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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

Objectives  To assess clinical failure and symptom recurrence after uterine artery embolisation (UAE) and to define predictive factors.

Design  Prospective study of a case series.

Setting  Gynaecology and radiology departments of a French University Hospital.

Population  Eighty-five women who underwent embolisation for the treatment of uterine fibroids.

Method  Vascular access was obtained via the right common femoral artery. Free-flow embolisation was performed using 150–250 μm polyvinyl alcohol particles and an absorbable particle sponge.

Main outcome measures  Clinical failure was defined as persistence of symptoms at three months of follow up and recurrence as return of symptoms. The main outcome measure was the need for further treatment after UAE.

Results  Results are available for 81 patients. Median follow up was 30 months. There were 15 clinical failures and recurrences requiring further treatment (eight hysterectomies, five hysteroscopic resections for submucous fibroids, one second embolisation and one woman refusing further treatment). Recurrence-free survival rate at 30 months (no clinical failure, no recurrence) was 82.8% (95% CI 73.7–91.8%). Multivariate analysis identified two predictive factors: dominant fibroid size on ultrasound imaging (each 1 cm increase: HR = 1.68, 95% CI 1.10–2.69) and number of fibroids (each additional fibroid: HR = 1.34, 95% CI 1.08–1.66).

Conclusions  Symptom recurrence rate 30 months after fibroid embolisation was 17.2%. Fibroid size and number were predictive factors for recurrence. As most recurrences occurred after two years, we recommend that patients be monitored clinically and that imaging be for more than two years after UAE.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

Uterine artery embolisation (UAE) is an effective treatment for symptomatic uterine fibroids; symptoms are controlled in 85–95% of women.1–10 However, most published studies concern women who have completed child-bearing and in whom the disorder will resolve with the menopause. In addition, follow up times rarely exceed two years.4–6,10 Immediate complications and early clinical failures are well documented,9–19 but there is little information on late recurrences. In a recent retrospective study with a follow up ranging from 37 to 59 months, UAE patients were more likely than myomectomy patients to have had further invasive treatment for fibroids10 In our ongoing prospective study of 85 women, new fibroids have occurred or an old one has progressed in eight women and, in six of these women, recurrence occurred after two years.20

To be able to offer UAE to younger, especially infertile women, we need to study recurrence rates over the long term. We also need to know what are the factors predictive of symptom recurrence after UAE in order to select the most appropriate treatment for each patient. The aims of this study are therefore to assess clinical failure rate and to define risk factors for failure and additional treatment.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

Between 1 January 1997 and 30 June 2000, UAE was offered as an alternative to surgery to all women with one or several symptomatic uterine fibroids, excluding women with associated lesions (e.g. adnexal mass), uterine prolapse or stress incontinence. Fibroids had to be well documented by recent suprapubic and transvaginal ultrasound and by power Doppler imaging of the genital tract. Women with submucous or subserosal pedunculated fibroids were excluded. All the women signed an informed consent form according to local Ethics Committee recommendations.

The UAE technique has been described in detail.7,20 Vascular access was obtained via the right common femoral artery. Free-flow embolisation was performed in the left and right uterine arteries using 150–250 μm polyvinyl alcohol particles (PVA). An absorbable particle sponge achieved more definitive proximal embolisation after PVA administration and minimised the risk of particle reflux. A post-embolisation arteriography was used to demonstrate successful bilateral uterine artery occlusion.

Each patient underwent the same clinical and sonographic examinations before UAE and during follow up (at 3, 6, 12 months and yearly thereafter). We report intermediate results at 30 months but follow up will last five years. Clinical symptoms (abnormal bleeding, pelvic pain and bulk-related symptoms) were classified as increased, unchanged, improved or resolved. Fibroids size (diameter), volume, location and vascularisation were determined by ultrasound and Doppler imaging.8 When hysterectomy was performed, histological features of the uterus and fibroids were reported.

Clinical failure was defined as persistence of symptoms at three months of follow up and recurrence as return of symptoms necessitating further treatment. The main outcome measure was the need for further treatment after UAE. Recurrence-free survival (no clinical failure, no recurrence) was estimated using the Kaplan–Meier method.

Variables selected as possible risk factors were: age; body mass index (BMI); myoma size, location, number and vascularisation; haemoglobin before surgery; clinical symptoms (menometrorrhagia, pain and bulk-related symptoms). Univariate Cox models were used to detect any relationships between these variables and recurrence. Multivariate Cox proportional hazards analysis was performed to detect confounding.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

The study population consisted of 85 women. There was one technical failure which was not excluded from the study. Four women were lost to follow up and were excluded from the statistical analysis as there are no data available on them. Median follow up in the remaining 81 women was 30 months (range 3–57 months). Median age was 43.8 years (31–65 years). The main symptoms leading to embolisation were abnormal bleeding (n= 65), bulk-related symptoms (n= 30) or pelvic pain (n= 56). The median number of fibroids was 2 (95% CI 0.8–2.2). The mean uterus volume was 373 mL (95% CI 276–471); The dominant fibroid was intramural in 62 women, subserosal in 13 and partly submucous in 6 women. Its mean main diameter was 59 mm (95% CI 53–65) and mean volume 157 mL (95% CI 113–200). Larger dominant fibroid mean diameter measured by ultrasound was 40, 38, 36, 35, 37 and 40 mm, respectively, at 3, 6, 12, 24, 36 and 48 months.

A total of 51 women have seen their symptoms resolved by UAE, 15 women were improved, 7 women have persistent symptoms and 8 had recurrence symptoms.

Persistence or reappearance of symptoms was menometrorrhagia in 11 women, pelvic pain in 12 and bulk-related symptoms in 5.

Symptoms were not abated (clinical failure) in seven women and recurred within three months in eight women. All these 15 women were offered further treatment (either repeat UAE, hysteroscopic resection or hysterectomy) within a mean time of 26 months (range 4–50 months) of UAE. The seven women with unabated symptoms were: (i) three women with large subserosal but not pedunculated fibroids, two refused the offer of a repeat UAE and underwent a hysterectomy and a myomectomy, respectively. Their fibroids showed hyalinising and ischaemic necrosis. The last one had a second UAE and is free of symptoms at 45 months of follow up; (ii) two women with adenomyosis, which was diagnosed on histological examination of hysterectomy specimens; (iii) a woman with endometrial cancer, in whom the presenting symptom was menometrorrhagia. She was a 37 year old G0 P0 woman with a BMI of 20. Sonography showed a unique 10-cm interstitial leiomyoma. Six months after UAE, her symptoms had not improved although the results of ultrasound imaging results were good. Hysteroscopy revealed endometrial cancer. A hysterectomy was performed. (iiii) The woman with a dissection of the right iliac artery, who refused a second embolisation and underwent a hysterectomy.

Symptoms recurred in eight women. New fibroids were found in seven of these eight women by ultrasound. An earlier fibroid had progressed in the eighth woman. In five of these eight women, hysteroscopic resection of submucous fibroids was performed (at 6, 14, 30, 40 and 50 months, respectively). Symptoms improved after resection and follow up was pursued. Two of the eight women refused repeat UAE and underwent a hysterectomy. The eighth patient returned two years after UAE because of bulk-related symptoms but declined treatment (repeat UAE or hysterectomy).

Menopause occurred in 21 women and 14 had taken or still take a HRT. Three women have been probably menopaused by UAE. Only one was younger than 49 years old.

Recurrence-free survival rate was 82.8% (95% CI 73.7–91.8%) at 30 months (Fig. 1). A univariate analysis revealed three significant factors (Table 1): (i) a 100-mL increase in fibroid volume multiplied recurrence rate by a factor of 1.31 (95% CI 1.07–1.60); (ii) each 1-cm increase in the size of the dominant fibroid multiplied recurrence rate by 1.32 (95% CI 1.07–1.64); (iii) each additional fibroid multiplied rate by 1.72 (95% CI 1.10–2.69). A multivariate analysis was performed and allowed to identify two independent predictive factors: the size of the dominant fibroid (HR = 1.68 for each cm increase, 95% CI 1.13–2.49) and the number of fibroids (HR = 1.34 for each new fibroid, 95% CI 1.08–1.66).

image

Figure 1. Recurrence-free survival after UAE for symptomatic fibroids.

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Table 1.  Predictive factors for fibroid recurrence after UAE.
 Women (n)Events (n)Hazard ratio95% CIP
Location
Intramural62121.00  
Subserous1331.380.37–5.100.63
Partly submucous60
 
Fibroid volume (increase in 100 mL)75131.311.07–1.600.008
Uterus volume (increase in 100 mL)52101.100.97–1.260.15
No. of fibroids (increase in 1)74151.721.10–2.690.02
Dominant myoma size at ultrasound (increase in 1 cm)75131.321.07–1.640.009
 
Nulliparity
No6391.00  
Yes1862.520.89–7.080.11
 
Age
<40 years1861.00  
≥40 years6390.510.18–1.460.21
 
BMI (kg/m2)
<2558121.00  
≥252330.670.19–2.360.53
 
Menometrorrhagia
Absent1641.00  
Present65110.750.24–2.380.63
 
Pain
Absent2531.00  
Present66121.590.44–5.670.48
 
Bulk-related symptoms
Absent5181.00  
Present3071.510.55–4.180.43
 
Central vascularisation
Absent3641.00  
Present523.560.65–19.530.14

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

Of the 81 women in our study, 15 were candidates for further treatment after UAE (either repeat UAE, hysteroscopic resection or hysterectomy). The clinical failure rate 30 months after UAE was 17.2% (95% CI 8.2–26.3%). Symptoms recurred for several reasons: failure of the procedure including incomplete embolisation, associated adenomyosis or incorrect patient selection (concomitant cancer, submucous or subserosal fibroids); fibroid revascularisation; occurrence of new fibroids.20 Fibroid size and number were factors predictive of recurrence.

There are few reports of symptom recurrence after UAE in studies of large patient numbers. Walker and Pelage3 reported 23 cases of clinical failure or recurrence (6%) in a prospective study of 400 women with a mean clinical follow up of 16.7 months. Ravina et al.21 reported a 9.6% recurrence rate at six months in 433 women. However, these studies are incomplete because most recurrences will occur after 20 months.10,20

In Broder et al.'s10 long term study (mean follow up was 46 months), 27% (15/51) of UAE patients required invasive treatment and one woman had a second UAE. This is a higher percentage than the 18.5% crude rate (15/81) of patients who required further treatment in our study over a slightly shorter follow up time. However, no recurrence-free survival rate was available in the study of Broder et al.10 and all 51 embolisation women had prior surgery for fibroids including myomectomies (78%), suggesting that recurrence after UAE is a second recurrence. We can also compare our findings with those for long term follow up after conventional treatment (i.e. laparoscopy or laparotomy). (Medical treatment is short term and does not lead to a cure.) In the randomised study by Rossetti et al.,22 with a median follow up of 26 months, recurrence rates were 23% and 27% after abdominal and laparoscopic surgery, respectively. Recurrence was defined as a new fibroid measuring over 1 mL on ultrasound imaging. In Doridot et al.'s23 series of 196 laparoscopic myomectomies, the cumulative recurrence risk was 12.7% at two years and 16.7% at five years. Recurrence was defined as return of symptoms, recurrence on clinical examination and a new fibroid 2 cm or larger on ultrasound imaging. In Fedele et al.'s24 study in 145 women, the cumulative probability of recurrence after myomectomy reached 51% in five years using routine ultrasound imaging for follow up. However, detecting a fibroid by ultrasound does not warrant a change in the management of a patient without symptoms. Clearly, a consensus definition of recurrence is needed. We consider, like others, that the need for further treatment is the best parameter to evaluate a first procedure. Subramanian et al.25 estimated the rate for additional surgery after myomectomy as 8.3% at six months, 10.6% at one year and 16.5% at two years. Such estimates are not yet available for UAE. Our result of 17.2% at 30 months is a fairly good result and could be explained by complete treatment of all, even small, fibroids by UAE. However, recurrence may just be delayed.

The reasons for recurrence have not yet been elucidated but to reduce recurrence rate we need to identify factors that will predict clinical failure after UAE. The most important drawback of our study is the small number of events that reduces the statistical power of our analysis. And we shall wait for the result of a larger study with long follow up to confirm our results. However, we can compare our findings with those for UAE and myomectomy.

In our study, fibroid size and volume were predictive factors for subsequent surgery after UAE. Large fibroids were more difficult to treat, as observed by Katsumori et al.,26 who found an increased non-significant risk of additional surgery for fibroids larger than 10 cm. Spies et al.27 found less improvement in bleeding as baseline fibroid volume increased. Improvement in bulk-related symptoms at three months was not demonstrated. Submucosal or partial submucosal fibroids were more likely to shrink. McLucas et al.28 also reported baseline fibroid diameter greater than 8.5 cm as a predictor of failure.

A reason for this may be that collateral pathways, which are maintained as shown by contrast enhanced ultrasound29 or MRI,17 may be more highly developed in large than in small fibroids.17 Another reason might be redistribution of embolic material and restoration of flow minutes or hours after UAE.27 However, this would account for early rather than late recurrences. Vascularisation of the ‘embolised’ fibroid needs to be studied to understand recurrence, especially of large fibroids.

Size, but small size, is a predictive factor that has been identified in myomectomy studies. In Stewart et al.'s30 study of abdominal myomectomy in 65 women followed up for 83 months, 34% of the women required additional surgery (15% major surgery; 20% hysteroscopic resection). The women with smaller uteri at the time of index surgery were at higher risk of subsequent surgery, maybe because small fibroids were overlooked. By reducing the size of small fibroids, GnRH analogue pretreatment can also increase recurrence rate31 but the evidence from a systematic review of 26 randomised controlled trials was inconclusive.32 Small size is not an issue with regard to UAE, which targets all fibroids, even small ones.21

We found that the risk of subsequent treatment increased with each additional fibroid, even though all fibroids present were embolised. This is in line with results from Fauconnier et al.'s study, in which the number of fibroids removed by laparoscopic myomectomy predicted recurrence,31 but contrasts with Stewart et al.'s30 results on abdominal myomectomy. The mean number of fibroids per women might explain the discrepancy: 1.9 and 2.2 in our study and Fauconnier et al.'s, respectively, but 9.9 in Stewart et al.'s study.30 However, to explain this risk factor, collateral pathways may be also more important in larger uterus or women themselves may be at high risk of recurrence with high serum oestrogen levels. The results from the study by Broder et al.10 lead support to this hypothesis as 29% of the women undergoing UAE with previous fibroid surgery had recurrence and need further treatment.

Adenomyosis, which is often associated with fibroids, may have accounted for failure in three women, but it was not detected on ultrasound imaging before UAE. McLucas et al.28 found four out of six patients who underwent hysterectomy following UAE had adenomyosis. Pelvic ultrasound, together with Doppler analysis33,34 and MRI34,35 of the pelvis, can also be used to detect adenomyosis but was not performed routinely when we initiated our study in 1997. Adenomyosis should not be a contraindication to UAE because most patients show clinical improvement after UAE34 and because surgery does not yield better results than UAE in this case. Our number of patient is too small to conclude on the subject, and more studies are needed.

Nulliparity was not a predisposing factor for failure in our study and weight gain after puberty was not studied. Both are risk factors for failure after myomectomy.30,31

Moreover, Spies et al.27 do not find this factor significant in his 200 women study analysing successful outcome predictive factors after UAE.

CONCLUSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

The rate of UAE failure requiring further invasive treatment appears higher in women with numerous and large size fibroids. Although non-comparative with myomectomy and despite low statistical power, our study provides new data on the middle term outcomes of UAE, which can be useful for the choice between the two procedures and may be helpful for determination of a prognosis. These results suggest that women with these risk factors need to be informed of such recurrence rate especially. However, this risk is low, and depending on the woman's age, fibroid embolisation should be offered as an alternative treatment instead of myomectomy or hysterectomy.

References

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. References

Accepted 20 August 2004