chemotherapy at end of life?????

A recent multi-institutional longitudinal cohort study assessed the use of chemotherapy in patients with progressive metastatic cancer, assessing survival, quality of life (QOL), and the relationship to performance status (see cancer ctx endoflife jamaonc2015 in dropbox, or doi:10.1001/jamaoncol.2015.2378).

background:

--the American Society of Clinical Oncology (ASCO) in 2012 published a list of their "Choosing-Wisely" 5 opportunities to improve care and decrease costs, noting that chemotherapy use among patients with no evidence of clinical benefit was the most wasteful, unnecessary and widespread practice in oncology, especially in those with poor performance status with an Eastern Cooperative Oncology Group (ECOG) score of 3 or more ("capable of only limited self-care, confined to bed or chair >50% of waking hours"). Older studies from the 1980s have confirmed that those with poor performance had low response rates to chemotherapy, high rates of toxic effects, and shorter survival.

--but, despite lack of evidence to support the practice, a paper in 2012 found that 40% of patients with non-small cell lung cancer and  ECOG score of 3-4 received palliative chemotherapy, with almost no hope of benefit. A Norwegian study also found that 53% of patients with ECOG performance score of 2 (in bed <50% of time) and 16% with scores of 3-4 received palliative chemotherapy, with 10% having chemotherapy in the last 30 days of their lives.

details:

--312 patients were reviewed with a diagnosis of end-stage metastatic cancer,  refractory to at least 1 line of chemotherapy and MD-estimated life expectancy of <6 months. 158 received chemotherapy and 154 did not.

--54.8% male, average age 58.6, 12.4 years of education, 61.5% white/20.5% black/16.7% hispanic.

--the baseline performance status was assessed on average 3.8 months before death: 122 patients had ECOG score of 1 (somewhat restricted in strenuous physical activities but ambulatory), 116 with score of 2 , 58 with score of 3

results:

--on multiple logistic regression, those receiving chemotherapy were much more likely to be in an academic medical center than community clinic (adjusted odds ratio of 17.1, with the vast majority receiving chemotherapy at the academic centers at Yale, Simmons in Dallas, and Dana-Farber in Boston; about 50/50 at the West Haven VA and Parkland; and a significant minority in New Hampshire Oncology-Hematology); had better ECOG performance scores (AOR=0.67); had pancreatic (AOR= 4.07) and breast cancer (AOR=2.45); and were younger (AOR=0.96)

--patients' risk of death was NOT significantly associated with whether they received chemotherapy or not, after adjusting for enrollment site and baseline ECOG score

--in assessing QOD (QOL near death, asking the caregiver most knowledgeable about the health care of the patient in his/her final week of life by a validated questionnaire), by performance status:

                                --ECOG 1: lower QOD !!! [odds ratio 0.35 (0.17-0.75), p=0.01]

                                -- ECOG 2: QOD [relative risk 1.06 (0.51-2.21), p=0.87, NS]

                                --ECOG 3: QOD [relative risk 1.34 (0.46-3.89), p=0.59, NS]

so, a few issues:

--this was a retrospective analysis of a cohort study and is therefore limited by not having individual data on the people who had chemotherapy vs not. Also there was likely a significant selection bias in those choosing a prestigious academic medical center vs a community-based center for their care.

--but, it is still quite striking that of those in the academic medical centers 79% had chemotherapy, vs 46% at the VA and 22% in the community-based practice.

--one of the most useful findings was that despite no difference in survival (again, not the most conclusive data, given limitations of study design/data), those with the best performance scores as assessed by their closest caregivers​​ <4 months prior to death actually had much worse QOL when given chemotherapy

--a a related issue, I have some concern about palliative care being a separate discipline from oncology. Although I assume that oncologists in general do get significant training in end-of-life management, i have heard examples of oncologists just referring patients to palliative care specialists to discuss these issues. To the extent that there is a separation, this creates the unfortunate dynamic of oncologists pushing therapies, even not terribly beneficial ones, on the one side, and the palliative care specialists pushing for a more rational discussion of the benefits and risks of therapy (which they may not understand fully, given lack of oncology training in many cases). Without an integrated, coherent approach, the patient is caught in the middle, perhaps being emotionally swayed by the thought that there is a potential therapy. In addition, oncologists historically have had a significant financial interest in giving meds. There was a major rollback of the huge profit margin oncologists had received prior to 2005 for administering medications they bought and administered. Now there is a 6% markup of the Average Sales Price, though Congress realized that this would dramatically decrease oncologist income, so they significantly increased the fees paid for chemotherapy administration. Coincident with this reimbursement change, "physicians switched from dispensing the drugs that experienced the largest cuts in profitability... to other high-margin drugs" --see Health Affairs July 2010; 29: 1391-9.  And the office-based administration fees skyrocketed in some cases (i suspect more so in the large cancer centers). So there still is a significant financial incentive for many oncologists to give drugs... and the concern is that this financial incentive, especially if the oncologist is not so involved in the individual’s end-of-life/palliative care issues, could lead to inappropriate/unnecessary, potentially harmful, and expensive care.