Marriage predicts for survival in patients with stage III non–small-cell lung cancer

In contrast, some other studies have failed to demonstrate an OS advantage with marital status in patients with NSCLC. For example, in a meta-analysis that evaluated the influence of race, gender, and marital status on 1,365 nonoperative NSCLC patients who were enrolled in 9 Radiation Therapy Oncology Group (RTOG) trials, the investigators did not find marital status to be independently predictive of survival.¹¹ In addition, for the 5,898 patients who were prospectively enrolled in a Mayo Clinic Lung Cancer Cohort (MCLCC), marital status was also found not to be prognostic for NSCLC outcomes when all stages of the disease were analyzed together.⁴ There are some possible confounding factors in these studies. Patients recruited for clinical trials tend to be healthier with a better performance status and have a support system (including close monitoring by the study team) when compared with the general population diagnosed with lung cancer. About 70% to 76% of the patients in both the RTOG and MCLCC studies were married, which is significantly higher than both the national average (51%) and our group (52.1%). Like other population-based studies, the MCLCC included patients with all stages getting a variety of treatments. Although no overall impact on survival was noted, the investigators noted that single, divorced, and widowed patients were more likely to not receive cancer therapy(P < .0001). The marital status also influenced the choice of therapy, with subgroup analysis revealing inferior outcomes in widowed and divorced patients with stage IA, IIB, or IIIB disease. The authors also recognized an inherent referral bias from patients, with support system being typically seen at the Mayo clinics, which may have played an additional role. All of the patients in our analysis were appropriately staged and received curative-intent treatment by a team of physicians using essentially identical therapeutic strategies, thus minimizing some of these confounding factors. This allowed us to explore the impact of marital status while a patient was undergoing stage-appropriate treatment. We demonstrated a strong association with marital status and survival that even overcame the effects of stage (IIIA vs IIIB) on clinical outcomes (Figure 1B).

Furthermore, our analysis allowed us to explore the interaction of race and marital status more definitively because the demographics of the patients in the RTOG and MCLCC included 14% and less than 3% of patients identified as being nonwhite, respectively, in contrast to our analysis in which 41% of the patients self-identified as black.¹² In our black population, marital status was associated with an observable improvement in OS, similar to our nonblack, predominantly white (97%) cohort (Figure 2B). Also, the results of our analysis may be a more accurate representation of the general population living in large urban or semiurban settings and further implies that an intact social support system could have a greater influence on clinical outcomes.

The current analysis is unique when compared with previous published studies in that beyond conventional demographic and treatment-related factors, we have comprehensively explored potential mechanisms that may explain the survival advantage seen in married patients by evaluating additional factors, such as functional status (ECOG and Charlson’s scores), nutritional status (BMI and albumin), immunologic characteristics (NLR), and other social factors (race, income, insurance status). Although married patients were more likely to have a higher BMI and albumin at diagnosis, when controlling for these factors in the multivariable analysis, marital status remained strongly prognostic (Table 2), suggesting that nutrition alone does not fully account for the observed survival advantage demonstrated. A similar conclusion can be drawn about immunologic status. NLR has previously been shown to be prognostic in a number of cancers,^13-16 including in our own cohort.⁸ Although immune status remains an important predictor for OS in our locally advanced NSCLC population, when we take NLR into consideration in our analysis, marital status continues to be a strong indicator for survival (Table 2). In terms of other variables analyzed, insurance status was a significant predictor of OS in the MVA, though functional status and other social factors including race were not significant.

We also explored cancer control outcomes in the form of FFR. Married patients had an observable, although not statistically significant, improvement in FFR when compared with the single cohort (Figure 2). In our study, married patients were more likely to undergo trimodality therapy (Table 1), which has likely translated to the improvement of FFR seen in our group. In this case, marriage may serve as a surrogate for availability of a support system to undergo aggressive, potentially toxic treatment.^3,17,18 Even in the setting of bimodality therapy, the RTOG 0617 study noted about 17.5% treatment interruptions because of adverse effects or illness, with more than 30% of patients experiencing grade 3 or more esophagitis, irrespective of radiation technique.¹⁹ In these scenarios, in addition to receiving better attention to nutrition and care, significant others often provide emotional and social support that, in turn, can lead to better compliance. Social supports and socio-demographic factors are especially critical in patient populations in which access to health care is challenging.

Despite the compelling outcomes presented, our study suffers from the common limitations of retrospective analyses. Marital status, in this setting, most likely correlates with improved socioeconomic status and greater support, which have resulted in improved survival. Furthermore, although patients were self-classified as married or single, our data were not able to capture whether patients were single but lived with another adult or had other types of social support. However, even if there was a proportion of the unmarried cohort that had an alternate support system, separating them out is likely to further expand the differences. Quantifying the amount of social, emotional, or even spiritual support was not possible to accomplish in our analysis, though we know that all 3 can play a role in cancer outcomes.^20,21 Further prospective studies would have to be done to completely understand how marital status can influence clinical decisions. Understanding whether marital status is a proxy for social provisions may help to identify populations at risk for inferior outcomes. These at-risk patients may benefit from targeted clinical interventions, such as closer physician follow-up, more aggressive supportive care, access to support groups, or nurse navigator visits.