Original article Clinical outcome after laparoscopic ...

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hysterectomy, bilateral salpingo-oophorectomy, peritoneal cyto- logy, omentectomy and multiple peritoneal biopsies. Although conservative management in ...
Annals of Oncology 15: 605–609, 2004 DOI: 10.1093/annonc/mdh149

Original article

Clinical outcome after laparoscopic pure management of borderline ovarian tumors: results of a series of 34 patients S. Camatte, P. Morice*, D. Atallah, A. Thoury, P. Pautier, C. Lhommé, P. Duvillard & D. Castaigne Institut Gustave Roussy, Villejuif, France Received 23 October 2003; revised 23 December 2003; accepted 6 January 2004

Background: The aim of this study was to assess clinical outcome after laparoscopic treatment of borderline ovarian tumor (BOT).

Introduction

Materials and methods

Borderline ovarian tumor (BOT) is an epithelial ovarian tumor with two major characteristics: it occurs in patients younger than those with epithelial ovarian cancer and has a better prognosis than the latter. Standard treatment of BOT is total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology, omentectomy and multiple peritoneal biopsies. Although conservative management in such patients remains a major concern, it does appear to be the case that conservative surgery can be performed safely in young patients with careful follow-up [1–5]. Numerous studies have demonstrated the advantage of a laparoscopic approach over laparotomy for the surgical management of benign adnexal diseases. Such an approach improves (i) the immediate postoperative quality of life and (ii) the fertility results by reducing adhesions due to a possible laparotomy. But very few authors have studied the results of laparoscopic treatment in BOT [6–8]. The aim of this study was to consider the clinical outcome of a large continuous series of patients treated with a laparoscopic pure approach for BOT, in order to clarify what role laparoscopy should play in the management of this tumor.

Patients

*Correspondence to: Dr P. Morice, Service de Chirurgie Gynécologique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. Tel: +33-1-42-11-44-39; Fax: +33-1-42-11-52-13; E-mail: [email protected] © 2004 European Society for Medical Oncology

From January 1984 to January 2002, data from 54 patients treated in, or referred to, the Institut Gustave-Roussy after laparoscopic management (without immediate conversion to laparotomy) of BOT were reviewed. Twenty patients who underwent reassessment surgery by laparotomy, after an initial laparoscopic approach, were excluded from this series. No patient who underwent a laparoscopic pure procedure for BOT during the same period was excluded. Histopathological review of the ovarian tumor and peritoneal implants was performed by one of the authors (P.D.). Histological criteria to characterize ovarian tumor and peritoneal implants have been previously reported [9]. Peritoneal implants were classified as either non-invasive or invasive, according to the absence or presence of stromal invasion of the peritoneum, respectively [9–12]. The staging used was the 1987 International Federation of Gynecology and Obstetrics (FIGO) classification [13].

Preoperative assessment Patients underwent preoperative ultrasonography. Some patients underwent a preoperative determination of CA 125 level before the surgical procedures.

Treatments Radical treatment was defined as bilateral salpingo-oophorectomy (BSO) with or without hysterectomy. Conservative treatment was defined as a surgical procedure with conservation of the uterus and the salvaging of at least a portion of one ovary. Therefore, four possible types of conservative surgical procedure could be performed: unilateral adnexectomy (UA); UA plus contralateral

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Patients and methods: Thirty-four patients treated initially and/or for recurrent disease using a laparoscopic approach for BOT from 1984 to January 2002. Results: Thirty-four patients underwent laparoscopic pure treatment (without conversion by laparotomy and/ or reassessment surgery by laparotomy) for BOT. Conservative treatment was performed in 31 (91%) patients. Median follow-up time was 45 months (range 6–228). Six (17%) patients recurred (in the remaining ovary following conservative surgery in five patients and in the peritoneum in one patient). Two port-site metastases were observed. None of the patients had recurrent disease in the form of ovarian carcinoma. Nine spontaneous pregnancies were observed in six patients from a group of 15 patients desiring pregnancy. All patients are alive today and disease-free. Conclusion: These results seem to demonstrate that laparoscopic treatment can be safely performed in young patients with early stage BOT. Such a procedure is then feasible, but should be evaluated in patients with BOT and peritoneal implants. Key words: borderline tumor, conservative surgery, fertility, laparoscopy, pregnancy

606 cystectomy (UA+CC); unilateral cystectomy (UC); and bilateral cystectomy (BC). It was possible that additional surgical procedures were performed: peritoneal washings, biopsy of the remaining ovary, omentectomy, appendicectomy, multiple peritoneal biopsies and pelvic and/or para-aortic lymphadenectomy. The performance of some of these surgical procedures depended on the date at which treatment was given, the teams who surgically treated those patients and the diagnosis of BOT during or after the surgical procedure. Complete and accurate surgical staging included peritoneal cytology and omentectomy with or without systematic multiple peritoneal biopsies.

Table 1. Characteristics of patients who underwent laparoscopic pure management of a borderline tumor (group A, management of the primary tumor; group B, management of a recurrent borderline tumor) Group, n (%) B

No. of patients

23 (68)

11 (32)

34

Ultrasonography

19 (83)

11 (100)

30 (88)

Suspicious

12 (63)

8 (72)

20 (67)

Non-suspicious

7 (37)

3 (28)

10 (33)

CA 125 level UI/l

Follow-up and outcome Follow-up of patients included clinical examination, blood tests (CA 125 and eventually CA 19.9 levels) and an ultrasonographic scan (US) every 3 months during the first year following the procedure, then every 6 months for 2 years, and finally annually. Patient characteristics, the number and type of recurrences, and the fertility results were analyzed. Survival curves and cumulative pregnancy rates were determined using the Kaplan–Meier method.

15 (65)

11 (100)

26 (76)

35 UI/l

6 (40)

Suspicious

6 (23)

4 (36)

10 (29)

7 (64)

24 (71)

14 (61)

1 (9)

15 (44)

BOT

4 (44)

10 (91)

14 (41)

Benign tumor

4 (44)

0

4 (12)

Ovarian cancer

1 (12)

0

1 (3)

Not performed

Histological subtype Serous Mucinous

15 (65)

10 (91)

25 (73)

5 (22)

1 (9)

6 (18)

Mixed

0

0

0

Endometrioid

3 (13)

0

3 (9)

Stage (FIGO-1987)a I

20 (87)

IA

17 (74)

IB

1 (4)

6 (54)

26 (76)

6 (54)

23 (67)

0

1 (3)

IC

2 (9)

0

2 (6)

II

1 (4)

2 (18)

3 (9)

III

2 (9)

3 (27)

5 (15)

Non-invasive

3 (13)

5 (45)

8 (24)

Invasive

0

0

0

Type of implants

a

Stage of the disease at the time of the laparoscopic procedure. BOT, borderline ovarian tumor; FIGO, Federation of Gynecology and Obstetrics.

cavity plus para-colic gutters (one case), and in the pelvic cavity and peritoneum of the diaphragm (one case). Five patients in group A underwent reassessment surgery using a laparoscopic approach after a median delay of 90 days following the initial laparoscopic procedure. Four of them (treated initially by simple cystectomy at the time of first surgery) underwent unilateral salpingo-oophorectomy and peritoneal biopsies and the fifth one underwent resection of the peritoneum. One of these patients had isolated non-invasive implants in the peritoneum.

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6 (26) 17 (74)

Frozen section analysis

Patient characteristics and treatment Thirty-four patients had laparoscopic pure treatment of their BOT. Twenty-three patients (group A) underwent laparoscopic treatment of their primary BOT (four of them after an initial surgical procedure based on simple biopsies performed by a laparotomy) and 11 patients (with previous history of BOT) underwent laparoscopic treatment of a recurrent ovarian tumor (group B). The median patient age was 28 years (range 16–76) and the mean age of patients in both groups were 31.3 ± 11.5 (group A) and 28.5 ± 8.5 years (group B). The main patient characteristics are detailed in Table 1. Details about the surgical procedures are given in Table 2. The median size of the tumor was 50 mm (range 20–120). The stage of disease is given in Table 1. In 11 patients who underwent laparoscopic treatment of recurrent disease (group B), the initial stage of disease was stage I in six patients (stage IA), stage II in two patients and stage IIIA in three patients. No patient with mucinous tumor and peritoneal disease (peritoneal pseudomyxoma) was treated laparoscopically. Two patients had tumor implantation in the port-sites. The first patient underwent a laparoscopic salpingo-oophorectomy for a mucinous tumor with extraction in a 12 mm supra-pubic trocar, but without the use of an endoscopic bag. She underwent radical surgery by laparotomy 1 month later and mucinous implants were found in the aponevrosis of the medially supra-pubic trocar. The second patient underwent laparoscopic treatment of a recurrent serous borderline tumor (treated by oophorectomy with biopsies on the contralateral ovary). She had a bilateral serous tumor. Eleven months later the patient developed recurrent disease on the right lateral port-site of 5 mm. A simple surgical resection with laparoscopic exploration was performed. This recurrent disease was isolated (absence of intra-peritoneal spread). The patient is actually disease-free 1 year after surgical resection of the trocar-site. Six patients had laparoscopic pure conservative treatment of a serous ovarian tumor, associated with peritonectomies for the treatment of non-invasive peritoneal implants. Large peritonectomies were performed in the pelvic cavity (four cases), in the pelvic

0

Aspect during laparoscopy

Non-suspicious

Results

Total

A

607 Table 2. Surgical procedures (group A, management of the primary tumor; group B, management of a recurrent borderline tumor) Groups, n (%)

No. of patients

A

B

23 (68)

11 (32)

Total

34

No patient recurred in the form of invasive ovarian cancer. No patient died. Both patients with tumor implantation in port-sites were still alive 12 and 48 months after the surgical procedure. The mean follow-up time in six patients who underwent large peritonectomies was short (16 ± 15 months), but none of them recurred.

Radical treatment HBSO

1 (4)

0

1 (3)

BSO

2 (9)

0

2 (6)

Conservative treatment

20 (87)

11 (100)

31 (91)

9 (45)

5 (45)

14 (45)

USO + CC

2 (10)

0

2 (6)

UC

1 (5)

0

1 (3)

BC

8 (40)

6 (55)

14 (46)

USO

Additional surgical procedures Peritoneal cytology

10 (91)

20 (59)

1 (4)

4 (36)

5 (15)

11 (100)

17 (50)

1 (9)

1 (3)

Peritoneal biopsies

6 (26)

Biopsies contralateral ovary

0

Lymphadenectomy

0

0

0

Appendectomy

2 (9)

0

2 (6)

Use of endoscopic bag Yes

12 (52)

No

11 (48)

0

11 (32)

12 (53)

3 (27)

15 (44)

Peroperative rupture

11 (100)

23 (68)

BC, bilateral cystectomy; BSO, bilateral salpingo-oophorectomy; CC, contralateral cystectomy; HBSO, Hysterectomy & BSO; UC, unilateral cystectomy; USO, unilateral salpingo-oophorectomy.

Concerning functional and fertility results, three patients underwent radical surgery (bilateral salpingo-oophorectomy plus or minus hysterectomy) at the time of initial or reassessment surgery. Two patients were menopausal at the time of laparoscopic surgery. Two patients underwent radical surgery for the treatment of recurrent disease (without trying to be pregnant). Twelve patients were still taking contraceptives, or did not desire pregnancy, and 15 were trying to become pregnant. Ten pregnancies were observed in six patients: nine spontaneous ones and one induced. Nine pregnancies were normal (with vaginal delivery in seven and Cesarian delivery in two). One of the two patients who underwent a Cesarian delivery had multiple peritoneal biopsies and exploration of the retained ovary at the time of the Cesarean (with absence of macroscopic and/or microscopic disease). The median delay between treatment of their tumor and pregnancy was 5 months (range 1–15). Four spontaneous pregnancies were observed in three of six patients who underwent laparoscopic resection of peritoneal implants. Two infertile patients actually underwent in vitro fertilization procedures without becoming pregnant. No recurrence was observed following pregnancy. None of the patients (without recurrent disease) underwent radical surgery in order to remove the remaining ovary.

Discussion Recurrences The median time of follow-up was 45 months (range 6–228). One patient was lost to follow-up immediately after the surgical procedure. Six (17%) recurrences were observed in six patients (three in each group). The median delay of recurrence was 29 months (range 8–60). Recurrent disease was borderline ovarian tumor on the retaining ovary after conservative surgery in five patients: four patients with initial stage I disease (stage IA in three patients and IB in one patient) and in one patient with stage IIIA and noninvasive implants. Those recurrences were treated laparoscopically. In one patient, recurrence was observed in the peritoneum: this patient had a previous history of salpingo-oophorectomy for BOT several years ago. She underwent a laparoscopic procedure for recurrent disease on the remaining ovary (completion of salpingooophorectomy). Non-invasive peritoneal implants were observed, but their resection was not performed. A new laparoscopic procedure was performed 6 months later and residual implants were laparoscopically removed (non-invasive peritoneal implants). In fact, this patient had been considered as having recurrent disease, whereas it was probably only the persistence of the nonresected peritoneal tumor. This patient is alive, without evidence of disease, 15 months following laparoscopic resection of peritoneal implants.

Several authors have reported cases of laparoscopic management of BOT [14–16]. Although in those series, the diagnosis of the borderline tumor was sometimes performed at the time of permanent histological examination (after laparoscopic management) and the choice to use a laparoscopic approach for the borderline tumor was not deliberate. In contrast, in the present series the choice of a laparoscopic approach to treat borderline tumors was a deliberate one in 20 patients (patients in whom frozen section analysis demonstrated the presence of a borderline tumor or patients with recurrent disease following a previous history of borderline tumor). Typically, treatment of these patients occurred during the 10 last years of this study. Only three series focus on the evaluation of intentional laparoscopic management of BOT [6–8]. The number of patients included in those series varies from 18 to 26, the majority of which had stage I disease [6–8]. The present study includes the largest number of patients treated using laparoscopic management published to date. Furthermore, some of those patients had ‘advanced stage disease’ (BOT associated with peritoneal implants). Our results seem to confirm that laparoscopy could be safely used in BOT, particularly in patients with an early stage of the disease. Among the recurrences observed in the present series, five out of six were the ‘usual’ recurrent diseases of borderline type after conservative surgery.

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10 (43)

Resection or biopsies omentum

Fertility results

608 In clinical practice, however, most BOT diagnoses (in patients with no previous history of ovarian tumor) are not performed during the surgical procedure (the main reasons are as follows: the cyst is not suspect; frozen section analysis is not available; or this perioperative analysis misdiagnoses the diagnosis of BOT). Here, BOT diagnosis was not carried out during the surgical procedure by frozen section analysis, but during the post-operative routine pathological examination. Only laparoscopic cystectomy was carried out during initial surgery in most of those patients. Would it then be necessary to re-operate when the initial surgery was a cystectomy? Two possibilities should be debated: (i) restaging surgery by laparoscopy (including completion of unilateral oophorectomy, peritoneal washings, multiple peritoneal biopsies and, possibly, an omentectomy); or (ii) careful follow-up (based on clinical examination, ultrasonography and blood markers), in order to reconsider a new surgical approach, only in case of ovarian recurrence. A recent series from Winter et al. seems to demonstrate that survival and recurrence rates of patients with BOT adequately staged is similar to that of unstaged patients [22]. Therefore the real impact of complete staging in patients with BOT macroscopically limited to the ovary should be evaluated. We think that careful follow-up without restaging surgery could be considered in young patients, in whom only cystectomy or unilateral salpingooophorectomy was performed during the laparoscopic procedure (if the normality of the abdomino-pelvic cavity is clearly stated in the initial operative report). But further studies are needed in order to confirm such behavior. The results of this series seem to demonstrate that laparoscopic surgery could be safely performed in patients with early stage BOT (if technically feasible). Such management concerns are particularly important in young patients treated conservatively, in order to optimize the fertility results by reducing adhesions due to eventual laparotomy. In patients with more advanced stage and non-invasive implants, laparoscopic treatment is feasible, but should be evaluated by further studies.

Acknowledgements We would like to thank Gilles Charrot for editing the manuscript.

References 1. Gotlieb W, Flikker S, Davidson B et al. Borderline tumors of the ovary: fertility treatment, conservative management, and pregnancy outcome. Cancer 1998; 82: 141–146. 2. Lim-Tan S, Cajigas H, Scully R. Ovarian cystectomy for serous borderline tumors: a follow-up study of 35 cases. Obstet Gynecol 1988; 72: 775–780. 3. Morice P, Camatte S, El Hassan J et al. Clinical outcomes and fertility results after conservative treatment for ovarian borderline tumor. Fertil Steril 2001; 75: 92–96. 4. Morris RT, Gershenson DM, Silvia EG et al. Outcome and reproductive function after conservative surgery for borderline ovarian tumors. Obstet Gynecol 2000; 95: 541–547. 5. Zanetta G, Rota S, Chiari S et al. Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study. J Clin Oncol 2001; 19: 2656–2664.

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Our recurrence rates [six of 31 (19%) treated conservatively] are similar to those following conservative surgery by laparotomy observed in the literature [5]. The recurrences we have observed following conservative surgery are probably not related to the approach itself (laparotomy or laparoscopy), but to the type of conservative surgery used (cystectomy or oophorectomy). The number of recurrences is particularly high following cystectomy, as has been reported in other studies with values of 30–35% [3, 6]. The high rate of relapse after cystectomy reported in the literature implies that optimal treatment in young patients with intraoperative diagnosis of BOT, is unilateral adnexectomy, which reduces the risk of relapse. Cystectomy should only be performed in cases of bilateral tumor (with oophorectomy in the contralateral tumor) and/or in patients with only one ovary (previous history of adnexectomy). But since most relapses (if not all?) in the ovary after conservative surgery have borderline histology, such an increased rate of recurrence after conservative surgery did not affect survival rates [2–4, 6, 17, 18]. In cases of recurrence in a spared ovary, new conservative surgery could be performed in order to preserve subsequent fertility [1, 3, 17]. What are the limitations of laparoscopic treatment in BOT? The first apparent limitation is the stage of disease. Most reported cases are of early stage disease. According to the literature, only two patients with peritoneal disease were treated using laparoscopy [6, 7]. One of the originalities of the present series was to report six patients with noninvasive implants who underwent laparoscopic peritonectomies. All of them are today disease-free, and four pregnancies have resulted, although follow-up is still short. Such results seem to suggest that in the case of young patients with a low number of noninvasive peritoneal implants, the laparoscopic procedure is feasible and appears to be safe, although more studies are needed in order to ensure such management. A second limitation of laparoscopy is both the size and structure of the tumors. If tumors are bulky and/or with a solid pattern, an initial laparotomy should be performed. Sometimes young patients have solid and bilateral tumors which are so massive that conservative surgery with preservation of part of an apparently tumor-free ovary is not feasible. In such cases, bilateral adnexectomy should be performed by laparotomy, but with preservation of the uterus, in order to preserve fertility [19]. In such patients, pregnancies have been reported after ovum donation or embryo transfer [20, 21]. The main objective of laparoscopic treatment in patients with BOT is to optimize the results of conservative surgery, thus reducing adhesions due to potential laparotomy. So, if a young patient is treated for a suspicious adnexal tumor (elevated blood markers and/or ‘suspicious’ ultrasonography), the surgical procedure should ideally be performed in a center where frozen section analysis is available. If the tumor is unilateral and if the diagnosis of BOT is raised intraoperatively at the time of the frozen section analysis, a unilateral adnexectomy by laparoscopy (if technically feasible) could be safely performed with peritoneal cytology, multiple peritoneal biopsies and omentectomy. In the case of a bilateral ovarian tumor, a unilateral adnexectomy and a contralateral cystectomy may be proposed.

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