Thank you for this kind introduction and for having me tonight. I hope the coffee is working and some people are changing positions. I hope to provide you some information today about Cancer Pearls for the Geriatrician. It’s by no means meant to be a thorough, detailed presentation but I’m hoping that this presentation will help you with your preparation for your geriatric medicine Board Exam, both certification or recertification. I hope for also a little bit your patient care.  And so what I will talk about first is a brief introduction followed by treatment approaches of nonmetastatic cancers and I picked the top three cancers both for men and women, followed by a brief presentation about some survivorship topics and a conclusion and then I know I’m the final thing between you all going home, so I will try and do this as fast as I can.

So cancer treatment is often individualized, there are local regional options as well as systemic treatment options that are combined in a variety of combinations determined by the cancer itself, biology anatomy stage and genetics plays a role more and more, but also patient preferences and life expectancy. And so certain guidelines have been created and I’m presenting here the NCCN guidelines for senior adult oncology to try and help physicians take care of older patients who have cancer in terms of deciding which treatment options will be best for them. And so one of the first questions that they recommend asking is does this patient have a life expectancy that puts him or her at risk for moderate or high risk of dying or suffering from cancer during their lifetime, and that’s easier said than done.  And there are some materials available that can help you with this decision making. I’m a little bit preaching to the choir here because I think geriatricians know this reasonably well trying to estimate remaining life expectancy based on in this case health status and in certain circumstances a 65 year old can live shorter, will have a lesser life expectancy as opposed to an 80 very healthy year old.  And there are certain risk factors that have been selected and identified in terms of further refining this risk in terms of 4 year mortality.

Now we are working on this from the cancer perspective as well and genomic health studies such as here Oncotype DX have created genomic testing on cancer tissue such as here for breast and colon that can help you further refine what is the cancer related prognosis and most importantly what the benefit would be potentially of chemotherapy and hormonal therapy if relevant.  And so if these two pieces of information together indicate that a patient will not be at risk of suffering from the cancer during their lifetime and the recommendation is to focus on supportive care.  If a patient does have potential suffering from the cancer during their lifetime it becomes important to have an informed conversation either through their proxy or the patient themselves. And if their goals and wishes are consistent with mild supportive care treatment then that is the way to go, but if a patient indicates that they want to try everything they can then we need to look at which risk factors they have in terms of suffering adverse effects from their cancer.

And a geriatric examination can really help here because it looks at a lot of different domains and this is usually a standard part of a geriatrician’s evaluation but sometimes also a general internist.  But not of an oncologist, and that sometimes poses a problem because it can serve many benefits from predicting complications and side effects from treatment to other healthful items such as detecting problems throughout the cancer treatment and sometimes even preventing them.  Now the problem with assessment of risk factors for the development of side effects from the cancer treatment is challenging. There is not one particular tool that is better than the other, obviously a comprehensive geriatric assessment is very long, very elaborate and it’s not always feasible to involve a geriatrician before you start the cancer treatment.  Now on the other hand a simplified version of the Karnofsky Performance Scale alone is not enough either, and so there are a lot of researchers working on trying to find screening tools that will help identify those patients who can benefit from more thorough examination and so one of those studies I wanted to present here.

This is by Dr. R. T. Hurria who is at the City of Hope, who has tried to pull together a certain amount of risk factors that take patient, age, cancer characteristics and laboratory tests as well as their physical function into account.  And based on how many factors they score she found that this particular set of risk factors can very nicely predict – I don’t think the mouse is working – but as you can see in Figure A on the left the risk factors determined by Dr. Hurria’s study were very nicely able to predict development of adverse effects during cancer treatment.  On the other hand, picture B, illustrates the Karnofsky Performance Scale and as you can see this really doesn’t predict any adverse effects and it’s not statistically significant.

Other researchers would argue that there is maybe even a simpler test such as the Mobility Test that is feasible, objective, easy, quick to do and even a test such as walking speed has been found to be helpful in terms of predicting mortality. And you’ve probably heard this presentation from Dr. Stephanie Studenski, a local researcher who has published this in the JAMA of 2011 where different gait speeds are really able to predict one’s mortality and morbidity. 

Regardless of how you get to these risk factors if a person has risk factors we need to look at whether these are reversible and more definable and if there are any special considerations needed.  If there are no risk factors they might be able to be treated just like any other relatively healthy young person, or if these risk factors are not modifiable we have to talk with the patient that maybe it’s in the best interest to focus on supportive care. 

So some of these special considerations in elderly with cancer who can undergo treatment but need to have perhaps adapted regimens are listed here; and so some general concepts for surgery include, and again I’m preaching to the choir here, that surgery can be performed in any person even older individuals and that biological age alone is not enough, you need to look at their physiology too. And in general emergency surgery is not always the best thing to do, and if possible delaying surgery until the active situation has been settled decreases one’s risk for complications.

In terms of radiation, in particular if you add chemotherapy to a radiation regimen the elderly tend to be at higher risk for the development of toxicity and then sometimes it’s necessary to reduce the dosing of chemotherapy. It’s very important in elderly who undergo radiation to support them very aggressively in terms of nutrition as well as pain.  In chemotherapy there are many more special considerations. Generally set elderly often receive the same relative but a smaller absolute benefit due to their competing morbidities, and in particular it is relevant to avoid neurotoxic drugs as much as you can, and if you cannot you really need to monitor their toxicity when they are on certain drugs such as mentioned here, Taxane, Cytarabine.  Cardiac toxicity is also very relevant, in particular in those individuals who already have baseline compromised cardiac function, anthracyclines are very well known but newer agents such as Trastuzumab, which is Herceptin, for breast cancer patients is also a potential candidate. The interesting thing about Trastuzumab or Herceptin is that if it depresses one ejection fraction that this is often transient and potential reexposure can be considered if their ejection fraction normalizes.

So now I’m going to talk about the top three most commonly observed cancers in both men and women, and here is the top three in terms of incidence.  For a man the top three include prostate cancer, lung cancer and colorectal cancer. And for women in 2012 the most commonly newly diagnosed cancers included breast, lung and colorectal. And similarly in terms of mortality the top three reasons in men in terms of mortality from cancer included lung, prostate and colorectal; and for women, lung, breast and colorectal. 

So we will start first talking about colorectal cancer, and as you can see here not surprisingly the incidence of colorectal cancer in elderly is higher than in those who are younger.  But overall there seems to be a downgoing trend which is probably related to the fact that we tend to earlier detect and resect precancerous polyps through screening colonoscopies.  Risk factors for colorectal cancer are various and they are listed here and their relative risk priority and the highest risk of colorectal cancer is in those individuals who have a family history or inflammatory bowel disease or diabetes, but health behaviors play a role in terms of colorectal cancer development as well. 

In terms of preventing colorectal cancer, current recommendations for the prevention include getting screened regularly, improving your health behaviors and at present time despite the fact that several studies have been published or are ongoing in terms of looking at certain medications or supplements, the American Cancer Society does not really recommend using any of these at the current time to prevent the development of colorectal cancer.  There is more increasing evidence coming for users of NSAIDs in high risk patients as well as adjuvant setting where one already has developed cancer and you are trying to prevent developments of new primary colorectal cancers, but again it’s not standard of care. 

Colorectal screening should start at age 50 and be performed on a interval that is dictated by the finding of polyps yes or no, when you should stop screening really depends on your remaining life expectancy, in general a recommendation is maybe to stop screening for colorectal cancer if your life expectancy is somewhat less than 7 to 10 years, but you also have to take into account whether able to tolerate the procedure or any further diagnostic or therapeutic interventions.  Even if one has decided to not undergo screening with colonoscopies if older patients develop new symptoms I’d still recommend that you then possibly consider the performance of colonoscopy because the yield is much higher in those who are symptomatic.

So treatment of nonmetastatic colorectal cancer, surgery is the main intervention for colorectal patients, it’s the only option that can accomplish cure, should not be denied simply based on age. Yes, older patients tend to have more comorbidity, but it’s important that you take into account their physiology and their ability to tolerate surgery.  And again you can buy time and avoid emergent surgery with placement of for example colorectal stents.

Chemotherapy is another very important treatment for colorectal cancer.  Elderly seem to obtain a similar relative but a smaller absolute benefit and toxicity is not much different in those who are older versus those who are younger. The treatment often includes 5FU either IV or orally administered as a pro-drug called Capecitabine and they have somewhat different side effects profiles and IV 5FU tends to be administered for those higher staging colorectal cancers and in those who are not thought to be able to tolerate this or in whom it’s inconvenient to do this or those who have smaller, lower staging tend to be treated with either single agent or oral agents.

Prognosis in general tends to go down as one’s staging goes up, and follow-up is individualized, it really needs to include a history and a physical exam on an interval basis asking them if they have any new symptoms that possibly might indicate a recurrence of disease.  You test tumor markers for those who have advanced tumors at baseline, include CT scan imaging for those who are at high risk for cancer recurrence and of course you need to continue doing a colonoscopy depending on how the findings are at one year after their completion of cancer treatment depending on whether you find a polyp versus not, you will then repeat this on an annual basis or less frequent 3 to 5 years, so highly individualized.

In terms of lung cancer similar trend here, lung cancer incidence goes up in those who are older. At the current time there are absolutely more male lung cancer patients than female. Risk factors are smoking, that’s the big number one, but radon gas, a secondhand exposure and genetic susceptibility plays a role as well and particular for those females who are diagnosed and therefore the screening at the current time, many studies are ongoing to see if plain chest x-rays or more advanced CT scans or sputum testing will be of any yield.  Really at the current time there are not applied as routine practice, they have actually setup a website for this purpose that I’ve shown here where you can follow what are the most current guidelines or recommendations. They still need to consider evaluating what are benefits versus the risks in terms of, of course, cost and risks of radiation exposure and the yield in terms of survival.  And so we haven’t heard the last about this, but at the current time screening for lung cancer is not ready for clinical practice.

Treatment of lung cancer, I will start with non-small cell lung cancer, which represents 85% of the newly diagnosed lung cancer patients. If they have localized disease the treatment often includes surgery as well as chemotherapy.  Well selected older adults can tolerate surgery very well, but the limitation here is that most evidence we have was from retrospective studies and so that evidence is a little bit limited.  In terms of chemotherapy studies have shown that if well selected they can tolerate the treatments well, it doesn’t really affect their quality of life and gain similar benefits.

 If their disease is a little more advanced and involves lymph nodes and mediastinal areas then often we tend to include radiation therapy in their regimen as well, which really then at that point makes their toxicity risk go up in terms of esophagitis, pneumonitis and sometimes myelosuppression depending on how much bone marrow we hit.  If one has an EGFR mutation evidence seems to indicate more and more that one could possibly either add or in those who cannot tolerate treatment replace chemotherapy with an EGFR inhibitor. 

In terms of small-cell lung cancer which represents 15% of the newly diagnosed lung cancer patients, very, very few data in elderly.  The standard treatment tends to be chemotherapy plus or minus radiation therapy depending on how localized the disease is. And the trick here is that doublet treatment has similar efficacy in those who are older versus younger, but of course much more toxicity and if you give them a single agent they have much more acceptable toxicity but at that point they have lesser benefit and inferior survival. And so it’s a balancing game in elderly the small-cell lung cancer.  In those who did have advanced small-cell lung cancer that responded very well to this chemotherapy treatment one could consider administering prophylactic cranial radiation although there are no data in elderly and it can really be of socially significant morbidity.

The prognosis in general for lung cancer is somewhat poor, poorer for those who have small-cell lung cancer and surveillance should again be individualized.  But in general for non-small cell lung cancer history and physical is very important with sometimes addition of imaging, but for small-cell lung cancer imaging is the main part of surveillance testing including laboratory blood work.

The next cancer I’m going to discuss is breast cancer.  There are a lot of cases of breast cancer, the morbidity as you can see here is relatively good for breast cancer patients. There are lots of risk factors for breast cancer, research has been very advanced in the field of breast cancer and so what we know in terms of relative risk is that the highest risk is for those who are older, for those who have family histories or genetic mutations, monographically dense breasts or of course a personal history of breast cancer. But again for breast cancer health behaviors play a very large role as well.

Screening guidelines differ slightly for those who are younger than 40 and those who are older than 40, and depending on which guidelines you look at and which health insurance plan you have most still continue to recommend an annual mammogram for those who are 40 and over together than an annual breast examination and we still tend to promote a self exam even though the evidence for this is very limited at the current time.  So when do you stop screening for breast cancer?  Also very controversial topic, in general we really don’t know when to stop cancer screening for any tumor, for breast cancer however it’s recommended to maybe stop screening if one’s life expectancy is 3 years or less.  Again this should be highly individualized. 

Breast cancer treatments, the main treatment is local therapy with radiation plus or minus – sorry, with surgery plus or minus radiation therapy.  Most women these day can undergo a lumpectomy, sometimes we would opt for a mastectomy to be able to omit the need for radiation therapy, in particular for those who are older and cannot commit back and forth for 4 to 6 weeks on a daily basis.  So really the decision is being determined by both tumor characteristics but also the patient characteristics. The benefit and toxicity are really similar in elderly, the only caveat is that if you do perform lumpectomy you really need to add radiation therapy to obtain the same survival data. 

Axillary dissection includes the removal of lymph nodes in the site of the breast cancer, very much associated with morbidity, along with lymph edema.   Now we have the availability of a central lymph node procedure that I’m not sure everybody is aware of what that includes, but what we do during this procedure is inject die in the primary tumor site and wait for the die to drain towards the nearest 1, 2, 3 lymph nodes and we take those lymph nodes out at color blue as an indicator of first spot of drainage.  And if they are negative for cancer we often usually don’t perform a complete axillary dissection.  If they are positive at the current time we still mostly do an axillary dissection in particular if it will help us in terms of how aggressive to be the systemic treatment options.  It’s a measure of how advanced the disease is and the risk of recurrence.  Now the performance of an axillary dissection is really becoming controversial in certain settings, for example where it won’t change our treatment plan or when one is too frail or has many comorbidities.  In certain circumstances we will opt to omit.

Radiation therapy is indicated when one has undergone a lumpectomy as I explained, when one has a large tumor even though they have undergone a mastectomy and also when a certain amount of lymph nodes are involved.  Studies have shown though and more and more it’s clinically decided that if one is older than 70 and has very benign tumor characteristics that we try to possibly omit the performance of radiation therapy.  Studies have shown that there is overall similar survival if they are well selected. 

 System therapy for breast cancer can include chemotherapy where elderly often receive similar benefit, but slightly more toxicity. We can support them through this, if they still don’t tolerate we can adjust our regimen.  Most benefits of chemotherapy in those who are older is in those who are hormone receptor negative. 

 Hormonal therapy is often an important systemic treatment for those who are older and have breast cancer because elder tend to have usually hormone receptor positive breast cancer and elderly seem to tolerate this similarly if not better than those who are younger.

Targeted therapy is becoming more and more important. The most well known agent already administered for years now is Trastuzumab which is Herceptin in those women who are positive for a certain marker called HER2 New, this treatment as I had mentioned earlier can predispose to a transient development of CHF, often reversible. And so we tend to screen for this so we catch it early and can hold the treatment to allow recovery before one becomes clinically symptomatic.  

Bone agents such as Bisphosphonate and there is a new kid on the block called Denosumab are being investigated at the current time for their ability to decrease the onset of bony metastases but really evidence has been inconsistent and confusing and at the current time it’s not recommended to prescribe them only for the purpose of decreasing a breast cancer recurrence.  Now many breast cancer survivors in particular are on a bone agent because they have poor bone health and maybe in those individuals you hit two birds with one, but in general not only for the purpose of reducing cancer recurrence.

 I wanted to briefly address this slide because it relates to the differences in mechanism between Tamoxifen-like agents and aromatase inhibitors such as Arimidex, Aromasin and Femara. Tamoxifen works at the receptor site and depending on which organ we are talking about it can have positive or negative affects but in terms of Aromatase inhibitors they tend to decrease the total amount of circulary estrogen in your body by inhibiting the conversion systemic within your fat tissue from male hormones to female hormones. And this is why Aromatase inhibitors are contraindicated in those women who are premenopausal because their ovaries still function and could sense this peripheral blockage and might try to compensate if not overcompensate for this peripheral blockage. And that’s why if you have a woman on an Aromatase inhibitor and for some reason she develops menstrual bleeding it’s very important that you talk with their gynecologist and oncologist to sort out if this treatment is still appropriate for them.

Survivor rate, as I mentioned, for breast cancer is very good.  And breast cancer follow-up should again be individualized but in breast cancer we have much more evidence and an organization who supports on paper that the surveillance for breast cancer should only include a history and a physical exam where we look for intermittent symptoms and decide if they need to be worked up or not. It should not include any blood work, should not include any imaging or they are exceptions there, but in general no blood work, no imaging except for an annual mammogram.  And it’s important for those who are on Tamoxifen to stress the importance of seeing their gynecologist on an annual basis because Tamoxifen has a very low risk of predisposing to uterine cancer in those who are postmenopausal, and similarly in those women who are on an Aromatase inhibitor it’s important to monitor their bone health because most women who are on Aromatase inhibitor tend to lose some bone, some more than others. But it’s important to be aware of this.

 This is the last cancer and this is a male cancer, median age of diagnosis is 71 years old, but most men are thought to develop prostate cancer at one point in their lifetime and die with it rather than of it. There has been a huge confusion in terms of whether we should or should not screen for prostate cancer and I’m not sure I have the golden answer for you tonight, other than it really should be an informed conversation.  This is a summary of the three large cancer organizations including actually U.S. Preventive Services Taskforce and that last one actually does not recommend screening for prostate cancer while the two, while the Cancer and the Urological Association do. And so it really depends on an informed conversation looking at their family history and explaining to them what it means if a PSA is positive and what workup may need to be done and come to a decision together. But it’s not an easy conversation.

Staging for prostate cancer relies very highly on the Gleason Score, which is basically a measure of how angry the tumor looks under the microscope together with the tumor staging as well as the level of PSA.  And if one has localized and low risk prostate cancer some people would argue in particular in those men who are older that one can monitor this over time, although this is still somewhat investigational.  Most people would pursue definite with treatment with either surgery or radiation.  Intermediate and high risk prostate cancer really should be treated with treatment either surgery versus radiation. This has not been really compared head to head, they have some slight differences in terms of side effects and I guess the most relevant side effects include incontinence as well as erectile dysfunction, where erectile dysfunction can happen years after the fact in those who underwent radiation treatment.

 Androgen deprivation therapy where one basically undergoes treatment with androgen lowering just like in women antiestrogen treatment, so that is really associated with morbidity such as weight gain and even hot flashes in men, and it’s not pleasant but it’s often recommended for those men who had, who were found to have lymph node involvement at the time of either prostate surgery or for those who underwent radiation therapy if they were thought to have a higher risk prostate cancer. 

The prognosis is good, as we said median age at death is 78, lifetime risk of death is only 2.8%, this disease often smolders very slowly from biochemical recurrence to the point that there is truly micrometastatic disease can take about 8 years and metastatic progression to death at that point is 5 years. And follow-up in terms of those patients who had their prostate cancer treated with a curative intent really differs based on where you have surgery versus radiation therapy, and in particular in terms of PSA monitoring in terms of radiation therapy PSA levels can fluctuate and it surely becomes a little bit difficult to interpret testing, and so an expert should usually be involved.

Now why are we doing this?  Why are we giving all these toxic treatments?  And the reason why we do that is to try and prolong their survival and I’m happy to say that fortunately the cancer survivorship group is increasing both in terms of number and at the current time 2/3 of survivors are age 65 and over for reasons that are well known to all of us.  Advances in the cancer treatment, we detect cancer earlier, they have an increased life expectancy and a growing age population. But we also see that cancer survivors live longer and longer, they can easily live 5, 10, 15, 20 years after their diagnosis and some are even alive, a minority, 25 years after their diagnosis.  Most of these are female.

We have learned from the literature that cancer outcomes are being determined not just by the tumor itself, not just by the benefits of the treatment but also by their health behaviors and the risks of these treatments.  And that’s what I wanted to spend some time on right now.  And these are data obtained through a survey in 2010 administered by the Lance Armstrong Foundation called Live Strong where they probed cancer survivors for somatic as well as emotional symptoms. And as you can see here, somatic symptoms are very highly prevalent and the top three somatic symptoms include problems with energy, a lack of energy; lack of concentration and sexual dysfunction.  And what this figure also tells you is that the yellow piece of each bar indicates the fact that they did not receive care for these symptoms.  And at least half of all cancer survivors indicated that they did not receive help for any of these symptoms listed here.  And a similar story applies to emotional symptoms where the top three symptoms include fear of recurrence, sadness and depression as well as issues with grief and identity  These symptoms are very common and here at least 2/3 of the survivors indicated that they did not receive help for these symptoms.

Research has also shown and this might be nice for you to hear, I found it very interesting that changes in cancer survivors are very similar to those changes seen in the aging population in terms of development of impairment, functional limitation and eventually disability. And so researchers are really thinking that cancer survivors should be treated in a similar manner as the geriatric population with a multifactorial management approach where we try and make many little – where we try and change many little things to try and make a big difference for the patient. 

And so there is many gaps in cancer survivorship care, one of which is the many persistent and interacting symptoms as we have seen. Cancer survivors also often change their health behaviors after their diagnosis, either for the better or the worse depending on how they cope. And cancer survivors also tend to drop their adherence to routine maintenance medical care they are so preoccupied with their cancer diagnosis that they forget to go back to their dentist, their primary care physician, their gynecologist.  They sometimes forget taking their medications including their maintenance cancer treatments such as hormonal therapies. And this all can lead to overutilization, decreased quality of life and even decreased survival, in particular if you stop taking your medications.

So the CDC has noted all these trends and issued a statement last year trying to raise awareness for the fact that health professionals really should advance these long term somatic and emotional symptoms, psychosocial symptoms, provide survivors with coordinated care and also promote the importance of healthy behaviors and health maintenance as gender and age appropriate.  Now this is easier said than done because there is a lot of things that we really don’t know, for example we don’t know what is the best way of taking care of this large impending wave of cancer survivors who often reside out in the community.  In terms of which provider should be doing this, a general provider, an oncology provider, physician extender, a social worker, what is the content of how we take care of them and how do we do this, face to face or utilizing telemedicine or any other encounter venue.

What we also don’t know is which interventions are most appropriate, most effective for these symptoms.  We are lacking really head to head comparisons of pharmacological treatments that can help these symptoms in cancer survivors, but also comparison with complementary medicine efforts.  Cancer survivors have often been treated with a lot of toxic treatments and they would prefer to not be treated with any other pharmacological agents for their symptoms.  And so there is an interest in acupuncture, yoga.  We are lacking evidence and as a result of that it’s often not covered by their health insurance. And lastly what we are really lacking are cancer specific health behavior recommendations.  And so we have a large need for a perspective cohort that allows us inside into the change of symptoms and their contributors over time as well as comparatives and cost effectiveness studies.

So the take-home message for today, I think they may ask you in your exam the top three incidents and mortality data for men and women. I hope you’ve learned that the elderly can often receive the same benefit but might also be able to increase the risk for toxicity and that’s important to be aware of new development of symptoms and be open to communication with the oncologist and vice-versa.  I say the same to oncologists when I give them this lecture, trying to stimulate communication between the two.  And elderly cancer patients require often individualize proactive and synergistic care that starts at the beginning when you make decisions about their cancer treatment and really all the way through to multifactorial symptom management where you set expectations but we cannot always accomplish 100% resolution of their symptoms, but we do our best to make them more tolerable including health behavior and improvements where some cancer survivors are developing a guilt feeling if their cancer has come back thinking that they did this to themselves, and so it’s important to stimulate them to do their best and also realize that health behaviors don’t – are not able to 100% prevent the cancer recurrence. 

And so having said that, I think there are two more slides about our survivorship program which is physically located at Magee Women’s Hospital as well as the Hillman Cancer Center.  They have a website here that hopefully will be of benefit to both you as well as your patients.  We offer consultative services. I’m not alone, we have a team of providers that includes a dietician, a physical therapist and a psychologist.  We really can help and most commonly we are asked to help with management of side effects that include both symptomatic symptoms such as emotional and physical symptoms but also prevention of for example fractures and management of their bone health.  We can help with health behavior improvement as desired, we coordinate care between all their providers by sending letters related to the encounter to all the involved providers as patients give us permission to do so. And we also provide access to relevant research studies. 

I wanted to note that we don’t change anything without consulting the patient’s primary providers, so we won’t bypass you in any way.  If you are not the surgeon, if the patient is ineligible or a patient is hesitant to come I’m more than willing to talk with them, just send me an email and I will call them beforehand.  If you want to provide phone numbers to your patients to come and see us we have a number here for Magee that’s mainly reserved for women’s cancer survivors as well as a number for at Hillman that’s accessible for any cancer survivor, it doesn’t matter which age they have. 

This is the end of my presentation, I hope you found it helpful, and thank you for your attention.