The Role of Comorbidities in Treatment Decision-Making across the Spectrum of Prostate Cancer: A Podcast

00:00:00:

00:00:06: Welcome to this podcast, where we'll be delving into an often underappreciated but vital aspect of prostate cancer care, the role of probabilities in treatment decision making.

00:00:16: And today I'm delighted to have two friends and experts in the field, Dr.

00:00:21: Kersti Balachandran and Mr.

00:00:23: Peter Whelan.

00:00:24: Kersti, Peter, would you like to introduce yourself, Kersti first maybe?

00:00:27: Yes,

00:00:27: hi there.

00:00:30: I'm Dr.

00:00:30: Kersi Bella Chandran.

00:00:32: I'm a medical oncologist that specialises in prostate cancer.

00:00:37: And I also have a specialist interest and some experience in the emerging field of geriatric oncology, looking after older adults who are receiving treatments for cancer.

00:00:48: Thank you, Kersi and Peter.

00:00:51: Hi, my name is Peter Wheelan.

00:00:52: I'm a retired urological surgeon from St.

00:00:55: James's and Leeds.

00:00:57: I've had a great interest in prostate cancer for many years.

00:01:02: I chaired the RTC prostate cancer group and also the MRC one when it was in existence.

00:01:11: And I continued to both do some work and to follow the great changes that have occurred over the last forty years or so.

00:01:23: Wonderful.

00:01:24: Thank you both for being here today.

00:01:26: And I'm Kendrick Gung.

00:01:27: I'm a consultant medical oncologist in Bart's Health.

00:01:31: And I treat prostate cancer, particularly in the advanced setting.

00:01:36: So, just for an introduction, prostate cancer, whether a patient is dealing with localized disease or advanced prostate cancer, their overall health, including chronic conditions like cardiovascular disease, respiratory problems, or mental health issues can significantly influence both the treatments we offer and the outcomes we expect.

00:01:59: And while prostate cancer itself may progress slowly in many men, it's frequently the presence of competing health risks that shapes the patient's prognosis and quality of life.

00:02:09: So in this podcast, what I hope we'll do is to start by looking at the evidence in localised prostate cancer, where patients typically live longer and so comorbidities really matter when deciding how aggressively to treat the patient.

00:02:24: We'll then move on to the metastatic setting.

00:02:27: And once considered universally life-limiting, metastatic hormone-sensitive prostate cancer or MHSPC has seen remarkable progress in recent years.

00:02:36: With better survival, there is renewed focus on how other health issues should guide our decisions around treatment intensification.

00:02:44: And this is where the CURSTY's ochre geriatric assessment tools can come really helpful, offering structured ways to evaluate frailty, functional status, cognition, and life expectancy beyond just age or performance status.

00:02:59: By incorporating tools like the G-Eight screening tool or the comprehensive geriatric assessment, we can better personalize treatment decisions to align with each patient's overall health and course of care.

00:03:11: So really two sections to today's podcast, first in the localized setting.

00:03:15: We'll then move on to the metastatic setting, discussing different options of treatment intensification, treatment strategies, and we'll also cover broadly the idea of geriatric assessment tools.

00:03:30: So naturally, let's start with the localized setting, starting with some of the major studies that have shaped our understanding of treatment of localized cancer, especially developments in recent years.

00:03:41: Now, Peter, you mentioned that you have been following the developments in this field.

00:03:46: You're obviously a heavily experienced urologist practicing for many decades now.

00:03:52: What do you think have been the highlights in recent years in managing localized and locally advanced prostate cancer?

00:04:02: If I may, can I just take you back a hundred years or more?

00:04:07: The first radical prostatectomy was by Hugh Ampton Young in the early part of the twentieth century.

00:04:13: And it never caught on, principally, because although all surgeons like to take out lumps and kill people, the left patients but completely impotent, and in most cases incontinent.

00:04:26: The change that really occurred in the Seventy-Nine when Pat Walsh, along with Duncan, his Dutch colleague, described the anatomic radical cross-detecting, which reduced incontinence rates to well under fifty percent, and even impotent rates were preserved in thirty-fourty percent of oceans.

00:04:47: Allied with this was the concept at that time, that a small tumor would inevitably have left become an aggressive and then eventually metastatic tumor.

00:04:58: So there's a great many radical prostatectomies with only the eighties and the nineties because of this concept, mostly patients with not at all aggressive disease.

00:05:10: And this went against our practice at the time.

00:05:13: Many patients who had a TURP were found to have some cancer.

00:05:18: and we're actually told that that they had a touch of cancer.

00:05:21: but not to worry and we'd check them each year if there was any things that were changing.

00:05:28: The protex study, which is the one I've been involved in and St James, this was one of the contributors to that, was to try and put the record straight because this massacre of the prostates that seem to be occurring in North America did not seem correct.

00:05:48: either scientifically, or even in good medical care of patients.

00:05:54: And you can see that there's some of the guidance of Fr.

00:05:57: Hamley, who's a professor in Oxford, recruited over sixteen hundred patients.

00:06:03: And in essence, the three arms of the study, which was surgery, radiotherapy, and watchful waiting for active surveillance, if you might take more for example, in essence showed As we got out to almost twenty years, there was no difference in survival.

00:06:21: And that reinforced the prejudice of many people.

00:06:26: And the American Pivot Study, the just-compared surgery against septic surveillance, was a similar in outcome.

00:06:36: And as a surgeon, you must understand that I take out a bladder or a kidney, partial pynectomy, orchidectomy.

00:06:44: And I expect to cure patients in at least fifty, but not greater percentage of times.

00:06:49: And it's very hard not to go for an operation.

00:06:53: But the evidence has always been that this is not the thing to do.

00:06:57: Wonderful.

00:06:58: Thank you very much, Peter, for putting things into context and how things have evolved across the past few decades.

00:07:06: I guess, can I just ask, mainly for my own education, How have these two studies shaped the way we think about prostatectomies or radical treatment?

00:07:16: And if you were practicing today, how would you do things differently?

00:07:22: The major difference was that there was a greater version to treating patients with high risk disease.

00:07:29: So patients with Gleason eight, nine, ten in the eighties and nineties did not have radical prostatectomies.

00:07:38: And the difference that has happened now is people have gone.

00:07:41: for what you would have thought was logical, in that the most aggressive disease was the one that you would try and deal with aggressively yourself, whether it was with radiotherapy or by using surgery.

00:07:55: So that is the major change that I've seen.

00:07:57: And people have, because of the side effects and the fact that great many patients have curve over disease, which we'll discuss later on, it seemed to be logical.

00:08:09: but it was very difficult to actually get this logic across to the generality of urologists, which you can remember until the Intanet study of two thousand and four with Tamsol was an exclusive the urological disease as there was little in no input from medical oncologists and only a minor input from radiotherapists who felt that there were radiotherapy volume into the process.

00:08:38: who is suboptimal to say the least.

00:08:41: I think you're right and it's quite a potent reminder isn't it that metaconcology and prostate cancer has only been there for you know the past ten to fifteen years.

00:08:49: I remember when I started I was taught by somebody that you know in the twenty tens or early twenty tens that you could count in the number of metaconcologists in the country.

00:09:00: and really you know, things have changed.

00:09:03: So thank you very much for sharing your insight there, Peter, really appreciate it.

00:09:08: I just wanted to ask you to share your thoughts about a slightly different treatment landscape and this is the landscape in which, you know, we have delivered radical treatment but there was rising PSA after initial treatment.

00:09:26: What do you think about this area of biochemical recurrence especially in the context of next generation imaging with PSMA pets etc.

00:09:35: coming about?

00:09:36: Well I think I find this very interesting and I hope we'll be able to elucidate where the director of travel should be.

00:09:47: When I was with the RRTC prostate group we actually had a consensus meeting And it was almost chicken on a railway line as to how high a PSA level you could live with before you felt you needed to treat it at that time, virtually always with hormones.

00:10:07: And the Europeans came up with a value of twenty based on emergency data that showed only PSAs over forty seem to inevitably lead to metastases.

00:10:21: But with the same data, the SWAB group, very respected group in the States, came up with a value of fifteen.

00:10:29: So I think anything that actually puts some science or logic into it would be very helpful.

00:10:36: Thank you very much.

00:10:37: I wonder if there have been any new studies with PSMA pets about looking at thresholds like this, or are we saying that?

00:10:46: This group of patients is an increasingly small entity.

00:10:50: Are we saying that if the PSA was rising rapidly, it's more about kinetics or absolute values?

00:10:55: Do you think that feel has changed at all on the basis of imaging and interpretation of PSA kinetics?

00:11:03: I do.

00:11:03: I think two things.

00:11:05: One is that the nadir that the PSA reaches after primary treatment is extremely helpful.

00:11:16: from surgical perspectives.

00:11:18: I mean, you often think that if you're doing high-risk patients and the PSA is not a decimal point, then there's probably disease there already, which you haven't been able to sort out with your imaging.

00:11:35: And I think the rate of change, especially, again, we'll come into depending on how fit the patient is and how young the patient is, and what their cone morbidities are, you can, with these very general, and as I say, flip of a coin, parameters that actually try and e-counter route for each individual patient, because you can always fall back on some form therapy.

00:12:05: But I think the panetics are helpful, but obviously what everybody would like is something immensely better than the BSA.

00:12:13: No, I think you're absolutely right, Peter.

00:12:15: It would be good to have.

00:12:18: I mean, the PSA has been an extremely useful marker for prostate cancer.

00:12:22: But, you know, I think we need to start looking at other dimensions as well, CTDNA, amongst other biomarkers and whatnot.

00:12:29: But I think this kind of brings in the theme as well.

00:12:31: You know, we look at patients with rising PSAs, post-radical treatment, and bringing us back to this theme of comorbidities, the question is, do we react to a number?

00:12:40: Do we react to kinetics?

00:12:42: do we react to imaging and when and where do we take comorbidities into account and competing comorbidities which might impact on survival.

00:12:53: So I think it's all very interesting and thank you again for sharing your insights.

00:12:58: I'm just going to take this opportunity to move on to the metastatic space for a bit.

00:13:03: We've seen a real shift in treatment in recent years and as you alluded to Peter, metaconcology wasn't really a thing in prostate cancer until about ten, fifteen years ago.

00:13:18: There were very limited numbers of metaconcologists and we can see that historically metastatic hormone-sensitive prostate cancer had a relatively grim outlook.

00:13:28: Median survival, of course, depending on volume of disease and response to treatment, was typically between between two to three years.

00:13:36: But with the advent of newer systemic therapies as treatment intensification, we are now seeing median overall survival granted in clinical trials exceeding five or even six years.

00:13:47: And that's quite a game changer.

00:13:49: But with this greater overall survival comes also greater complexity, deciding whether to escalate treatment at the offset or waiting to sequence treatment requires a very nuanced approach.

00:14:00: And I'm glad that.

00:14:01: I've got my colleague Kirsty Balachandra with me today to discuss some of these nuances.

00:14:06: Now, Kirsty, we have obviously, you and I have trained in an era where we've seen a lot of development in treatment of prostate cancer.

00:14:15: But I just wanted to start this section by talking about antidepropagation therapy or what I prefer to call testosterone suppression.

00:14:24: You know, the Degrelix, the luperal relins.

00:14:28: Do you think it has space in an era where the standard of care is generally treatment intensification?

00:14:35: And do you think there's a role still of intermittent ADT in our patient population with metastatic cancer?

00:14:44: Thanks, Kenarick.

00:14:45: Yes, I think we still see a role for testosterone.

00:14:50: suppression.

00:14:51: I mean as we've heard it's been the mainstay of treatment for you know a remarkable time and clearly it is effective at controlling prostate cancer.

00:15:02: However it comes with its own toxicities and I think sometimes we underestimate the potential of festivities in terms of cardiac, metabolic, mood changes that can be associated with it and you know really quite debilitating and distressing symptoms such as fatigue and and loss of libido.

00:15:21: I think for some of our patients it's a good balance in terms of response in terms of disease response but also in terms of the side effect profile.

00:15:36: One area that has been quite helpful is offering patients intermittent testosterone suppression which offers the patient breaks in which to improve their quality of life and have periods of time without those side effects.

00:15:52: Although it hasn't been proven non-inferior to continuous therapy in terms of survival, it can be a sensible and pragmatic choice for some people, but I think that's a really careful discussion to be had with a patient in terms of attaining their goals and their priorities in terms of quality of life and maintaining independence.

00:16:16: Thanks very much, Kirsty.

00:16:17: And on that note, it's interesting how intermittent testosterone suppression is no longer really talked about in an era where treatment intensification appears to dominate the news.

00:16:28: But there's certainly, I hope to share my opinion, a population who are perhaps a bit more comorbid, more competing comorbidities, where actually they will die with the prostate cancer rather than of the prostate cancer.

00:16:42: And although we don't have a non-inferiority study showing that intermittent ADT is non-inferior to continuous ADT, if the patient is appropriately consented to treatment, I think it's still a reasonable option, don't you?

00:16:56: I agree.

00:16:57: I agree.

00:16:57: I think there are some patients who anything more than ADT monotherapy is not appropriate given competing other medical... conditions and I think there is another cohort of patients who actually would decline other treatments because of the increase in side effect profiles.

00:17:14: So yes, I think there is a group for whom ABT monotherapy still has a place.

00:17:19: If I may, it's just that we set off a competition with SWOG, the first intermittent study with what were then the new injectable hormones.

00:17:31: We remember this would have progressed from orchidectomy where intermittent therapy was sadly not an option.

00:17:38: And we found, and this is anecdotally, the data is published in RTCs and SWOG studies, and as you quite rightly say, it wasn't able to show equivalence, but we found very few patients went off.

00:17:56: And to emphasise, patients do suffer from side effects from ADT, and Often the relatives are quite distressed at the change of personality that the man undergoes and the men themselves distressed at the tiredness that they have and the sorts of jobs they were happy to do.

00:18:20: They find it quite overwhelming.

00:18:22: So I think there is a role, but again, it's selecting the patients that would best benefit from this.

00:18:31: And of course, you can always drop and change it.

00:18:33: they may do well for two or three years and then you have to come back to get on to continual therapy or additional therapy.

00:18:40: Peter, thank you very much for your comments and I think you're absolutely right.

00:18:44: You're part of many of these very key studies which drive our decision making today as well.

00:18:51: So thank you.

00:18:55: I was going to move on briefly to talk about treatment intensification now.

00:18:59: The purpose of today's podcast is not to talk about, you know, and receptor pathway inhibitors versus triplets and choosing between these.

00:19:08: But as you are an expert in the field of oncogeriatrics, we've spoken a lot about choosing population not to intensify treatment and perhaps watching and waiting.

00:19:21: What about, you know, using quite intensive treatment like triplet treatment, dosataxyl darylutamine ADT for the elderly population and underrepresented population in clinical trials.

00:19:33: But I found myself saying, you know, biologically, if you're actually quite well, why shouldn't you benefit from triplet therapy?

00:19:40: What are your thoughts about that area of things?

00:19:44: Should we try to intensify patients above the age of eighty to eighty five, although the arisen's trial really only had one in six patients above the age of seventy five?

00:19:56: I think that's a really good point.

00:19:58: First of all, obviously, that these patients are hugely underrepresented in clinical trials.

00:20:03: And therefore, if we're trying to use an evidence base, we are heavily extrapolating from the data that we do have available.

00:20:10: I think the first thing I would always point out is that chronological age, I think, is a very poor marker of the patient's fitness and appropriateness for treatment intensification.

00:20:23: I think we really need to move away from that.

00:20:26: And, you know, as a junior trainee, I remember sitting in MDTs where the age was counted as a significant factor.

00:20:32: But actually,

00:20:34: what

00:20:34: I think we need to be moving towards is how do we assess a patient's biological age?

00:20:38: And there's a whole host of factors that will come into play here.

00:20:41: So, of course, when we see a patient, we're considering their tumor biology.

00:20:45: As oncologists, we always look at, you know, ECOG or Konowski performance status.

00:20:50: But I think we need to be moving.

00:20:52: deeper from just looking at a list of co-morbidities to actually doing a more formal frailty assessment to really ascertain and try and stratify which patients are likely to benefit from treatment intensification and which patients actually it's likely to do more harm than good overall.

00:21:12: I think one of the things with this is, again, being very clear with the patients what they're hoping to get out of treatment.

00:21:23: and being very clear in terms of their their future goals.

00:21:29: I think there is some suspicion amongst oncologists perhaps that geriatric oncology is all about stopping patients access and treatment but I think the the opposite is true.

00:21:39: This is all about sensible stratification and then optimization of patients for whom you know these treatment options are are potential.

00:21:48: so I think It's absolutely not about using treatment lines down for patients.

00:21:54: I think the other thing to point out is that we know, for example, we know that from studies like the Friedman study that a significant number of patients don't go on to receive second line treatment after an initial AR pathway inhibitor failure.

00:22:14: for a variety of reasons that may include side effects or deteriorating health or performance statements.

00:22:20: So I think giving your best treatment up front, if possible and safe, it is definitely something to consider up front.

00:22:29: Thank you very much, Kirsty.

00:22:30: Just one final question from me, if that's okay, regarding your area of expertise.

00:22:35: Now, hands up, I'm not particularly familiar with oncogeriatric assessment tools, but I know that there's been a drive to, as you as you indicated, to start utilizing these more formal structured frameworks in assessing our patients.

00:22:52: In answering the question, not so much can we treat, but should we treat?

00:22:55: And if so, how can we optimize the patient?

00:22:58: So as an oncologist in clinic, if I was to see a patient with a few comorbidities above the age of, say, seventy-five, eighty, how can I best utilize these tools practically to aid my decision-making?

00:23:16: Good question.

00:23:17: I think there are a number of screening tools that are now available and are widely used.

00:23:24: In the UK, I think the most commonly used is the Rockwood clinical frailty scale, which is a really simple pictorial scale that goes from one to ace in oncology.

00:23:34: So it's very easy to pick out where a patient sits on that frailty scale.

00:23:39: Another tool that's used is the G-eight screening tool, which is much more commonly used in France and has a kind of stronger emphasis on nutrition.

00:23:47: In real terms, I don't think it really matters which screening tool is used.

00:23:51: I think it is the one that is going to be done is the best one.

00:23:55: So if there's one that's on your truck electronic patient records, then absolutely use that one because it will be standardized across the truck.

00:24:04: I think the other thing to say is frailty screening should be done at the point of referral and the point of seeing a patient but this is a dynamic process.

00:24:12: so it's something that in an ideal world will continue at every point of either progression or disease response at every change in treatment because it's not something that will be static and your treatment decisions will be guided by changes in it.

00:24:30: There are a number of services across the UK now that have fully fledged geriatric oncology services.

00:24:37: Some which have geriatrician inputs and some which are purely therapist led.

00:24:42: And I think the gold standard for geriatric oncology is undertaking what we call comprehensive geriatric assessment or CGA, which is this multi-dimensional.

00:24:55: multidisciplinary process of screening a patient, assessing them, coming up with interventions and recommendations, and then feeding through.

00:25:04: Now, in an ideal world, this is done in a joint clinic with an oncologist, potentially a geriatrician, and then therapy input, so physiotherapist, occupational therapist, perhaps a dietitian, and a pharmacist.

00:25:19: But I think we're all aware that at the moment, resources are not always plentiful.

00:25:24: And sometimes that's not possible for a lot of services.

00:25:28: So then I think coming back to your question, Kenra, in terms of as an oncologist, how can we approach this in clinic?

00:25:34: I think it's going back to the basics and thinking about components of frailty that can really make a big impact.

00:25:41: So for example, in the GAP Semity Study, they found that twenty percent of patients in the in the control harm.

00:25:49: so those who had no comprehensive

00:25:50: geriatric

00:25:51: assessment had a fall within the first three months of staffing.

00:25:55: Now I find that number staggering and actually going back to that first consultation and remembering to ask the patient have you had a fall in the last year.

00:26:03: I think can be a really valuable piece of information and then shifts your recommendations going forwards.

00:26:09: So I think there are a few things like that that every oncologist could have very quickly in their head, like have you had a fall in the last year?

00:26:16: Having a really good look at drugs, to look at polypharmathy, for example, many of our patients are on a number of anti-hypertensives, but actually years down the line, their blood pressures and their boots, which then puts them at a higher risk of falls.

00:26:28: And again, cognition, we talked about it with ADT, but again, something that would be very quickly screened for with a mini cog in three minutes

00:26:36: flat.

00:26:37: Thank you so much.

00:26:38: that with me.

00:26:39: I mean I know we work together and this is one of the first opportunities I've had to really listen to all the amazing work you do with setting up services for oncogeriatrics and really thinking about structured assessments for our patient population.

00:26:53: So I found that incredibly insightful and I hope our listeners do as well.

00:26:58: So thank you for sharing your expertise.

00:27:01: Peter, I wonder if I could ask you one more question before I close our podcast.

00:27:07: I mean, you know, you have had a wealth of experience of treating prostate cancer patients across the entire spectrum and have witnessed the evolution and growth of clinical oncologists being involved in now-medicine oncologists.

00:27:23: Would you say that I think survival has improved objectively?

00:27:28: Do you think the service and the progress is moving in the correct direction, not just in terms of survival, but also quality of life?

00:27:36: And do you think that multidimensional care is generally a positive thing?

00:27:42: So things getting a bit too complicated now?

00:27:46: Well, I've came into the.

00:27:50: the era of MDTs, but before which we'd only had the radiologist telling us what the film showed and the pathologist telling us it was cancer.

00:28:00: And the MDT really did broaden out things.

00:28:04: And we were lucky to have an oncology department, remember Peter Selby, the first oncology here in Leeds, and he came or one of his colleagues came.

00:28:16: And so even when they hadn't much to offer, other than often steroids, their input was extremely helpful.

00:28:23: So I think that having a multidisciplinary group, my concern has always been is how do you organise or get everybody together.

00:28:38: There seems to be It's my prejudice, I'm afraid to show my age, but quite a lot of doctors around these days compared with perhaps the twenty five or thirty years ago.

00:28:49: But whether they can all function and with colleagues, it's cursed to be saying from dieticians, physios, even occupational health individuals, therapists, they would be extremely useful.

00:29:05: So I think it is going in the right way.

00:29:09: And I think somehow or other there needs to be a borderline where there are patients that will have primary therapy and hopefully are cured but need a follow-up of some description.

00:29:24: The one gray area is in the middle where it seems to be fading but not very quickly.

00:29:29: And then the area where some sort of treatment is necessary, otherwise the disease will run away with them.

00:29:36: And I'm not certain that we're No, not yet, I'm afraid.

00:29:40: Peter, thank you very much again for your comments and for sharing your experience.

00:29:44: Thank you both really.

00:29:45: So just to quickly wrap up, I think.

00:29:48: What we've done in this podcast is we've looked through the advancements in prostate cancer treatment, different perceptions of existing treatments in the localized and locally advanced prostate cancer, and we've reviewed briefly about treatment intensification and ADT monotherapy in the metastatic setting.

00:30:09: But importantly, the overall theme is one of considering holistic care for the patient, not just being too oncocentric at times.

00:30:18: looking at survival, but also focusing on patient comorbidities, mental health, physical, psychological and social health as well alongside the cancer.

00:30:29: And you know, we have, Kirsty particularly has shared how we can use structured frameworks, assessment tools and apply them in a practical sense in clinic to best benefit our patients.

00:30:44: So I just want to say thank you again Dr.

00:30:46: Kirsty Balachandra and Mr.

00:30:47: Peter Whelan for joining me today and to the Journal for the opportunity to share our thoughts.

00:30:53: Have a good evening all.

00:30:54: Thank you.

00:30:56: Thank you.

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