Prof Amit Bahl – University Hospitals Bristol, Bristol, UK
Prof Nicolas Mottet – University Hospital of Saint-Etienne, St. Etienne, France
Prof Jean-Pierre Droz – Centre Léon-Bérard, Lyon, France
Henriette Breunis – Princess Margaret Hospital, Toronto, Canada
AB: Hello everyone, it’s a real pleasure for me, I’m Amit Bahl, consultant oncologist from Bristol, to be chairing this session with three dignitaries here. This is from the SIOG meeting session looking at the management of elderly with prostate cancer. So we’ve got Professor Jean-Pierre Droz who is the President of the SIOG Prostate Cancer Guidelines and to complement him we’ve got Professor Nicolas Mottet who is the President of the EAU Prostate Cancer Guidelines. I think to bring realism and sense into the whole conversation we’ve got Henriette Breunis who is a research co-ordinator from Princess Margaret Hospital, Toronto. I hope you’ll find this discussion very inspiring because the population dynamics are changing, we have to manage elderly patients more and with newer treatment options that are coming it is incumbent on us to make sure that we are well versed with the tools that are out there courtesy of all the research that goes on. So, Professor Mottet, would you be able to give us some idea regarding how the EAU guidelines are coming to terms with the elderly population and the changing face of radical treatment in the elderly?
NM: The first point is the EAU guidelines are linked to the SIOG guidelines because they are both co-endorsed. Probably the first message is age is probably a marginal issue, it’s mainly comorbidities. So if you check, for example, early diagnosis and individual early diagnosis there is no age limit. There’s no age limit but there is a life expectancy limit and it’s between 10-15 years, that’s based on the radical treatment that has showed benefit beyond ten years and not before. The second message is low risk disease, low risk prostate cancer disease, standard of care should be active monitoring; probably active surveillance for these men is probably too aggressive because it’s based on a repeated biopsy. We have to remember that the PROTECT trial that was for low risk, mainly, but also close to 40% intermediate risk, at ten years the specific survival was exactly the same in the active monitored patients and the actively treated patients. So it’s probably an overactive treatment to treat them if they belong to the low risk.
For the intermediate risk, and even worse for the high risk local disease, they must be treated provided they will benefit from the local treatment. As surgeons, surgery is feasible whatever the age but the patients have to be prepared for more side effects the older they are and that’s directly related to age. The more urinary incontinence they have after surgery and also the more impotence rate they have after surgery. If the patient is prepared for that that’s fine but they have to be prepared for that. We strongly believe that the local treatment, either surgery or radiotherapy are both as effective so it’s a complete nonsense to say one is better than the other. The problem with the high risk disease is that it’s not radiotherapy monotherapy it’s radiotherapy combined with systemic treatment, especially with long-term systemic treatment. As we are jumping to the side effects of long-term treatment probably Jean-Pierre will discuss that more than I. Clearly we have to balance always for local disease the benefit of the local treatment with the side effects that we induce with the local treatment and the benefit must really be there.
The real thing is that local aggressive disease is clearly under-treated. Probably the most important mistake to make is to think, ‘Well, he’s old, the local treatment is too aggressive, I’ll just give ADT.’ We know that’s clearly not the way to go.
AB: I think you’ve made some really very important points because it’s like reducing the over-treatment for the low risk and improving the under-treatment for the high risk. That’s where the bulk of our efforts should be going into really.
NM: I absolutely agree
AB: Jean-Pierre, what would you say about assessing these patients regarding their fitness? Because we know age is a number but what we want to know is how best can we assess these patients in a more practical way rather than a very convoluted manner which is very difficult in regular clinical practice when people have busy clinics, you see.
JPD: I think that really it’s true that the chronological age is not the good manner to take in charge these patients. So comorbidities are well-known as prognostic factors and the major factor of duration of life and of side effects of treatment and particularly of local treatments. But additionally there are other aspects we must take care. So comorbidities, but not only the number of comorbidities but the importance and reversibility of comorbidities. Second is not only the performance status but also the activity of daily living or instrumental activity of daily living. Finally not only but malnutrition. There are other points which are important as social and familial aspects and economic aspects because a lot of older patients are poor, it’s important to consider. So in the SIOG guidelines we introduced three steps, in fact, the screening with the G8 tool which is only a tool and screening of cognitive impairment with the Mini-Cog. But it is not a diagnosis, it is only a screening so we have to go to the diagnosis. Then the second step for health status should be to consider comorbidities, malnutrition and activity of daily living and on the other side the diagnosis of cognitive impairment if Mini-Cog is abnormal. The third step is geriatric assessment to propose geriatric interventions.
I am not sure that busy clinics and a short time to evaluate older patients is really good medicine so if we want to decrease the side effects and increase the benefits, so to increase the balance between the two parts, we need time. It is very important to consider that.
AB: That’s a very important message, also for me personally, because we almost always consider the busy clinics as an excuse, in a way. We adopted the G8 tool in our practice and actually when patients come in and register at the reception they get given that form. By the time you call them into the clinic room they have filled that form so it doesn’t take much longer to assess that. But I found two points you made which were really very crucial to me, and I hope to the audience, because, one, you talked about comorbidities and making sure to check reversibility of comorbidities which, whilst people record comorbidities, they tend not to look at the reversibility or managing the comorbidity because that should not, in itself, preclude a patient from a life-extending or life-prolonging treatment. The second thing that you mentioned is how do we establish that support because doing the assessment is fine but it is then requiring people with expertise who will help us out with managing these patients because we need the geriatrician support, maybe a geriatric oncologist should be the one looking after these patients at that phase of disease. I’m not yet clear in my mind how well-established those roles are in regular practice.
JPD: This is increasing in activity and also organisation. So you are right, maybe geriatric oncology subspecialty or work together with a geriatrician. Second, the geriatric networks. In our rich countries there are a lot of initiatives which are taken to organise the management of older patients at their home and not only at the hospital but with a network.
AB: Good. Henriette, when we talk about research and even though in the majority of the research trials age is not a criteria itself, but what I’m fascinated with is that we then have subset analyses showing men above the age of 70, men below the age of 70. In your role as a research coordinator, because not every man above the age of 70 is frail or vulnerable, there are many men who are fit, do you feel that adopting the sub-classification in the elderly and then showing the benefit of those agents would be a better way of doing things?
HB: That’s interesting, it’s an interesting approach. Usually men with metastatic castrate resistant prostate cancer are older so we have older patients in study. Even if they are not frail at the beginning of a treatment they can become frail very fast. So designing studies with a geriatric assessment as a tool is important.
AB: I was just going to say that the general perception, and this might be my inherent bias and I admit that, but when you have trials in your centre which are open you have a younger patient with metastatic castrate resistant prostate cancer you are very keen to offer the trial. But you have an elderly patient walking in to the clinic and, like Nicolas said, there is that nihilism about do I really need to treat him? How do you approach that, what do you feel patients, the elderly patient population, wants as support or their understanding of research and how much open can we be with them? We should be fully open but how do we do that?
HB: We do need to be open otherwise we’ll never have evidence of efficacy in the older population if you exclude them. So we need to exclude the patients in that but we have to do that in a way so that it’s for patient safety that they are well monitored and that comorbidities that can be reversed are reversed.
AB: So if you were designing trials for metastatic CRPC, apart from putting the tools in there for cognitive function and for health evaluation like the G8 tool, given your vast experience having talked to these patients on a daily and regular basis, do you feel that sometimes the patient information leaflets can become too daunting for some of them?
HB: They are often very daunting for patients. Also the patient’s family will read the leaflets but not necessarily the patient. There comes a point where the patient doesn’t have all the information and doesn’t fully understand what his treatment entails. That can lead to other safety issues for patients.
AB: It’s a very challenging job and I think that’s why the research faculty or the research fraternity are to be complemented on enabling these patients to take part in trials, thereby giving us the evidence to improve their outcomes.
AB: So what we will do now is, Jean-Pierre if you can give me your top two messages from the session today which you would want people to look at, follow or imbibe in their practice.
JPD: Apart from the need to evaluate health status, the first is to consider that treatment, a local treatment or a medical treatment for advanced disease, is as active in older patients as in younger. This is one message. But the second is that maybe side effects are more important and then there are three different… this is not a balance, this is in fact a balance with three parts. The first is what could be not the life expectancy because this is a patient, not a population, but what is the chance of living of this patient apart from prostate cancer? Second, what is the benefit of treatment, expected benefit of treatment? And third, what are the side effects? Nicolas talked about side effects for local treatment, we must be aware of the fact that medical treatments have a lot of side effects and not only side effects but also relationship with health status. That means that older patients, it’s generally known, have some risk of osteopenia or osteoporosis but it is increased by androgen deprivation therapy. Not only that, it increases also the cardiovascular diseases in general; it increases the risk of diabetes, of hypertension. But it’s true also for the new drugs. Depending on the health status and these comorbidities, which may be pre-existent, there are side effects during the initial phase of treatment but maybe if the patient is living sufficiently there are long-term side effects. We must weigh this very carefully and there are tools, however, but it is a clinical problem.
AB: Thank you very much for that. I think that message encompasses a lot of knowledge and experience behind that. This is incumbent on all of us to be looking at these patients and treating them as a complete entity rather than just focussing on their prostate cancer. Henriette, what would be your two messages to the audience regarding encouraging them from research-based activities?
HB: If doctors are giving systemic therapy or treatment for metastatic prostate cancer they should think of trials where older people could be involved but also the importance of including a geriatric assessment for this population.
AB: Thank you. Finally, Nicolas, I always like to give you the final word. So two pieces, gems of advice from you.
NM: The first one is senior adults, or older patients, I don’t know how you want me to call them, when we treat them we have to base our treatment decision on two things. The first one is on very clear and good evidence that it’s not related to age. A simple example – newly diagnosed M1 disease with minimal disease, does this patient really need to be treated immediately? This has nothing to do with age. So we clearly need absolute good evidence independent of age. Second, as Jean-Pierre said, the second message is it’s not because you’re old that you will not benefit from an active treatment, even an aggressive active treatment provided you will benefit from it. The message, at least for surgeons and probably also for radiotherapists, is there must be a balance between the benefit and the side effects and it has to be individualised. It’s easy to have a low PSA, it might be completely useless to have a low PSA because you will die far before your disease will kill you.
AB: Thank you. So we’ve seen that the messages are simple but they’re very clear that elderly patients deserve the same benefits of treatments as any other patient population but managing them involves managing their whole general health related fitness and, as was pointed out, the metabolic syndrome and the side effects that the ADT therapy can also cause. So I hope you’ve found this discussion lively, I personally did. Thank you very much.