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Predictors of Leiomyoma Recurrence After Myomectomy

Hanafi, Magdi MD

doi: 10.1097/01.AOG.0000156298.74317.62
Original Research
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OBJECTIVE: The purpose of this study was to evaluate the factors associated with the recurrence of leiomyomata after myomectomy.

METHODS: One hundred forty-five consecutive cases of myomectomy by laparotomy were studied retrospectively. Leiomyoma recurrence, diagnosed by transvaginal ultrasonography, was evaluated by life-table analysis and log-rank tests according to clinical characteristics of patients.

RESULTS: The 5-year cumulative rates for leiomyoma recurrence and subsequent major surgery were 62% and 9%, respectively. At 5 years, the cumulative probability of recurrence was significantly lower in patients with a single leiomyoma removed (11%), compared with patients with multiple leiomyomata (74%) (P = .011); it was also lower in patients with intraoperative uterine size 10 menstrual weeks or less (46%), compared with more than 10 menstrual weeks (82%) (P = .032). However, there was a strong association of uterine size with the number of leiomyomata removed (P = .009). Childbirth after myomectomy was associated with a lower recurrence rate; the 5-year cumulative probability of recurrence was 26% in patients with subsequent parity, compared with 76% in those without subsequent parity (P = .010).

CONCLUSION: Solitary myomectomy and smaller intraoperative uterine size are associated with lower rates of leiomyoma recurrence after myomectomy; the significance of uterine size may be affected by its correlation with the number of leiomyomata removed. Subsequent parity is associated with a lower probability of recurrence, but the cause and effect relationship between these two variables is unclear.

LEVEL OF EVIDENCE: II-3

Solitary-type myomectomy, smaller intraoperative uterine size, and subsequent parity are associated with a lower rate of leiomyoma recurrence after myomectomy.

From Saint Joseph's Hospital of Atlanta, Georgia.

The author thanks Jennifer Ryan, ba, for providing data collection and analysis.

Address reprint requests to: Magdi Hanafi, MD, Saint Joseph's Hospital of Atlanta, 5673 Peachtree Dunwoody Road, Suite 750, Atlanta, GA 30342; e-mail: Mhanafi@aol.com.

Received June 29, 2004. Received in revised form December 13, 2004. Accepted December 22, 2004.

Leiomyomata are the most common benign tumors in the female pelvic organs. The available surgical options for treatment of symptomatic leiomyomata are hysterectomy, myomectomy, and uterine artery embolization. The treatment choice will depend on the patient's age, the desire for future fertility, the size and number of tumors, and the expected likelihood of recurrence of the tumors.

By having a statistical evaluation of the factors that may have an impact on the recurrence of leiomyomata, the gynecologist will be able to give the patient appropriate advice regarding the choice of treatment. This information will also make it easier for the patient to understand what to expect about the chances of recurrence of the tumors and associated symptoms. The objective of this retrospective study was to calculate the probability of leiomyoma recurrence (confirmed by transvaginal ultrasonography and adjusted for variations in length of follow-up) and to evaluate the possible predictors of recurrence.

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MATERIALS AND METHODS

Clinical outcomes were analyzed in 145 consecutive patients undergoing myomectomy by exploratory laparotomy between January 1992 and October 2002. All of the myomectomies were done by one surgeon at Saint Joseph's Hospital of Atlanta. None of the women received gonadotropin-releasing hormone (GnRH)-agonist therapy before surgery because of conflicting reports of its effect on leiomyoma recurrence.1,2

A chart review provided information about patient characteristics at the time of surgery, recurrence status upon subsequent transvaginal ultrasonography, and any further treatment for recurring leiomyomata. Institutional review board approval was not required according to exemptions provided by the National Research Act (45 Code of Federal Regulations Part 46 Section 102f). However, all of the procedures followed were in accordance with the revised Declaration of Helsinki, and patients gave informed consent before surgery.

Patients had subsequent transvaginal ultrasound examination for one of the following reasons: symptoms recurred, suggesting redevelopment of leiomyoma (eg, menorrhagia, dysmenorrhea); pelvic examination indicated presence of leiomyomata; or the patient requested ultrasound examination for her own knowledge of her condition. Recurrence was defined as the presence of a leiomyoma of at least 2 cm in diameter, and any associated symptoms or subsequent surgeries for leiomyomata were recorded and analyzed separately. The following prognostic variables were evaluated: uterine size at time of surgery, number of leiomyomata removed, location of the tumor(s) in the uterus, concurrent adenomyosis, patient age, and patient body mass index (BMI). Subgroups for each variable were determined by category for categorical variables and by the median value for numerical variables.

A diligent effort was made to contact all patients with insufficient follow-up data in the chart; these patients were contacted by phone or mail and asked whether they had had any additional treatment for leiomyomata. Inquiries were also made about any postmyomectomy pregnancies and their outcome. Records of any subsequent pelvic ultrasonography or surgery for uterine leiomyomata were requested from the patients’ current physicians.

Statistical calculations were performed using SAS statistical software (SAS Institute, Cary, NC). To account for variations in length of follow-up, cumulative recurrence curves were calculated by using life-table analysis. Log-rank tests assessed the relationships between recurrence and the prognostic variables. Student t tests and Wilcoxon rank-sum tests were used where appropriate to make between-group comparisons. Association between the statistically significant factors was considered by using Fisher exact tests. A P value of less than .05 was considered statistically significant.

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RESULTS

Before myomectomy, 89% of the patients indicated that their families were not yet complete; therefore, hysterectomy was not an acceptable option. The patients had a median gravidity of 2 (range 0–12) and a median parity of 1 (range 0–6). Twenty-two patients (15%) had no previous pregnancy.

Most of the myomectomy patients had associated symptoms, including menometrorrhagia (91%), dysmenorrhea (82%), dyspareunia (41%), and other noncyclic pelvic pain (22%). Additionally, 59% of the patients had a history of anemia and 30% had infertility. Only 5 patients (3%) had no significant associated symptoms; leiomyomata were discovered during regular physical examinations and verified by pelvic ultrasound examination.

Leiomyomata were confirmed on the pathology reports for all cases included in this study. Some other findings were adenomyosis (14 patients), endometriosis (10 patients), and endometrial polyps (22 patients). Only 28 pathology reports included total leiomyoma weight, which ranged from 8 to 590 g (median 103 grams). The median diameter for the largest leiomyoma removed per patient was 3.0 cm (range 0.2–13.2 cm). This value was higher in the patients with multiple leiomyomata (median 3.5 cm) compared with solitary leiomyomata (median 2.4 cm) (P = .012).

At the time of surgery, the median uterine size was 10 gestational weeks. Thirty-seven patients (26%) had a solitary leiomyoma, and 108 (74%) had multiple leiomyomata. A median of 3 leiomyomata were removed. Thirty-four patients (23%) had subserous tumors; 98 patients (68%) had intramural tumors or a combination of subserous and intramural; 6 patients (4%) had submucous tumors or a combination of intramural and submucous; and 7 patients (5%) had tumors in all of these locations. The median patient age was 36 years (range 24–49), and the median BMI was 28 (range 18–50).

One hundred thirty-two patients (91%) were followed for a mean of 38 ± 31 months from surgery (range 2–136 months). The remaining 13 patients were lost to follow-up after their initial postoperative examinations. Eighty-nine patients (61%) had transvaginal ultrasound examination during their follow-up, and the mean duration from surgery to last available ultrasound result was 29 ± 23 months. The cases followed with ultrasonography were clinically comparable with those that were not, in terms of the factors being evaluated (P ≥ .072). There were no significant differences in duration of follow-up between the subgroups for each variable (P ≥ .146).

All but one patient had resolution of menometrorrhagia and dysmenorrhea after surgery, but there was a gradual increase in these symptoms over the follow-up period (Fig. 1). By 5 years after surgery, the cumulative recurrence rate for menometrorrhagia was 50%. Recurrence of dysmenorrhea was less frequent; the 5-year cumulative recurrence rate was 24%, or less than one third of the presurgery rate.

Figure 1

Figure 1

The cumulative probability of leiomyoma recurrence increased steadily after surgery, reaching 62% at 5 years (Fig. 2). The cumulative probability of having subsequent surgery for recurring leiomyomata was much lower; at 5 years, the rate of having any surgery (including minor surgery) was 17%, and the rate of having major surgery was 9%.

Figure 2

Figure 2

The cumulative probability of recurrence was significantly lower in patients with a single leiomyoma removed compared with patients with multiple leiomyomata (Fig. 3); it was also lower in patients with intraoperative uterine size of 10 menstrual weeks or less compared with more than 10 menstrual weeks (Fig. 4). However, there was a strong association between uterine size and number of leiomyomata removed (P = .009). None of the other factors evaluated had a significant association with leiomyoma recurrence.

Figure 3

Figure 3

Figure 4

Figure 4

Of 27 patients with known leiomyoma recurrence, 14 (52%) had subsequent surgical intervention for their leiomyomata. Six (22%) had hysteroscopy with dilatation and curettage, 5 (19%) had a second myomectomy, and 3 (11%) had hysterectomy. No statistically significant differences in surgery rates were detected according to the prognostic variables (P ≥ .120).

Forty patients conceived after surgery, with 52 pregnancies. There were 28 deliveries, 16 miscarriages, 4 ectopic pregnancies, and 4 ongoing pregnancies at the end of follow-up. Of the 28 patients with a full-term pregnancies, 2 of them had normal vaginal deliveries, while 15 had cesarean deliveries. In the remaining 11 patients, the type of delivery was unknown.

None of the patients with concurrent adenomyosis had a pregnancy during the follow-up period. There was no difference in the proportion of patients having a pregnancy loss or a delivery, according to the number of leiomyomata removed at surgery or the location of the tumor(s) in the uterus (P ≥ .122).

Four patients with subsequent parity also had recurrence of their leiomyomata. In 2 of these, the recurrence was detected early in pregnancy, and in the other 2, it was detected 22 and 47 months after delivery, respectively. The earliest of these 4 recurrences was diagnosed at 12 months after myomectomy. There was a significant negative association between childbirth after myomectomy and recurrence of leiomyomata (Fig. 5).

Figure 5

Figure 5

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DISCUSSION

A patient with symptomatic uterine leiomyomata wants to know the chances of recurrence of leiomyomata after myomectomy and the factors that may affect recurrence if she chooses myomectomy as her treatment option. Recent literature reviews3,4 have suggested that the variation in length of follow-up and criteria for recurrence make it difficult to compare the results of previous studies.

Recurrence of leiomyomata after myomectomy has been reported based on diagnosis by palpation,5 by systematic transvaginal ultrasonography,6,7 or by the need for a second surgery.8 The current study used transvaginal ultrasonography to diagnose recurrence, counting only tumors that were at least 2 cm in diameter. Subsequent surgery rates were also calculated for comparison with earlier studies.

Many previous studies reported leiomyoma recurrence after myomectomy without adjusting for variation in length of follow-up. However, the crude recurrence rate represents minimum leiomyoma recurrence and will underestimate the true recurrence rate, as explained previously in detail.4 This study accounted for disparity in length of follow-up by analyzing the cumulative probability of recurrence calculated by the life-table method. In other studies that accounted for differences in follow-up, the clinically diagnosed recurrence rate 10 years after myomectomy ranged from 27% to 38%.9,10 The current study found a much higher recurrence rate, which was consistent with another earlier study that used systematic transvaginal ultrasonography and adjusted for length of follow-up.6

Patients with parity after myomectomy had a much lower rate of leiomyoma recurrence, which agrees with the findings of earlier studies.6,9 Epidemiological studies have reported a lower risk of uterine leiomyomata in parous women compared with nulliparous women.11–13 The investigators attributed the difference to either reduced fertility resulting from the presence of leiomyomata or to a protective effect of pregnancy on leiomyoma development.

The higher probability of recurrence in patients with a larger intraoperative uterine size was the opposite relationship from that reported in an earlier study.8 The significantly higher recurrence rate in patients that had more than one tumor at the time of surgery was consistent with previous studies.5,6,14

Earlier studies found no association between leiomyoma recurrence and tumor location at surgery,9 patient age,6–8,14 or patient BMI.8 This study corroborates the earlier reports. Likewise, concurrent adenomyosis was not a significant factor, but very few patients had this condition at the time of surgery.

Although the probability of recurrence of detectable leiomyomata increases steadily after myomectomy and is relatively high by 10 years from surgery, the recurrence of associated symptoms—particularly dysmenorrhea—is much lower. It is likely that a majority of patients will not require a second major surgery within 10 years due to a lack of associated symptoms. Patients with a solitary leiomyoma or a smaller uterine size are less likely to have recurrence of their leiomyomata. For patients who desire to have children after myomectomy, subsequent parity may have a protective effect on leiomyoma growth, but the exact relationship between parity and recurrence is unclear.

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REFERENCES

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