EBM + EBM + EBM

EDITORIAL by Dr. L.J. de Souza
Surgeon/Oncologist

Just about 50 years ago, when I was first given the licence to practice medicine and surgery, we had to refer to our books and consult our teachers and peers to decide on what was the best line of treatment for a particular ailment of our patient, especially for cancer. Today, 50 years later, this is no longer enough with the rapid strides in science and research. We have now a much larger armamentarium to refer to, so as to give the best possible treatment to our patients. The foremost in clinical medicine is EBM or Evidence Based Medicine. This evidence is derived from scientific trials all over the world, to decide which is the best treatment for the patient. This highest level of Evidence Based Medicine or level I is based on well conducted randomised controlled trials with a meta-analysis of all those that have been performed to get a definitive answer to a problem. Based on this, guidelines have been formulated all over the world. For cancer, we have the National Comprehensive Cancer Network (NCCN) guidelines in the USA which guides us in our clinical decisions to give the best possible treatment to our patients.

In our own country, the Tata Memorial group along with many others all around India have formulated our own National guidelines for the management of the more common cancers in our country. While the guidelines are most useful to us to make our decision, it is important to realise that these are only guidelines and not commandments. We have to individualise these guidelines for a particular patient in his/her circumstances and his/her stage of the disease. That is when we have to take into consideration the addition of the other two EBMs i.e. Experience Based Medicine and Expense Based Medicine.

Evidence Based Medicine ranges from the most robust data in level one, which is derived from well conducted randomised controlled studies. This goes down the line with less and less evidence till it comes to level seven which is only based on personal experience. Experience Based Medicine is based on the experience of a particular physician or surgeon. For them, level seven or personal experience is in fact level one because although they do not have controlled trials to base their results on, they have the experience of 50 years or more of treating thousands of patients with the same problem. They have therefore developed a wealth of experience which guides them to handle a particular case in a particular manner. It is for this reason that, when there is a problem in treatment, the patient consults not only one but many doctors, to gain from their personal experience as to what the best choice of treatment should be.

Expense Based Medicine relates to the facilities which a patient has, to spend the finances needed for the treatment that is indicated. Also, other circumstances like co-morbidities, distances, availability of treatment facilities etc. can modify the choices available.

To illustrate what I mean, I would like to present two situations: one surgical and one medical where one has to make decisions as to the best line of treatment.

Surgical: Today there is level I evidence that for stage 1 and 2 breast cancer, in suitable cases, Breast Conservation Treatment (BCT) gives equivalent results as compared to a Modified Radical Mastectomy (MRM), in terms of DFS (Disease free survival), and OS (Overall Survival). In the first instance of BCT, only the breast lump is removed widely together with the axillary nodes and the treatment is completed with radiotherapy instead of removing the whole breast. In the second instance, the whole breast is removed with the axillary glands and in most instances in stage one and two, radiotherapy is not required, although adjuvant chemotherapy may be required in both instances.

A choice has to be made by both the doctor and the patient as to which operation, either BCT or MRM, should be done for a particular patient. The Evidence Based Medicine states that either one can be done in suitable cases with equivalent results. Who makes the choice? Considering the additional two EBMs, the experience of the surgeon knows that perhaps there are more local recurrences with breast conservation than with total removal of the breast with mastectomy. This is because the patients come back to him with the recurrences after conservation and then he has to do a repeat surgery to remove the breast in most instances. Hence, although Evidence Based Medicine says both treatments are equal, Experience Based Medicine suggests that in some cases it may not be so. Then, we have to add the Expense Based Medicine of the patient because they may not be able to bear the additional cost of radiotherapy with BCT which is sometimes more than the cost of surgery! Further, they may not be able to come from afar for the radiotherapy and also there may not be a suitable machine (which is a linear accelerator rather that the old cobalt 60 workhorse) available to them for the treatment. Also, there may be additional co-morbidities which may make the choice of BCT difficult for the patient.

Medical: Today, the advent of targeted therapy for the treatment of breast cancer has contributed greatly to the control of the disease with Trastuzumab (Herceptin) added to the treatment of the patient. This targeted treatment is only applicable when the patient has HER2 positivity (3+ confirmed by FISH test). Evidence based medicine states that HER2 positivity is a poor prognostic factor and the addition of Trastuzumab greatly improves the prognosis of the patient. We therefore use it as per the guidelines whenever there is a confirmed HER2, 3+ positivity of the tumour.

However, experience based medicine sometimes creates a doubt in the mind of the treating doctor. If in stage 1 and 2 breast cancers, all prognostic factors are good i.e. node negative, Estrogen Receptor (ER)/Progestrone Receptor (PR) positive, no lymphatic invasion, tumour size less than 2 cm, grade 2, low Ki67 (cancer antigen tumour marker), but HER2 is positive, do we still have to give Trastuzumab? Ideally, if HER2 was also negative we would probably treat such a patient with only hormonal treatment, but as HER2 is positive, Evidence Based Medicine says that we have to give Trastuzumab. Further, with Trastuzumab it is recommended that we have to give chemotherapy also as it is not advisable to give Trastuzumab in isolation. Such a patient would need no chemotherapy because of all the good prognostic factors if HER2 was also negative. In such a situation, experience based medicine creates a doubt whether Herceptin should be given or not. And then we have to consider the patient condition or Expense Based Medicine. Herceptin has to be taken for a course of 12 cycles, each cycle costing around Rs. 50,000 and the total cost going up to Rs. 6 lakhs for the entire treatment as recommended. Can the patient afford this comfortably? If they cannot, what does the doctor advise? In practice, we suggest to them to take as many cycles of Trastuzumab as they can afford because something is better than nothing but Evidence Based Medicine again suggests that it may not have the desired results if the full course is not given.

In both these surgical and medical conditions, a decision must be made- To do or not to do? For surgery either BCT or MRM and for medicine Trastuzumab or no Trastuzumab in stage 1 and 2 breast cancer cases with good prognostic features except HER2 +ve. It is mandatory for the treating doctor to explain all the pros and cons of the three EBMs to the patient and then let the patient decide which treatment he/she would opt for. In most cases the patient will throw the ball back into the doctor’s court asking the doctor “What do you advise?” There again the doctor has to make his own decision carefully considering all three EBMs as to which modality of treatment would be best for the patient. It is imperative however, that although he gives his opinion for the best line of treatment for that particular case, the final choice of treatment must be made by the patient. Then, if a recurrence occurs, as unfortunately it does in many cases, the patient cannot blame the doctor for a wrong choice of treatment as he/ she has made the choice themselves. They can blame nobody for their own decision– except perhaps God!