Is helium thermal coagulator therapy for the treatment of women with minimal to moderate endometriosis cost-effective? A prospective randomised controlled trial

This study compared the cost and time in- volved of helium thermal coagulator (HTC) treatment with medical therapy using gonadotrophin-releasing hormone analogues in women with minimal to moderate endometriosis. In a prospective randomised controlled trial, 35 women with history of pain were, upon confir- mation of minimal to moderate endometriosis at diag- nostic laparoscopy, randomised to immediate surgical or medical treatment. They were asked to complete ana- logue pain score sheets, and their symptoms were re- viewed before treatment and at 3, 6, and 12 months after treatment. The cost of the medical or surgical treatment was evaluated from the time of diagnosis to the time of cure or symptom relief. The average cost per Helica probe is £111.81 with the machine on free loan, and the total cost of a 6-month course of injectable Zoladex with add-back therapy is £811.92. The costs involved in the two treatment modalities were analysed using the Mann–Whitney test; a p-value <0.05 was considered significant. In the medical group, three women out of 18 were symptom-free, 11 required surgical treatment of endometriosis, one had a laparoscopically-assisted vaginal hysterectomy, and three became pregnant before their final reviews. In the surgical group, nine women were symptom-free at the end of 12 months, four re- quired Zoladex therapy, one required oral contraceptive pills, and three required repeat surgical treatment. The average cost per patient in the surgical arm was £323.29 and in the medical arm was £918.12 ( p<0.0001). Mean operating times in the surgical and medical arms were 32.35 min and 20.83 min, respectively. This suggests that when facilities and expertise are available, it is better to see and treat mild to moderate endometriosis. There were no surgical complications in our series. Surgical treatment with HTC therapy is safe and is a cheaper and more effective therapy. This is the first study that has looked at the cost-effectiveness of HTC therapy in managing mild to moderate endometriosis.

Endometriosis Æ Helium thermal coagulator Æ Cost-effectiveness

Endometriosis, characterised histologically by the pres- ence and growth of endometrial glands and stroma outside the uterine cavity, is a chronic recurring disease commonly encountered in women of reproductive age [1]. It is found in 71% of laparoscopies for pelvic pain and in 84% of cases in which pain and infertility are complaints [ 2]. Its frequent occurrence seen at laparos- copy in asymptomatic women has led to the suggestion that this may be a normal physiological process that becomes a disease only when the patient is symptomatic [3]. However, once symptomatic, it can be an extremely debilitating condition, causing chronic pelvic pain, dysmenorrhoea, dyspareunia, and infertility, and its management is often frustrating for both the patient and the gynaecologist [4]. The diagnosis of endometriosis can be elusive and confirmed only by visualisation, i.e. lap- aroscopy, which is considered to be the gold standard for diagnosing the disease [ 5]. Treatment for the condi- tion is either medical or surgical. S. Lalchandani ( &) Department of Obstetrics and Gynaecology, St. Munchin’s Regional Maternity Hospital, Ennis Road, Limerick, Republic of Ireland E-mail: [email protected] Tel.: +353-61-483148 Fax: +353-61-482731 A. Baxter Department of Obstetrics and Gynaecology, Jessop Hospital for Women, Leavy Greave Road, Sheffield, South Yorkshire, S3 7RE, UK E-mail: [email protected] K. Phillips Department of Obstetrics and Gynaecology, Castle Hill Hospital, Castle Road, Cottingham, East Yorkshire, HU16 5JQ, UK E-mail: [email protected] Gynecol Surg (2005) 2: 255–258 DOI 10.1007/s10397-005-0123-7 Several medical strategies are available for treating endometriosis. These include combined oral contracep- tive pills, progestogens, Danazol, gestrinone, and gonadotrophin-releasing hormone analogue (GnRH-a) with or without add-back therapy. Of these, the two main drugs used are GnRH-a and, until recently, Danazol. Both have been shown to decrease symptoms when compared with placebo [ 6, 7]. A large Cochrane metaanalysis of 26 randomised controlled trials con- firmed GnRH-a to be effective in relieving pain [ 8, 9]. However, long-term follow-up studies show a high recurrence rate following medical treatment [ 10, 11]. Surgical treatment for endometriosis is now usually performed laparoscopically. By this minimally invasive method, the endometriotic lesions are either excised or ablated using laser, monopolar, or bipolar diathermy or newer methods such as helium thermal coagulator (HTC) therapy. Although both medical and surgical therapy have been shown to satisfactorily treat endometriosis, no published studies have compared the cost or the operating time involved in the two treatment modalities, considering that a diagnostic laparoscopy will be involved in making a diagnosis before commencing medical therapy. Direct and indirect medical costs associated with this condition are estimated to be more than $3 billion in the United States annually before factoring in the costs of diagnostic testing [12]. Thus, it is important to make an appropriate choice for an optimal treatment.

All women presenting to the gynaecology outpatient clinic with a history of pelvic pain, dysmenorrhoea, dy- spareunia, and dyschesia suggestive of endometriosis or who had previously been diagnosed as having the disease were asked to enter the trial. All women who were less than 16 years of age, pregnant, or subfertile were ex- cluded from the study. Power studies were performed prior to the study, and 25 patients were required in each arm. However, only one in three women who were asked to enter the trial agreed because two in three wished to have surgical therapy if they were diagnosed with endo- metriosis. A total of 35 women between September 1999 and March 2001 were recruited for this study. All the women with suspected endometriosis were subjected to a diagnostic laparoscopy as a day-case procedure, and any endometriosis found was staged according to the American Fertility Society classification [13]. Randomisation into either HTC or GnRH-a ther- apy was done at the time of diagnostic laparoscopy. All women were given visual analogue pain scores preop- eratively and 3, 6, and 12 months postoperatively, and their symptoms were taken into consideration. Women in the surgical arm had either ablation or excision of all endometriotic lesions with HTC therapy. Women who had diagnostic laparoscopy had only a proper staging of the disease. All women in the medical arm were given six injec- tions of GnRH-a with add-back hormone replacement therapy (HRT) every 28 days. These women were seen in the outpatient clinic 3, 6, and 12 months after the end of treatment. Mechanism of action of HTC therapy and GnRH-a HTC generator An HTC generator is a device capable of producing low operating powers. It has a high-output impedance circuit that limits the flow of energy. It operates at power levels lower than 5 W but still produces a satisfactory caute- rising effect. Combining helium within the Helica gen- erator produces an ionised plasma beam/corona-type flame at very low levels of energy. The energy is deliv- ered to the target tissue via a probe. The discharged beam has a high molecular temperature typically of the order of 800 /C176C; the beam takes place within the plasma provided by the flowing inert gas (helium). The power emission can be regulated to emit levels from 1 to 33 W. For coagulation purposes only, the discharged plasma on 4-s bursts will achieve a maximum level of tissue penetration of 1.1 mm. In our trial, the same coagulat- ing probe was also used for cutting (energy can be concentrated by the probe with tension on the tissues). However, we are aware that the company has manu- factured probes with a coagulating and cutting compo- nent in the same probe. Our hospital negotiated with the company to have the machine on loan and buy more than 10 probes per month. Various financial arrangements can be made with the company. In the free loan option, the machine is free, and the average cost per probe is £111.81. In the machine purchase option, the machine costs £17,192, and the average cost per probe is £63.63. One probe is used per patient. GnRH-a therapy GnRH-a acts continuously on the GnRH receptors, resulting in the downregulation and desensitisation of the pituitary gonadotroph. This results in the chronic suppression of gonadotrophin secretion, luteinising hormone, and follicle-stimulating hormone and the cessation of ovarian activity and, consequently, a de- crease in circulating oestradiol levels, creating a pseudomenopausal state. This causes predictable side effects, namely those symptoms experienced by women at menopause. The other problem associated with a 6- month course of GnRH-a is a reduction in vertebral bone mineral density (BMD) of approximately 3–4%. This concern has therefore limited its use to a 6-month duration [ 8, 9]. In a multicentre randomised double- blinded trial using a 12-month course of GnRH alone, women experienced a BMD loss in the lumber spine of 3.2% at 6 months and 6.3% at 12 months and com- 256 plained of hot flashes, which were dramatically sup- pressed in the add-back HRT groups, whereas women receiving add-back HRT for 12 months had a signifi- cantly negligible (<1%) BMD loss [ 14]. Main outcome measures and statistics The main outcome measures were the costs and oper- ating times involved in the two treatment modalities. Analysis of costs was performed using the Mann– Whitney test. Analysis was undertaken using the Sta- tistics Package for Social Sciences (SPSS) for Windows. A p-value <0.05 was considered significant.

A total of 35 women were included in the study. Eigh- teen women received medical and 17 received surgical treatment of endometriosis. Their mean age was 32.8 years (range 20–45 years), and mean parity was 1 (range 1–3). The mean revised American Fertility Soci- ety scores were 5 (range 2–12) for the medical group and 6 (range 2–12) for the surgical group. All 35 women underwent diagnostic laparoscopy before being randomised into the two treatment modalities. Therefore, the basic cost incurred for diag- nostic laparoscopy was the same for all patients. There were no surgical complications reported in this series. All of the women were reviewed at 3, 6, and 12 months following their treatment. In the medical group, three women out of 18 were symptom-free (17%), 11 required surgical treatment of endometriosis, one had a laparoscopically-assisted vaginal hysterectomy, and three became pregnant before their final reviews. In the surgical group, nine women out of 17 were symptom-free at the end of 12 months (53%), four required Zoladex therapy, one required oral contracep- tive pills, and three required repeat surgical treatment. The costs involved were significantly higher in the medical group (Tables 1, 2; Mann–Whitney test p-value of 0.0001). An extra 11.5 min was required to surgically treat mild to moderate endometriosis in 17 patients who were allocated to the surgical group (Table 3). Analysis of the pain scores (using the Wilcoxon nonparametric test) and of the success rates of the two treatment modalities (using the chi-square test) will be discussed in our second paper comparing the effective- ness of medical versus surgical treatment.

Women with endometriosis have a symptom complex of pelvic pain, dysmenorrhoea, dyspareunia, and dyschezia, which can cause profound ill health and reduced quality of life. Various studies have looked at different medical and surgical treatment options. Additional complexity has been added to the healthcare decision-making pro- cess by the socioeconomic constraints of the industry and by a population that is increasingly educated about healthcare. As a result, decisions balanced on the basis of outcomes and economic realities are needed. This mod- elling of surgical versus medical treatment costs for chronic pelvic pain and endometriosis factors in the large number of women with chronic pelvic pain, direct and indirect costs of the condition, and the clinical benefits, projected costs, and savings of the therapies. This process of calculation becomes an aid for decision-making in the current healthcare system [ 15]. There has been debate about 3- versus 6-month GnRH-a therapy. Heinrichs and Henzl have suggested that GnRH-a administration for 3 months is a cost- effective approach. In their series, reduction in endo- metriosis symptoms and signs was similar at the end of 3 and 6 months [ 16]. Notably, various side effects are associated with GnRH-a therapy. Winkel suggested that medical treatment is cheaper and safer than surgical treatment [ 17]. In our study group, surgical treatment with HTC appeared to be a safer, cheaper, and more effective therapy. There were no surgical complications in our series, and patients had prompt relief of symptoms without the possible side effects of medical treatment. In our series, 12 out of 18 Table 1 Treatment outcomes in the two groups Group Further treatment Number of cases Cost per patient Medical None 6 £811.92 Medical Surgical 11 £923.73 Medical Hysterectomy 1 £1,493.63 Surgical None 9 £111.81 Surgical Medical 4 £923.73 Surgical Oral contraceptive 1 £123.81 Surgical Surgical (repeat) 3 £223.62 Table 2 Cost Mean total cost per patient ( p<0.0001) Surgical arm £323.29 Medical arm £918.12 Table 3 Operating time Mean operating time Surgical arm 32.35 min (range 20–50) Medical arm (diagnostic laparoscopy) 20.83 min (range 15–35) Difference 11.52 min Cost Injectable Zoladex (goserelin) 3.6 mg £122.27 Livial (tibolone; add-back), 28-pack £13.05 Total cost for 6 months £811.92 257 patients in the medical group underwent subsequent surgical treatment, adding to the cost of already expensive treatment. Apart from the cost-effectiveness of surgical treat- ment, another important point shown in our study is that by spending only an extra 11.5 min in the operating theatre, 53% of the patients with minimal to moderate endometriosis were successfully treated. To our knowledge, this is the first study that has looked at the cost-effectiveness of HTC therapy in managing mild to moderate endometriosis.

The authors gratefully acknowledge the help of Mr. Stephen Lindow.

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