Treatment refusal for small cell lung cancer studied: Small-cell lung cancer (SCLC) accounts for about 15% of all lung cancers, and the disease is not associated with a great outcome rate, with a 5-year survival of only around 6%. But SCLC is still treatable, with chemotherapy, radiotherapy, and more recently, immunotherapy.
In March 2019, the FDA approved the use of atezolizumab (Tecentriq) for the initial treatment of patients with extensive-stage SCLC based on results of the IMpower133 trial, while at the 2019 World Conference on Lung Cancer meeting in Barcelona, researchers from the CASPIAN trial presented positive survival results with durvalumab (Imfinzi) plus standard chemotherapy in that patient group.
But even the most well-planned treatment trial would be a bust if patients refused treatment, which is why Thanh P. Ho, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues looked at the disparities in patient refusal to undergo SCLC treatment.
Treatment refusal when SCLC is curable
“Limited-stage SCLC is potentially curable, so we wanted to evaluate if there was a patient population that would decline or refuse curative-intent therapy,” Ho told the Reading Room via email. “Extensive-stage SCLC, by comparison, is often associated with high risk of mortality, even with treatment. Patients with limited-stage SCLC ideally would be treated to avoid progression to extensive-stage SCLC.”
For the group’s retrospective study, presented at this year’s ASCO Quality Care Symposium, Ho and colleagues evaluated all incident limited-stage SCLC cases from the National Cancer Database (NCDB) from 2004 to 2014. Among 65,664 patients (44% male; median age of 68), 3.4% refused radiotherapy and 3.8% refused chemotherapy.
Treatment Refusal for Small Cell Lung Cancer
Women were found to be more likely than men to refuse radiation therapy and chemotherapy, but women who accepted treatment had longer overall survival versus those who refused radiation (19.8 versus 5.2 months) or chemotherapy (17.4 versus 3.9 months).
Also, older patients were more likely to decline radiation and chemotherapy, and having Medicaid as primary insurance predicted a higher risk of refusal for radiation and chemotherapy compared with private insurance. In addition, the Charlson comorbidity index (CCI) 2 was associated with more frequent treatment refusal compared with CCI 0.
Finally, Hispanic, black, and Asian patients were not more likely to decline treatment than white patients were, and treatment at an academic facility predicted a lower risk of radiation refusal but not chemotherapy refusal.
The take-home message for clinicians from the study, Ho said, is that “in patients with limited-stage SCLC who decline treatment, consider asking them about factors that affect their decision-making because there is a significant survival benefit from cancer-directed therapy.”
Ho added that he and his colleagues would consider additional research in this area, “especially as newer therapies, such as immunotherapy, are emerging.”
A ‘No’ in NSCLC
Ho and colleagues undertook their study due to a lack of clarity on patient refusal of SCLC treatment. One major reason for that could be that more research has been done in non-small cell lung cancer (NSCLC) than in SCLC. But can lessons be learned from these NSCLC studies?
An early study from South Korean investigators retrospectively reviewed data from 617 patients with diagnosed NSCLC, broken down into two groups: those who refused anti‐cancer treatment and allowed only palliative care (the non‐treatment group), and those who received anti‐cancer treatment (the treatment group). Individual factors, such as old age, low educational status, low weight, and poor performance status were found to influence refusal of NSCLC treatment.
Another U.S. group looked at the influence of sociodemographic factors in stage IV NSCLC patients’ refusal of treatment. From 2004 to 2014, the proportion of patients refusing radiotherapy and chemotherapy increased over time from 4.2% to 7.3% and 7.9% to 15%, respectively.
As did Ho et al, these researchers, including Ho’s co-author Aaron S. Mansfield, MD, of the Mayo Clinic, also reported that men were less likely to decline treatment than women, and that having Medicaid insurance was a factor for declining to undergo radiotherapy and/or chemotherapy.
Once again, “Asians had lower rates of chemotherapy refusal relative to non-Hispanic whites. Non-Hispanic whites, Hispanics, and Asians had increasing chemotherapy refusal rates over time, while non-Hispanic blacks had less pronounced trends over time,” the team stated.
Treatment Refusal and Ethnicity
But ethnicity was a more prominent factor for treatment refusal in a study done by researchers at the University of Southern California, who found that among approximately 166,000 patients with clinical stage 1A NSCLC, blacks, East Asians, Pacific Islanders, and Native Americans were statistically significantly more likely to decline surgery than white patients. Patients on Medicaid were more likely to refuse surgery than those on Medicare.
Finally, an ancillary study assessed if patients who refused conventional treatment did so partly because they opted to rely on complementary medicine instead. The retrospective observational study used data from the NCDB on 1.9 million U.S. patients diagnosed with lung cancer, among others, between 2004 and 2013. Patients who chose complementary medicine did not have a longer delay to initiation of conventional therapy, but did have higher refusal rates of surgery, chemotherapy, and radiotherapy.
Treatment Refusal and Payer Problems
Thus far, study findings point a finger at the type of payer coverage as a reason for treatment refusal among lung cancer patients, with those with Medicaid coverage more likely to decline treatment.
One potential reason may simply be frustration with the system: A survey of cancer patients by the Cancer Support Community found that cancer patients on Medicaid more often reported that they felt their doctors rushed through their appointments. Those on Medicaid were also more likely to report experiencing delays in getting appointments, were least likely to receive social and emotional support services, and were more likely to say they only “sometimes” got the coverage they needed compared with other individuals.
Asked about these survey results, Ho agreed “they can certainly contribute to higher treatment refusal in patients with Medicaid,” but noted that his team used a national database, and so were unable to assess specific reasons for patient refusal of treatment.
Another issue may be that the healthcare delivery system fails patients. For example, a study by Chicago researchers suggested possible “shortcomings” in cancer care delivery, showing that among 183,148 patients at 1,281 U.S. hospitals, 10.7% of lung cancer patients did not receive recommended chemotherapy. Patients were less likely to receive recommended chemotherapy if they were uninsured or on Medicaid.
Significant hospital variation was observed, with hospital-level rates of failure to administer recommended chemotherapy as high as 40% in lung cancers, the authors wrote. “Hospital variation in failure to administer recommended chemotherapy is masked by current quality measure definitions and may define a significant and unmeasured difference in hospital quality.”