Cancer Survivorship The Marriage Effect?
Abstract & Commentary
By Robert L. Coleman, MD
Professor, University of Texas; M.D. Anderson Cancer
Center, Houston
Dr. Coleman reports no financial relationships relevant to this field of study. This article originally appeared in the November 2013 issue of OB/GYN
Clinical Alert.
Synopsis: Compared to cancer patients who were never married, divorced, widowed, or separated, married patients are significantly more likely to present at an earlier stage, undergo therapy with definitive or curative intent, and live longer among each of the 10 most common cancers killers in the United States. The data suggest the effect is rooted in better social support mechanisms among this cohort and highlight a modifiable "at-risk" population.
Source: Aizer AA, et al. Marital status and survival in patients with cancer. J Clin Oncol 2013;31:3869-3876.
The positive effect of marriage on cancer survivorship previously has been reported but is not universal among various investigations.1,2 The authors set out to examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality between each of the 10 leading causes of cancer-related death in the United States. To interrogate a sample large enough to adjust for the various covariates, they identified more than 1.2 million cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) program who were diagnosed between 2004 and 2008. Ten primary tumor sites (lung, colorectal, breast, pancreatic, prostate, liver/intrahepatic bile duct, non-Hodgkin lymphoma, head/neck, ovarian, or esophageal cancer) were addressed, as they represented the most common diagnoses associated with cancer-specific morality. After eliminating cases with inadequate clinical and follow-up information, 734,889 patients were available for analysis. The authors found that married patients were less likely to present with metastatic disease (adjusted odds ratio [OR], 0.83; 95% confidence interval [CI], 0.82-0.84; P < 0.001), more likely to receive definitive therapy (adjusted OR, 1.53; 95% CI, 1.51-1.56; P < 0.001), and less likely to die as a result of their cancer after adjusting for demographics, stage, and treatment (adjusted hazard ratio, 0.80; 95% CI, 0.79-0.81; P < 0.001) than unmarried patients. These associations remained significant when each individual cancer was analyzed (P < 0.05 for all endpoints for each malignancy) and regardless of unmarried status (P < 0.001 for each unmarried category). The benefit associated with marriage was greater in males than females for all outcome measures analyzed (P < 0.001 in all cases). For prostate, breast, colorectal, esophageal, and head/neck cancers, the survival benefit associated with marriage was larger than the published survival benefit of chemotherapy. The authors concluded that unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer, even after adjusting for known confounders. This study highlights the potentially significant impact that social support can have on cancer detection, treatment, and survival.
COMMENTARY
"My wife says I never listen to herat least I think that's what she says."
The impact of marriage on survivorship in cancer patients has been extensively examined in previous reports, but with inconclusive independent results. Most have shown a benefit but have been confounded by small samples size for individual malignancies, regionality, lack of information regarding follow-up, and survival not linked to cancer-specific events. However, the current study's design and analysis, while not optimal (e.g., a randomized trial), does provide some confidence the association is credible. This comes from several considerations. First, the sample was based on cancer-specific survivorship, that is, those cases in which death was recorded as a cancer event. This type of analysis censors patients who die before progression or from causes not related to cancer. In treatment trials, this endpoint is often considered to be biased because elderly patients are more likely to die of intercurrent disease leading to extensive censoring. However, for the current analysis, it provides cleaner data to assess the effect of the variable (marriage at diagnosis) on cause-specific outcomes across a variety of tumors. The second aspect affording credibility to this study's hypothesis-generating suppositions is the multi-regional patient inclusion. The SEER database captures more than 95% of the incident cancers from registries representing more than a quarter of the U.S. population. There are well-documented deficiencies in this database (e.g., no pathology review, lack of information regarding chemotherapy, oversimplified, and lack of confirmation of staging), but the demographics, diagnoses, stage category, some treatment, and outcomes recorded have been continually validated and updated for years. Third, the sample is large enough to consider important covariates such as, age, race, gender, residence, income, education, tumor and nodal stage, and treatment. In the context of marriage, these are important variables since married cancer patients tend to be younger, have higher incomes and education level, may have broader and better access to health care, and live in rural homesteads with larger family support mechanisms.3 Considering these factors, marriage was still significantly protective and remained so for the 10 tumor types examined and relative to each unmarried category. Further, the effect in many tumor types (prostate, breast, colorectal, esophageal, and head/neck) was stronger than the impact of chemotherapy.
The primary takeaway message from this article, and others on the topic, is that marriage provides a critical internal social support system that is less often present among patients who are unmarried — these patients represent a risk group that deserves attention. While the quality of marriage among those married and the contribution of live-in unmarried cohabiters could not be directly assessed, it appears that marriage at the time of diagnosis is associated with important primary treatment variables that would be expected to result in better outcomes. For instance, most primary outcome measures, such as overall survival, progression-free survival, and objective response, are directly associated with tumor stage at presentation; earlier stage = better outcomes. Thus, tumors in which symptomatology may be reflective of an early-stage diagnosis (e.g., epistaxis in head and neck cancer) are more likely to be associated with better outcomes if a partner encourages ("nagging") a doctor's appointment at first occurrence.4 Earlier stage at presentation would also increase the likelihood of definitive treatment options and increase the odds of finishing a prescribed treatment plan. Each of these factors has been broadly associated with more favorable survival in a variety of cancers. In ovarian cancer, symptomatology is not associated with earlier stage at presentation, but may be associated with lower metastatic tumor burden, affording a higher likelihood to undergo primary surgical debulking, to have a better cytoreduction outcome, and complete definitive adjuvant therapy. Finally, chronic stress has been implicated as negatively impacting cancer survivorship, particularly in regard to immune function and the tumor microenvironment, where stress is associated with accelerated angiogenesis and immune escape.5,6 The hypothesis that married patients are less likely to suffer chronic stress and depression than their unmarried counterparts has been previously raised and may contribute to the study's findings.
So how can this information be leveraged? The knowledge that unmarried cancer patients represent an at-risk group provides an opportunity to develop and evaluate social support mechanisms that can act as surrogates for a live-in partner. Most cancer centers have regular patient supportive-expressive group therapy sessions. However, their impact on survival has been mixed in the few randomized controlled studies that have been conducted.7,8 Nevertheless, comprehensive programs that provide not only social-expressive opportunities but also assessment/management of depression and anxiety and assistance with decision making represent the best opportunity to close the "survival gap" observed in unmarried individuals. Increased awareness and assessment of depression/anxiety should be afforded to all cancer patients. However, knowing the risks that may further impact and complicate a patient's treatment program, clinicians are encouraged to thoroughly evaluate the social support structure of unmarried patients at presentation and during their follow-up.
References
- Nelles JL, et al. The impact of marriage on bladder cancer mortality. Urol Oncol 2009;27:263-267.
- Goodwin JS, et al. The effect of marital status on stage, treatment, and survival of cancer patients. JAMA 1987; 258:3125-3130.
- Ayanian JZ, et al. The relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med 1993;329:326-331.
- Aizer AA, et al. Multidisciplinary care and pursuit of active surveillance in low-risk prostate cancer. J Clin Oncol 2012;30:3071-3076.
- Sephton SE, et al. Diurnal cortisol rhythm as a predictor of lung cancer survival. Brain Behav Immun 2013; 30(Suppl):S163-S170.
- Sephton SE, et al. Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl Cancer Inst 2000; 92:994-1000.
- Spiegel D, et al. Effects of supportive-expressive group therapy on survival of patients with metastatic breast cancer: A randomized prospective trial. Cancer 2007;110:1130-1138.
- Temel JS, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733-742.
