Microwave ablation as treatment of benign uterine disease

BACKGROUND AND AIMS

Uterine fibroids and adenomyosis are common benign gynecological conditions with possible negative impact on women's lives. Hysterectomy is often recommended when medical treatment is ineffective, and the patient has no further desire for pregnancy. The use of minimally invasive methods as treatment for uterine diseases has been evolving rapidly the last 10-15 years, and patients wishing to preserve their uterus are increasing in numbers. Microwave ablation (MWA) is minimally invasive and has been used in clinical routine in Danderyd Hospital for many years, to treat malignant tumors in other organs than the uterus. Focus on minimizing symptoms without risks of invasive surgery, is of high value both for patients and health care resources. Even though published studies on MWA treatment of fibroids and adenomyosis, mainly from China, have showed promising results with low time requirements and few complications, this treatment modality is largely unknown in Europe.

The aim of this thesis was to evaluate effectiveness, acceptability, safety, and long-term effects of MWA treatment of symptoms related to fibroids and adenomyosis in women without desire to preserve fertility.

METHODS AND MAIN RESULTS

Study I is a randomized controlled trial comparing MWA and uterine artery embolization (UAE) for symptoms related to uterine fibroids. Patients were randomized to MWA (n=17) or UAE (n=17) treatment and filled in two validated questionnaires before and after treatment. Uterine fibroid-quality of life (UFS- QoL) questionnaire includes symptom severity score (SSS) and health related quality of life score (HR-QoL). Pictorial bleeding assessment chart (PBAC) evaluates amount of menstrual blood loss. Primary outcome was fibroid volume difference six months after treatment measured on MRI. Secondary outcomes included difference in symptoms (SSS), quality of life (HR-QoL), bleeding during menstruation (PBAC), postoperative pain, hospitalization, sick leave, and acceptability. Median fibroid volume reduction was 42% (IQR 14-63) in the MWA group and 62% (IQR 35-80) in the UAE group without significant difference between the groups (p=0.29). Symptoms and bleeding decreased, and quality of life increased in both groups at follow-up without significant difference between the groups. Acceptability was high and did not differ between groups. Patients treated with MWA had shorter hospitalization (1 day compared to 2, p<0.001) and sick leave (3 days compared to 7, p=0.001).

In study II long-term effect of MWA on fibroid shrinkage and symptom reduction was studied as well as fibroid characteristics that could predict more successful treatment effect. Of 17 MWA treated patients from study I, 16 were included (one had entered menopause). MRI was performed before, after six months and at long-term (16-36 months), and fibroid volume was measured. Patients filled in the same questionnaires as Study I at all timepoints. Fibroid location in uterus was registered and shrinkage was correlated to vascularization and T2 signal intensity (SI) on MRI. Continuous shrinkage was noted in 83% of treated fibroids from six months to long-term follow up, with median shrinkage of 77% at long-term. Compared to baseline 82% of patients reported symptom improvement. Symptoms increased between the six-month follow-up and long-term, but no change in quality of life during that time period was observed. Preoperative vascularization and high T2 SI predicted better treatment effect.

Study III is a prospective interventional cohort study on effectiveness and acceptability of MWA on symptoms related to uterine fibroids. A total of 123 patients were included and treated with MWA but 10 were lost to follow up. Primary outcome was symptom reduction (SSS) and increase in quality of life (HR- QoL) six months after MWA. Secondary outcomes included difference in menstrual bleeding, fibroid volume, hospitalization, postoperative pain, and acceptability. Symptoms decreased by 37% (p<0.001) and quality of life increased by 74% (p<0.001). Bleeding during menstruation decreased by 38% (p<0.001) and median fibroid shrinkage was 64% (p<0.001). Acceptability was high in 96% of cases on treatment day and in 90% at follow-up. Most patients (97%) left the hospital the same day.

In study IV 20 patients with symptomatic adenomyosis were randomized to MWA or UAE. Adenomyosis was confirmed on ultrasound and MRI and patients filled in the validated questionnaires before and six months after treatment. Primary outcome was symptom reduction (SSS) at follow-up. Secondary outcomes included quality of life, menstrual bleeding, dysmenorrhea, uterine volume, hospitalization, return to daily activities, use of pain medication and acceptability. Symptom reduction was seen in both groups at follow-up, by 36% in the MWA group (p=0.007) and 47% (p=0.067) in the UAE group but without significant difference between groups (p=0.755). Both groups had significantly higher quality of live, less bleeding and reduced dysmenorrhea after treatment but there was no significant difference between the groups. The MWA group had significantly shorter hospitalization (p=0.004), quicker return to daily activities (p=0.005) and used less pain medication postoperatively (p=0.029).

CONCLUSION

Microwave ablation is a promising treatment alternative for patients with symptoms from uterine fibroids and adenomyosis who seek uterus preservation. We could not confirm the superiority of MWA in shrinking fibroid size compared to UAE nor regarding symptom reduction, but absence from work, hospitalization and pain was less prominent in the MWA treated patients. Within the studies presented in this thesis one serious complication occurred. Acceptability was high. Fibroids treated with MWA continued to shrink over time and highly vascularized fibroids and submucosal fibroids responded better to the treatment. Further studies are needed to evaluate the effect of MWA in patients with impaired fertility.

List of scientific papers

I. Ultrasound guided microwave ablation compared to uterine artery embolization treatment for uterine fibroids - a randomized controlled trial. Jonsdottir G, Beermann M, Lundgren Cronsioe A, Hasselrot K, Kopp Kallner H. International Journal of Hyperthermia. 2022;39(1):341-347. @ copyright 2022, reprinted by permission of Informa UK Limited, trading as Taylor & Taylor & Francis Group. https://doi.org/10.1080/02656736.2022.2034991

II. Long term follow-up of uterine fibroids treated with microwave ablation: an up to 3-year observational study of volume, regrowth, and symptoms. Beermann M, Jonsdottir G, Cronsioe A, Hasselrot K, Kopp Kallner H. International Journal of Hyperthermia. 2022;39(1):1158-1163. @ copyright 2022, reprinted by permission of Informa UK Limited, trading as Taylor & Taylor & Francis Group. https://doi.org/10.1080/02656736.2022.2109764

III. Ultrasound guided microwave ablation treatment of uterine fibroids: clinical response and patient acceptability. Jonsdottir G, Beermann M, Lantz E, Nikodell A, Lundgren Cronsioe A, Hasselrot K, Kopp Kallner H. Acta Obstet Gynecol Scand. Published online 19 December 2024. https://doi.org/10.1111/AOGS.15041

IV. Symptom improvement in adenomyosis patients after ultrasound guided microwave ablation or uterine artery embolization, a randomized controlled pilot study. Jonsdottir G, Lantz E, Beermann M, Paschou M, Kopp Kallner H, Hasselrot K. [Submitted]