Beyond Survival: Quality of Life in Oncology

Steve Server // Cancer is conceptually as well-circumscribed as a tumor feels when you palpate it under the skin during a routine exam.  Its hardness imprints itself upon your sensorium, and then upon your psyche, as you feel the burden of the unpleasant truth that must soon make itself known.  Dense, solid, almost like a foreign body, as far removed from the plump give of living, healthy tissue as one could get. 

In the course of my medical education, I have seen and learned about a dizzying number of cancers.  Cancers of every organ of the gastrointestinal tract.  Cancers of brain, of skin, of bone, of liver and lung.  Leukemias and lymphomas.  Breast and cervical; prostate and penile; women and men.  Cancers from smoking, cancers from drinking, cancers from genetic abnormalities, cancers from environmental exposures.  Cancers from being old, cancers from being young.  Cancers that behave well, cancers that are bad actors.  Cancers that will kill you, cancers that you will die with.

And for as many types of cancer there are, there are vastly more ways that people come to live with their cancer diagnosis.  One of my patients wept openly and inconsolably about the prospect of their impending mortality, held by their elderly parents in a cruel subversion of the normal flow of life.  Another patient, with a similarly poor prognosis, responded stoically, simply stating that he planned to get a “F*ck Cancer” tattoo as soon as he was discharged from the hospital.

Despite this great diversity, however, the majority of research in oncology treats people with cancer as cancer patients, monolithically concerned with extending life, rather than making their remaining life as meaningful as possible.  The sine-qua-non of a successful RCT in oncology is showing either improved overall survival, or non-inferior survival with fewer life-threatening adverse events.  One would very rarely see data regarding the impact of novel agents on a person’s quality of life.  That is, our entire knowledge-making enterprise is organized around the idea that more life is always better. 

For instance, the evidence-based chemo regimen for lymphoma consists of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, known pithily as “R-CHOP”.  With this regimen, estimated rates of progression-free survival (time between administration of the regimen and clinical advancement of disease) are 70% at five years, while overall survival is 75% at five years.  The data is presented very simply using Kaplan-Meier curves— each drop on the line representing a patient’s death, the overall trend line tracing the likely trajectory of a patient undergoing treatment.  Patients are either alive or dead, represented in the survival line, or out of it.

Unfortunately, it is a central principle of pharmacology that there are no free lunches clinically—each beneficial drug comes with concomitant side effects.  The potential side-effects of R-CHOP are not insignificant.  Cyclophosphamide, a derivative of mustard gas, can cause bloody urine and infertility.  Doxorubicin has a maximum toxic dose above which patients are apt to develop heart failure.  Vincristine commonly causes peripheral neuropathy, or persistent tingling and numbness in hands and feet, which may be irreversible.  Most of the agents predispose to suppression of the bone marrow—meaning bleeding risk, anemia, and increased risk of infection.

Clearly, good oncologists discuss these potential—or, indeed, likely—side effects with their patients prior to first administration of the drugs and assess what would be an unacceptable regimen for the patient.  A concert violinist, for example, may be unwilling to undergo a vincristine-based regimen because the ability to feel the subtle vibrations of their strings may be worth more to them than two months of additional life without feeling the thrum of the violin.

But it becomes more difficult for doctors to have conversations about quality of life with patients when there aren’t quality data—either qualitative or quantitative—on how people experience various chemo regimens beyond specific, well-known side effects.  How do patients feel when on R-CHOP?  Do they feel in a cognitive fog?  How is their mood?  Are they depressed to the point where don’t enjoy much of anything?  Are they too nauseous to eat their favorite meals, or is their mouth too inflamed to be able to eat well?  Do they feel that their body is hospitable to them, enough to be able to enjoy the time granted by the chemo regimen?  Or do the regimens hasten the rebellion of the body against the self, making the improved survival ultimately not worth the suffering?

A fascinating study devoted to expanding our understanding of how to improve the quality of life of people with cancer was published in 2010 in the New England Journal of Medicine (Temel et al.)The primary outcome measured was the change in quality of life following 12 weeks of the intervention.  Patients were randomized to either standard oncologic care or standard oncologic care plus palliative care.  The authors of the study were evidently expecting that patients who were treated by palliative care physicians early would show improved quality of life relative to their peers who received standard oncologic treatment.  In general, palliative care specialists organize their treatments around patient wishes, beginning with a long conversation regarding goals of care.  These goals can be related to medical issues, but discussion can range from philosophical, abstract issues of suffering, such as spiritual and psychological well-being, to more concrete legal and insurance issues, homemaking, and, of course, mitigation of side effects.  In other words, palliative care aims to address the parts of health and well-being which exist outside of the chemotherapy infusion center or operating room.  It is organized around a patient’s life and values to ensure that a patient’s life looks as close to the way they would like it, considering the circumstances.

Indeed, the study found better quality of life among the palliative group, as well as better mood.  The surprising result, however, found that the palliative care group actually also had significantly better survival than the standard group—the median survival difference between the groups was 2.7 months (11.6 vs. 5.9 months).  Palliative care—often associated with de-escalating aggressiveness of treatment to preserve quality of life, theoretically at the expense of quantity—not only led patients to feel better about life with cancer, but also to survive for longer.  As the President of the American Academy of Hospice and Palliative Care put it, in a New York Times piece announcing the results, the study represented “the first concrete evidence of what a lot of us have seen in our practices—when you control pain and other symptoms, people not only feel better, they live longer” (qtd. in McNeil).

Ultimately, thinking about cancer as simply an obscure protean foe, single-mindedly committed to destroying life, structures our understanding of cancer treatment single-mindedly around preserving life.  Extending life becomes the point in and of itself, irrespective of the way that patients might feel about whether that additional time living is worth living.  But cancer is not incompatible with life, per se.  Rather, it is a condition which reorders the superstructure of our life.  People don’t stop being themselves when diagnosed with cancer, passing into another plane of existence—the post-well, the not-yet-recovered, the may-be-relapsed, the pre-deceased.  People are just themselves with cancer.  As such, the things that matter to them before their cancer diagnosis matter just as much, if not more, following the diagnosis.

Consequently, we need to do challenge ourselves to think beyond survival as the core metric of success in oncology, so that we may think more critically about how our regimens empower or hamper our patients’ ability to be authors of their time remaining.


References

Image: Mitchell Schnall, MD, PhD, “Mammography (Abnormal),” Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Mammogram_(abnormal).jpg).

Coiffier et. al. “CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma.” N Engl J Med 2002; 346:235-242
DOI: 10.1056/NEJMoa011795.

McNeil, Donald. “Palliative Care Extends Life, Study Finds.” New York Times. Aug 18, 2010. (https://www.nytimes.com/2010/08/19/health/19care.html).

Temel et. al.  “Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer.”  N Engl J Med 2010; 363:733-742.  DOI: 10.1056/NEJMoa1000678

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