical hysterectomy may be an option in carefully selected patients

Oncological results

Initial FIGO stage

IIIA

IB2

IIB

IIB

IIB

Para-aortic lymph node status

Negative 0/17

Negative 0/11

Positive 2/22

Negative 0/15

Positive 6/9

Initial tumour’s size by MRI (mm) Surgery indication Tumour’s size at post-treatment by RMN (mm) Surgical radicality type (Querleu) Histological results: residual tumour’s size (mm) Surgical margins status Follow-up (months) Patient status

30 Persistence 20 C1 No tumour Clear 18 Dead from urinary sepsis

42 Persistence 7 C1 1 Clear 58 Free of disease

40 Persistence 11 C1 No tumour Clear 11 Free of disease

Not available Persistence 17 C1 No tumour Clear 10 Free of disease

40 Incomplete treatment 0 C1 No tumour Clear 8 Free of disease

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with small central recurrences (<2 cm) limited to the cervix or vagina [8] (NCCN cervical cancer guidelines 2015). This treatment option has barely been published in literature [9–11]. In a series of 50 patients at Memorial SloanKattering Center [10] that were operated on by laparotomy (radical hysterectomy PIVER II, III), a 5-year survival rate of 90 % was found in lesions smaller than 2 cm, versus 64 % for bigger lesions. The high initial rates of serious postoperative complications (20–40 %) with 26 % of postoperative fistula [9] took to the practical abolishment of this technique. Most recent papers about completion surgery after CRT in LACC by laparotomy have had better results. However, we must consider that, perhaps, these improved results are due to the fact that surgeons tend to perform hysterectomy soon after CRT to avoid development of radiation-induced fibrosis. Ferrandina et al. [31] reported in a 362 consecutive LACC (FIGO stage IB2-IVA) patients submitted to RH after CRT (interval to radical surgery around 6 weeks) a 25.7 % postoperative complication rate. Classe et al. [21] showed that ureterovaginal fistulas occurred in 3.5 %, whereas Toubul et al. [5] found a urinary fistula rate of 7.3 % and 2 deaths linked to surgery. The literature describes radicality of the hysterectomy, residual disease and pelvic lymph node involvement as major risk factors for the occurrence of complications [5, 32, 33]. The effect of CRT on pelvic tissues had been proven to increase the difficulties of surgical dissection, due to an inflammation process, vascular fibrosis and firm adhesions. This effect promotes the loss of anatomical planes and determines an increased risk of morbidity. Firm pelvic tissue fibrosis is documented in almost 50 % of cases [14] and often involves the vesicouterine ligament and paracervix tissue. Due to these difficulties, a laparoscopic approach is generally not used to perform radical hysterectomy after CRT. In our knowledge, there are only five articles employing minimally invasive approach to perform a radical hysterectomy [6, 12–15]. All of them, except a case reported by Zygouris, [15] were performed as part of adjuvant surgery a few weeks after completion of CRT treatment. The principal study’s results are listed in Table 4. The two major studies published up to now with a minimally invasive approach by laparoscopy are a prospective phase II study by Gallota [14] and a retrospective cohort study by Colombo [6]. In Gallota’s study, with 58 patients submitted to a laparoscopic RH at 6–8 weeks after CRT the feasibility rate was 94.8 % with no intraoperative complications and a postoperative rate of grade II–III complications of 14.5 %. Colombo’s study with 46 patients with IB2, IIA and IIB cervical cancer submitted to laparoscopic RH at 4–6 weeks after CRT was compared with a cohort of 56 patients operated by laparotomy. The feasibility rate was 85 % in the laparoscopic group, with a conversion to laparotomy rate of 15 %. The intraoperative complication rate was 10.9 %, whereas

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postoperative complications rate was 23.9 % for grade II and 4.3 % for grade IV. Clear margins were obtained in 91.3 % of cases. Compared with the laparotomy group, the laparoscopic group showed significant reduction of morbidity, with fewer urinary complications, blood loss and hospital stay. Our feasibility rate was 100 %. The complication rate is higher than in the above-mentioned studies; nevertheless, we must take into account the small number of cases performed, but on the other hand we underline that most of our postoperative complications were grade 2, and compared with them, the surgery was performed at least 4 months after CRT therapy was finished. However, we had a severe complication which consisted of a vesicovaginal fistula with torpid evolution, probably due to an active tuberculosis infection diagnosed 72 h after intervention which could lead to a worse outcome. The patient finally died due to long-term postopertative complications and immunosuppressive status. The presence of postoperative fistulas on irradiated tissues is well documented in the literature. This higher rate of complications, compared to the other series, is justified by further delayed surgery and the progressive effect of radiation therapy over the time. We have been able to confirm the presence of retracted tissue due to fibrosis in all cases, whereas Gallota observed this effect in around 50 % of cases [14]. Toxicities that develop later than 3 months after the completion of radiation are termed late or chronic effects. The late effects of radiation are due to the damage at the capillary level where endothelial cell proliferation results in a lower diffusion of oxygen into the tissues, resulting in fibrosis. There is less resistance to infection, trauma or functional stress due to this change in vasculature and circulation [34]. Tissue fibrosis is related with major intraoperative complications and high morbidity rates particularly in the presence of preoperative brachytherapy [35]. On the other hand, the extent of surgery is related with high rate of morbidity especially urinary complications [5]. Compared with Gallota’s study, with almost 40 % of patients that underwent type B2 RH, our radicality was higher with 100 % of type C1 surgery, similar to Colombo’s series [6]. It is true that the extent of the surgery remains controversial in the setting of completion surgery, but our surgeries were performed on the setting of suspected persistence at 4–6 months. A radical hysterectomy is more Blogical^ in patients with residual disease to guarantee free margins. We tried to perform Btailored^ surgery according to intraoperative findings and to ensure clear surgical margins. We think that complete parametrial excision improves the percentage of complete resection, with a higher rate of clear margins. Although the dissection of the whole course of the pelvic ureter is difficult, it is necessary to avoid urinary injuries. Thanks to the guide of double-J stents and the magnified vision of laparoscopy, we think that this surgical step is easier and safer although this does not prevent all injuries. Moreover, we think that a laparoscopic approach could also be a way to decrease the morbidity of the surgery, especially in

c

b

a

R2: >3 mm (macroscopic) residual tumour

R1: 1–3 mm (microscopic) residual tumour

R0: Non residual tumour

n.d. not reported, MRI magnetic resonance

Recurrences

Postoperative transfusion Postoperative mortality Mean hospital stay, days (range) Histological results: residual tumour size

4.3 % 0.0 % 5 (3–13) R0a 67.4 % R1b 13.1 % R2c 19.6 % Loco-regional: 17.4 % Distant: 10.9 %

157 (70–265) Haemorrhage (2.2 %) Urinary injury (6.5 %) Digestive injury (2.2 %) 15.2 % II: 23.9 % 1 Haemorrhage, 10 urinary III–IV: 4.3 % 1 Digestive fistulae, 1 urinary fistulae

Operative time (mean, range) Intraoperative complications

Conversion to laparotomy Postoperative complications (ClavienDindo grade)

n.d. 100 %

40 (Initial) 85 %

Median tumour size by MRI (mm) Feasible rate

n.d. n.d. n.d. n.d.

Loco-regional: 12.5 % n.d. Distant: 12.5 %

0.0 % 0.0 % 4.5 (3–8) R0 93.8 % R1or R2 6.2 %

0%

0% 0% 5 1 Pelvic nodal involvement

0% 0%

n.d. n.d.

232 0%

n.d. 100 %

n.d.

Persistence at 6 months

1 IB2

n.d.

n.d. n.d.

n.d n.d.

II/B1-B2

Completion surgery

10 n.d.

MORICE 2012 ZYGOURIS 2013

II–III: 12.5 % 1 Lymphatic complication 1 Ureteral stenosis

267 (165–240) n.d.

n.d.

Completion surgery 4–6 weeks after CRT

Surgical indication

16 IB1 (6.2 %) IB2 (62.5 %) IIA (6.2 %) IIB (6.2 %) IIIB (12.4 %) IBA (6.2 %) Completion surgery

LAMBAUDIE 2010

Surgical radicality (PIVER/QUERLEU) III/C1 (100 %)

46 IB (30.4 %) IIA (8.7 %) IIB (60.9 %)

COLOMBO 2009

Comparison between the existing studies

Number of cases FIGO stage

Table 4

0% 0% 4 (2–9) R0 (41.4 %) R1 (29.3 %) R2 (29.3) Distant: 6.9 %

II–III: 17.2 % 1 Urinary incontinence 7 Lymphatic complications 2 Pelvic abscess requiring surgery

5.2 %

250 (130–380) 0%

B2 (39.6 %) C1 (53.4 %) C2 (6.9 %) 11 (6–29) Post-CRT 94.8 %

Completion surgery at 6– 8 weeks

58 IB2 (6.5 %) IIA2 (8.7 %) IIB (76.1 %) IIIA (1.7 %) IIIB (6.9 %)

GALLOTA 2015

1 case 0 9 (4–55) R0: 4 Cases R1: 1 Case R2: 0 0

1 Febrile urinary infection 1 Vesical dysfunction IV 1 Urinary and rectovaginal fistulae

II

1 Case

221 (140–360) 1 Urinary injury

14 (7–20) Post-CRT 100 %

C1: 5 Cases (100 %)

Persistence: 4 cases (4 months) Completion surgery: 1 case

5 IB2: 1 Case IIB: 3 Cases IIIA: 1 Case

REYES et al. 2015

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blood loss, wound infections and hospital stay, without a higher rate of positive margins [6]. Although radiotherapy inevitably affects the autonomous innervation of the bladder, and radiation fibrosis involves the vesicouterine ligament, with the magnified vision of laparoscopy, we found that nerve-sparing surgery is possible, with more accuracy and safety. This is demonstrated in our series throughout the fact that none of our patients developed vesical dysfunction with urinary retention. Other parameters such as operative time or postoperative transfusions needed are similar than other series with a laparoscopic approach; nevertheless, hospital stay was longer due to a case described before (case 1), which was discharged 55 days after surgery. The necessity to perform pelvic lymphadenectomy after preoperative CRT is discussed. Houvenaeghel et al. [36] and Ferrandina et al. [37] reported a rate of positive residual pelvic lymph node after CRT of 18 and 11 %, respectively. Pelvic lymphadenectomy may possibly have a therapeutic value in these cases to improve local control of the disease, but its usefulness in terms of optimizing survival is not proven. Moreover, lymphatic morbidity incurred by such a procedure is high in irradiated patients. In our series, two patients were submitted to pelvic lymphadenectomy at time of RH, none of them had a nodal involvement and no associated morbidity was documented. We are aware that despite the indications of this surgery were accepted by the current oncologic guideline recommendations, which determine the limit of radical hysterectomy to central tumours that are less than 2 cm (NCCN guidelines); we have failed in the proper selection of patients based on imaging test, given that 3 of 4 suspicion persistent disease cases had no residual tumour in the surgical specimen. Our intention was to offer a less mutilating surgery in cases of suspected persistent disease, but at the same time, to obtain free surgical margins. The associated morbidity to the procedure should be considered, and clinicians need to discuss this when the surgery is suggested. It is true that most of our complications were grade 2 and resolved early, but one case ended in death due to complications from surgery on irradiated tissues. Although RH for persistent central cervical cancer after primary treatment (CTR) is a valid option to avoid an exenteration in carefully selected cases, a multicentric prospectively study is needed at this time and some particular issues need to be evaluated as follows: When is the best time for surgery after CRT?; Is parametrectomy always needed?; Is pelvic lymphadenectomy always needed?; Is minimally invasive surgery the best approach?; and Which is the best imaging study to evaluate if there’s a real recurrence or persistent disease vs fibrosis postradiation?

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Conclusions We are aware of the limitations of this study due to the small number of patients, the retrospective character of the study and the heterogeneity of the cases included. Nevertheless, we think that indications and results are reasonable in the light of the published literature. Based in our experience, we can suggest that, in experienced hands, laparoscopic RH after CRT therapy in small central recurrent or persistent disease is feasible but we must take into account the possibility of severe complications. This kind of surgery and the laparoscopic approach could be a less mutilating surgery that we can offer to our patients, although these should be carefully selected. Compliance with ethical standards Conflict of interest The authors declare that they have no conflict of interest. Statement of human rights Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Statement author’s contribution A. Reyes has contributed in project development, data collection and manuscript writing. Á. Martín has contributed in project development and critical revision. A. Robles and M. C. Martínez have contributed in manuscript editing and data analysis. M. LLull has contributed in data collection and manuscript writing. A. Torrent has contributed in critical revision and data analysis.