Mrs L, Dr A (palliative care consultant), and Dr O (oncologist) were interviewed by a Perspectives editor 2 months after Mr L's death.
DR O (ONCOLOGIST): We discussed with Mr L and his wife that this [leptomeningeal carcinomatosis] was a very ominous turn of events and that without intervention, his prognosis was clearly going to be weeks to a couple of months or so. His choices were to just focus on his comfort or to try to see if we could reverse that and…do additional systemic therapy. Without hesitation, Mr L did not want…hospice care or [to] just focus on palliative care. He absolutely wanted to try.
MRS L: He had stage IV lung cancer, and we started with pretty aggressive chemo treatments. He was very much in the school of thought that he was going to beat this disease. He also started out with full brain radiation and back radiation. He was a very hardy man, and he withstood it pretty well. It seemed as if was doing pretty well. The biggest problem was trying to cope with food. It wasn't appetizing. The treatment also made him extraordinarily tired. I think our doctor in this case was amazing…He obviously knew what the outcome was going to be, but you always pray for the miracle. I think the miracle we got was another year of his life…You know my husband was extremely determined to remain positive, and he never was going to give in [to the fact] that this could eventually kill him…It didn't really dawn on my husband that he was going to die until he was in the hospital with pneumonia, which was 2 weeks before he passed away…I think my husband lived very well at the end, and he died well.
DR A (PALLIATIVE CARE CONSULTANT): When I saw him, he was only 56 years old, but he had this very advanced lung cancer. It was squamous cell, not small cell, poorly differentiated, very aggressive, and widely metastatic at the time of diagnosis, which was 14 months before I met him. So he had very advanced disease by the time I saw him. He'd also had a lot of therapy. He'd had 3 different kinds of chemotherapy and whole brain radiation. He developed leptomeningeal carcinomatosis, where the cancer had spread to the skull base and was knocking off his cranial nerves one by one.
He had started with cranial nerve number 4, so he had diplopia. Then it knocked off 5 and 7 and 8, so he couldn't hear as well, then 9, 10, and 11 went, so he couldn't swallow. That had all happened since February, so about 5 months before I met him. He had an Ommaya reservoir in his skull, so he could get chemotherapy subcutaneously [into the cerebrospinal fluid]. He'd already had 2 kinds of intrathecal chemotherapy. I was called by the primary medicine team, who were taking care of him for an aspiration pneumonia. They wanted me to talk to the patient about future options and hospice, but he was still getting chemotherapy. Before I saw the patient, I called the oncologist. He said he would talk to the patient about his prognosis and about his chemotherapy. I went by later that day and the patient was seeing a speech therapist. Instead of talking to him first, I talked to his son, who was a medical student, and his sister, who was visiting from abroad, separately. They were shocked about the prognosis that I offered…of days to weeks. They were still expecting more chemotherapy. Here I was, walking into the room and basically saying, "OK, folks, it's time for hospice."
Seeking Balance: The Goals and Use of Chemotherapy Near the End of Life
MRS L: Then, I guess it got into his spinal fluid, which is very hard to detect. It took a while to figure that out, and in the meantime he was losing control of his body. They started treating his brain separately. The Alimta [pemetrexed] failed. There was maybe one other option, but it was pretty brutal. My husband was ready to try it anyway, but then he started getting sicker, so he didn't do it. He was too sick to do it. He kept getting chemo to his brain. He got his last one a couple of weeks before he died, but it…didn't do anything. The cancer had already taken hold…
Too much was when they wanted to give him another chemotherapy drug. We discussed it with the doctor, and he told us that it was a very brutal chemo. In my husband's particular condition, it was going to be very hard on him, and it had a very low chance of actually working. It could actually make him worse. At that point, we decided to wait.
The appropriate role of chemotherapy near the end of life is a complex issue.1 As chemotherapy is increasingly available, and better tolerated, its use at life's end involves sophisticated oncologic assessment, a focus on the patient's goals of care, and a balancing of perspectives of the patient and treating oncologist. Ultimately, it may involve judgments about the use or restraint of use of costly resources despite little chance of benefit.2
In some respects, Mr L's care proceeded appropriately from a cancer diagnosis to hospice care. But were there missed opportunities to improve Mr L's care? How can clinicians help patients and families determine when further chemotherapy is no longer beneficial and when they have had enough? Using the case of Mr L as an example, we discuss how clinicians can help patients identify the goals of therapy, the ways that oncology and palliative care clinicians can work together, and strategies to improve communication when chemotherapy is being considered at the end of life.
From the viewpoint of oncologist Dr O, Mr L presented with stage IV lung cancer, with brain and bone metastases. His cancer initially responded to brain and spinal radiation and first-line chemotherapy but then progressed. It stabilized for several months on a second-line agent, but a third-line agent did not halt its growth. He died of leptomeningeal metastases that progressed despite 2 types of intrathecal chemotherapy. He lived 14 months, fairly typical for non–small cell lung cancer, but spent only 6 days in home hospice before death, a short duration but currently not atypical for home hospice care. At the time of the first visit by Dr A, the palliative care physician, Mr L was still a "full code" and had not made any financial transition plans, although he did have a designated power of attorney for health care, which may be more important,3 and Dr A believed that the family and patient were unprepared for the nearness of death. Dr A bore the brunt of some family anger when recommending hospice. He responded by stating that oncologists "need to be trained to involve palliative care folks earlier." However, the oncologist had brought up hospice, and the patient initially declined it, only accepting palliative care involvement when death was imminent. The admitting house staff and palliative care consultant had a sense that this patient with brain metastases was not always making informed choices and had lost opportunities to do other important things with his remaining time while pursuing further chemotherapies and clinical trials. They had concerns about providing care (such as the final dose of intrathecal chemotherapy) that really could not help the patient. (See also Chapter 4, Dealing With Conflict in Caring for the Seriously Ill.)
Identifying the Appropriate Goals of Chemotherapy
DR O: The first order of business was to take care of his brain metastases and make sure that we had done what we needed to do to control [their effects]. While I was fairly confident that with somebody as healthy as he was, we could get him through first-line, second-line, third-line, maybe even fourth line therapy, I would not be comfortable at all knowing that he had untreated brain metastases because then his prognosis could deteriorate fairly rapidly…At the same time, [he was receiving palliative radiation to his vertebral lesion].
Once he was treated, it was pretty straightforward to devise an aggressive chemotherapy regimen with the drug choices that we had. He would tolerate a once-every-week regimen better than a once-every-3-weeks regimen. I had the sense that Mr L needed to be doing something rather than doing something and then waiting and recovering. So, I picked a combination based around gemcitabine.
We did 4 cycles, so about 3 months of gemcitabine, and that took us to the end of August or so. When we rescanned him at the end of the summer, we weren't quite happy with the response. He achieved nice stabilization of his disease, but we weren't quite happy with where he was going…his CEA [carcinoembryonic antigen] was pretty high. It sort of dipped down while he was stabilizing with the first few rounds of chemotherapy, but it seemed it was rising again. At that point, I…elected to treat him with one of the newer drugs, [erlotinib]…Mr L stabilized beautifully on [erlotinib]. His CEA [declined]. His lesions did not disappear, but certainly didn't grow. Clinically, he was doing great. At that point, we immediately switched over to [erlotinib]…He seemed to be doing quite well.
That went on until about February or so, until, all of a sudden, Mr L started to complain of double vision. An MRI…suggested that there was some thickening of the meninges in the area of the cranial nerves. I had him see an oncologic ophthalmologist, and she felt that he had cranial nerve deficit. That was the beginning of the end.
It appeared to us that Mr L had carcinomatous meningitis. Carcinomatous meningitis is very difficult to treat and portends a very poor prognosis.
Reasons for Late-Stage Chemotherapy
Patients may find it hard to get or accept truthful information about the benefits and harms of palliative chemotherapy. In the largest study of 95 consecutive patients receiving palliative chemotherapy, prognosis was discussed by only 39% of medical oncologists.4 In a longitudinal study of hospitalized patients for whom death was believed imminent, families reported that the attending physician never discussed the possibility of death 62% of the time and no one on the medical team discussed the possibility of death with cancer patients in 39% of cases.5 In other studies, at least one-third of patients and families reported they did not believe the information given them that treatment was not curative despite receiving such information.6,7 Another study showed that physicians may "collude" in this hopefulness by giving such a wide range of outcomes that people choose the most favorable.8
It is critical to understand that people facing imminent death have a different perspective. Studies from the United States, England, Canada, Japan, Norway, and Italy consistently show that patients with cancer generally were willing to undergo aggressive treatment with major adverse effects for very small chance of benefit, different from what their well physicians or nurses would choose.9 Some patients with previously treated non–small cell lung cancer would accept chemotherapy for a survival benefit as short as 1 week, whereas others would not, even for a benefit of 2 years (the actual expected benefit was approximately 3 months).10 Most highly educated and motivated patients enrolled in phase 1 studies at the National Cancer Institute said that they would be willing to take an experimental drug—with a 10% mortality rate—for an unknown small chance of benefit.11 Box 22-1 lists some of the difficulties in giving and receiving information about prognosis in advanced cancer.
Box 22-1What Patients Know About Their Advanced Cancer and Its Prognosis |Favorite Table|Download (.pdf) Box 22-1 What Patients Know About Their Advanced Cancer and Its Prognosis
|PATIENTS ARE NEVER TOLD OR ARE NOT TOLD WELL |
|Lung Cancer |
|Thirty-five patients reported learning more about their prognosis from other patients in the waiting room than from their health care professionals. Physicians did not always want to pronounce a "death sentence," and patients did not always want to hear it.98 |
|High-Dose Chemotherapy (With Stem Cell Transplantation) |
|Physicians prescribing high-dose chemotherapy overestimated survival, especially for patients with poor prognosis who might most need to balance toxicity with outcomes.99 The optimistic patients had no better survival than those who were more realistic.100 |
|Terminally Ill With Cancer |
|Even if patients requested survival estimates, physicians said that they provided them with accurate estimates only 37% of the time. Physicians reported that they would provide no estimate, consciously overestimate, or consciously underestimate prognosis 63% of the time.101 |
|Solid Tumors |
|In Belgium, only 39% of oncologists reported ever reviewing prognosis with patients. Most of the interview was spent on active treatment, not alternatives.4 |
|Nearly all patients could name their diagnosis, but only 23% knew their stage, which is critical to appropriate goal setting.102 |
|Oncologists consistently overestimated prognosis by at least 30%.103 In our own study, physicians' estimate of survival could be divided by 3.5 for actual survival.104 |
|During consultations where treatment decisions were being made, most patients were not given clear information about the survival gain from palliative chemotherapy by their oncologist.105 |
|PATIENTS' BELIEFS ABOUT PROGNOSIS, BENEFITS, AND RISKS OF TREATMENT |
|Metastatic Lung Cancer |
|One-third of patients thought they were receiving therapy with curative intent despite being told prognosis and goals of care.6 |
|Head and Neck Cancer |
|Thirty-five percent of patients believed that their palliative radiation was supposed to be curative.7 |
|Phase 1: Overoptimistic |
|If told that a treatment helps 20% of people like them, patients reported a 44% chance of it helping them personally.87 |
|Negative Information |
|When oncologists made at least one statement of appropriate pessimism for incurable patients, patients were more likely to agree with their oncologist's estimated chance of cure.106 |
|PATIENTS CHANGE THEIR MIND ABOUT COMMUNICATION |
|Metastatic Breast Cancer |
|Between first and second lines of chemotherapy, 59% of 729 patients with advanced cancer changed their preference about involvement in decision making; 37% wanted a less active role, and 22% wanted a more active role.107 |
|Thirty-eight percent of women took an active role in decision making for first-line chemotherapy and 43% for second-line chemotherapy. The reasons to undergo chemotherapy shifted from the possibility of controlling the tumor (50% for first chemotherapy, 38% for second) to providing hope (19% for first-line chemotherapy, 43% for second-line); the proportion expecting to be cured decreased from 10% to 0% with second-line chemotherapy.108 |
|PATIENTS HAVE DIFFERENT PERSPECTIVES THAN THEIR WELL HEALTH CARE PROFESSIONAL CAREGIVERS |
|SOLID TUMORS |
|Patients would have toxic treatment for a 1% chance of cure, 10% chance of symptom relief, or chance to prolong life 12 mo. Their physicians and nurses would require a 50% chance of cure, 75% chance of symptom relief, and 24 to 60 mo of added survival.109 |
|Patients accepted a lower chance of benefit from chemotherapy than their physicians or nurses, even when treatment involved great toxicity.110 |
|Fifty-seven percent of patients would choose chemotherapy for a survival benefit of 10% at 1 y. Some chose more toxic treatments even if they offered no survival advantage, whereas others declined chemotherapy regardless of perceived advantage of treatment. It was difficult to predict what individual patients would choose.111 |
|Lung Cancer |
|Patients younger than 40 y would accept the toxic treatment with only a small benefit: chance of cure (median, 7%), life prolongation (3 mo), and symptom relief (8%).112 |
|Patients would be willing to undergo chemotherapy for small benefit, even if the physician presents the results pessimistically.113 |
|United States |
|Patients who had undergone chemotherapy for lung cancer would take it again if it added survival of 4.5 mo with mild toxicity or 9 mo with severe toxicity. When given the choice between supportive care and chemotherapy, 22% chose chemotherapy for a survival benefit of 3 mo, which was the actual expected benefit. Sixty-eight percent would choose chemotherapy if it substantially reduced symptoms without prolonging life. Only a quarter remembered hearing any options about treatment that did not involve chemotherapy, such as palliative care.4 |
|If their lives would be prolonged by 3 mo, 19% would choose to receive intensive treatment, and 21% would choose less intensive treatment. With a 70% chance of symptom relief, 73% of patients were willing to choose intensive chemotherapy.114 |
|PALLIATIVE CHEMOTHERAPY |
|Patients' choice for chemotherapy or palliative care was most strongly predicted by their preconsultation treatment preference.115 |
|Patients reporting higher quality of life were more likely to judge palliative chemotherapy as acceptable.116 |
|Phase 1 Participants |
|Of 163 patients participating in a phase 1 study, for which, by definition, the goal is to assess toxicity, only 7% considered no treatment at all; 81% were aware of hospice, but only 6% had seriously considered hospice for themselves.11 "More than 90% of patients said they would still participate in the study even if the experimental drug caused serious adverse effects, including a 10% chance of dying." |
Multiple studies document that palliative chemotherapy is increasingly given near death. Earle et al12 found that more than 20% of patients receiving Medicare who had metastatic cancer started a new chemotherapy treatment regimen in the 2 weeks before death. Similarly, they found that 17.1% of younger, commercially insured patients were still being treated with chemotherapy within 2 weeks of death.13 In Italy, 23% of patients with incurable cancer received chemotherapy within 30 days of death, and in Korea, 30.9% of patients received chemotherapy in the last month of life.2,14 In a US community practice, chemotherapy for patients with lung cancer was given within 30 days of death for 43% and within 14 days for 20% of patients.15 Patients are unlikely to benefit from chemotherapy when they have already been failed by the standard regimens, have poor performance status, and otherwise have a poor prognosis. The largest study of matched patients who received hospice and no chemotherapy vs those who did not receive hospice care but had chemotherapy showed that survival was significantly longer for hospice patients with lung cancer and pancreatic cancer, marginally longer for colon cancer, but no different with breast or prostate cancer. The authors concluded that this was consistent with chemotherapy not prolonging and possibly shortening life for those eligible for hospice.16 Furthermore, chemotherapy produces adverse effects, precipitates hospitalization and emergency department visits, precludes entry into most hospices, and may require additional supportive care with erythropoietin-like drugs and colony-stimulating factors that are expensive and contribute little to the patient's overall quality of life. For these reasons, the factors that go into patients' decisions to undergo chemotherapy near the end of life bear examination.
Is Distinguishing Curative From Palliative Chemotherapy Important?
Chemotherapy for metastatic solid tumors, such as lung, breast, colon, or prostate cancer, rarely if ever cures patients. The indication for such chemotherapy is to improve disease-free or overall survival, relieve symptoms, and improve quality of life. Palliative chemotherapy accounts for most of the work of everyday oncology given the rarity of curable disease. The American Society of Clinical Oncology could not decide on a minimal benefit for which chemotherapy was indicated, only that some benefit must be demonstrable.17 Consensus panels that include cancer advocates make little distinction between curative treatment and palliative treatment that could extend life18 because 6 months' added survival could be as important as an increased rate of cure.
The increasing effectiveness and lessened toxicity of palliative chemotherapy are well supported by randomized trial data. First-line chemotherapy for patients with non–small cell lung cancer improves survival by 2 to 3 months, relieves symptoms, and improves quality of life compared with best supportive care.19 Second-line treatment of patients with non–small cell lung cancer with docetaxel vs best supportive care is associated with significantly longer survival (7.0 vs 4.6 months, or 10 weeks, and a difference in 1-year survival, 29% vs 19%)20 and improvements in pain and less deterioration in quality of life.21 Even third-line treatment may improve survival or symptoms, especially with novel, relatively nontoxic oral agents, such as erlotinib, which, in 1 study, improved survival compared with best supportive care from 4.7 to 6.7 months with improved results for pain, dyspnea, and physical functioning.22 Palliative chemotherapy has also increased survival and quality of life in metastatic colorectal23 and prostate cancer24 (Table 22-1). Mr L benefited from receiving 3 separate types of palliative non–small cell lung cancer chemotherapy: gemcitabine and carboplatin, oral erlotinib, and pemetrexed. Although he never had particularly notable responses to treatment, his disease stabilized for months while he received the first 2 treatments, and his central nervous system disease was stable for weeks because of intrathecal methotrexate.
Table 22-1Palliative Chemotherapy for Metastatic Disease for Four Common Solid Tumors |Favorite Table|Download (.pdf) Table 22-1 Palliative Chemotherapy for Metastatic Disease for Four Common Solid Tumors
|Cancer Treatment ||Comment |
|Non–Small Cell Lung Cancer |
|First-line chemotherapy with modern regimens ||Improves survival by at least 3 mo with acceptable toxicity, better symptom control, manageable toxicity19 |
|Second-line (docetaxel) ||Improves survival by about 2 mo vs best supportive care, with better symptom control while taking treatment20,21 |
|Second- or third-line (erlotinib) ||Improves survival by about 2 mo vs placebo, with acceptable toxicity22 |
|Third- or fourth-line ||Response rate only 2% and 0% when patients have previously received docetaxel and platinum25 |
|Breast Cancer |
|First-, second-, and third-line chemotherapy ||Average survival has improved during the past decades with lessened adverse effects from chemotherapy, but no randomized clinical trials have compared treatment with best supportive care26 |
|Colon Cancer |
|First-, second-, and third-line chemotherapy ||Average survival from diagnosis of metastatic disease has improved from 9 to 22 mo with the new drugs available (eg, oxaliplatin, irinotecan, cetuximab, bevacizumab)23 |
|Prostate Cancer |
|First-line chemotherapy ||Docetaxel every 3 wk improves survival by 2.4 mo, with no adverse effect on quality of life27 |
| ||Second-line chemotherapy can palliate symptoms and decrease prostate-specific antigen level but does not improve survival28 |
How Can Clinicians Help Patients With Decision Making?
Mr L's palliative care specialist noted that because patients are vulnerable to fastening on slim hopes, oncologists must improve their skills in helping patients think clearly about the appropriateness of chemotherapy.29,30 To help their patients make wise decisions, oncologists can start with a prompt list of questions, proven to enhance communication31-33 and similar to a list in use in several oncology practices,34,35 including ours (Box 22-2). This can be provided to the patient in the waiting room for discussion with his/her physician. Another important communication is a straightforward discussion of the quality and quantity of life with or without chemotherapy. In most cases, there will not be a randomized trial of best supportive care vs best supportive care plus chemotherapy, but at least the important discussion points can be raised. There must be some definable benefit before chemotherapy can be recommended. It also may be helpful for practitioners to explore how patients interpret and assign meaning to their ongoing experience with the disease and treatment, which can ultimately give some insight to their treatment preferences and decisions.36 Patients often look to their oncologist for both information and emotional support to resolve their concerns and to assist with shared decision making.37 Table 22-2 provides some examples of helpful communication strategies. (See also Chapter 2, Beyond Advance Directives.)
Box 22-2Helpful Questions to Consider Asking About Palliative Chemotherapy |Favorite Table|Download (.pdf) Box 22-2 Helpful Questions to Consider Asking About Palliative Chemotherapy
|What is my chance of cure? |
|What is the chance that this chemotherapy will make my cancer shrink? Stay stable? Grow? |
|If I cannot be cured, will I live longer with chemotherapy? |
|How much longer? |
|What are the main adverse effects of the chemotherapy? |
|Will I feel better or worse? |
|Are there other options, such as hospice or palliative care? |
|How do other people make these decisions? |
|Are there clinical trials available? |
| What are the benefits? |
| What are the risks? |
| Am I eligible? |
| What is needed to enroll? |
|What are the likely things that will happen to me? |
|How long will I live? (Ask for a range, the most likely scenario for the period ahead, and when death might be expected.) |
|Are there other things I should be doing? |
| Preparing a will? |
| Completing advance directives? |
| Assigning a durable power of attorney for health care who can speak for me, if I am unable? |
| Addressing financial or family legal issues? |
| Assigning a durable power of attorney for financial affairs? |
| Creating a trust? |
|Address family issues |
| Will you help me talk with my children? |
|Address spiritual and psychological issues |
| Who is available to help me cope with this situation? |
|Reflect on legacy and life review |
| What do I want to pass on to my family to tell them about my life? |
|Other concerns? |
Table 22-2Things to Do or Say (and Not to Do or Say) About Chemotherapy for Advanced Cancera |Favorite Table|Download (.pdf) Table 22-2 Things to Do or Say (and Not to Do or Say) About Chemotherapy for Advanced Cancera
|Do ||Do Not ||Comment |
|Ask patients how much they want to know. ||Do not assume that people will or won't want to know their diagnosis. ||Although cultures vary, most patients want to know their prognosis and options. They may underestimate their odds, too, and forgo useful chemotherapy. |
|Ask patients how much they want to be involved in the decision making. ||Do not assume that people will want to make decisions themselves or have you make them. Ask. ||People vary, and their participation will vary. They may be ready to evaluate all the options or for you to choose what to do next. |
|Define "response" and "cure." || ||Patients can mistake a 20% chance of response with a 20% chance of cure. |
|Write down a list of potential benefits of and adverse effects from chemotherapy. ||Do not assume that patients will know their likelihood of being helped. ||Chemotherapy must have some definable benefit to be justifiable. |
|Ask patients their goals. || ||Surviving 2 extra months may be critical to some people, unimportant to others. |
|Respond to emotional concerns. ||Do not assume that intense emotion means you should not have disclosed diagnosis or prognosis. ||Physicians can respond empathetically in verbal and nonverbal ways, which can ameliorate patient distress.37 |
|Begin a discussion about what to do if or when the cancer is resistant to chemotherapy. || ||This is a good place to say, "We hope to control the disease, but at some point it may grow so that it will end your life. We need to prepare for that, too." |
|Say, "The cancer is shrinking but is still there." ||Do not say, "The cancer is responding." If you say this, estimate that it will likely last for [some number of] months. ||Important to emphasize what is likely to happen, so that people can make plans. |
|Be hopeful if there is reason to hope about the cancer. || ||Most people can be hopeful about something, even if their cancer is growing. |
|Begin a discussion about do-not-attempt-resuscitation orders. || ||This is a good time to say, "The cancer is growing and may end your life. There are some important issues to discuss. Tell me how much you want to know." |
|End of Life or Cancer Progression |
|Bring up hospice when there are still some oncology treatment options, not at the end of life. ||Do not ask hospice to just manage the last stages of dying at home. ||Make hospice an option that is part of usual medical care for someone with cancer. |
|Ask for your own patients' hospice length of stay and the number of your patients who die within 7 d of enrollment. || ||Make it a performance improvement goal for the practice to meet or exceed the national length of stay in hospice. |
|Tell people you will not abandon them if they enroll in hospice. || ||Some physicians make appointments for every 2 weeks even for hospice patients. If they are too sick to attend, it is a good reminder to check in by telephone or visit. |
Studies consistently document that patients want and use such information. Of 126 terminally ill patients, 98% said they wanted their oncologists to be realistic,38 and patients want oncologists to be truthful and compassionate and to continue caring for them during their illness.39 A comprehensive review found that randomized trials of decision aids in oncology yielded increased patient knowledge and more involvement in decision making,40 and a decision aid for adjuvant therapy of breast cancer (http://www.adjuvantonline.com) improved medical decision making and helped low-risk patients avoid unnecessary chemotherapy.41,42 A preliminary study showed that directly giving patients information about prognosis and treatment to share with their oncologist is desired and helpful.43 (See also Chapter 19, Complexities in Prognostication in Advanced Cancer.) We use decision aids in our own practice that address prognosis with and without chemotherapy in a question-and-answer format, using simple terms (ie, "10 in 100 people" instead of "10%") and figures.
What Should the Clinician Do When the Patient Wants to Continue Chemotherapy at the Very End of Life?
DR O: I couldn't get him to stop thinking that he needed one more treatment. One more treatment was what he needed to spring him loose.
In the difficult situation faced by Dr O and Mr L, when the oncologist thinks further chemotherapy is not indicated, a number of strategies may be tried: holding family conferences to identify the decision makers in the family and getting the same information to all involved, informing people of and giving them access to the actual medical research studies and results, or writing the options down in concrete terms.44 Much of the time, patients and families may simply need more time to adjust to a difficult situation. Sometimes, they just have a different perspective that must be valued as much as the health care professional's.45
Transitioning to Palliative or Hospice Care
When Should Patients Stop Chemotherapy and Transition to Palliative or Hospice Care?
MRS L: I think that he felt he was in control until the last 2 weeks of his life, and that was important. The kids were very involved. We had a lot of closure.
DR O: [Within weeks of his death,] Mr L was still in a "I've got to do something" mode, but I was telling him,…"We've got to get hospice going so that you can relax and everyone [in your family] can get what they need, and they can move on." He was not having any of it, though.
DR A: I was going in there to talk hospice, prognosis less than 6 months, and he was still "full code." He had to be made "no code." He was still expecting chemotherapy, [and] at least some of the members in his family were, and he was getting chemotherapy…I went in to see him on a Thursday night, but didn't get to talk to him until Friday. When I went in on Saturday morning, it was a totally changed picture. The patient and his wife were now demanding to go home on hospice. So, clearly I had somehow gotten through. He was now "no code," per the medicine team. They wanted hospice immediately.
I left the room and went to engage hospice on the weekend, which wasn't easy. I couldn't get the hospital bed delivered until the next day, so he went home with his regular bed, propped up on pillows so he wouldn't aspirate overnight. I gave them some suggestions as to how he could eat. I pulled the nasogastric tube, which was the major source of his discomfort, and he went home.
The next day, I called to make sure that he was OK and that the hospital bed had arrived. That was Sunday.
The mother and the brother called me on Monday, and they were extraordinarily angry at me…for stopping artificial nutrition and stopping chemotherapy. I explained that the decision about chemotherapy was [between the patient and] the oncologist, and it was necessary if he was to go onto hospice, which was the right thing for [him] at this point. They wanted to know why we didn't put a PEG [percutaneous endoscopic gastrostomy tube] and start enteral liquid artificial nutrition or TPN [total parenteral nutrition]. They wanted TPN at home. I explained that we don't do that on hospice and usually it just prolongs the patient's suffering.
In the meantime, the patient was at home. I called every day to see how he was doing. The patient declined quickly and died on Thursday. His last dose of chemotherapy had been 6 days before.
Making the transition to palliative care or hospice is difficult for both patients and oncologists. There are usually some treatment options, even for relapsed disease. The available lung cancer treatment data suggest that each 3.3% of response rate leads to better survival of 1 week and increases survival at 1 year by 1.6%, which might be important to some patients.46 The National Comprehensive Cancer Center Network guidelines recommend that after 2 chemotherapy regimens have failed to benefit the patient or if the patient's performance status declines to 3 or more, such that chemotherapy will not be tolerated, a switch to palliative or hospice care be made.47
The American Society of Clinical Oncology and other major professional societies have long recommended hospice as the best available care for dying patients.48 (See also Chapter 36, The Role of Hospice and Other Services.)
In our experience, many families and patients who choose, like Mr. L, to enroll in hospice wish they had done so sooner. The median length of stay on hospice has decreased from 26 days in 2005 to 20 days in 2007, with 30.9% enrolling in the last week of life.49,50 Hospice care may help the family and the patient. One study showed that hospice care was associated with a 0.5% lower absolute risk of death for the Medicare-age surviving spouse.51 Families' perception of late referral is associated with lower satisfaction with hospice care overall.52 In the most recent and largest study, among those with hospice stays of less than 30 days, 16% of families said they were referred too late.53 Of note, the perception of being referred too late, but not the actual length of stay, was associated with more unmet needs, lower satisfaction, and more concerns. One study found that patients would have liked palliative care consultation earlier in their course.54 It is unknown whether this view of "too-late" referrals to palliative care and hospice will change with the new relatively nontoxic chemotherapy treatments.
Improving Communication About Hospice and End of Life
MRS L: He wanted to keep fighting. There was also a lot of animosity [from the overseas family members] toward Dr A, who is the most honest and incredible person on the planet. They felt that he had talked my husband into stopping treatment, and that was not the case at all. Dr A never really had anything to do with that. It was strictly between my husband and his oncologist.
DR A: I think that when the patient developed leptomeningeal carcinomatosis, which has a prognosis of 6 to 12 months, I would have brought in the palliative care folks at that point and begun the discussion of setting up hospice. I would have really made it clear that we were going to give X number of cycles of palliative chemotherapy through the Ommaya reservoir and see if it worked, sort of as a therapeutic trial. That's what needed to be done here. We needed to say, "We're going to try X for this long and see if it works" [and start discussing plans in the event of treatment failure]. This man had made no substantive financial estate planning. There was a woman who was a good friend of his and had been appointed as the executor of his estate. While I was trying to arrange hospice on the last day of his hospitalization,…she wanted to know if he was competent to sign a bunch of documents, [which] you must do much earlier. The tragedy here is that the children, the wife, and the mother and brother who didn't even arrive in time to see him alive, were not prepared for his death. They had not had the full benefit of hospice care. If they had started hospice care in April, and he died in July, as he did, things might have gone a lot more smoothly, and people would have been better prepared.
Dr O suggested hospice enrollment to Mr L and he was even visited by a hospice intake worker, but he chose not to enroll until it was explicitly clarified that there were no further chemotherapy options. This is not unusual: Teno et al53 estimated that 23% to 61% of short-stay hospice patients could not have been referred earlier because of late diagnosis or patient refusal.
In our opinion, oncologists should note the availability of hospice from the beginning as part of routine good care of the seriously ill patient. After all, in 2007 hospices enrolled more than 1.4 million patients, representing 38.8% of all deaths in the United States, with 41% of enrolled patients having cancer.50 Unfortunately, families often receive little information from physicians about hospice.55 In 1 study, physicians initiated the discussion about hospice about half the time, whereas patients or families initiated one-third of the discussions. Patients and families identified as important in deciding about hospice the frequency of visits, payment, and the practical help it provides.56 (A list of the resources that hospices can provide to patients is found in the Resources.) Barriers include physicians' lack of knowledge of hospice philosophy, services, and patient eligibility requirements. Brickner et al57 found that 84% of physicians surveyed were unable to identify appropriate hospice diagnoses and that only 12% were aware of the National Hospice Organization Medical Guidelines for Determining Prognosis in Selected Non-Cancer Diagnoses. In a randomized trial of nursing home residents, a structured interview on admission—in essence bypassing physician reluctance and making the hospice benefit known to families and patients—increased appropriate hospice enrollment from 1% to 20%.58
In our opinion, patients and families should receive all of the necessary information about hospice and palliative care to permit the most informed decision about how to spend their last few weeks or months. We also recognize that even after the most earnest communication efforts, patients and families may continue to want chemotherapy.29 Communication about prognosis, what to expect with disease progression, and advanced directive and financial planning can all be done independently of a hospice decision and should remain a high priority for patients with advanced disease.
Why Don't Patients and Oncologists Discuss Prognosis?
DR O: I thought that it would help everybody for Mr L to hear that he couldn't get into a clinical trial because physically he wasn't up to the standards of the trial. That, I thought, would have allowed Mr L to accept palliative care sooner than he did.
MRS L: I never thought "too much" was too much. You always hope that he can come out of this by some miracle. The "too much" was when he became ill in the hospital.
DR A: When I saw the patient, there was clearly no understanding about the real prognosis. In fact, I gave a prognosis of days to weeks and said that it could be less than 2 weeks. He died in 6 days.
When the prognosis is predictable, as with Mr L, why do most oncologists not directly address it? One paradoxical explanation is that patients do not want to discuss such terrible issues with their oncologist. Of 101 inpatients with cancer admitted without advance directives, only 23 wished to discuss the issue with their oncologists; however, 56% of those without advance directives (44 of 78) supported discussing it with the admitting physician and not the oncologist.59 An analysis of consecutive admissions to a single oncology unit showed that only 5 of 75 ill patients had discussed advance directives with their oncologist, and the oncologist initiated that discussion in only 2 of 75 patients.60
More than 85% of patients found it acceptable to discuss advance directives with the admitting physician and thought it was important. Although they did not want to discuss advance directives with their oncologist, more than half the patients would choose their oncologist for an advance directive discussion. One study found that limiting talk about prognosis may even be a type of tacit agreement between patient and oncologist to avoid an uncomfortable topic.61 (See also Chapter 1, Initiating End-of-Life Discussions With Seriously Ill Patients.)
As oncologists, we know we should, and most patients want to have these discussions, but we do not. Surprisingly, having an advance directive is associated with a 2-fold increase in surviving high-dose chemotherapy and stem cell support,62 so we can reassure patients that having an advance directive will not lead to an increased chance of death. One explanation is that such discussions may be simply too difficult and painful for even the most experienced clinicians. A qualitative study asking oncologists to describe their emotions during these conversations included statements such as "draining," "unpleasant," "exhausting," and "hard." Prior surveys documented "serious shortcomings in the training and current practices of oncologists" of palliative care and that only 25% of oncologists found end-of-life care highly satisfying.63 A study in Italy confirmed what most oncologists know: that giving really terrible news causes negative emotions for the clinician that persist and that it is easier on the physician to avoid the grim truth.64 More recently, as part of a study by the Cancer Care Outcomes Research and Surveillance Consortium involving more than 10 000 patients diagnosed as having lung or colorectal cancer between 2003 and 2005 in the United States, Keating and colleagues65 conducted a national survey of physicians caring for patients newly diagnosed as having metastatic disease. Physicians were queried about timing of discussions regarding prognosis, do not resuscitate (DNR) status, hospice, and preferred site of death for patients who were currently feeling well but whom they estimated had 4 to 6 months to live. Among the 4074 physician respondents (61% response rate), 65% said they would discuss prognosis "now." Fewer would discuss DNR status (44%), hospice (26%), or preferred site of death (21%) "now." At the time of the survey, national guidelines from the National Comprehensive Cancer Network and the National Consensus Project for Quality Palliative Care recommended discussion of all of these topics with terminally ill patients (defined as a life expectancy of 1 year or less). In multivariate analyses, young physicians more often discussed prognosis, DNR status, hospice, and site of death "now" (P < .05 for all). Oncologists and surgeons were more likely than noncancer specialist physicians to discuss prognosis "now" (P = .008), but noncancer specialists were more likely to discuss DNR status, hospice, and preferred site of death "now" (P < .001 for all). Female physicians were less likely than male physicians to report discussing prognosis "now" (P = .05), but physicians with a greater number of terminally ill patients were more likely to do so (P = .003). Asian physicians were less likely than other physicians to discuss prognosis "now" (58.9% vs 65.9%, P = .02), and Hispanic physicians were most likely to discuss DNR status "now" (55.1% vs 47.6%, P = .05). Finally, when asked if they felt knowledgeable enough to discuss end-of-life options with their terminally ill patients, 55% of physicians "strongly agreed" and 30% "somewhat agreed," and these 2 groups of physicians were more likely than physicians who "neither agreed nor disagreed," "somewhat disagreed," or "strongly disagreed" to discuss prognosis "now."
Given the incurability of some cancers, such as with Mr L, there is a need for these conversations and consideration of hospice care. At the very least, finding out how much a patient wants to know and then providing that information should be addressed by all clinicians.66(See also Chapter 19, Complexities in Prognostication in Advanced Cancer.)
Shifting Goals of Care to Palliation: Why Is It So Difficult for Physicians?
Clinicians often struggle with initiating discussions about shifting treatment goals and in particular transitioning to palliative care. Patients may respond with denial, anger, or sadness. These are all normal responses to the associated loss of control, a fear of the immediate future, or an underlying fear of death. For the most part, patients and families will have their own unique timetable and method for processing this information.7 Clinicians should generally respond with patience, emphasizing support (nonabandonment) and assurance of aggressive symptom management67 (Table 22-2).
Not surprisingly, physicians may respond to their patients, particularly those with whom they share a long-term relationship, with powerful emotions of their own.68 These emotions can include a personal and professional sense of failure and frustration, guilt, powerlessness against the illness, grief, a need to rescue the patient, or a desire to separate from and avoid patients to escape these feelings.69 Clinicians' feelings of medical ineffectiveness can lead to failure to identify patient-specific and family-specific values influencing decisions, which may lead to a lack of clarity about care goals. Avoidance of the discussion altogether can lead to mistrust of the health care system and medical profession, inappropriate use of life-sustaining medical technologies, increased medical complications, and long hospital stays.70 Recognizing, accepting, and reflecting on the normalcy of such feelings allow the professional to make a conscious choice about how to proceed in the relationship with the patient. Finding a trusted colleague in whom to confide can be part of a plan to prevent isolation, improve objectivity, and avoid burnout.71 (See also Chapter 42, Self-Care of Physicians Caring for Patients at the End of Life.)
Doesn't Honesty Take Away Hope?
No data are available that show hope can be taken from patients, as was once thought, or that patients are harmed by carefully provided information.72,73 As the Education on Palliative and End-of-Life Care for Oncology curriculum74 states, "Information carefully shared is a gift to the patient and the family who want it and minimizes the risk that patients will distrust the cancer care team." In pediatric oncology, full prognostic disclosure supported hope, even when the prognosis was poor.75 Even in the face of a terminal diagnosis, patients and families have a wide range of hopes: being free from pain and other symptoms, preparing for death, contributing to others, having spiritual peace, spending time with loved ones, and even having trust in one's physician.76,77
Ways That Oncologists and Palliative Care Specialists Can Work Together
DR A: I think oncologists, in general, need to get more comfortable with palliative care. It's not an "either, or" situation, it's a "both, and." I think physicians, in general, including people like this excellent oncologist, need to be bolder at offering more real prognoses.
Evidence, albeit far from conclusive, suggests that "concurrent" palliative or hospice care alongside routine oncology care improves health outcomes (Table 22-3). Project Safe Conduct was started to integrate hospice care into lung cancer care at the Ireland Cancer Center. Before the study, 13% of patients with advanced lung cancer were referred to hospice; afterward, 75% of such patients died after enrolling in hospice, and the average length of stay in hospice increased from 10 days to 36 days.79,84 The 1 randomized trial of concurrent hospice care plus usual oncology care vs usual oncology care alone has been published only in abstract form.78 The group with concurrent care lived slightly longer (not statistically significant), had quality of life preserved longer, used less chemotherapy, and transitioned to hospice enrollment sooner. The clinical care differences were modestly in favor of the concurrent care approach, but the hospice cost was substantial and much higher than the cost of hospitalizations avoided (John Finn, MD, Ascension Health Systems, Detroit, Michigan, oral communication, October 2004). Meyers and colleagues81 enrolled patients in a phase 1 and 2 cancer treatment study and into a simultaneous care program that emphasized symptom management and transition to hospice. The uptake of the program was excellent. Patients received as many cycles of chemotherapy as without simultaneous care and were referred to hospice more frequently and earlier. A study at the Dana Farber Cancer Institute showed that cancer patients will use a free palliative care service alongside their usual oncology care, but health outcomes are not yet available.1 The 1 large randomized controlled trial of usual care plus palliative care consultation, in which 27% to 34% of patients had cancer, showed no difference in symptoms or survival but showed a $4855-per-patient cost savings.85 Proof of symptom control or survival improvement at a cost society can afford will require rigorous testing, preferably in randomized clinical trials.
Table 22-3Studies of Concurrent Palliative Care With Oncology Care |Favorite Table|Download (.pdf) Table 22-3 Studies of Concurrent Palliative Care With Oncology Care
|Source ||Results ||Comments |
|Finn et al,78 2002 ||Randomized oncology patients to standard care with or without hospice or palliative care consultation. Intervention group had longer preserved quality of life, fewer symptoms, and (nonsignificantly) better survival. No difference in symptom control but quality of life declined less in the intervention group. Intervention cost >$1.5 million, or >$17 800 per patient, but was associated with cost savings of >$2500 per person by avoided hospitalizations. Final results are in process (John Finn, MD, oral communication, January 2004). ||Only shows some improvement in symptoms but no difference in survival at increased cost due to the high cost of interdisciplinary hospice services when used for palliative care (John Finn, MD, oral communication, January 2004). |
|Ford Pitorak et al,79 2003 ||Project Safe Conduct gave modified hospice consultations for all patients with lung cancer starting treatment. After the program, 75% died in hospice care vs 13% before, with a median length of stay in hospice of 36 d after vs 10 d before. Program expanded to include advanced cancers, specifically lung, gastrointestinal, and head and neck cancers. ||Project Safe Conduct has been sustained, is highly successful, and has been well received with demand for more teams at the Ireland Cancer Center (Elizabeth Pitorak, RN, PhD, written communication, February 2, 2004). |
|Elsayem et al,80 2004 ||For patients at a comprehensive cancer center referred to palliative care, severe distress on admission and severe symptoms of distress significantly improved after palliative care consultation. Mean daily charges in the patient care information system were 38% lower than the mean daily charges for the rest of the hospital. ||First published demonstration of better symptom control and lower costs for patients at a tertiary comprehensive cancer center; not really concurrent care. |
|Meyers et al,81 2004 ||44 Patients in phase 3 trials "simultaneously enrolled into a defined home care program focused on supportive care needs of the patient and family, as well as assessment of the toxicities of investigational therapy" vs 20 usual care patients. Quality of life improved but not significantly; 35 of 44 receiving supported care were referred to hospice vs 8 of 15 receiving usual care (P = .03), with longer mean but not median stay. Use of 2.5 cycles of chemotherapy did not differ and was well accepted. ||Supportive care may enhance coordination of care and facilitate patients' explicit transition from curative intent to palliative intent; a comparative randomized trial evaluating supportive care has yet to be completed. |
|Temel et al,1 2007 ||51 of 53 Patients with lung cancer enrolled in a study during which they were seen concurrently by oncology and a palliative care team, which visited most several times and visited all who survived 6 mo, and continued team visits in addition to oncologist visits. Only 2 (of 53 patients) refused to meet with the team. No outcome data. ||Concurrent care is feasible, but whether it improves health outcomes (effectiveness) and cost-effectiveness vs usual care should be evaluated in a randomized trial. |
|Spettell et al,82 2009 ||A comprehensive case management and expanded hospice benefits program was offered to approximately 5000 seriously ill patients insured by Aetna; a precomparison and postcomparison was done. ||Comprehensive management was associated with an increase in hospice use from approximately 30% to 70%; mean hospice days increased by more than 14 d to approximately 30 d; and the number of inpatient and intensive care unit days were reduced by more than half. |
|Bakitas et al,83 2009 ||Project ENABLE II (Educate, Nurture, Advise, Before Life Ends), a randomized controlled trial with 322 cancer patients, compared those who received usual oncology care with those who received a concurrent nurse-led, palliative care–focused intervention addressing physical and psychosocial needs and care coordination. ||Intervention group had higher scores for quality of life and mood but did not have improved symptom intensity scores, reduced days in the hospital or intensive care unit, or reduced number of emergency department visits. |
One of the largest barriers to hospice in the United States is the way it is defined in the Medicare Hospice Benefit. Patients must have a life expectancy of 6 months or less and must forgo curative treatment. Funding for chemotherapy and radiation is limited; thus, being enrolled in hospice can significantly limit useful palliative treatment. Several hospice programs have begun to respond to these eligibility barriers and are providing a broader range of services.30 Some have changed to palliative care programs under home health care services, integrating palliative chemotherapy and radiation and related treatments (paid for by the patient's insurance or Medicare drug benefit) with elements of traditional hospice care. Passik and colleagues86 at Hospice of the Bluegrass showed that patients who transition from acute care to palliative care then to the hospice benefit, compared with those who transition directly from acute care to the hospice benefit, may prove to be both financial and care burdens to the hospice. A randomized trial showed palliative care consultation alongside usual medical care saved the insurer $4855 per patient with no decrement in survival or symptoms.85 Several larger insurance-sponsored trials are ongoing.
The Aetna trial of providing expanded case management and clarifying hospice options to people with life-ending illnesses, mostly cancer, is illustrative.82 Aetna identified patients by a software program and offered the Compassionate Care Program to eligible patients directly via telephone. It was rarely declined because it did not take away any benefits. As noted in Table 22-3, the results were impressive. Comprehensive management was associated with an increase in hospice use from approximately 30% to 70%, mean hospice days increased by more than 14 days to approximately 30 days in all groups, and the number of inpatient and ICU days were reduced by more than half. The program cost an additional $400 per person for the case management but more than paid for itself through reduced hospitalizations and ICU days. This trial result is consistent with other studies that show that offering options to patients directly, without interference by a physician, can lead to better end-of-life care. The only methodologic problem with this study is the lack of a randomized control group, but such studies are ethically difficult to perform. One proof of its success is that many other insurers have begun offering similar options.
Integrating Other Cancer Care Issues Into Decision Making at the End of Life
DR O: We were continuing the current course of treatment because he wanted it, but it was quite appropriate to initiate palliative care. Then Mr L and his wife embarked on this idea that he needed to get into a clinical trial…Dr A was able to help the family put aside their differences in order to allow Mr L to enter into palliative care and go home and stay home.
Patients on clinical trials have as good an understanding of the risks and benefits as we can give them—after all, they have read and signed informed consent documents—but this understanding is far from perfect. Despite written information, many will still overestimate their own particular chance of success.87 Mrs L expressed, as do many patients and families, that they hoped Mr L would survive long enough to receive a new treatment, or even a cure. And as noted, informed phase 1 patients are willing to undergo new treatments with a 10% mortality risk for an unknown but low chance of benefit.
Reimbursement and Economic Issues: Why Oncology Is Different
Most palliative care is relatively inexpensive. However, palliative chemotherapy regimens have a huge price tag, for example, at a cost of up to US $100 000 a year per patient, and even insured patients can be burdened by a 20% copayment requirement. The cost of palliative chemotherapy for colorectal cancer could easily be $50 000 a year, not counting supportive care drugs or imaging.88 Patients with cancer account for approximately 40% of all US Medicare drug costs, totaling an estimated $5.3 billion in 2006, with $1.5 billion for erythropoietin-like drugs alone.89 Some drugs (oxaliplatin for metastatic colon cancer90 and docetaxel for metastatic prostate cancer27) have acceptable cost-effectiveness ratios in which treated patients gain several weeks or months of life, at a cost less than $100 000 per additional year of life saved, but for Medicare, these are new costs to pay. For Mr L, his last dose of intrathecal cytarabine given 6 days before his death would cost $3400 at our institution.
The manner in which oncologists are reimbursed may play a role in chemotherapy use. During the past 10 years, oncologists have become some of the highest paid medical specialists.91 Some of oncologists' practice income comes from administering and selling chemotherapeutic agents and supportive care drugs (eg, bisphosphonates, erythropoietin-like drugs, and colony-stimulating factors). As is the case in other medical specialties, oncologists are reimbursed more for their specialized treatment of chemotherapy than for lengthy discussions about prognosis and palliative care options.92 This potential for conflict of interest has been the subject of controversy. The only published study was conducted before Medicare chemotherapy reimbursement was reduced in 2003 and found that reimbursement did not affect the decision to give palliative chemotherapy but that oncologists tended to choose chemotherapy that gave the highest profit to the practice.93 Although hospice care and inpatient palliative care94 may save money during the last month of life, total disease costs are unchanged or increased,95 so hospices cannot save enough money to allow more chemotherapy. It is critical to improve reimbursement incentives. For example, in 1 study, more than 25% of oncologists reported insufficient reimbursement for time spent in discussion with patients and families as "the most troublesome" reimbursement barrier to providing better end-of-life care.63
If societal resources become limited and maximizing health benefit becomes more difficult, there are only a few ways to reduce the cost of oncology care:
Reduce the services provided (eg, "stopping rules,"96 in which no more than 3 lines of chemotherapy would be given for refractory metastatic breast cancer or no erythropoietin-like drug treatment for anemia would be given unless the hemoglobin level is < 10 g/dL [100 g/L]).
Reduce requested services by increasing patient copayments.
Reduce the amount that Medicare or insurers pay for chemotherapy and supportive care drugs, health care professional services, or hospitalizations.
Prevent or delay new drugs from entering the market or delay reimbursement for them.
Reduce the payment to oncologists for administering chemotherapy and supportive care drugs, perhaps influencing the type of chemotherapy administered.
Ultimately, unless resources are unlimited, patients and families (or society at large) may be asked to balance individual patient needs against those of society.97