Aetna considers microwave thermotherapy (also known as focused microwave thermotherapy and focused microwave phase array thermotherapy) experimental and investigational for the treatment of the following indications (not an all-inclusive list) because of insufficient evidence of its effectiveness for these indications.
Recent clinical investigations have examined the feasibility of thermotherapy that uses focused microwaves for the treatment of primary breast cancer, based on the theory that heat could destroy microscopic carcinoma cells in the breast and reduce cancer recurrence. Heating the tumor and killing a large percentage or all of the tumor cells before surgery may improve the margins and reduce the possibility of inadvertently seeding viable cancer cells during the surgical procedure, thus reducing local recurrences in the breast. In addition, if a sufficient thermal dose is applied, thermotherapy treatment of early-stage breast cancer may destroy the tumor and completely eliminate the need for any further breast surgery or radiation therapy.
Gardner et al (2002) reported on the results of a pilot study of focused microwave phased array thermotherapy in the treatment of 10 patients with primary breast carcinomas beneath the skin ranging from 1 to 8 cm in maximum clinical size. After focused microwave phased array treatment, all patients underwent mastectomy. Eight of 10 patients had a significant tumor response (on the basis of tumor shrinkage measured by ultrasound) or tumor cell kill (on the basis of necrosis and aptosis measurements).
Singletary (2002) commented on the study by Gardner et al (2002) in an accompanying editorial: "These interesting preliminary results should provide needed background information for the implementation of a well-designed clinical trial to definitively test the usefulness of this new approach …. Nonetheless, as surgical excision with negative margins now offers excellent results, surgeons should be cautious about adopting these technologies outside the arena of clinical trials".
Food and Drug Administration-approved multi-center phase II studies of focused microwave phased array thermotherapy in larger groups of patients are currently ongoing (Gardner et al, 2002). In a phase II non-randomized clinical trial on dose-escalation study of microwave treatment for the treatment of early stage breast cancer (n = 25), Vargas et al (2004) concluded that thermotherapy causes tumor necrosis and can be performed safely with minimal morbidity. The degree of tumor necrosis is a function of the thermal dose. Future studies will evaluate the impact of high doses of thermotherapy on margin status and complete tumor ablation. In an editorial that accompanied the paper by Vargus and colleagues, Copeland and Bland (2004) stated that “current enthusiasm for minimally invasive techniques must be measured against the gold standard results available from segmental mastectomy .... These techniques should not replace the tried and proven effective treatment of small cancers of the breast with segmental mastectomy, sentinel lymph node biopsy, and intact breast radiotherapy until these newer approaches have been thoroughly studie ....”.
Agnese and Burak (2005) stated that a number of minimally invasive techniques for the treatment of early stage breast cancers are being investigated. Ablative therapies such as laser ablation, focused ultrasound, microwave ablation, radiofrequency ablation, and cryoablation have been described. All of these techniques have shown promise in the treatment of small cancers of the breast; however, additional research is needed to determine the efficacy of these techniques when they are used as the sole therapy and to determine the long-term local recurrence rates and survival associated with these treatment strategies. This is in agreement with the observations of Houston and Simmons (2005) who noted that “it is cautiously optimistic that these therapies can be used as a routine adjunct in the treatment of selected breast cancers. The challenge will lie in the ability to identify multifocal disease and in situ carcinoma as well as to ensure complete and effective eradication of the breast cancer”.
In a review on minimally invasive ablative therapies for invasive breast carcinomas, van Esser and colleagues (2007) concluded that all studies on minimally invasive ablative modalities published so far show that these techniques are feasible and safe. However, at this stage only T1 tumors should be ablated in a clinical trial setting; it is unclear which of the modalities is most suitable.
Dooley et al (2010) stated that pre-operative focused microwave thermotherapy (FMT) is a promising method for targeted treatment of breast cancer. These researchers reviewed results of 4 multi-institutional clinical studies of pre-operative FMT for treating invasive carcinomas in the intact breast. Externally applied wide-field adaptive phased-array FMT were investigated both as a pre-operative heat-alone ablation treatment and as a combination treatment with pre-operative anthracycline-based chemotherapy for breast tumors ranging in ultrasound-measured size from 0.8 to 7.8 cm. In phase I, 8 of 10 (80 %) patients receiving a single low-dose FMT prior to receiving mastectomy had a partial tumor response quantified by either ultrasound measurements of tumor volume reduction or by pathologic cell kill. In phase II, the FMT thermal dose was increased to establish a threshold dose to induce 100 % pathologic tumor cell kill for invasive carcinomas prior to breast-conserving surgery (BCS). In a randomized study for patients with early-stage invasive breast cancer, of those patients receiving pre-operative FMT at ablative temperatures, 0 of 34 (0 %) patients had positive tumor margins, whereas positive margins occurred in 4 of 41 (9.8 %) of patients receiving BCS alone (p = 0.13). In a randomized study for patients with large tumors, based on ultrasound measurements the median tumor volume reduction was 88.4 % (n = 14) for patients receiving FMT and neoadjuvant chemotherapy, compared with 58.8 % (n = 10) reduction in the neoadjuvant chemotherapy-alone arm (p = 0.048). The authors concluded that wide-field adaptive phased-array FMT can be safely administered in a pre-operative setting, and data from randomized studies suggest both a reduction in positive tumor margins as a heat-alone treatment for early-stage breast cancer and a reduction in tumor volume when used in combination with anthracycline-based chemotherapy for patients with large breast cancer tumors. They stated that larger randomized studies are needed to verify these conclusions.
Zhao and Wu (2010) performed a systematic review on minimally-invasive thermal ablation of early-stage breast cancer. A broad search was conducted in Pubmed, Embase and the Cochrane databases between January 1990 and December 2009. Clinical results of the relevant articles were collected and analyzed. The analyzed studies were almost all feasibility or pilot studies using different energy sources, patients, tumor characteristics and ablation settings. They were conducted in research settings for the assessment of technical safety and feasibility, and none of those was used alone in clinical practice. Despite many methodological differences, complete tumor ablation could be achieved in 76 to 100 % of breast cancer patients treated with radiofrequency ablation, 13 to 76 % in laser ablation, 0 to 8% in microwave ablation, 36 to 83 % in cryoablation, and 20 to 100 % in high-intensity focused ultrasound ablation. The authors concluded that minimally-invasive thermal ablation is a promising new tool for local destruction of small carcinomas of the breast. Moreover, they stated that large randomized control studies are needed to evaluate the long-term advantages of minimally-invasive thermal ablation techniques compared to the current breast conserving therapies.
Lammers et al (2011) stated that due to the suboptimal clinical outcomes of current therapies for non-muscle-invasive bladder cancer (NMIBC), the search for better therapeutic options continues. One option is chemo-hyperthermia (C-HT): microwave-induced hyperthermia (MwHT) with intravesical chemotherapy (ICT), typically mitomycin C (MMC). During the last 15 year, the combined regimen has been tested in different clinical settings. These investigators performed a systematic review to evaluate the efficacy of C-HT as a treatment for NMIBC. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. An electronic search of the Medline, Embase, Cochrane Library, CancerLit, and ClinicalTrials.gov databases was undertaken. Relevant conference abstracts and urology journals were also searched manually. Two reviewers independently reviewed candidate studies for eligibility and abstracted data from studies that met inclusion criteria. The primary end-point was time to recurrence. Secondary end-points included time to progression, bladder preservation rate, and adverse event (AE) rate. A total of 22 studies met inclusion criteria and underwent data extraction. When possible, data were combined using random effects meta-analytic techniques. Recurrence was seen 59 % less after C-HT than after MMC alone. Due to short follow-up, no conclusions can be drawn about time to recurrence and progression. The overall bladder preservation rate after C-HT was 87.6 %. This rate appeared higher than after MMC alone, but valid comparison studies were lacking. Adverse events were higher with C-HT than with MMC alone, but this difference was not statistically significant. The authors concluded that published data suggested a 59 % relative reduction in NMIBC recurrence when C-HT is compared with MMC alone; C-HT also appeared to improve bladder preservation rate. However, due to a limited number of randomized controlled trials (RCTs) and to heterogeneity in study design, definitive conclusions cannot be drawn. They stated that in the future, C-HT may become standard therapy for high-risk patients with recurrent tumors, for patients who are unsuitable for radical cystectomy, and in cases for which bacillus Calmette-Guerin (BCG) treatment is contraindicated.
Colombo and Moschini (2013) provided an updated review concerning the role of combined regimen (CT) based on MwHT (CT-MwHT) with ICT as a treatment for NMIBC. The review process followed the PRISMA guidelines. An electronic search of the Medline, Embase, Cochrane Library, CancerLit, and ClinicalTrials.gov databases was undertaken. Relevant conference abstracts and urology journals were also included. The primary end-point was the time to recurrence. Secondary end-points included time to progression, bladder preservation rate, and AE rate. A total of 24 studies met inclusion criteria and underwent data extraction. When feasible, data were combined using random-effects meta-analytic techniques. Recurrence was seen 59 % less after CT-MwHT than after MMC alone, however, due to the short follow-up, no definitive conclusions can be drawn about the impact on the time to recurrence and progression. The overall bladder preservation rate after CT-MwHT was 87.6 %. This rate appeared higher than after MMC alone, but valid comparison studies could not be drawn due to the absence of RCTs in neo-adjuvant settings. Adverse events were higher with CT-MwHT than with MMC alone, but this difference was not statistically significant. The authors concluded that published data suggested that recurrence rates for chemo-hyperthermia are substantially reduced compared with chemotherapy alone in adjuvant settings. Patients with refractory disease fared worse than those being treated with chemo-hyperthermia for their first tumor. Progression rates to muscle-invasive disease were markedly lower after combination treatment than after chemotherapy alone, with very high rates of bladder preservation. Tolerability was good, with few drop-outs in the clinical trials. The authors concluded that these findings support CT-MwHT in the future as a standard procedure for high-risk recurrent patients, for subjects in whom the treatment with BCG is contraindicated, and those unsuitable for radical cystectomy.
The 2013 update of the European Association of Urology’s guidelines on “Non-muscle-invasive urothelial carcinoma of the bladder” (Babjuk et al, 2013) did not mention microwave thermotherapy as a therapeutic option.
Furthermore, National Comprehensive Cancer Network (NCCN)’s clinical practice guideline on “Bladder cancer” (Version 2.2015) does not mention microwave thermotherapy as a therapeutic option.
Wasser and Dupuy (2008) noted that recent years have witnessed the refinement and significant growth of several new, minimally invasive approaches for the non-surgical treatment of primary lung malignancies. For select patients, these technologies offer an attractive treatment option given their availability in the outpatient setting and low associated morbidity and mortality. Microwave ablation (MWA) represents the most recent addition to the growing armamentarium of available ablative technologies. Administered in a manner similar to radiofrequency ablation, the lung tumor is localized under imaging guidance, and a microwave antenna is placed directly into the tumor bed. In contrast to existing thermos-ablative technologies, however, microwave treatment offers several key theoretical advantages. These include consistently higher intra-tumoral temperatures, larger ablation volumes, reduced treatment times, and improved convection profile. The authors concluded that as a nascent technology, efficacy and outcomes data for MWA of pulmonary malignancies remained relatively lacking compared with other thermos-ablative techniques; however, early trials have demonstrated promising results. It is hoped that further refinements in the clinical application of this technology will continue to improve the care of patients with lung cancer.
In a retrospective study, Carrafiello et al (2010) evaluated the feasibility, safety and effectiveness of MWA in 9 patients with unresectable lung tumor. Ten lesions were treated in 10 ablation sessions in 9 patients. The treatments were performed with a microwave generator with 45 W and 915 MHz connected to a 14.5-gauge antenna for 10 mins. Antenna placement was performed with computed tomography (CT) fluoroscopy guidance or XperGuide. All patients underwent CT follow-up at 1, 3 and 6 months from the procedure. Technical success was obtained in all cases; mortality at 30 days was 0 %. The authors concluded that the findings of this study showed that in selected patients, MWA is a valid alternative to other ablative techniques. Moreover, they stated that further studies are needed to demonstrate the short- and long-term effects of this technique and to make a comparison with other available ablation systems, especially with radiofrequency.
An UpToDate review on “Image-guided ablation of lung tumors” (Dupuy, 2015) states that “Multiple, image-guided ablative techniques are being developed for use in patients with primary non-small cell lung cancer or oligometastatic pulmonary lesions in whom surgery is not an option. Radiofrequency ablation is the most studied technique, but other approaches under development include microwave ablation, laser ablation, cryoablation, and irreversible electroporation”.
Furthermore, NCCN’s clinical practice guideline on “Non-small cell lung cancers” (Version 7.2015) does not mention microwave thermotherapy as a therapeutic option.
In a retrospective study, Wen and colleagues (2014) evaluated the contribution of intra-cavitary hyperthermia in patients with nasopharyngeal carcinoma who received radiation therapy. Patients with nasopharyngeal carcinoma were treated with radiotherapy alone or with radiotherapy plus hyperthermia of the primary tumor. All patients were treated in a uniform fashion by definitive-intent radiotherapy in both groups. In the radiotherapy plus hyperthermia group, patients were treated with microwave heating hyperthermia delivered twice-weekly in combination with radiation. Between November 1992 and September 1994, a total of 225 patients were recruited; with 98 patients matched to the criteria of either treatment group (49 in the radiotherapy and 49 in the radiotherapy plus hyperthermia group). Ninety-eight patients were included in the treatment response and 87 patients in the survival analysis according to the intent-to-treat principle (11 patients were lost to follow-up). Overall survival (OS) did not show a significant difference between the 2 groups (81 versus 86 months of median survival time, respectively, p = 0.068). However, there were significant differences not only in progression-free survival (PFS; median months of 60 versus 100, respectively, p = 0.036), but also in local PFS (median months of 54 versus 111, respectively, p = 0.029) between the radiotherapy and radiotherapy plus hyperthermia groups. No statistical difference was noted in the cumulative incidence of grade 3 adverse events or late radiation morbidity during follow-up between the 2 study groups. The authors concluded that the findings of this retrospective study showed that hyperthermia combined with radiation therapy can improve PFS as well as local PFS; however no increase in OS was observed. Thus, the inclusion of hyperthermia in the treatment of nasopharyngeal carcinoma using radiation offers no survival benefit but may help to improve the current standard of care consisting of radiation and chemotherapy.
Furthermore, NCCN’s clinical practice guideline on “Head and neck cancers” (Version 1.2015) does not mention microwave thermotherapy as a therapeutic option.
Keane and colleagues (2014) stated that unresectable locally advanced pancreatic cancer (LAPC) with or without metastatic disease is associated with a very poor prognosis. Current standard therapy is limited to chemotherapy or chemoradiotherapy. Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed. Thermal and laser based ablative techniques are widely used in many solid organ malignancies. Initial studies in the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high quality imaging such as computed tomography and intra-operative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety. The authors conducted a systematic review of the literature up to October 2013; search terms included microwave ablation. They noted that initial studies suggested that ablative therapies may confer an additional survival benefit over best supportive care; however RCTs are needed to validate these findings.
Rombouts et al (2015) noted that LAPC is associated with a very poor prognosis. Current palliative chemoradiotherapy provides only a marginal survival benefit of 2 to 3 months. SSeveral innovative local ablative therapies have been explored as new treatment options. These researchers provided an overview of the clinical outcomes of these ablative therapies. They performed a systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before June 1, 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. After screening 1,037 articles, 38 clinical studies involving 1,164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for post-operative, procedure-related morbidity and mortality were reported only for RFA (4 to22 and 0 to 11 %, respectively), IRE (9 to 15 and 0 to 4 %) and SBRT (0 to 25 and 0 %). Median survival of up to 25.6, 20.2, 24.0 and 12.6 months was reported for RFA, IRE, SBRT and HIFU, respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results.
Furthermore, NCCN’s clinical practice guideline on “Pancreatic adenocarcinoma” (Version 2.2015) does not mention microwave thermotherapy as a therapeutic option.
|CPT Codes / HCPCS Codes / ICD-10 Codes|
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":|
|ICD-10 codes will become effective as of October 1, 2015:|
|CPT codes not covered for indications listed in the CPB:|
|0301T||Destruction/reduction of malignant breast tumor with externally applied focused microwave, including interstitial placement of disposable catheter with combined temperature monitoring probe and microwave focusing sensocatheter under ultrasound thermotherapy guidance|
|Other CPT codes related to the CPB:|
|77280 - 77295||Radiation therapy|
|ICD-10 codes not covered for indications listed in the CPB:|
|C11.0 - C11.9||Malignant neoplasm of nasopharynx|
|C25.0 - C25.9||Malignant neoplasm of pancreas|
|C33 - C34.92||Malignant neoplasm of trachea, bronchus and lung|
|C67.0 - C67.9||Malignant neoplasm of bladder|
|C50.011 - C50.929||Malignant neoplasm of breast|
|C79.81||Secondary malignant neoplasm of breast|
|D05.00 - D05.92||Carcinoma in situ of breast|