Recurrence of Leiomyomata after Laparoscopic Myomectomy

November 2001, Vol. 8, No. 4

The Journal of the American Association of Gynecologic Laparoscopists

Recurrence of Leiomyomata after Laparoscopic Myomectomy Virginie Doridot, M.D., Jean-Bernard Dubuisson, M.D., Charles Chapron, M.D., Arnaud Fauconnier, M.D., and Katayoun Babaki-Fard, M.D. Abstract Study Objective. To assess recurrence of leiomyomata after laparoscopic myomectomy (LM) and evaluate predictive factors of recurrence. Design. Observational study (Canadian Task Force classification II-2). Setting. University hospital. Patients. One hundred ninety-six women. Intervention. Laparoscopic myomectomy with mean follow-up of 47 months. Measurements and Main Results. Myoma recurrence included recurrence of initial symptomatology before LM, recurrence at clinical examination, and appearance of a myoma 2 cm or larger on ultrasound examination. Recurrence was observed in 45 patients (22.9%). The mean time before recurrence was 42 months (range 4–95 mo). Eight women (4.08%) required reoperation. The cumulative recurrence risk was 12.7% at 2 years and 16.7% at 5 years. Predictive factors for recurrence were number of myomas and nulliparity. Conclusion. According to our results, the cumulative rate of myoma recurrence within 5 years appears greater after LM than after laparotomy. However, this should not lead us to reject laparoscopy, which has many advantages compared with laparotomy, in particular its low morbidity. (J Am Assoc Gynecol Laparosc 8(4):495–500, 2001)

Uterine myomas are one of the most frequent pathologies in women of childbearing age.1 In general, those that are asymptomatic do not require treatment. Those that cause symptoms or complications should receive medical or surgical therapy.2 Medical treatment is associated with a high risk of recurrence of functional symptoms when treatment ceases.3,4 Although radical surgery (hysterectomy) carries no risk of recurrence, it cannot be proposed for all patients. When conservative surgical treatment is indicated, myomectomy may be performed by laparotomy, laparoscopy, vaginal surgery, or hysteroscopy. The risk of recurrence after myomectomy by laparotomy is widely documented.5 Although laparoscopic myomectomy (LM) is reliable, reproducible,6–9 and

suitable for women desiring pregnancy,10–12 the risk of recurrence requires clarification. We assessed the frequency of recurrence after LM and attempted to establish risk factors for it. Materials and Methods Between March 1989 and December 1996, 196 women (mean age 36.6 ± 6.6 yrs, range 18–54 yrs; Table 1) underwent LM. The technique is described elsewhere (mean operating time 126 ± 63 min, range 20–320 min; mean hospital stay 2.5 ± 0.8 days).1–7 Indications for LM were functional signs such as menometrorrhagia (22.9%) and pain (26.1%), discovery of a myoma during infertility investigations

From the Service de Chirurgie Gynécologique, Clinique Universitaire Baudelocque, CHU Cochin–Saint Vincent de Paul, Paris, France (all authors). Address reprint requests to Jean-Bernard Dubuisson, M.D., Clinique Universitaire Baudelocque, 123, Boulevard Port Royal, 75014 Paris, France; fax 33 1 40 51 7762. Accepted for publication June 19, 2001. Reprinted from the JOURNAL OF THE AMERICAN ASSOCIATION OF GYNECOLOGIC LAPAROSCOPISTS, November 2001, Vol. 8 No. 4 © 2001 The American Association of Gynecologic Laparoscopists. All rights reserved. This work may not be reproduced in any form or by any means without written permission from the AAGL. This includes but is not limited to, the posting of electronic files on the Internet, transferring electronic files to other persons, distributing printed output, and photocopying. To order multiple reprints of an individual article or request authorization to make photocopies, please contact the AAGL.

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Recurrent Leiomyomata after Laparoscopic Myomectomy Doridot et al

Recurrence was defined as recurrence of symptomatology, recurrence of myomas(s) on clinical examination, and appearance of a myoma of 2 cm or more on ultrasound. It was determined by questionnaires sent to patients and surgeons. All women contacted underwent vaginal ultrasound examination. Probability of and calculated risk for recurrence were determined by actuarial analysis. Criteria for statistical analysis were date of operation and date of recurrence (clinical or ultrasound). Recurrence curves were compared by log rank test for various recurrence factors and Cox’s model for multivariate analysis.

TABLE 1. Characteristics of 288 Women Undergoing Laparoscopic Myomectomy Characteristic Age (yrs) 18–29 30–34 35–39 ≥40 Parity 0 1 2 3 Gestation 0 1 2 ≥3 Indication for LM Pain Menometrorrhagia Infertility Size Pressure Recurrent miscarriage Number of myomas 1 2 ≥3 Size of myomas (mm) <50 50–70 ≥70 Location of myomas Anterior Fundus Posterior Type of myoma Intramural Subserous Pedunculated

Number

%

31 60 43 62

15.8 30.6 21.9 31.7

143 40 10 3

72.9 20.4 5.2 1.5

132 38 19 7

67.3 19.4 9.7 3.6

51 45 63 32 3 2

26.1 22.9 31.6 16.8 1.6 1

114 36 46

58.1 18.4 23.5

86 67 43

43.9 34.2 21.9

55 34 107

28.1 17.3 54.6

74 97 25

37.8 49.5 12.6

Results Twenty-three patients (11.7%) were lost to followup. The other 173 women were seen regularly. The mean duration of follow-up was 47.4 ± 23.2 months (range 4.3–97.8 mo) and rate of recurrence was 22.9% (45 patients). The mean length of time before recurrence was 42 ± 22 months (range 4–95 mo). Of the 173 women, 8 (4.6%) were reoperated for reasons connected with myoma recurrence. For these women, the second operative procedures were LM (3), myomectomy by laparotomy (1), and hysterectomy by laparotomy (4). The cumulative risk of recurrence was 12.7% at 2 years and 16.7% at 5 years. One factor emerged as predictive of recurrence myoma after LM: nulliparity (p = 0.0025; Table 2). The following did not appear to be risk factors for recurrence: number of myomas (p = 0.16), location of myomas (anterior, fundus, posterior; p = 0.53); size of myomas (p = 0.17), age (p = 0.56), distortion of the uterine cavity before LM (p = 0.6), and preoperative gonadotrophin-releasing hormone (GnRH) agonist therapy (p = 0.98). On multivariate analysis, two factors appeared to be risks of recurrence: nulliparity (p = 0.004, CI 1.4, 8.7) and more than one myoma (p = 0.05, CI 0.27, 0.98). Discussion

(31.6%), enlarged uterus with myomas (16.8%), pelvic compression (1.6%), and history of recurrent spontaneous abortion (1%). Preoperative work-up consisted of pelvic ultrasound and diagnostic hysteroscopy to establish the volume and consistency of the uterus, together with the number, size, locations, and types of myomas. Myomectomy was attempted by laparoscopy in all cases13 and was successful in all cases.

The frequency of recurrence after LM in our series was satisfactory (45 patients, 22.9%). To our knowledge, only two other studies specifically addressed the rate of recurrence after LM.13,14 In one study the rate was 46%.13 However, that rate was global and included not only cases of LM but cases of laparotomy. Another group reported 33.3% recurrence,14 more than our study.

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TABLE 2. Myoma Recurrence at 2 and 5 Years

Variable Number of myomas 1 2 ≥3 Size of myomas (mm) <50 50–70 ≥70 Location of myomas Anterior Fundus Posterior Type of myoma Intramural Subserous Pedunculated Age (yrs) 18–29 30–34 35–39 ≥40 Distortion of the cavity No Yes Parity at LM 0 1 Preoperative GnRH agonist No Yes

No. (%)

At 2 Yrs (%)

At 5 Yrs (%)

102 (58.9) 40 (23.2) 31.49 (17.9)

13 4.8 19.4

26.9 13.3 37.5

0.16

75 (43.3) 69 (35.3) 37 (21.4)

7.4 17.1 17

14.6 28.6 47.4

0.17

49 30 (17.4) 94 (54.3)

14.3 4.8 6.1

22.2 26.7 31.9

65 (37.6) 85 (49.1) 23 (13.3)

11.1 11.4 14.3

12.9 10.2 6.7

0.45

25 (14.5) 53 (30.6) 39 (22.5) 56 (32.4)

6.12 10.7 21.7 12

20 26.9 37.5 20

0.56

94 (60.3) 62 (39.7)

12.7 16.3

17.1 18.2

0.6

67 (56.3) 52 (43.7)

12.8 8.3

47.6 15.8

0.0025

122 (70.5) 51 (29.5)

12 13.8

22.9 33.3

00.98

pa

0.53

aLog rank test.

tion. It may be that when numerous small intramural myomas are found during preoperative work-up, laparoscopy is not the most suitable approach for dealing with them. Comparing results of various series, notably those of myomectomy by laparotomy, is difficult for several reasons. The frequency of recurrence after laparotomy varies greatly, ranging from 3.8% to 55.6%.5 Among reasons for difficulty comparing results from the literature,15–23 the following deserve mention. First, recurrence is not defined the same in all publications. The rate of recurrence after laparotomy is on average 11% (Table 3). Second, the mean lapse of time between surgery and recurrence varies considerably from one patient to another. Third, patient populations are not

Analysis in terms of cumulative rates appears to show a greater frequency of recurrence after operative laparoscopy than after laparotomy. There may be a simple explanation for this difference. With operative laparoscopy, it is difficult to recognize and palpate small intramural myomas a few millimeters in diameter. In certain cases these tiny lesions can develop and cause symptoms several months or years later. Consequently, it seems essential that all myomas, even the smallest, be detected during preoperative investigations and an attempt made to assess the degree to which they may evolve. Color Doppler ultrasound and magnetic resonance imaging can provide some of these data; however, more work is necessary to assess prognostic advantages of studying myoma vasculariza-

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Recurrent Leiomyomata after Laparoscopic Myomectomy Doridot et al

TABLE 3. Recurrence Rates after Myomectomy

No. of Patients 5015 2316 8117 9518 6219 62220 311 3221 10322 1423 6713 11414 19610

Access

Recurrence, No. (%)

Reoperation, No. (%)

Laparotomy Laparotomy Laparotomy Laparotomy Laparotomy Laparotomy Laparotomy Laparotomy Laparotomy Laparotomy Laparoscopy and laparotomy Laparoscopy Laparoscopy

3 (6) 1 (4) 5 (8) 13 (14) 4(6) 84 (27) 5 (16) 15 (47) 18 (17) 7 (9) 31 (46) 38 (33.3) 45 (22.9)

3 (6) 1(4) 2(2) 13 (14) 3 (5) — 2 (6) 4 (12) 12 (12) 6 (8) — 14 (36.8) 8 (4.0)

regard. Results in the literature give rise to considerable debate. Some studies agree with our conclusions,14,21 but not all.28 The literature is also contradictory with respect to preoperative luteinizing hormone-releasing hormone analogs. Some authors reported similar results to ours and considered that preoperative GnRH agonists do not influence recurrence29; others noted an increased risk in women receiving such treatment.30 No prospective randomized study has addressed this question, which is difficult to answer. Some authors recommend 3 months of postoperative GnRH treatment with the aim of reducing the risk of long-term recurrence.31 Here, too, additional work is necessary to establish if preoperative or postoperative medical treatment is required in cases of myomectomy and if so, what and how long.

always similar among studies. It is evident that patients operated by laparotomy cannot be compared with those operated by operative laparoscopy. Women who undergo operative laparoscopy by definition have a limited number of myomas (generally 1 or 2) that are small (biggest <8–9 cm in diameter). In addition, several works highlighted a genetic predisposition24–26 as well as anomalies in certain growth factors27 to the physiopathology of myomatous disease. Finally, simple comparison of results of operative laparoscopy versus laparotomy may introduce tremendous bias. As patients operated by laparotomy have significantly more myomas, they may also have a greater predisposition to myomatous disease and risk of recurrence than those treated by LM. We detected two risk factors for recurrent myomas after LM: more than one myoma and nulliparity. The literature agrees that the number of myomas at operation is undeniably a risk factor. Two explanations can be put forward for this. First, the more myomas, the more difficult the surgical procedure and consequently the greater the risk of leaving a myoma in place. Second, a large number of myomas may be an indication, as noted, of a predisposition to myomatous disease and an associated higher risk of recurrence. The risk of recurrence is greater for nulliparous than for parous women. This was also noted by another group.20 Nulliparous patients are most often young, and their risk of developing myomatous disease increases their risk of recurrence. This appears to contradict the fact that no effect is observed for age in this

Conclusion It is difficult to evaluate the risk of recurrence after myomectomy, whether the approach is laparoscopy or laparotomy. Although the cumulated risk at 5 years appears to be greater after LM, this is probably due to the fact that palpation and assessment of small residual myomas is far more difficult by laparoscopy than by laparotomy; these results must not lead us to reject LM, however. The results of LM in terms of recurrence will be good as long as indications are clearly defined. Thus this technique must be reserved for nulliparous patients with only one or two myomas.

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In addition, progress must be made with techniques that remain to be defined (imaging, molecular biology, etc.) to pinpoint women with a risk of recurrence, those with many small myomas of only a few millimeters that are very difficult to remove by operative laparoscopy.

13. Sudik R, Husch K, Steller J: Fertility and pregnancy outcome after myomectomy in sterility patients. Eur L Obstet Gynecol Reprod Biol 65:209–214, 1996 14. Nezhat F, Roemisch M, Nezhat C, et al: Recurrence rate after laparoscopic myomectomy. J Am Assoc Gynecol Laparosc 5:237–240, 1998 15. Berkeley AS, De Cherney AH, Polan ML: Abdominal myomectomy and subsequent fertility. Surg Gynecol Obstet 156:319–322, 1983

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31. Vavala V, Lanzone A, Monaco A, et al: Postoperative GnRH analog treatment for the prevention of recurrences of uterine myomas after myomectomy. A pilot study. Gynecol Obstet Invest 43(4):251–254, 1997

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