Version Control - Australian Government Department of Health



Application 1485:Sentinel Lymph Node Biopsy for Intermediate Thickness MelanomaDRAFT PICO Confirmation(to guide a new application to MSAC)(Version 1.0)This PICO Confirmation Template is to be completed to guide a new request for public funding for new or amended medical service(s) (including, but not limited to the Medicare Benefits Schedule (MBS)). It is relevant to proposals for both therapeutic and investigative medical services. Please complete all questions that are applicable to the proposed service, providing relevant information only. Should you require any further assistance, departmental staff are available through the Health Technology Assessment (HTA Team) on the contact number and email below to discuss the application form, or any other component of the Medical Services Advisory Committee process.Phone: +61 2 6289 7550Email: hta@.auWebsite: ControlDocument HistoryVersion NumberDate ChangedAuthorReason for Change0.110 March 2016MSAC ReformsFinal for Publication0.219 May 2016MSAC WEBAccessibility complianceDocument ApprovalVersion NumberDate ChangedAuthorReason for Change1.019 May 2016MSAC WebDocument released for Online publicationSummary of PICO/PPICO criteria REF _Ref487792010 \h Table 1 describes the PICO/PPICO criteria to define the question(s) to be addressed in an Assessment Report to the Medical Services Advisory Committee (MSAC).Table SEQ Table \* ARABIC 1 Summary of PICO/PPICO criteriaComponentDescriptionPatientsPatients with intermediate thickness malignant cutaneous melanoma (depth >1.0mm to 4mm)Prior testsExcision biopsy of melanomaInterventionSentinel lymph node biopsy (SLNBx) with excision of lymph node(s) identified by a combination of blue dye (lymphotropic dye injection) and lymphoscintigraphy/gamma probeComparatorClinical surveillance of the regional lymph nodes (by GP, 1-2 per year); or SLNBx under existing MBS itemsOutcomesEfficacy/effectivenessOverall survivalMelanoma-specific survivalDisease-free survivalTime to progressionCumulative rate of nonsentinel-node metastasis(Hazard) rate of local recurrenceTime to recurrenceChange in patient management (e.g. complete lymph node dissection, close surveillance, adjuvant treatment)Quality of lifeSafetyFrequency of adverse reactions (e.g. lymphoedema, nerve injury, infection)Patient-reported adverse reactions (e.g. reassurance, anxiety)Cost-effectivenessCost per life year gainedCost per QALY gainedHealthcare resourcesCost of lymphoscintigraphy and lymphotropic dye injection Cost of nuclear medicine services for lymphoscintigraphy Cost of removing sentinel lymph node(s)Cost associated with changes in clinical management (e.g. increased follow-up)Total Australian Government Healthcare costsTotal cost to the Medical Benefits Schedule (MBS)Total cost to the Pharmaceutical Benefits Scheme (PBS)Total cost to other healthcare servicesPICO or PPICO rationale for therapeutic and investigative medical services onlyPopulationThe intervention is proposed in Australia for the use in patients undergoing wide excision of intermediate thickness malignant cutaneous melanoma. Melanoma is a malignancy of skin pigment cells (melanocytes). The lifetime risk for melanoma in Australia is 1 in 24 for males and 1 in 35 for females. There are more than 12,000 new cases diagnosed in Australia each year, and more than 1,500 people die each year from the disease. A commonly used classification scheme for melanoma staging is based on Breslow tumour depth analysis, which describes lesions as thin (<1 mm), intermediate thickness (1–4 mm), or thick (>4 mm). Most cases are diagnosed at an early stage (<1.0mm thickness) where 5-year survival is >95%. With increasing depth, there is a stepwise decline in survival.In addition to tumour depth, the presence or absence of nodal disease impacts on long term survival. Lymph node positive patients may subsequently be considered for a nodal clearance for local disease control. There are also a number of medical treatments with survival benefits for stage IV patients (distant metastases) that are currently being trialled in stage III patients (lymph node positive). Preliminary evidence of these trials suggests that sentinel lymph node positive patients may be eligible for adjuvant treatment in the future that could provide survival benefits.RationaleSentinel node status is the most significant prognostic indicator in patients with intermediate thickness melanoma. Patients with intermediate thickness melanoma (greater than 1.0mm depth) have an increased risk of lymph node involvement and hence poorer survival.SLNBx is increasingly being performed in Australia, but this procedure is not coded in the MBS and alternative item numbers do not accurately reflect its use or procedural requirements.Prior test (investigative services only - if prior tests are to be included)Excision biopsy of the primary melanoma is performed to identify patients with intermediate thickness melanoma.If the biopsy is incomplete/partial, a complete biopsy is considered to gauge depth (according to NHMRC guidelines).InterventionThe intervention is sentinel lymph node biopsy with excision of lymph node(s) identified by a combination of blue dye (lymphotropic dye injection) and lymphoscintigraphy/gamma probe, ideally performed at the time of the primary melanoma wide excision (although this is not always possible). The admission duration is usually shorter than 24 hours.Eligible patients are identified by excision biopsy, and informed consent is obtained from these patients for the proposed SLNBx. Pre-operative lymphoscintigraphy is then performed to identify the nodal basin: Lymphoscintigraphy requires an injection of technetium antimony sulphur colloid prepared by a nuclear physician, injected into the site of the primary melanoma with a needle and syringe.During melanoma excision surgery, Patent Blue V 1ml is injected subcutaneously around the site of the primary melanoma by the surgeon. Using a combination of a hand-held gamma probe and visualisation of blue lymphatics, the sentinel lymph node is identified, removed and referred for histopathology. The reusable hand-held gamma probe (same as that used in breast cancer surgery) is covered with a disposable sterile plastic sleeve for the procedure.The primary melanoma is cleared based on NHMRC guidelines. The wound for the SLNBx is closed with the same suture material as the primary melanoma site.RationaleIt is possible to perform SLNBx with blue dye (lymphotropic dye injection) alone, although identification rates are lower. The best results are achieved with the proposed combination of lymphoscintigraphy and blue dye (greater than 95% identification) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5WaWRhbDwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (Vidal, Vidal-Sicart et al. 2012).ComparatorCurrently patients with intermediate thickness melanoma either have clinical surveillance of the regional lymph nodes by the General Practitioner (1-2 per year) or SLNBx depending on patient wishes, after an informed discussion with their general practitioner, dermatologist, or surgeon.Hence, SLNBx for melanoma is already being performed within the MBS but cannot be identified from other indications for lymph node biopsy (MBS items 30075, 30329, 30332, 31420, 31423). Details on these existing MBS items are listed in the Appendix.If patients in the observation only group develop clinical or radiological evidence of nodal disease during follow-up (about 20%) then a therapeutic lymph node dissection is offered to those patients, provided no distant metastases are detected.RationaleA new MBS item number is proposed to replace existing non-specific item numbers, which encompass a broad range of indications, of which SLNBx for melanoma is just one.OutcomesPatient relevantIt is claimed that SLNBx provides important prognostic information, allowing for improved local disease control and more effective treatment selection in patients with intermediate thickness melanoma. In sentinel lymph node positive patients, complete lymph node dissection may be considered/avoided, and adjuvant molecular and immune therapies may be introduced in the future. This may result in improved overall survival, melanoma-free survival and disease-free survival; and health-related quality of life may be improved.Safety outcomes to be considered include the frequency of adverse reactions (e.g. lymphoedema, nerve injury, infection) and patient-reported adverse reactions (e.g. reassurance, anxiety). Healthcare systemThe management of patients with a positive sentinel lymph node changes in that close specialist follow-up will be performed, potentially avoiding a complete lymph node dissection, which may be necessary if nodal disease develops during general surveillance. More accurate prognosis, treatment and management plans may result in savings to the health system as fewer procedures are needed due to better risk stratification, lower progression rates, longer time to progression and lower rates of and longer time to recurrence. However, future costs could rise if effective adjuvant therapy were to become available for node positive patients.About 30% of new cutaneous melanoma cases detected in Australia are staged as intermediate thickness melanoma. In these 2,500 - 3,000 patients (including patients treated within the public health sector), SLNBx could be utilised. As mentioned above, SLNBx is already widely performed in Australia, but its use is not quantifiable. It is unclear whether the number of SLNBx will increase or whether the interventions will just be coded differently under a specific MBS item number. A SLNBx specific item number would enable accurate documentation of the prevalence of this procedure. A significant proportion of cutaneous melanomas are treated in General Practice. For SLNBx to be performed, referral to appropriately trained specialists is required. Lymphoscintigraphy requires nuclear medicine services. SLNBx can be performed by a surgeon trained in the technique (including General Surgeon, Plastic and Reconstructive Surgeon, ENT, procedural dermatologist). Similar to surgeon training in SLNBx in breast cancer, it is suggested that the first 20 cases be supervised. Surgeons already performing SLNBx in the management of breast cancer will not need additional training.The projected costs are commensurate with SLNBx for breast cancer (30299-30303), i.e. between the costs of lymph node biopsy (30075) and lymph node clearance (30330, 30335, 30336, 31426, 31429, 31438, 35551).RationaleThe evidence provided in the application reports the following results:Biopsy based staging versus nodal observationThe staging of intermediate-thickness primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3J0b248L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (Leiter, Stadler et al. 2016), although this trial did not achieve the required number of events, leading to the trial being underpowered.The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) showed that immediate completion lymph node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXJpZXM8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (Eggermont, Chiarion-Sileni et al. 2015).Current clinical management algorithm for identified populationAs the intervention is already widely used, the clinical management algorithm is the same for both current management and proposed management below. The only difference proposed is that there would be a new specific MBS item number for SLNBx for melanoma, to distinguish it from other indications for lymph node biopsy (currently MBS items 30075, 30329, 30332, 31420, 31423).Proposed clinical management algorithm for identified populationFigure SEQ Figure \* ARABIC 1 Proposed clinical management algorithm for identified populationProposed economic evaluationThe clinical claim is that SLNBx is non-inferior in safety and superior in clinical effectiveness to standard skin surveillance. According to the Technical Guidelines for preparing assessment reports for the Medical Services Advisory Committee: Investigative the required economic analysis is therefore a cost-utility or a cost-effectiveness analysis.Proposed item descriptorTable SEQ Table \* ARABIC 2 Proposed item descriptorCategory 3 – THERAPEUTIC PROCEDURESSENTINEL LYMPH NODE BIOPSY OR BIOPSIES for cutaneous melanoma, where the primary lesion is 1.0mm or greater in depth, and appropriate excision of the primary melanoma has occurred, using preoperative lymphoscintigraphy and lymphotropic dye injection (Anaes.) (Assist.) Fee: $637.45References ADDIN EN.REFLIST Eggermont, A. M., V. Chiarion-Sileni, J. J. Grob, R. Dummer, J. D. Wolchok, H. Schmidt, O. Hamid, C. Robert, P. A. Ascierto, J. M. Richards, C. Lebbe, V. Ferraresi, M. Smylie, J. S. Weber, M. Maio, C. Konto, A. Hoos, V. de Pril, R. K. Gurunath, G. de Schaetzen, S. Suciu and A. Testori (2015). "Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial." Lancet Oncol 16(5): 522-530.Faries, M. B., J. F. Thompson, A. J. Cochran, R. H. Andtbacka, N. Mozzillo, J. S. Zager, T. Jahkola, T. L. Bowles, A. Testori, P. D. Beitsch, H. J. Hoekstra, M. Moncrieff, C. Ingvar, M. Wouters, M. S. Sabel, E. A. Levine, D. Agnese, M. Henderson, R. Dummer, C. R. Rossi, R. I. Neves, S. D. Trocha, F. Wright, D. R. Byrd, M. Matter, E. Hsueh, A. MacKenzie-Ross, D. B. Johnson, P. Terheyden, A. C. Berger, T. L. Huston, J. D. Wayne, B. M. Smithers, H. B. Neuman, S. Schneebaum, J. E. Gershenwald, C. E. Ariyan, D. C. Desai, L. Jacobs, K. M. McMasters, A. Gesierich, P. Hersey, S. D. Bines, J. M. Kane, R. J. Barth, G. McKinnon, J. M. Farma, E. Schultz, S. Vidal-Sicart, R. A. Hoefer, J. M. Lewis, R. Scheri, M. C. Kelley, O. E. Nieweg, R. D. Noyes, D. S. B. Hoon, H. J. Wang, D. A. Elashoff and R. M. Elashoff (2017). "Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma." N Engl J Med 376(23): 2211-2222.Leiter, U., R. Stadler, C. Mauch, W. Hohenberger, N. Brockmeyer, C. Berking, C. Sunderkotter, M. Kaatz, K. W. Schulte, P. Lehmann, T. Vogt, J. Ulrich, R. Herbst, W. Gehring, J. C. Simon, U. Keim, P. Martus, C. Garbe and G. German Dermatologic Cooperative Oncology (2016). "Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial." Lancet Oncol 17(6): 757-767.Morton, D. L., J. F. Thompson, A. J. Cochran, N. Mozzillo, R. Elashoff, R. Essner, O. E. Nieweg, D. F. Roses, H. J. Hoekstra, C. P. Karakousis, D. S. Reintgen, B. J. Coventry, E. C. Glass, H. J. Wang and M. Group (2006). "Sentinel-node biopsy or nodal observation in melanoma." N Engl J Med 355(13): 1307-1317.Morton, D. L., J. F. Thompson, A. J. Cochran, N. Mozzillo, O. E. Nieweg, D. F. Roses, H. J. Hoekstra, C. P. Karakousis, C. A. Puleo, B. J. Coventry, M. Kashani-Sabet, B. M. Smithers, E. Paul, W. G. Kraybill, J. G. McKinnon, H. J. Wang, R. Elashoff, M. B. Faries and M. Group (2014). "Final trial report of sentinel-node biopsy versus nodal observation in melanoma." N Engl J Med 370(7): 599-609.Vidal, M., S. Vidal-Sicart, A. Torrents, A. Perissinotti, I. Navales, P. Paredes and F. Pons (2012). "Accuracy and reproducibility of lymphoscintigraphy for sentinel node detection in patients with cutaneous melanoma." J Nucl Med 53(8): 1193-1199.Appendix – MBS items for lymph node biopsyTable SEQ Table \* ARABIC 3 MBS item 30075Category 3 – THERAPEUTIC PROCEDURESGroup T8 – SURGICAL OPERATIONSSubgorup 1 – GENERALDIAGNOSTIC BIOPSY OF LYMPH GLAND, MUSCLE OR OTHER DEEP TISSUE OR ORGAN, as an independent procedure, where the biopsy specimen is sent for pathological examination(Anaes.)Fee: $149.75 Benefit: 75% = $112.35 85% = $127.30Table SEQ Table \* ARABIC 4 MBS item 30329Category 3 – THERAPEUTIC PROCEDURESGroup T8 – SURGICAL OPERATIONSSubgorup 1 – GENERAL LYMPH GLANDS of GROIN, limited excision of(Anaes.)Fee: $246.95 Benefit: 75% = $185.25 85% = $209.95Table SEQ Table \* ARABIC 5 MBS item 30332Category 3 – THERAPEUTIC PROCEDURESGroup T8 – SURGICAL OPERATIONSSubgorup 1 – GENERALLYMPH NODES of AXILLA, limited excision of (sampling)(Anaes.) (Assist.)Fee: $346.75 Benefit: 75% = $260.10Table SEQ Table \* ARABIC 6 MBS item 31420Category 3 – THERAPEUTIC PROCEDURESGroup T8 – SURGICAL OPERATIONSSubgorup 1 – GENERALLYMPH NODE OF NECK, biopsy of (Anaes.) Fee: $183.90 Benefit: 75% = $137.95 85% = $156.35Table SEQ Table \* ARABIC 7 MBS item 31423Category 3 – THERAPEUTIC PROCEDURESGroup T8 – SURGICAL OPERATIONSSubgorup 1 – GENERAL LYMPH NODES OF NECK, selective dissection of 1 or 2 lymph node levels involving removal of soft tissue and lymph nodes from one side of the neck, on a person 10 years of age or over (Anaes.) (Assist.)Fee: $401.75 Benefit: 75% = $301.35 85% = $341.50 ................
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