Medico-economic Study of Three Strategies of Sentinel Lymph Node Analysis in Operable Breast Cancer
Condition: Breast Cancer; Surgery
MeSH terms: Breast Neoplasms
Study type: Interventional

Summary: 
      Breast carcinoma requires frequently an adjuvant therapy after surgical excision: in this
      way, one of the major criteria indicating the need of adjuvant chemotherapy is the diagnosis
      of a metastatic lymph-node invasion, mainly in the axillary field. Axillary surgery is
      therefore mandatory at the diagnosis of breast carcinoma. For many years, in order to avoid
      unnecessary complications due to extensive axillary surgery (for instance, arm enlargement by
      lymphedema), a limited surgery is frequently performed on the first supposed invaded
      lymph-nodes (LN) called "sentinel" LN technique; if the sentinel LN are not invaded,
      extensive axillary surgery can be omitted. To decide it during the surgery, removed sentinel
      LN are cut in 3 to 4 slices which are examined immediately as smears (cytology) or frozen
      slices (pathology). However, due to hazard in cutting the LN, micro-metastases can be
      misdiagnosed. That is why a recent molecular biology method has been developed in which the
      total LN are crushed and blended, then analyzed by OSNA technique (One Step Nuclear Acid
      analysis) so as to amplify and detect the mRNA coding for cytokeratin-19 protein witnessing
      the LN metastatic invasion. A standardized automated technique is available with a mean time
      of 30 to 50 minutes according to the number of analyzed LN.

      In 12 international studies (2830 cases) the consistency between OSNA technique and final
      pathology is of 91 to 98% and the sensitivity seems higher. Less than 5% of all breast
      carcinomas cells don't express CK-19 protein.

      The use of OSNA technique requires a dedicated machine and a skilled pathologist, increasing
      slightly the operation time; however it allows to avoid the immediate and long-term
      complications due to the radical LN axillary surgery in case of negativity of the sentinel LN
      procedure. To date, the three techniques including extemporaneous examinations (OSNA or
      classical methods) or not (classical pathological analysis) have their own advantages and
      drawbacks.

      "SAGE" study main objective is to compare these three techniques in terms of direct costs and
      Quality of Life impacts. The superiority of any of these three techniques is not the purpose
      of SAGE study, but the economic burden of OSNA technique in comparison with the 2 others in
      the standard setting in France.

      Quality of Life and Pain evaluations will be performed immediately after surgery and during
      the 6 months after.
    

Detailed description: 
      Today, standard treatment for early Breast carcinoma starts with a surgical step consisting
      of the tumor resection and sentinel lymph-node (SLN) detection, in order to select patients
      to be proposed for complementary axillary lymphadenectomy. This requested information may be
      obtained during the same operation time by intra operative examination, or after surgery with
      the consequence of a second surgical procedure when lymphadenectomy appears to be indicated.
      In France, three strategies are currently used for the management of sentinel lymph nodes:

        -  intra operative pathological frozen section examination followed by final pathological
           diagnosis,

        -  intra operative molecular biology using the OSNA technique (One Step Nuclear Acid
           analysis)

        -  no intra operative examination, but the final pathological examination. Each of these 3
           strategies has advantage and drawbacks and their own cost. With more than 50000 new
           cases per year in France, Breast carcinoma, thanks to population screening, more and
           more small tumors are detected where such information about sentinel LN invasion is
           needed.

      Our proposed study is a prospective, cost-effectiveness and comparative non randomised study
      where three strategies are evaluated in the current practice of the participating teams.

      Main Objective :

      • to evaluate in each of these 3 strategies for sentinel LN diagnosis, cost-effectiveness and
      cost-utility (QALY), Quality of Life,…

      Secondary Objectives :

        -  rate of second surgery needed

        -  rate of mico-metastases or macro-metastases detected to build a decision score,

        -  follow-up of non re-operated patient despite positive sentinel LN,

        -  RNA collection from the crushed and blended sentinel LN

        -  Quality of Life evaluation through the surgical times using QLQ C30 and Br 23 scales.

      Medical section :

      At pre-operative consultation, patients will be informed to consent participating in our
      observational study, without any change in their treatment strategy. Inclusion parameters are
      strictly the same in the three groups.

      At the time of surgery, if intra operative examination is planned, patient will be informed
      that a complete axillary dissection could be indicated.

      Included patients will be followed 15 days after surgery and at 3 and 9 months. Then every 6
      months during 2 years, then yearly.

      Economical section :

      Main objective of " SAGE " study is to light up decision maker in striking the balance of
      each strategy (induced costs and prevented costs) and results in terms of health as expressed
      by individuals preference depending on different health status, treatment strategies and
      clinical practice in French centers.

      In our study, the medico-economical evaluation on such a quite National scale (17 different
      centers) takes place in a practice standardization prospect.

      General methodology :

      In each participating center, one of the 3 strategies for the sentinel LN analysis is
      currently used (with or without extemporaneous procedure).

      Cost-effect evaluation will inventory all undertaken costs in each strategy and all induced
      positive or negative consequences, both at a qualitative and quantitative level using micro
      costing and macro costing evaluations. Evaluation of Quality of Life adjusted to health will
      be included to the cost effect analysis.

      In our study, population studied with a localized breast carcinoma, are women aged between 18
      and 65 years old and likely to be active : inclusion criteria are strictly the same in the 3
      strategies studied.

      In our study, we will consider Hospital and Health Insurance point of view. Hospital prospect
      will identify and value the cost paid by health institution due to the use of any of these 3
      techniques.

      Insurance Health prospect will value the costs of each treatment strategy including direct
      costs related to private medical care and not only those to be reimbursed to the hospital.

      The study starts at the time of the sentinel LN excision and ends 9 months later, including
      the post-operative complications and the possible second surgery for axillary LN excision.

      At all 920 patients will be included in the 20 participating team.
    

Intervention name(s): SLN detection +/- complementary axillary lymphadenectomy
Intervention type(s): Procedure
Intervention description(s): breast cancer surgery with SLN detection +/- complementary axillary lymphadenectomy Whatever the detection method used in the lab (Arm A: OSNA; Arm B: Pathological Examination; Arm C: Extemporaneous) to assess the positivity of sentinel lymph-node invasion, if negative result (no tumor invasion in the sentinel LN), a complementary lymph-node dissection is not mandatory if positive result (tumor invasion in the sentinel LN), a complementary lymph-node dissection is performed, either immediately (Arm A and C) or in a second surgical procedure (Arm B)
Other intervention name(s): Surgical complementary dissection of axillary lymph-node.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: breast cancer, sentinel lymph node, extemporaneous, OSNA