I’ve recently had the pleasure of leading the development of new bone health guidelines for ESMO. These update and replace the previous guidelines from 2014 and are somewhat different in scope and content than those in that these are really the first set of clinical guidelines that have looked at bone health right through from early disease where we have concerns about preventing treatment induced bone loss and also trying to prevent cancer from spreading to bone, through to metastatic disease where the emphasis is much more on symptom control, palliation and improving quality of life. In addition, the guidelines this time reflect all diseases that commonly affect bone so that’s breast cancer, prostate cancer but also multiple myeloma and other solid tumours that affect bone.
So they’re pretty broad in scope and for that reason the authorship is quite diverse, reflecting the multidisciplinary management that’s required for these patients. So not just medical oncologists but also radiation specialists, nuclear medicine expertise, imaging expertise and the role of orthopaedic surgery and palliative medicine.
What has changed specifically in the guidelines?
In addition to the broader scope of the guidelines we’ve obviously incorporated new information arising from trials that have been published over the last few years. If we look in early disease, first of all, what has clearly emerged is the role of bisphosphonates as adjuvant treatment for postmenopausal women with early breast cancer. In common with other national and international guidelines, we now recommend use of those agents for postmenopausal women at intermediate to high risk for recurrence.
In advanced disease the developments have been perhaps not as dramatic as that but they include important things such as the ability to reduce the frequency of administration of bisphosphonates which is very important now that our patients are living longer and longer periods of time with the developments in systemic therapy. So we now have evidence that instead of having to give an agent like zoledronate every month throughout the advanced disease course, we can cut back to three monthly treatment pretty safely. That’s obviously better for the patient in terms of convenience and also from a health economics point of view, it makes good sense.
We’ve also looked at data that has emerged about the role of bisphosphonates in prostate cancer where it’s clear that they are important for castrate resistant prostate cancer patients alongside endocrine treatments but also alongside other bone targeted therapies like radium-223 but that they don’t really have a major role in endocrine sensitive disease.
Lastly, thinking about multiple myeloma, which can be quite challenging to manage because of concomitant renal dysfunction, we now know that denosumab is a highly effective agent to prevent skeletal morbidity and is at least as good as the bisphosphonates. It doesn’t have the issue of particular concerns about renal toxicity so it’s well suited to using in patients with renal dysfunction.
So we take all that information and in addition to describing the key developments have created some algorithms which help the clinician work out what they should be doing when and how to use the agents in an optimum way.
Was your decision-making at all affected by the current pandemic?
We haven’t specifically addressed COVID because we hope these guidelines will long outlive the current pandemic. But issues like scheduling of treatment is important so clearly less frequent visits to hospital will follow from that. We’ve talked also quite a bit about discontinuation of treatment and the risks of that. Those are much less with the bisphosphonates because they have a very long duration of action so stopping for 3-6 months probably is not going to have a major impact on the patient, particularly if their disease is under control.
On the other hand, denosumab is handled in a different way, has different pharmacokinetics and if you discontinue that agent you get a rebound effect with excessive bone breakdown which potentially can lead to fractures and increased pain. So it’s important that clinicians realise that if they need to stop denosumab, either for clinical reasons or for, in this case, COVID reasons, that they should suppress that rebound with the use of a single infusion of a bisphosphonate.
One of the things that we were really keen to try and get across to clinicians is the importance of treating patients with metastatic bone disease with bone targeted agents. Everybody is so excited about the latest developments in immunotherapies and targeted therapies but we need to support our patients through their clinical course. So we’ve tried to impress on clinicians that giving a bone targeted agent is important from diagnosis right through the clinical course of disease and we can’t just rely on our underlying systemic therapies to prevent very unpleasant skeletal morbidity.
In fact, conversely, the longer patients live, the longer they have the chance to develop things like fractures and severe bone pain. So we really need to protect our patients and we’ve really tried to impress that on the clinicians that that’s an important part. It’s not the most exciting area of oncology but it’s a really important part of patient management.