There are a number of options for the treatment of metastatic prostate cancer, starting with purely best supportive care on the one end of the spectrum. On the other end of the spectrum would be starting with androgen deprivation therapy and chemotherapy in combination. So there is increasing evidence and a number of studies have shown different treatments that have strong evidence, prolonging survival and improving quality of life in appropriate selected older adults with metastatic prostate cancer. One of the challenges is figuring out who to select for more aggressive therapies and who might be more appropriate for less aggressive therapies.
Are there any markers that could lead the way in this?
One of the important markers is looking at the overall fitness of the older adult. In particular when we think about suitability for treatment we’re also looking at the competing risks from, for example, comorbidity, serious cognitive impairment, functional impairment. The more of these burdens that an older adult has, the less likely they’re going to benefit from prostate cancer treatment and the less likely they will die of their prostate cancer, more likely that they will die of other causes.
What do we need to take into account specifically in elderly patients?
As people get older there’s not an absolute age at which there’s a transition between being fit and being frail. We do know that as people get older their risk of these burdens with increasing comorbidity, functional impairment and cognitive impairment go up per decade and they start to rise rather dramatically after about age 70-75. So in the under 70 year old it’s uncommon to find these and they rarely impact on treatment decision making; they can be identified by the average oncologist with a fairly standard history and physical. Whereas as people get older one needs to be more aware and cautious and more systematic in assessing these patients and may need to use more standardised geriatric assessment tools to be able to detect some of these parameters because they do get missed often enough in the average oncologist’s office.
Are any of the recent prostate cancer research breakthroughs also beneficial to elderly patients?
No, one needs to look very broadly at the older adult population because there are really three groups when I look at them in clinical practice. There’s those who are very fit, don’t have significant comorbidities, are functionally independent, they’re cognitively intact and, yes, they may be 75 or 83 but they can tolerate aggressive therapies. In those kinds of patients who have been enrolled in clinical trials those clinical trials have included people like that who are fit and elderly, if you wish, and the subgroup analyses have shown that in the 20-40% of older adults in those trials abiraterone, enzalutamide, chemotherapy, radium-223, they have all shown survival benefits and improvements in quality of life in the older patients similar to the younger patients. That’s in the more fit older adults. On the other end of the spectrum we have the relatively frail older adult who has multiple comorbidities, typically severe comorbidities, not just one or two that are well-controlled. They have significant functional impairments and often they have cognitive impairment or social vulnerability or other factors that make them much more frail. In those individuals the data are much less clear because the clinical trials didn’t enrol them. So there we have to be much more cautious and understand whether their current level of frailty could be due to the burden of their metastatic cancer or is it due to all of their other conditions that they have. If the burden is more likely due to their cancer then there’s a good chance they will tolerate the therapy and in fact stabilise or improve in areas such as quality of life and function and level of symptoms and some of our data have looked at that. Whereas those who may have a major burden of comorbidity and functional impairments from other conditions besides their prostate cancer, most of them will still tolerate therapies but one has to be more careful because the toxicity starts to rise significantly. Often one finds that they tolerate androgen deprivation therapy fairly well, they can tolerate abiraterone and enzalutamide fairly well as well as radium-223 but chemotherapy starts to become more challenging and the ability to be able to get eight, nine or ten cycles of docetaxel, for example, even with a gentle dose reduction of 20% is more difficult but still possible in probably half or more of them. But the risk of neutropenia and other toxicities rises so then one has to look at trade-offs and have a frank discussion with the patient about the pros and cons of these different approaches, the potential benefits as well as the potential risks.
Are the latest SIOG guidelines a good place to start?
The latest SIOG guidelines are a great place to start. There is some controversy in them, they are not perfect because the evidence base is still developing and maturing but the guidelines in principle talk about a couple of key things – assessing patients for fitness or frailty or vulnerability, whatever term we want to use. So whether we choose to use the G8 which is the ones the SIOG guidelines recommend, it’s a good place to start, there are other options but I’m not sure any other option is superior or just different and maybe easier in one setting or another. So the G8 is a good place to start. There’s a new version of the G8, the modified G8 or the G6, which may be slightly superior but they’re very similar. The other thing that the SIOG guidelines emphasises is taking a serious look at cognitive function and making sure the patients are cognitively intact. Whatever specific tool we use, SIOG recommends the Mini-Cog or others, for example some have used the Blessed Scale or the Mini-Mental or the MoCA, these are alternatives but the Mini-Cog is a good one and it’s one that we use in our practice as the first screening tool. So if people are not frail by the G8 and they don’t have any suggestion of cognitive impairment with the Mini-Cog we can be fairly confident that they can be treated as aggressively as the younger patient if that’s consistent with their goals and preferences. If they have an abnormality on screening with the G8 or the Mini-Cog then we need to take a step back and do a more thorough assessment and decide are they really frail, are they a little bit more vulnerable and need some extra support but could probably go through treatment or are they, in fact, fairly fit. Because we know that the G8 has reasonably high sensitivity but it will catch a number of people who are not frail and suggest that they need more detailed assessment but on that detailed assessment they end up being fairly fit. So we need a more complex process but the SIOG guidelines are as good a place to start as any.
Is there anything important you’d like to add?
One of the areas is that I think we under-appreciate the importance of optimising their comorbidities and their functional status either before or during treatment, in particular taking advantage of optimising the home environment, looking at issues around home safety, gait aids and even physiotherapy is particularly important for these more functionally impaired older adults. A second important area is providing education and supports around reducing cancer related fatigue because that ends up being one of the most important side effects that patients complain to me about in my clinics. Whether it’s with one of the oral agents, whether it’s with chemotherapy or with radium, fatigue seems to come out as one of the top three symptoms over and over again. Although we can’t always manage the fatigue there are a number of things we can do ranging from education to basic investigations to optimising comorbidities and exercise that can improve fatigue in a significant proportion of patients.
The other thing to pay careful attention to is around falls and bone health because many of these older adults are at risk of falls and the therapies increase the risk. They also may have underlying osteoporosis, particularly if they’ve been on androgen deprivation therapy for years before they develop advanced cancer and then one starts them down subsequent therapies but that androgen deprivation has already increased their falls risk, given them osteoporosis and these things are not emphasised enough in the current guidelines. The current guidelines are a step forward compared to the previous ones and they’re more aware but from my own clinical practice I still see many clinicians who are ignoring or not optimising these factors for a number of reasons and we need to pay more attention to those to help these patients along the way.
So treating the patient and not the disease?
Absolutely, and there are many challenges to doing that. I appreciate the time pressures, the training, the expertise but it’s not a one person show and it’s not even necessarily a medical show. We can certainly involve allied health professionals, our nursing colleagues, physiotherapy colleagues, exercise scientists or kinesiologists and the whole team can support the patient along with the oncologist, it’s not just that the oncologist has to do it on their own.
The challenge in many centres is that these collaborations and interdisciplinary teams haven’t yet been built or people who are practising in very small centres or resource constrained centres have a more difficult time. Even there providing basic education, linkages to the community and advice so that some things can be implemented by patients or through their family physician in other environments so that they are collaborating, there are still many opportunities to do that that are under-utilised. It’s rare that it’s just the oncologist with no support system around, that’s unusual in my experience, no matter what setting I go to.