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Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy
International Journal of Gynecology and Obstetrics 133 (2016) 206–211
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International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
CLINICAL ARTICLE
Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy Bernhard Krämer a, Markus Hahn a,⁎, Florin-Andrei Taran a, Dorit Kraemer a, Keith B. Isaacson b,c, Sara Y. Brucker a a b c
Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany Minimally Invasive Surgery, Newton-Wellesley Hospital, Newton, MA USA Harvard Medical School, Boston, MA USA
a r t i c l e
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Article history: Received 7 August 2015 Received in revised form 9 October 2015 Accepted 18 December 2015 Keywords: Acessa Laparoscopic myomectomy Laparoscopic ultrasound Fibroid Radiofrequency ablation Radiofrequency volumetric thermal ablation
a b s t r a c t Objective: To compare 24-month patient-reported outcomes following laparoscopic radiofrequency volumetric thermal ablation (RFVTA) and laparoscopic myomectomy in patients with uterine fibroids. Method: An interim analysis of 24-month follow-up data from a randomized controlled trial was performed at Tübingen University Women’s Hospital between November 1, 2012 and May 30, 2015. Premenopausal patients, at least 18 years of age, who were menstruating, were randomly assigned to be treated for symptomatic uterine fibroids with either RFVTA or laparoscopic myomectomy. The outcomes included in the present per-protocol analysis were patients’ responses to validated questionnaires and long-term safety. Results: The study enrolled 51 patients; 21 and 22 patients in the RFVTA and laparoscopic myomectomy groups, respectively, completed 24 months of follow-up. Improvements in the severity of symptoms from baseline were reported by participants in both the RFVTA (P b 0.001) and laparoscopic myomectomy groups (P = 0.001). A significant improvement in health-related quality of life was observed in the laparoscopic myomectomy group (P = 0.040); a non-significant improvement was recorded in the RFVTA group (P = 0.083). A trocar-site hematoma occurred in one patient in the laparoscopic myomectomy group. Further surgical interventions were recorded in three patients in the RFVTA group but these were unrelated to fibroid symptoms. Conclusions: These 24-month data suggest equivalence in safety and patient-reported efficacy of RFVTA and laparoscopic myomectomy. ClinicalTrials.gov: NCT01750008 © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Targeted radiofrequency ablation (RFA) of tissue for palliative and therapeutic applications has been well documented in the literature for the treatment of cardiac arrhythmias [1], neurological and spinal disorders [2,3], and cancers of the liver [4], kidney [5], prostate [6], breast [7], lung [8], and skin [9]. However, to date only one RFA system, employing radiofrequency volumetric thermal ablation (RFVTA) has received FDA approval for the treatment of symptomatic uterine fibroids in the United States (Acessa; Halt Medical, Inc, Brentwood, CA, USA). RFVTA has also been approved for use in Europe. Uterine fibroids are the most ubiquitous benign uterine masses in reproductive-aged women, occurring in up to 80% of this group; of ⁎ Corresponding author at: Department of Obstetrics and Gynecology, University of Tübingen, Women’s Hospital, Calwerstrasse 7, 72067 Tübingen, Germany. Tel.: + 49 7071 29 82211; fax: + 49 7071 29 5381. E-mail address: [email protected] (M. Hahn).
these individuals, 25%–30% experience related bleeding, pain, and bulk symptoms [10,11]. Symptomatic fibroids are a significant healthcare and economic burden worldwide, significantly affecting patients’ quality of life. Treatment success is usually evaluated in terms of improvements in quality of life. Traditionally, hysterectomy was the approach employed in the treatment of fibroids; however, patients have increasingly sought minimally invasive, uterinesparing therapies that also preserve reproduction function. Consequently, excisional laparoscopic myomectomy is considered the gold standard by most clinicians [12]. Similarly, RFVTA is a minimally invasive and uterine-sparing procedure. It is guided intraoperatively using laparoscopic ultrasound, which has been demonstrated to detect more uterine fibroids (regardless of their location and size) than either transvaginal ultrasound or contrast-enhanced magnetic resonance imaging [13]. RFVTA delivers well-controlled thermal treatment zones without affecting surrounding tissues or organs and it can be applied to large fibroids, multiple fibroids, and deep intramural fibroids [14,15].
http://dx.doi.org/10.1016/j.ijgo.2015.10.008 0020-7292/© 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Patient responses to various validated questionnaires are useful in gauging the success of any treatment for uterine fibroids. The Uterine Fibroid Symptom and Quality of Life (UFS–QOL) questionnaire provides valid, and highly responsive and reliable measures for assessing the symptoms and health-related quality of life in patients with symptomatic uterine fibroids; additionally, it can be used to compare outcomes of fibroid therapies [16,17]. Similarly, the EuroQoL (EQ-5D) health-state survey is a validated, multi-attribute health-state classification system that indicates the burden of illness in terms of mobility, self-care, ability to complete normal activities, pain/discomfort, and anxiety or depression [18]. The menstrual impact questionnaire (MIQ) is especially useful for gauging the burden of menstrual bleeding a patient is experiencing at the time of questioning [19]. The aim of the present interim analysis was to analyze the 24-month efficacy and safety outcomes from an ongoing randomized controlled trial of laparoscopic ultrasound-guided RFVTA and laparoscopic ultrasound-guided myomectomy (ClinicalTrials.gov: NCT01750008) [15,20] for the treatment of symptomatic uterine fibroids.
2. Materials and methods An interim analysis was performed on data from an ongoing randomized, prospective, single-center, longitudinal trial of laparoscopic myomectomy and RFVTA that began November 1, 2012. Premenopausal patients who were menstruating, aged at least 18 years, with symptomatic fibroids, who desired uterine conservation, and were indicated for surgical intervention for their fibroid symptoms were referred to Tübingen University Hospital, Germany, for study enrollment between November 1, 2012 and June 30, 2013. Eligible patients had a uterine size of no more than 16 gestational weeks, no individual fibroid with a largest dimension of greater than 10 cm on transvaginal ultrasound, and a normal Papanicolaou test. Exclusion criteria included being at risk for, or known to have, significant intra-abdominal adhesions that would require extensive dissection to mobilize and view all surfaces of the uterus; pregnancy or lactation; having received any depot gonadotropin-releasing hormone agonist within the 3 months prior to the procedure; the presence of an implanted intrauterine or fallopian tube device at any time up to 10 days before treatment; known or suspected endometriosis or adenomyosis; pelvic inflammatory disease; gynecologic malignancy or pre-malignancy in the 5 years before enrollment; history of pelvic radiation; the presence of a non-uterine pelvic mass larger than 3 cm at its greatest diameter or the presence of a cervical fibroid; one or more intracavitary (Type 0 or Type 0/1) fibroids that would be better treated by hysteroscopic means; and not willing to be randomized for treatment. The study protocol required that patients provide written informed consent after agreeing that they understood the study purpose, the associated testing, procedures, and follow-up assessments, as well as the potential risks and benefits of participation. The Clinical Ethics Committee of Tübingen University Hospital in Tübingen, Germany approved the study, and all enrollees were treated at Tübingen University Hospital. Data were collected and monitored (CenTrial GmbH, Tübingen, Germany) in Tübingen and were analyzed by an independent biostatistics firm in the United States (Innovative Analytics Inc, Kalamazoo, Michigan USA). Patients were randomly allocated in a 1:1 ratio to receive either laparoscopic myomectomy or RFVTA. Randomization occurred as an intraoperative step after the surgeon mapped the patient’s uterus for the location, number, and types of fibroids using laparoscopic ultrasound. The use of laparoscopic ultrasound provided additional imaging information to the surgeon regarding the patient’s fibroids, regardless of their treatment assignment. After mapping, the operating room staff drew an envelope containing the patient’s computergenerated treatment assignment. Assignments were generated by an independent biostatistician in blocks of six or four. The surgeon and
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patient were masked to treatment assignment prior to the beginning of surgery. Patients assigned to undergo myomectomy were placed in the lithotomy position and underwent standard laparoscopic myomectomy [15]. If deep intramural fibroids or transmural fibroids not encroaching on the serosal borders were encountered, two-layer suturing was used. Although the excision of all fibroids was allowed per protocol, intramural fibroids 1.0–1.5 cm in diameter were not excised owing to the clinical standard of care at the study institution. The RFVTA treatment procedure and the methods for pretreatment tissue sampling for histopathology have been described in detail previously [15,20–23]. RFVTA treatment involved the use of a monopolar radiofrequency generator, a percutaneously placed handpiece incorporating an electrode at its distal tip with a deployable array, two large dispersive electrode pads, extension cables, and an activating foot pedal. Current was delivered to the small electrode tip and array; this facilitated the localization of ablative treatment to the fibroid tissue. The current was removed via large dispersive electrode pads that were placed on each patient’s thighs above the patella. The electrical current resulted in the oscillation of intracellular ions, generating resistive or frictional heating. The heat spread by conduction, decreasing rapidly with increasing distance from the electrode (1/d4) (Fig. 1A, B, and C). The current continued through the body to the dispersive electrode pads, where it returned to the source. The ablated tissue underwent coagulative necrosis and was naturally reabsorbed by the surrounding myometrium. The target ablation temperature was 100 °C and the required time at the target temperature was a function of the length of array deployment. An algorithm was used to define the deployment and time at 100 °C. Following the completion of the recommended ablation time the surgeon depressed the foot pedal, ending the ablation. The array was then withdrawn into the handpiece shaft, the probe was switched from ablation to coagulation mode, and the track was coagulated during handpiece withdrawal. Hemostasis was confirmed through laparoscopic viewing. Following the ablation of all fibroids, the pelvis was irrigated and inspected, the port sites were closed using intracutaneous sutures, and patients were discharged from the clinic on the same day. The primary outcome of the ongoing 5-year randomized controlled trial is the length of hospital stay. The secondary outcomes are patients’ responses to questionnaires. The analyses of patient hospitalization and perioperative outcomes have been described previously [15]. The present interim analysis of the study reports 24-month postoperative qualitative outcomes in terms of participants’ responses to questionnaires (UFS–QOL, EQ-5D, overall treatment effect survey, and the MIQ [16–19]), re-interventions for fibroid symptoms, and pregnancy outcomes. According to the study method, the participants will be followed for a total of 5 years. The calculation of the sample size has been described in detail previously [15] and was based on hospitalization times for patients in each group. Briefly, the null hypothesis was that the duration of hospitalization for patients who underwent the RFVTA procedure would be more than 10% longer than that experienced by patients who underwent laparoscopic myomectomy. The alternative hypothesis was that this would not be the case, resulting in a one-sided noninferiority test of RFVTA in comparison with laparoscopic myomectomy, with an alpha level of 0.025. Based on procedures in the USA (unpublished data), the null hypothesis would be rejected if the mean length of hospital stay for patients undergoing RFVTA was 7 ± 4 hours. The mean length of hospital stay for women undergoing laparoscopic myomectomy has been demonstrated to be approximately 15 ± 16 hours [24]. The pooled standard deviation of the difference in length of hospital stay between these two procedures is 11.7 hours, which is the square root of the mean of the estimated variances of the two procedures. The power yielded under these assumptions is 0.80, resulting in a necessary sample size of 50 participants (25 in each group).
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Fig. 1. Representative illustrations of the radiofrequency volumetric thermal ablation sequence. (a) At the beginning of treatment, the tissue temperature along the electrodes begins to increase rapidly. (b) Approximately halfway through treatment, the tissue closest to the electrodes reaches the target temperature while a thermal front 55 °C in temperature expands. (c) At the end of the treatment, the ablation volume reaches its maximum size and the outer boundary has reached thermal equilibrium with the surrounding tissue. Abbreviation: RFVTA, radiofrequency volumetric thermal ablation.
Data were analyzed on a per-protocol basis. Continuous variables for secondary-outcome analyses were summarized using descriptive statistics, and categorical variables were expressed as frequencies and percentages. The precision of the questionnaire response outcomes was summarized using 95% confidence intervals (95% CIs). The two groups were compared using a Student t test unless noted otherwise. P b 0.05 was considered statistically significant. All analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC, USA). 3. Results A total of 51 patients were enrolled in the present study; 26 were randomized to undergo RFVTA treatment and 25 were allocated to the laparoscopic myomectomy group (Fig. 2). At 24 months, 21 patients in the RFVTA group and 22 patients in the laparoscopic myomectomy were available for analysis. The baseline demographics and intraoperative fibroid characteristics are detailed in table 1. Participants in both groups were similar in terms of their height, weight, and ethnicity; however, participants allocated to the RFVTA group were found to be significantly older (P = 0.006). Intraoperative mapping revealed the location and size of fibroids in patients in each group, with a greater number of fibroids found in patients in the RFVTA group compared with in patients in the myomectomy group (72 vs 61). Of the fibroids
mapped, 71 (99%) were accessible and were treated in the RFVTA group compared with 49 (80%) fibroids that were accessible for excision using laparoscopic myomectomy [15]. Symptoms experienced by participants at baseline and at 24 months are detailed in table 2. Participants were asked at both timepoints whether they had experienced each symptom; all responses were binary (yes or no), with the severity of each symptom not recorded. There were no significant differences observed between the treatment groups in terms of the symptoms experienced at baseline and at 24-month follow-up. Changes in mean transformed UFS–QOL scores from baseline to 24-month follow-up are presented in Fig. 3a and b, respectively. Significant improvements in symptom severity from baseline (indicated by decreasing values) were recorded in the RFVTA (− 54% [95% CI − 72.3 to − 34.8]; P b 0.001) and laparoscopic myomectomy (−45% [95% CI −68.9 to −20.9]; P = 0.001) groups. An improvement from baseline (indicated by increasing values) in health-related qualityof-life scores were reported for the laparoscopic myomectomy group (21% [95% CI 1.1 to 40.5]; P = 0.040); a non-significant improvement was observed in the RFVTA group (11% [95% CI − 1.6 to 23.0]; P = 0.083). As can be observed from Fig. 3a and b, at baseline, participants in the laparoscopic myomectomy group had higher symptom severity and lower quality of life than patients in the RFVTA group.
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Assessed for eligibility (n=110)
Excluded (n=54) Did not meet inclusion criteria (n=54) Intraoperative mapping (n=56)
Excluded (n=5) Patient had a large fibroid (>10 cm) and an intrauterine device implanted (n=1) Patient had many fibroids that would have necessitated a hysterectomy if assigned to the laparoscopic myomectomy group (n=2) Patient had no fibroids (n=1) Patient had only 1 large pedunculated fibroid (>10 cm) (n=1)
Randomized (n=51)
Allocated to RFVTA (n=26)
Allocated to laparoscopic myomectomy (n=25)
Excluded (n=5) Did not receive allocated intervention owing to unrelated emergency in the operating room (n=1) Missing data (n=1) Withdrew owing to hysterectomy (n=2) Withdrew to undergo myomectomy (n=1)
Excluded (n=3) Missing data (n=3)
Analyzed at 24 months (n=21)
Analyzed at 24 months (n=22)
Fig. 2. Flow of participants through the study.
Table 1 Baseline characteristics and intraoperative fibroid characteristics following treatment.a Variable
RFVTA group (n = 25)
Laparoscopic myomectomy group (n = 25)
Age, y Height, cm Weight, kg Ethnicity White Intraoperative fibroid characteristicsb Total fibroids No. of fibroids per patient Fibroid type Submucosal Transmural Intramural Intramural fibroid abutting the endometrium Subserosal Pedunculated subserosal
40.0 ± 7.8 166.0 ± 5.8 62.4 ± 8.9
34.4 ± 6.1 165.2 ± 5.8 64.9 ± 13.5
25 (100)
25 (100)
72 2.9 ± 2.6 (2; 1–9)
61 2.4 ± 1.6 (2; 1–6)
0 0 33 (46) 2 (3)
2 (3) 3 (5) 26 (43) 0
37 (51) 0
34 (56) 2 (3)
Abbreviation: RFVTA, radiofrequency volumetric thermal ablation. a Values are given as mean ± SD, number (percentage), number, or mean ± SD (median; range), unless indicated otherwise. b Intraoperative fibroid characteristics were evaluated by laparoscopic ultrasound mapping of the uterus prior to ablation/excision.
Participants’ responses to the EQ-5D questionnaire demonstrated improvements in mean scores between baseline and 6-month followup for the RFVTA group (81.7 ± 11.2 vs 88.9 ± 13.7) and the laparoscopic myomectomy group (72.3 ± 18.2 vs 85.3 ± 14.1). However, lower 12-month EQ-5D scores were reported by both the RFVTA (85.5 ± 14.1) and laparoscopic myomectomy (82.9 ± 16.1) groups. At 24 months, the EQ-5D score had improved slightly in the RFVTA group (86.4 ± 9.7) and had decreased further in the laparoscopic myomectomy group (79.3 ± 25.2). In the overall treatment-effect survey, participants were asked to compare their symptoms at 24 months with their symptoms at 12 months. In total, 21 patients responded in each group; 8 (38%) patients in the RFVTA group reported that their fibroid symptoms were better, 12 (57%) reported that they were about the same, and 1 (5%) reported that their symptoms were worse. In the laparoscopic myomectomy group, 5 (24%) participants reported that their symptoms had improved and 16 (76%) reported that their symptoms had remained the same. In terms of treatment satisfaction, 19 (90%) and 21 (100%) patients in the RFVTA and laparoscopic myomectomy groups, respectively, were satisfied with the treatment they received. Among the RFVTA and laparoscopic myomectomy groups, 19 (90%) and 20 (95%) patients, respectively, reported that they would recommend the treatment they received to a friend who had uterine fibroids. Finally, in response to the overall treatment effect survey, 14 (67%) and 4
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Table 2 Symptoms experienced by patients at enrollment and 24 months.a Symptom
Baseline analysis
Heavy menstrual bleeding Pelvic discomfort/pain Increased abdominal girth Frequent urination Urinary retention Dysmenorrhea Dyspareunia Backache Sleep disturbances Uterine pain Localized pain Other
24-month analysis
RFVTA group (n = 25)
Laparoscopic myomectomy group (n = 25)
P value
RFVTA group (n = 21)
Laparoscopic myomectomy group (n = 22)
21 (84) 10 (40) 7 (28) 13 (52) 4 (16) 7 (28) 3 (12) 7 (28) 0 3 (12) 5 (20) 0
18 (72) 11 (44) 5 (20) 9 (36) 8 (32) 8 (32) 6 (24) 6 (24) 1 (4) 1 (4) 5 (20) 1 (4)
0.31b 0.77b 0.51b 0.25b 0.19b 0.78b 0.46c 0.75b N0.99c 0.61c N0.99b N0.99c
6 (29) 2 (10) 3 (14) 4 (19) 0 8 (38) 2 (10) 3 (14) 2 (10) 5 (24) 2 (10) 0
3 (14) 5 (23) 1 (5) 2 (9) 0 7 (32) 3 (14) 8 (36) 2 (9) 3 (14) 1 (5) 0
P value 0.28c 0.41c 0.35c 0.41c 0.67b N0.99c 0.10b N0.99c 0.46c 0.61c
Abbreviation: RFVTA, radiofrequency volumetric thermal ablation. a Values are given as number (percentage) unless indicated otherwise. b χ2 test. c Fisher exact test.
(19%) participants from the RFVTA group described their treatment as moderately effective and very effective, respectively, in eliminating their symptoms. In the laparoscopic myomectomy group, 5 (24%) and 13 (62%) patients reported treatment to be moderately effective and very effective, respectively. The MIQ survey was used to assess participants’ perceptions of menstrual bleeding from each patient’s previous period to the point the survey was conducted. Data from the MIQ survey were available for 18 patients in the RFVTA group; 7 (39%) described their blood loss
a 100
Mean Transformed Symptom Severity Scores
90 80 70 60 50
41.8
40
30
27.9
38.9
30 20
25.3
10
21.9
24.7
22.3
26 16
0 Baseline
3 mo
RFVTA
6 mo
12 mo
24 mo
Laparoscopic Myomectomy
b Mean Transformed Health-Related Quality-of-Life Scores
100 85.2
90 77.1
89.4
87
77.9
80 70 60
77.7
80.3
85.6
83
70.2
50 40 30 20 10 0 Baseline
as, “better” than during their previous period and 11 (61%) described the blood loss as, “about the same”. Among the 20 patients in the laparoscopic myomectomy group who responded to the MIQ survey, 4 (20%) described their blood loss as, “better”, 13 (65%) thought it was, “about the same”, and 3 (15%) described it as, “worse”. In the RFVTA group, one serious complication occurred in a participant who presented with hypermenorrhea shortly after the RFVTA procedure. A physician not affiliated with the present study performed a dilation and curettage procedure; this resulted in uterine perforation and subsequent hysterectomy. Another patient underwent a preemptive hysterectomy after a biopsy demonstrated the presence of a smooth muscle tumor of uncertain malignant potential. A histopathology report describing the uterus and fibroids revealed no atypia and confirmed an absence of malignancy. A third participant in the RFVTA group, who was asymptomatic at 6 months and who stated a desire to become pregnant in the future, sought a myomectomy procedure after a 4-cm fibroid was observed during an ultrasound examination. In the laparoscopic myomectomy group, one patient experienced a hematoma at the trocar site. No participants in the laparoscopic myomectomy group sought surgical re-intervention owing to fibroid symptoms. No other adverse events occurred among the study participants. In the RFVTA group, three patients conceived; two pregnancies concluded with vaginal deliveries of healthy neonates and one pregnancy resulted in a cesarean delivery of a healthy neonate. In the laparoscopic myomectomy group, six conceptions were experienced by a total of five patients. Of these, one induced abortion, two vaginal deliveries, and two cesarean deliveries were recorded, with one pregnancy ongoing at the time of writing.
3 mo
RFVTA
6 mo
12 mo
24 mo
Laparoscopic Myomectomy
Fig. 3. Uterine fibroid symptom and quality-of-life scores between study initiation and 24month follow-up. (a) Symptom severity scores. (b) Health-related quality-of-life scores. Abbreviation: RFVTA, radiofrequency volumetric thermal ablation.
4. Discussion The present study demonstrated benefits in terms of safety, symptom reduction, and improvements in quality of life in patients at 24 months after treatment for symptomatic uterine fibroids with RFVTA and laparoscopic myomectomy. The evaluations included in the present study were based on patient responses to validated questionnaires. The analyzed data from patient responses to these questionnaires suggests long-term utility of both RFVTA and laparoscopic myomectomy as treatment options for patients with symptomatic uterine fibroids who desire uterine conservation. Although, three patients in the RFVTA group sought further surgical interventions, none of these was related to fibroid symptoms. Rather, one decision to undergo hysterectomy was based on the histopathological diagnosis of a smooth muscle tumor of uncertain malignant
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potential, which could not be confirmed in the final specimen of the removed uterus. Another patient required a hysterectomy following the perforation of the uterus during a dilation and curettage procedure. Finally, a patient who wished to become pregnant sought treatment to excise a newly discovered or re-growing 4-cm fibroid, which was diagnosed using ultrasound and was not clinically symptomatic. Guido et al. reported 2-year clinical outcomes of a prospective multicenter trial of RFVTA conducted in the USA, Guatemala, and Mexico [25]. Although this study provided strong evidence for the use of RFVTA in the treatment of symptomatic fibroids, it lacked the strength of a comparative randomized trial. That the participant population in the present study was racially homogenous can be considered to be both a strength and a limitation. A racially homogenous group provides a control for outcomes based on ethnicity but does not provide the heterogeneity observed in real-world populations of individuals with symptomatic fibroids. Another limitation is the size of the study. Although it was powered for the primary outcome of hospitalization time, it was not sufficiently powered to perform a statistical analysis of the secondary outcomes (the various questionnaire responses) described in the present interim analysis. However, the outcomes recorded in the present study are comparable those observed in a larger prospective study of RFVTA [25]. In summary, 24-month data from the present interim analysis of a randomized controlled trial suggest equivalence in safety and patientreported outcomes of RFVTA and laparoscopic myomectomy. Treatment with RFVTA could be considered in the treatment of patients with symptomatic uterine fibroids who desire uterine conservation. Acknowledgments Halt Medical Inc (Brentwood, California USA) provided materials and funding for the procedures and for independent third-party data monitoring, statistical analysis, and editorial support. Conflict of Interest Halt Medical, Inc. (Brentwood, California USA) sponsored the study and provided materials and funding for the described procedures and for independent third-party data monitoring, statistical analysis, and editorial support. K. B. I. is a member of Halt’s Clinical Events Committee. The authors have no other conflicts of interest. References [1] Theodoreson MD, Chohan BC, McAloon CJ, Sandhu A, Lancaster CJ, Yusuf S, et al. Same-day cardiac catheter ablation is safe and cost-effective: Experience from a UK tertiary center. Heart Rhythm 2015;12(8):1756–61. [2] Strickland BA, Jimenez-Shahed J, Jankovic J, Viswanathan A. Radiofrequency lesioning through deep brain stimulation electrodes: a pilot study of lesion geometry and temperature characteristics. J Clin Neurosci 2013;20(12):1709–12. [3] Eckmann MS, Martinez MA, Lindauer S, Khan A, Ramamurthy S. Radiofrequency ablation near the bone-muscle interface alters soft tissue lesion dimensions. Reg Anesth Pain Med 2015;40(3):270–5.
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CLINICAL ARTICLE
Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy Bernhard Krämer a, Markus Hahn a,⁎, Florin-Andrei Taran a, Dorit Kraemer a, Keith B. Isaacson b,c, Sara Y. Brucker a a b c
Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany Minimally Invasive Surgery, Newton-Wellesley Hospital, Newton, MA USA Harvard Medical School, Boston, MA USA
a r t i c l e
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Article history: Received 7 August 2015 Received in revised form 9 October 2015 Accepted 18 December 2015 Keywords: Acessa Laparoscopic myomectomy Laparoscopic ultrasound Fibroid Radiofrequency ablation Radiofrequency volumetric thermal ablation
a b s t r a c t Objective: To compare 24-month patient-reported outcomes following laparoscopic radiofrequency volumetric thermal ablation (RFVTA) and laparoscopic myomectomy in patients with uterine fibroids. Method: An interim analysis of 24-month follow-up data from a randomized controlled trial was performed at Tübingen University Women’s Hospital between November 1, 2012 and May 30, 2015. Premenopausal patients, at least 18 years of age, who were menstruating, were randomly assigned to be treated for symptomatic uterine fibroids with either RFVTA or laparoscopic myomectomy. The outcomes included in the present per-protocol analysis were patients’ responses to validated questionnaires and long-term safety. Results: The study enrolled 51 patients; 21 and 22 patients in the RFVTA and laparoscopic myomectomy groups, respectively, completed 24 months of follow-up. Improvements in the severity of symptoms from baseline were reported by participants in both the RFVTA (P b 0.001) and laparoscopic myomectomy groups (P = 0.001). A significant improvement in health-related quality of life was observed in the laparoscopic myomectomy group (P = 0.040); a non-significant improvement was recorded in the RFVTA group (P = 0.083). A trocar-site hematoma occurred in one patient in the laparoscopic myomectomy group. Further surgical interventions were recorded in three patients in the RFVTA group but these were unrelated to fibroid symptoms. Conclusions: These 24-month data suggest equivalence in safety and patient-reported efficacy of RFVTA and laparoscopic myomectomy. ClinicalTrials.gov: NCT01750008 © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Targeted radiofrequency ablation (RFA) of tissue for palliative and therapeutic applications has been well documented in the literature for the treatment of cardiac arrhythmias [1], neurological and spinal disorders [2,3], and cancers of the liver [4], kidney [5], prostate [6], breast [7], lung [8], and skin [9]. However, to date only one RFA system, employing radiofrequency volumetric thermal ablation (RFVTA) has received FDA approval for the treatment of symptomatic uterine fibroids in the United States (Acessa; Halt Medical, Inc, Brentwood, CA, USA). RFVTA has also been approved for use in Europe. Uterine fibroids are the most ubiquitous benign uterine masses in reproductive-aged women, occurring in up to 80% of this group; of ⁎ Corresponding author at: Department of Obstetrics and Gynecology, University of Tübingen, Women’s Hospital, Calwerstrasse 7, 72067 Tübingen, Germany. Tel.: + 49 7071 29 82211; fax: + 49 7071 29 5381. E-mail address: [email protected] (M. Hahn).
these individuals, 25%–30% experience related bleeding, pain, and bulk symptoms [10,11]. Symptomatic fibroids are a significant healthcare and economic burden worldwide, significantly affecting patients’ quality of life. Treatment success is usually evaluated in terms of improvements in quality of life. Traditionally, hysterectomy was the approach employed in the treatment of fibroids; however, patients have increasingly sought minimally invasive, uterinesparing therapies that also preserve reproduction function. Consequently, excisional laparoscopic myomectomy is considered the gold standard by most clinicians [12]. Similarly, RFVTA is a minimally invasive and uterine-sparing procedure. It is guided intraoperatively using laparoscopic ultrasound, which has been demonstrated to detect more uterine fibroids (regardless of their location and size) than either transvaginal ultrasound or contrast-enhanced magnetic resonance imaging [13]. RFVTA delivers well-controlled thermal treatment zones without affecting surrounding tissues or organs and it can be applied to large fibroids, multiple fibroids, and deep intramural fibroids [14,15].
http://dx.doi.org/10.1016/j.ijgo.2015.10.008 0020-7292/© 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Patient responses to various validated questionnaires are useful in gauging the success of any treatment for uterine fibroids. The Uterine Fibroid Symptom and Quality of Life (UFS–QOL) questionnaire provides valid, and highly responsive and reliable measures for assessing the symptoms and health-related quality of life in patients with symptomatic uterine fibroids; additionally, it can be used to compare outcomes of fibroid therapies [16,17]. Similarly, the EuroQoL (EQ-5D) health-state survey is a validated, multi-attribute health-state classification system that indicates the burden of illness in terms of mobility, self-care, ability to complete normal activities, pain/discomfort, and anxiety or depression [18]. The menstrual impact questionnaire (MIQ) is especially useful for gauging the burden of menstrual bleeding a patient is experiencing at the time of questioning [19]. The aim of the present interim analysis was to analyze the 24-month efficacy and safety outcomes from an ongoing randomized controlled trial of laparoscopic ultrasound-guided RFVTA and laparoscopic ultrasound-guided myomectomy (ClinicalTrials.gov: NCT01750008) [15,20] for the treatment of symptomatic uterine fibroids.
2. Materials and methods An interim analysis was performed on data from an ongoing randomized, prospective, single-center, longitudinal trial of laparoscopic myomectomy and RFVTA that began November 1, 2012. Premenopausal patients who were menstruating, aged at least 18 years, with symptomatic fibroids, who desired uterine conservation, and were indicated for surgical intervention for their fibroid symptoms were referred to Tübingen University Hospital, Germany, for study enrollment between November 1, 2012 and June 30, 2013. Eligible patients had a uterine size of no more than 16 gestational weeks, no individual fibroid with a largest dimension of greater than 10 cm on transvaginal ultrasound, and a normal Papanicolaou test. Exclusion criteria included being at risk for, or known to have, significant intra-abdominal adhesions that would require extensive dissection to mobilize and view all surfaces of the uterus; pregnancy or lactation; having received any depot gonadotropin-releasing hormone agonist within the 3 months prior to the procedure; the presence of an implanted intrauterine or fallopian tube device at any time up to 10 days before treatment; known or suspected endometriosis or adenomyosis; pelvic inflammatory disease; gynecologic malignancy or pre-malignancy in the 5 years before enrollment; history of pelvic radiation; the presence of a non-uterine pelvic mass larger than 3 cm at its greatest diameter or the presence of a cervical fibroid; one or more intracavitary (Type 0 or Type 0/1) fibroids that would be better treated by hysteroscopic means; and not willing to be randomized for treatment. The study protocol required that patients provide written informed consent after agreeing that they understood the study purpose, the associated testing, procedures, and follow-up assessments, as well as the potential risks and benefits of participation. The Clinical Ethics Committee of Tübingen University Hospital in Tübingen, Germany approved the study, and all enrollees were treated at Tübingen University Hospital. Data were collected and monitored (CenTrial GmbH, Tübingen, Germany) in Tübingen and were analyzed by an independent biostatistics firm in the United States (Innovative Analytics Inc, Kalamazoo, Michigan USA). Patients were randomly allocated in a 1:1 ratio to receive either laparoscopic myomectomy or RFVTA. Randomization occurred as an intraoperative step after the surgeon mapped the patient’s uterus for the location, number, and types of fibroids using laparoscopic ultrasound. The use of laparoscopic ultrasound provided additional imaging information to the surgeon regarding the patient’s fibroids, regardless of their treatment assignment. After mapping, the operating room staff drew an envelope containing the patient’s computergenerated treatment assignment. Assignments were generated by an independent biostatistician in blocks of six or four. The surgeon and
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patient were masked to treatment assignment prior to the beginning of surgery. Patients assigned to undergo myomectomy were placed in the lithotomy position and underwent standard laparoscopic myomectomy [15]. If deep intramural fibroids or transmural fibroids not encroaching on the serosal borders were encountered, two-layer suturing was used. Although the excision of all fibroids was allowed per protocol, intramural fibroids 1.0–1.5 cm in diameter were not excised owing to the clinical standard of care at the study institution. The RFVTA treatment procedure and the methods for pretreatment tissue sampling for histopathology have been described in detail previously [15,20–23]. RFVTA treatment involved the use of a monopolar radiofrequency generator, a percutaneously placed handpiece incorporating an electrode at its distal tip with a deployable array, two large dispersive electrode pads, extension cables, and an activating foot pedal. Current was delivered to the small electrode tip and array; this facilitated the localization of ablative treatment to the fibroid tissue. The current was removed via large dispersive electrode pads that were placed on each patient’s thighs above the patella. The electrical current resulted in the oscillation of intracellular ions, generating resistive or frictional heating. The heat spread by conduction, decreasing rapidly with increasing distance from the electrode (1/d4) (Fig. 1A, B, and C). The current continued through the body to the dispersive electrode pads, where it returned to the source. The ablated tissue underwent coagulative necrosis and was naturally reabsorbed by the surrounding myometrium. The target ablation temperature was 100 °C and the required time at the target temperature was a function of the length of array deployment. An algorithm was used to define the deployment and time at 100 °C. Following the completion of the recommended ablation time the surgeon depressed the foot pedal, ending the ablation. The array was then withdrawn into the handpiece shaft, the probe was switched from ablation to coagulation mode, and the track was coagulated during handpiece withdrawal. Hemostasis was confirmed through laparoscopic viewing. Following the ablation of all fibroids, the pelvis was irrigated and inspected, the port sites were closed using intracutaneous sutures, and patients were discharged from the clinic on the same day. The primary outcome of the ongoing 5-year randomized controlled trial is the length of hospital stay. The secondary outcomes are patients’ responses to questionnaires. The analyses of patient hospitalization and perioperative outcomes have been described previously [15]. The present interim analysis of the study reports 24-month postoperative qualitative outcomes in terms of participants’ responses to questionnaires (UFS–QOL, EQ-5D, overall treatment effect survey, and the MIQ [16–19]), re-interventions for fibroid symptoms, and pregnancy outcomes. According to the study method, the participants will be followed for a total of 5 years. The calculation of the sample size has been described in detail previously [15] and was based on hospitalization times for patients in each group. Briefly, the null hypothesis was that the duration of hospitalization for patients who underwent the RFVTA procedure would be more than 10% longer than that experienced by patients who underwent laparoscopic myomectomy. The alternative hypothesis was that this would not be the case, resulting in a one-sided noninferiority test of RFVTA in comparison with laparoscopic myomectomy, with an alpha level of 0.025. Based on procedures in the USA (unpublished data), the null hypothesis would be rejected if the mean length of hospital stay for patients undergoing RFVTA was 7 ± 4 hours. The mean length of hospital stay for women undergoing laparoscopic myomectomy has been demonstrated to be approximately 15 ± 16 hours [24]. The pooled standard deviation of the difference in length of hospital stay between these two procedures is 11.7 hours, which is the square root of the mean of the estimated variances of the two procedures. The power yielded under these assumptions is 0.80, resulting in a necessary sample size of 50 participants (25 in each group).
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Fig. 1. Representative illustrations of the radiofrequency volumetric thermal ablation sequence. (a) At the beginning of treatment, the tissue temperature along the electrodes begins to increase rapidly. (b) Approximately halfway through treatment, the tissue closest to the electrodes reaches the target temperature while a thermal front 55 °C in temperature expands. (c) At the end of the treatment, the ablation volume reaches its maximum size and the outer boundary has reached thermal equilibrium with the surrounding tissue. Abbreviation: RFVTA, radiofrequency volumetric thermal ablation.
Data were analyzed on a per-protocol basis. Continuous variables for secondary-outcome analyses were summarized using descriptive statistics, and categorical variables were expressed as frequencies and percentages. The precision of the questionnaire response outcomes was summarized using 95% confidence intervals (95% CIs). The two groups were compared using a Student t test unless noted otherwise. P b 0.05 was considered statistically significant. All analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC, USA). 3. Results A total of 51 patients were enrolled in the present study; 26 were randomized to undergo RFVTA treatment and 25 were allocated to the laparoscopic myomectomy group (Fig. 2). At 24 months, 21 patients in the RFVTA group and 22 patients in the laparoscopic myomectomy were available for analysis. The baseline demographics and intraoperative fibroid characteristics are detailed in table 1. Participants in both groups were similar in terms of their height, weight, and ethnicity; however, participants allocated to the RFVTA group were found to be significantly older (P = 0.006). Intraoperative mapping revealed the location and size of fibroids in patients in each group, with a greater number of fibroids found in patients in the RFVTA group compared with in patients in the myomectomy group (72 vs 61). Of the fibroids
mapped, 71 (99%) were accessible and were treated in the RFVTA group compared with 49 (80%) fibroids that were accessible for excision using laparoscopic myomectomy [15]. Symptoms experienced by participants at baseline and at 24 months are detailed in table 2. Participants were asked at both timepoints whether they had experienced each symptom; all responses were binary (yes or no), with the severity of each symptom not recorded. There were no significant differences observed between the treatment groups in terms of the symptoms experienced at baseline and at 24-month follow-up. Changes in mean transformed UFS–QOL scores from baseline to 24-month follow-up are presented in Fig. 3a and b, respectively. Significant improvements in symptom severity from baseline (indicated by decreasing values) were recorded in the RFVTA (− 54% [95% CI − 72.3 to − 34.8]; P b 0.001) and laparoscopic myomectomy (−45% [95% CI −68.9 to −20.9]; P = 0.001) groups. An improvement from baseline (indicated by increasing values) in health-related qualityof-life scores were reported for the laparoscopic myomectomy group (21% [95% CI 1.1 to 40.5]; P = 0.040); a non-significant improvement was observed in the RFVTA group (11% [95% CI − 1.6 to 23.0]; P = 0.083). As can be observed from Fig. 3a and b, at baseline, participants in the laparoscopic myomectomy group had higher symptom severity and lower quality of life than patients in the RFVTA group.
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Assessed for eligibility (n=110)
Excluded (n=54) Did not meet inclusion criteria (n=54) Intraoperative mapping (n=56)
Excluded (n=5) Patient had a large fibroid (>10 cm) and an intrauterine device implanted (n=1) Patient had many fibroids that would have necessitated a hysterectomy if assigned to the laparoscopic myomectomy group (n=2) Patient had no fibroids (n=1) Patient had only 1 large pedunculated fibroid (>10 cm) (n=1)
Randomized (n=51)
Allocated to RFVTA (n=26)
Allocated to laparoscopic myomectomy (n=25)
Excluded (n=5) Did not receive allocated intervention owing to unrelated emergency in the operating room (n=1) Missing data (n=1) Withdrew owing to hysterectomy (n=2) Withdrew to undergo myomectomy (n=1)
Excluded (n=3) Missing data (n=3)
Analyzed at 24 months (n=21)
Analyzed at 24 months (n=22)
Fig. 2. Flow of participants through the study.
Table 1 Baseline characteristics and intraoperative fibroid characteristics following treatment.a Variable
RFVTA group (n = 25)
Laparoscopic myomectomy group (n = 25)
Age, y Height, cm Weight, kg Ethnicity White Intraoperative fibroid characteristicsb Total fibroids No. of fibroids per patient Fibroid type Submucosal Transmural Intramural Intramural fibroid abutting the endometrium Subserosal Pedunculated subserosal
40.0 ± 7.8 166.0 ± 5.8 62.4 ± 8.9
34.4 ± 6.1 165.2 ± 5.8 64.9 ± 13.5
25 (100)
25 (100)
72 2.9 ± 2.6 (2; 1–9)
61 2.4 ± 1.6 (2; 1–6)
0 0 33 (46) 2 (3)
2 (3) 3 (5) 26 (43) 0
37 (51) 0
34 (56) 2 (3)
Abbreviation: RFVTA, radiofrequency volumetric thermal ablation. a Values are given as mean ± SD, number (percentage), number, or mean ± SD (median; range), unless indicated otherwise. b Intraoperative fibroid characteristics were evaluated by laparoscopic ultrasound mapping of the uterus prior to ablation/excision.
Participants’ responses to the EQ-5D questionnaire demonstrated improvements in mean scores between baseline and 6-month followup for the RFVTA group (81.7 ± 11.2 vs 88.9 ± 13.7) and the laparoscopic myomectomy group (72.3 ± 18.2 vs 85.3 ± 14.1). However, lower 12-month EQ-5D scores were reported by both the RFVTA (85.5 ± 14.1) and laparoscopic myomectomy (82.9 ± 16.1) groups. At 24 months, the EQ-5D score had improved slightly in the RFVTA group (86.4 ± 9.7) and had decreased further in the laparoscopic myomectomy group (79.3 ± 25.2). In the overall treatment-effect survey, participants were asked to compare their symptoms at 24 months with their symptoms at 12 months. In total, 21 patients responded in each group; 8 (38%) patients in the RFVTA group reported that their fibroid symptoms were better, 12 (57%) reported that they were about the same, and 1 (5%) reported that their symptoms were worse. In the laparoscopic myomectomy group, 5 (24%) participants reported that their symptoms had improved and 16 (76%) reported that their symptoms had remained the same. In terms of treatment satisfaction, 19 (90%) and 21 (100%) patients in the RFVTA and laparoscopic myomectomy groups, respectively, were satisfied with the treatment they received. Among the RFVTA and laparoscopic myomectomy groups, 19 (90%) and 20 (95%) patients, respectively, reported that they would recommend the treatment they received to a friend who had uterine fibroids. Finally, in response to the overall treatment effect survey, 14 (67%) and 4
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Table 2 Symptoms experienced by patients at enrollment and 24 months.a Symptom
Baseline analysis
Heavy menstrual bleeding Pelvic discomfort/pain Increased abdominal girth Frequent urination Urinary retention Dysmenorrhea Dyspareunia Backache Sleep disturbances Uterine pain Localized pain Other
24-month analysis
RFVTA group (n = 25)
Laparoscopic myomectomy group (n = 25)
P value
RFVTA group (n = 21)
Laparoscopic myomectomy group (n = 22)
21 (84) 10 (40) 7 (28) 13 (52) 4 (16) 7 (28) 3 (12) 7 (28) 0 3 (12) 5 (20) 0
18 (72) 11 (44) 5 (20) 9 (36) 8 (32) 8 (32) 6 (24) 6 (24) 1 (4) 1 (4) 5 (20) 1 (4)
0.31b 0.77b 0.51b 0.25b 0.19b 0.78b 0.46c 0.75b N0.99c 0.61c N0.99b N0.99c
6 (29) 2 (10) 3 (14) 4 (19) 0 8 (38) 2 (10) 3 (14) 2 (10) 5 (24) 2 (10) 0
3 (14) 5 (23) 1 (5) 2 (9) 0 7 (32) 3 (14) 8 (36) 2 (9) 3 (14) 1 (5) 0
P value 0.28c 0.41c 0.35c 0.41c 0.67b N0.99c 0.10b N0.99c 0.46c 0.61c
Abbreviation: RFVTA, radiofrequency volumetric thermal ablation. a Values are given as number (percentage) unless indicated otherwise. b χ2 test. c Fisher exact test.
(19%) participants from the RFVTA group described their treatment as moderately effective and very effective, respectively, in eliminating their symptoms. In the laparoscopic myomectomy group, 5 (24%) and 13 (62%) patients reported treatment to be moderately effective and very effective, respectively. The MIQ survey was used to assess participants’ perceptions of menstrual bleeding from each patient’s previous period to the point the survey was conducted. Data from the MIQ survey were available for 18 patients in the RFVTA group; 7 (39%) described their blood loss
a 100
Mean Transformed Symptom Severity Scores
90 80 70 60 50
41.8
40
30
27.9
38.9
30 20
25.3
10
21.9
24.7
22.3
26 16
0 Baseline
3 mo
RFVTA
6 mo
12 mo
24 mo
Laparoscopic Myomectomy
b Mean Transformed Health-Related Quality-of-Life Scores
100 85.2
90 77.1
89.4
87
77.9
80 70 60
77.7
80.3
85.6
83
70.2
50 40 30 20 10 0 Baseline
as, “better” than during their previous period and 11 (61%) described the blood loss as, “about the same”. Among the 20 patients in the laparoscopic myomectomy group who responded to the MIQ survey, 4 (20%) described their blood loss as, “better”, 13 (65%) thought it was, “about the same”, and 3 (15%) described it as, “worse”. In the RFVTA group, one serious complication occurred in a participant who presented with hypermenorrhea shortly after the RFVTA procedure. A physician not affiliated with the present study performed a dilation and curettage procedure; this resulted in uterine perforation and subsequent hysterectomy. Another patient underwent a preemptive hysterectomy after a biopsy demonstrated the presence of a smooth muscle tumor of uncertain malignant potential. A histopathology report describing the uterus and fibroids revealed no atypia and confirmed an absence of malignancy. A third participant in the RFVTA group, who was asymptomatic at 6 months and who stated a desire to become pregnant in the future, sought a myomectomy procedure after a 4-cm fibroid was observed during an ultrasound examination. In the laparoscopic myomectomy group, one patient experienced a hematoma at the trocar site. No participants in the laparoscopic myomectomy group sought surgical re-intervention owing to fibroid symptoms. No other adverse events occurred among the study participants. In the RFVTA group, three patients conceived; two pregnancies concluded with vaginal deliveries of healthy neonates and one pregnancy resulted in a cesarean delivery of a healthy neonate. In the laparoscopic myomectomy group, six conceptions were experienced by a total of five patients. Of these, one induced abortion, two vaginal deliveries, and two cesarean deliveries were recorded, with one pregnancy ongoing at the time of writing.
3 mo
RFVTA
6 mo
12 mo
24 mo
Laparoscopic Myomectomy
Fig. 3. Uterine fibroid symptom and quality-of-life scores between study initiation and 24month follow-up. (a) Symptom severity scores. (b) Health-related quality-of-life scores. Abbreviation: RFVTA, radiofrequency volumetric thermal ablation.
4. Discussion The present study demonstrated benefits in terms of safety, symptom reduction, and improvements in quality of life in patients at 24 months after treatment for symptomatic uterine fibroids with RFVTA and laparoscopic myomectomy. The evaluations included in the present study were based on patient responses to validated questionnaires. The analyzed data from patient responses to these questionnaires suggests long-term utility of both RFVTA and laparoscopic myomectomy as treatment options for patients with symptomatic uterine fibroids who desire uterine conservation. Although, three patients in the RFVTA group sought further surgical interventions, none of these was related to fibroid symptoms. Rather, one decision to undergo hysterectomy was based on the histopathological diagnosis of a smooth muscle tumor of uncertain malignant
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potential, which could not be confirmed in the final specimen of the removed uterus. Another patient required a hysterectomy following the perforation of the uterus during a dilation and curettage procedure. Finally, a patient who wished to become pregnant sought treatment to excise a newly discovered or re-growing 4-cm fibroid, which was diagnosed using ultrasound and was not clinically symptomatic. Guido et al. reported 2-year clinical outcomes of a prospective multicenter trial of RFVTA conducted in the USA, Guatemala, and Mexico [25]. Although this study provided strong evidence for the use of RFVTA in the treatment of symptomatic fibroids, it lacked the strength of a comparative randomized trial. That the participant population in the present study was racially homogenous can be considered to be both a strength and a limitation. A racially homogenous group provides a control for outcomes based on ethnicity but does not provide the heterogeneity observed in real-world populations of individuals with symptomatic fibroids. Another limitation is the size of the study. Although it was powered for the primary outcome of hospitalization time, it was not sufficiently powered to perform a statistical analysis of the secondary outcomes (the various questionnaire responses) described in the present interim analysis. However, the outcomes recorded in the present study are comparable those observed in a larger prospective study of RFVTA [25]. In summary, 24-month data from the present interim analysis of a randomized controlled trial suggest equivalence in safety and patientreported outcomes of RFVTA and laparoscopic myomectomy. Treatment with RFVTA could be considered in the treatment of patients with symptomatic uterine fibroids who desire uterine conservation. Acknowledgments Halt Medical Inc (Brentwood, California USA) provided materials and funding for the procedures and for independent third-party data monitoring, statistical analysis, and editorial support. Conflict of Interest Halt Medical, Inc. (Brentwood, California USA) sponsored the study and provided materials and funding for the described procedures and for independent third-party data monitoring, statistical analysis, and editorial support. K. B. I. is a member of Halt’s Clinical Events Committee. The authors have no other conflicts of interest. References [1] Theodoreson MD, Chohan BC, McAloon CJ, Sandhu A, Lancaster CJ, Yusuf S, et al. Same-day cardiac catheter ablation is safe and cost-effective: Experience from a UK tertiary center. Heart Rhythm 2015;12(8):1756–61. [2] Strickland BA, Jimenez-Shahed J, Jankovic J, Viswanathan A. Radiofrequency lesioning through deep brain stimulation electrodes: a pilot study of lesion geometry and temperature characteristics. J Clin Neurosci 2013;20(12):1709–12. [3] Eckmann MS, Martinez MA, Lindauer S, Khan A, Ramamurthy S. Radiofrequency ablation near the bone-muscle interface alters soft tissue lesion dimensions. Reg Anesth Pain Med 2015;40(3):270–5.
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