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Benjamin L. Schlechter, MD: I'm Dr Benjamin Schlechter. Welcome to Medscape's InDiscussion series on colorectal cancer. Today we're discussing the care of older adults with colon cancer with Dr Nadine McCleary. Dr McCleary is an associate professor of medicine at Harvard Medical School and a medical oncologist at the gastrointestinal cancer center at the Dana-Farber Cancer Institute. She's also a leading voice in the care of older adults with cancer. First, I'd love to hear more about your path to GI oncology and what led you to focus on the care of older adults with this disease.
Nadine McCleary, BSN, MD, MPH: Thank you so much, Dr Schlechter. I would say my interest started when I was growing up in Miami, Florida, and witnessing the variety of older adults who I met throughout my days there, through volunteering in the hospital and seeing those who were at their most frail and vulnerable. In my general community, particularly within my church, I also saw older adults who were quite vibrant and active and actively engaged within their community. When I matriculated first to my undergraduate program in nursing and then medical school, I understood that there was a formal study of older adults and their needs and their capacities, and ways to build and measure resilience. That fascinated me in the field of geriatric oncology, and I selected gastrointestinal oncology because of the breadth of disease and ages that it affects, but also the volume of older adults who are diagnosed with gastrointestinal cancers every day.
Schlechter: When you see older adults with cancer, what assessments or techniques do you use to fit your care to their specific needs as a cancer patient?
McCleary: The first assessment that needs to happen is defining their goals of care, asking, "What are the things that are most important to you?" I always ask about functional ability: "How do you move through your day? What does your day typically look like? Who are the folks you like to have around you? How do you like to spend your time?" Understanding who my patient is is probably the best and most important assessment. But there is a formal assessment called the comprehensive geriatric assessment; we use that in gerontology quite frequently as a primary measure of geriatric syndromes or disease states or conditions that older adults may be faced with — things like cognitive impairments or physical frailty and functional ability. Those are very important topics that come up in the field of older adults or geriatric medicine. When we add on a layer of cancer, there is an assessment that has been modified for the field of oncology by Dr Arti Hurria and Dr Martine Extermann and others, borrowing from geriatrics to understand the implications of a cancer diagnosis in the older adult and in an aging person. How do we capture concurrent medical conditions and concerns about multiple medications or polypharmacy? What about concerns about social status and sometimes the need to have care partners or care proxies? How do we factor all of that in along with some of the physiologic changes that happen? Organ reserve tends to decline for patients. There's a concern about interactions with medications and nutritional status, for example, that needs to be considered. The comprehensive geriatric assessment, as it applies to cancer, becomes incredibly important. It has yielded a lot of optimal measures of outcomes so we can better understand how a patient may progress through their care.
Schlechter: In terms of thinking about a busy clinician seeing patients on a day-to-day basis, what are some basic pearls — things that I can use as a GI oncologist? What would you want me to be asking my patients that might get me part of the way there? Maybe not with the expertise of a geriatric oncologist but to maximize the benefit for patients.
McCleary: There are emerging first-line measures that we'd love to promote, from the geriatric oncology perspective, for all clinicians to use. One measure is gait speed — meaning, how fast that older person can walk over a certain prescribed distance. It's highly predictive of outcomes, toxicity, and of frailty in general, but it's not always easy to do. You may not always have the space to do it, particularly in this post-COVID era. In the post–COVID pandemic era where we're doing more and more virtual visits, that may not be practical. Grip strength has also been recommended as a measure, but again, having the tools to do grip strength is not always feasible. I like to ask a question about falls or number of falls within a 6-month period because, whether cancer has or hasn't been diagnosed, falls have been associated with survival. And so having one fall in a 6-month period certainly is associated with inferior survival or outcomes and is associated with frailty. If you have a patient who has fallen within the past 6 months, as a clinician your ears should perk up for signs that this patient may need additional support at home. I also ask about social status. We know that older adults who are living alone and facing a cancer diagnosis and treatment decisions may have a harder time navigating that space. We should be thinking about how to increase that support for patients in the form of social work, consultation, and other adjuncts within their communities, such as meal preparation services. The next piece that I think a busy clinician could easily do is count the number of medications that your patient is taking on a day-to-day basis. There's a growing body of literature that suggests that polypharmacy, or having more than eight medications on a daily basis that need to be managed, is indicative of a risk for poor outcomes because that increases the likelihood of medication errors, in terms of administration and/or drug interactions.
Schlechter: Excellent. Super-helpful and really high-yield information. Let's move into chemotherapy. I want to focus on colorectal cancer and early-stage disease. How do you think about adjuvant therapy, curative-intent therapy, in this special, older adult population?
McCleary: If we are fortunate enough to meet with an older adult, as a medical oncologist, we should acknowledge that many older adults are not referred to meet with a medical oncologist for this discussion. One of the first things that's important for us to acknowledge is the person's baseline functional status, presuming they're well enough. With an ECOG (Eastern Cooperative Oncology Group) status of 0 to 1 and a low geriatric frailty score, where they're deemed to be more fit and robust, you do want to think about their life expectancy on balance and consider whether they are diagnosed with multiple medical conditions or not. You can look at the NCCN (National Comprehensive Cancer Network) guidelines, which are helpful in terms of life expectancy. There are also many prognostic scoring tools from ePrognosis, through the UCSF website, that can be quite helpful in predicting prognosis. But if you determine that the life expectancy with untreated cancer is shorter than the life expectancy with treated cancer, then you should certainly talk about offering treatment. The data from the IDEA trial showed us that giving a shorter duration of chemotherapy is as beneficial in patients with disease that is at lower risk for recurrence. I am more prone now to offer full adjuvant therapy for my patients, including the use of oxaliplatin. But I and others have shown in the past that oxaliplatin is not always beneficial for all older adults who are diagnosed with a potentially curable cancer. Being open about the potential risks and benefits, particularly for those who have more invasive disease or disease that is at higher risk for recurrence — for example, T4N2 disease, where 6 months of chemotherapy may be recommended — is really a conversation. What I have learned from our work with the ACCENT database and our colleagues with NSABP C-07, and the MOSAIC studies, is that not all older patients derive benefit from oxaliplatin. I may offer it for the first 3 months, reassess after that point, and continue only with fluoropyrimidine through month 6 for those patients with more aggressive yet curable disease.
Schlechter: Which fluoropyrimidine do you reach for? In my clinical practice I'm generally more comfortable with infusional 5-fluorouracil (5-FU), and it feels like it's easier on patients, but it's hard to know where opinion ends and science begins. What's your choice, and are there risks and benefits that are known for, say, capecitabine vs 5-FU?
McCleary: I would say there's opinion, there's science, and then there's the issue of logistics. With older adults, thinking about organ reserve, if someone has renal insufficiency, clearly capecitabine is not, and should not be, your choice of agent. For that, infusional fluorouracil is the better option. In patients who have preserved renal function where you truly do have an opportunity to make a choice, even in those patients prescribed 3 months of therapy, I also tend to lean toward infusional fluoropyrimidine. I recall an editorial that Dr Bob Mayer published many years ago considering logistical implications of capecitabine in patients, even though the science showed similar efficacy. Logistically, taking an oral medication that you have to take in multiple strengths throughout a particular period of time can be somewhat complicated for an older adult, who tends to have more medications on board to manage anyway. Infusion offers you the opportunity to meet with your patient prior to administering that therapy and to have a timelier check of their tolerance of the treatment, and then make timely adjustments. For those who do proceed with taking capecitabine therapy or prescribing that, I strongly advise that you check in with your patients more often in the beginning, certainly within the first one to two cycles on a weekly basis, to ensure that they truly are tolerating their therapy. We know that at least some older adults may not want to bother you, may not want to share that they're not having an easy time or are not tolerating their therapy. Those check-ins can be high yield to keep your patient out of the emergency department, out of the hospital, and to reduce any morbidity from treatment.
Schlechter: Super-helpful. Do we know anything about the economic impact on patients? This may be beyond the scope, but can we talk about the economic impact on patients having infusional 5-FU vs capecitabine, which may fall to a drug plan, which can be more challenging for adults on Medicare? Is that something you're aware of or has it been studied or looked at?
McCleary: I recall that in Dr Mayer's editorial, that was one of the key take-home points at that time. Capecitabine was a bit newer and novel, and so the cost was fairly higher. I think it's important to consider that there are unmeasured costs in oral medications. I alluded to some of the unplanned resource utilization in terms of ED visits and hospitalizations. But to my knowledge, that has not been formally studied and measured compared with infusional fluorouracil. I think, though, there are some unintended consequences when we think about the convenience of a medication for patients who opt not to be compliant with that medication, and we know that to be a challenge with any oral therapeutic that we prescribe. I recall an example of a patient who had a curable cancer who certainly confirmed that they were compliant with their medication. And it wasn't until a diagnosis of metastatic disease that they revealed that they had not been compliant with taking that medication. It is very hard for us to capture that earlier. We do have to rely on our patients telling of their compliance. If there's any concern that we are running into a risk of not having the best outcome from therapy and you want to monitor that carefully, infusional would probably be not only the most effective clinically, but also cost-effective in the long run.
Schlechter: Excellent. Thanks for that. You mentioned a patient who developed advanced disease, so let's talk about advanced disease. You recently published some troubling data on outcomes in older adults with metastatic colorectal cancer. In particular, you showed that the benefit in PFS (progression-free survival) was pretty good with combinational chemotherapy in the first line, but OS (overall survival) was inferior. I was really concerned when I read this. Can you help us understand this issue and how we should incorporate these findings into clinical practice?
McCleary: Yes, thank you. You bring up another excellent data source, which is the ARCAD database, which is a pooled analysis of many of the studies that are published around advanced colorectal cancer. One of the challenges, and the reason that we can't fully understand the lower overall survival that was observed with first-line therapy, is because we don't have clear measures of the causes of death for patients diagnosed with colorectal cancer as a population, but specifically for older adults where there are other competing causes of death. In the past I've looked at (and others have as well) concurrent medical conditions and the frequency in which those occur for older adults. In terms of cause of death, those data are rarely, if ever, included in prospective clinical trials, which is where we derive our treatment recommendations. To fully understand the overall survival decrease that we're seeing and to understand if that is attributable to the cancer diagnosis or some other cause, like diabetes or unmanaged heart failure, we'd really need to prospectively collect that data.
Schlechter: That's helpful. When I read that, my thought was that we're making CT scans look better but patients look worse, and that the toxicity of therapy was overcoming any benefit.
McCleary: I think that's one possibility. You bring up another excellent point, which is that in clinical trials, the endpoints that we're looking at often in oncology are survival based, and that may not be the most relevant outcome to measure for older adults. What has been proposed by Dr Hurria, Dr Extermann, and many others is this idea of quality of survival or time to deterioration in symptoms — this concept of patient-reported outcomes and really measuring the quality of life over the quantity. That is probably the most relevant to decision-making for older adults.
Schlechter: Thank you for that clarification. Now, you also published data showing that older adults are less likely to receive second-line therapy, but they also do just as well as younger patients when they do receive second-line therapy. Could some of this decrement in survival be a lack of second-line therapy that older patients are deprived of, since the ones who do receive it are driving benefit, at least in the second-line trials?
McCleary: That is one of our hypotheses; if those patients were able to receive second-line therapy, they would still derive benefit. In fact, the survival benefit that we saw in the second line mirrored that of the first-line studies. It remains to be seen. There are some gaps in the data, and I think it really encourages all of us as we define our studies to be careful in collecting information that's going to help us to answer these questions better. That is, how do we select those patients who go on to second-line trials, and what happens to those who don't? Or how do we select in the real-world patients who opt for ongoing therapy and those who decide not to? It reminds me of work that Dr Sanoff and others have published, looking at the SEER-Medicare database, which better captures what happens in the real world. At least in the first line, they were seeing similar findings of lower referral and lower receipt of therapy for older adults. It would be interesting to look at that data in regard to second-line therapy as well.
Schlechter: When you're seeing a patient who has made it through first-line therapy successfully, such as it is, but needs second-line therapy, what do you look for that makes you think this is the right person to move on? Does the prior regimen's toxicity — let's say, going from FOLFOX to FOLFIRI — inform your decision? Is it the frailty of the patient? What are some of the things that you look for when you make the decision to proceed to second-line treatment?
McCleary: I guess it's similar to what I look for when I make the decision for first line, which is, how does this align with the patient's goal of care? How did we improve upon their quality of life? Even if the scans are not as we would like them to be and show progression of disease, we still consider the question: Is that patient continuing to function well? Are they remaining as independent as they choose to? Do they have the social support that is needed? And then, of course, we want to look at the disease measures and how much benefit we derived from that therapy — how many hospital visits did they have to get through with that therapy to make it "successful"? If all of those things measure up, again, after having that full conversation with the patient and their care partners, then you would certainly want to move forward. I always add the caveat, however, that when we make these decisions about therapy with a first line, second line, or beyond, we always leave the opportunity for re-discussion and a new decision. If we are not meeting our goals of disease control and quality of life, maintenance of relative independence, and it remains the patient's choice, then maybe we need to reconsider.
Schlechter: Dr McCleary, if you had a blank check to do the perfect clinical trial to help us understand how to deliver care for older adults with colorectal cancer in the palliative setting, for example, what would you do? What's the perfect clinical trial for these patients?
McCleary: That is an easy question. It turns out, between the NCI (National Cancer Institute), ASCO (American Society of Clinical Oncology), EACR (European Association for Cancer Research), RTOG (Radiation Therapy Oncology Group), Alliance, NCORP (NCI Community Oncology Research Program) — all of these groups now coalescing but led by leaders from the Cancer and Aging Research Group — we've answered that question. Step one, we need to incorporate outcomes that are relevant to the needs of older adults. And we need to include measures that really give us a more comprehensive picture of the patient that we are screening for trial and are enrolling to study. That includes incorporating a comprehensive geriatric assessment in each of these clinical trials, including more pragmatic eligibility criteria for each of these clinical trials where we lessen restrictions by age arbitrarily, and we must send restrictions by concurrent medical conditions where they are well controlled and do not interfere in the benefit of the potential therapeutic agent. In this world where we're thinking about patient-reported outcomes more and more and thinking about them as potential outcome measures, but also quality measures, we have to acknowledge that geriatric assessment is one of the first and earliest validated patient-reported outcome measures. For us to be able to answer these questions again with that life check in front of us is valuable. We should be incorporating all of these concepts. The last thing I would say is that often when we speak about older adults, we are still speaking about them as a monolithic group. They are not. They are an incredibly diverse population of folks. I think a part of our measure should reflect not only that diversity in terms of functional status and social status, but also in terms of identity, in terms of sociodemographic, in terms of financial distress. All those views of who an older adult is would help us to have the highest-yield clinical trial.
Schlechter: Although we hear a lot about young-onset colorectal cancer, which is a critically important topic, this remains a disease of older adults. Our experience as clinicians is refined by the work that you're doing. I appreciate the work that you've done to help us know what we can do to help improve the outcomes for these patients and to study how they're doing, because it's a real challenge to try to average patients into a clinical trial when clinical practice really doesn't always reflect clinical trials. Today we've been speaking with Dr Nadine McCleary, discussing the management of older adults with colorectal cancer. We've been discussing the risk-to-benefit ratio of adjuvant therapy, and in particular that when we talk about fluoropyrimidine backbone, there may be advantages to infusional 5-FU or capecitabine — not just advantages in terms of quality, but also the economic impact of an oral drug and the burden on the patient of an oral drug. We also talked about the fact that oxaliplatin remains an effective drug, and we can use the data from the IDEA collaborative study, which showed that 3 months of chemotherapy can still give substantial benefit to fit adults. In the palliative setting, Dr McCleary has shown us that there are some troubling signs about overall survival outcomes, but it's not clear that these are cancer-related decrements in overall survival or related to general health. And finally, we've had some important points about how to care for these patients and maximize benefit. I think we might need to resuscitate walking our patients from the exam room to see how they do. I know from my practice and seeing you do that; I think that's some good, old-fashioned doctoring that we need to bring back. It's a time to talk to our patients, to see them walk, and that is our geriatric assessment: Can you make it from here to there? Ask them about falls and their balance. I love the term that you used: We need to assess quality of survival. I think it's a great way to assess outcomes in a really holistic and thoughtful manner. Thank you again for this really fascinating discussion.
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Cite this: Quality of Survival and the Management of Colorectal Cancer in Older Adults - Medscape - Jun 01, 2023.