CORR Insights®: Which Bone-Modifying Agent is Associated with Better Outcomes in Patients with Metastatic Bone Disease from Lung Cancer? A Systematic Review and Network Meta-Analysis

Where Are We Now?

Testing for metastatic bone disease is an important component of managing patients with cancer, and treating skeletal metastases is best done using a multidisciplinary approach in which the surgical, systemic, and radiation treatment options can be considered and selected thoughtfully. All of this needs to be done in view of the fact that metastatic cancer usually is not curable, and so the patient’s goals, his or her quality of life, and the anticipated prognosis—whether measured in months or years—must be considered [8]. Reducing pain and increasing function in patients with skeletal metastases disease is critically important, as is decreasing the risk of pathologic fracture. These goals are front-of-mind when treating patients with metastatic bone disease from lung cancer, because of the typically reduced survival time among this patient population compared to other forms of metastatic disease, such as prostate cancer.

The current study reported by Bozzo et al. [1] provides evidence regarding the pharmacologic management of metastatic bone disease among patients with metastatic lung cancer. Specifically, they noted that denosumab was superior to zoledronate regarding overall survival and time to skeletal events, although there was no difference in the incidence of skeletal events between the two treatments. Based on these discoveries, patient outcome and quality of life can be improved through treatment with denosumab. In the management of patients with metastatic lung cancer, orthopaedic surgeons should ensure that a medical oncology evaluation regarding pharmacologic management of bone metastases has been obtained. Given the large burden of metastatic bone disease among those with metastatic lung cancer, such an evaluation can benefit the patient in both disease-specific treatment and quality of life. Providing the best systemic treatment to decrease the risk and impact of skeletal metastases is an important component to the overall management of patients with metastatic cancer.

The comprehensive-care approach brings in diverse clinical perspectives. When this is done well, our care teams go beyond the biologic aspects of the disease; ideally, we care for the whole patient. But in my experience, this does not always occur. And even less frequently, in my experience, do our approaches engage with our patients’ families. Although doing so may not directly impact disease-specific outcomes, I think falling short in these areas is a real missed opportunity because there is more to treating the patient and family with metastatic disease than solely the disease-specific outcomes. The potential for a greater positive impact exists when we provide more comprehensive treatment for the body, mind, and spirit that helps the patient and family improve their quality of life and maximize their well-being through their course of treatment.

Where Do We Need to Go?

The overall goal of this approach is to “make people feel better,” particularly for patients with metastatic disease where a cure may not be possible. To improve our approaches in this area, further developments of traditional treatments through systemic therapy, radiation therapy, and surgical management are needed. For example, the timing and duration of initiation of pharmacologic treatment, such as denosumab, specific to management of skeletal events requires further elaboration. A better understanding regarding the optimal delivery of radiation therapy for bone metastases, including the specific type of radiation and number of fractions, in order to improve treatment would be beneficial. Further development of minimally invasive surgical techniques to address structurally significant bone metastases would be of benefit so that the interruption in systemic therapy and risk of complications can be minimized.

But I believe we also need to consider ways to more fully integrate holistic methods like mindfulness, sleep science, and nutrition into the care paradigm. In my view, advancements in the fields of medical oncology, radiation oncology, and surgery are more familiar to most healthcare professionals, while the integration of holistic methods are less commonly discussed. There is, however, plenty of evidence regarding the positive impact mindfulness, sleep, and nutrition can have in the overall care of patients with metastatic cancer [2-7, 9, 10]. Mindfulness can provide enhanced coping with the inherent stress of a cancer diagnosis and its treatment. Gratitude training can be beneficial in decreasing depressive symptoms and creating an optimistic outlook. Improved sleep has numerous benefits for our physical and mental health, and given the animal studies, may have benefit in disease-specific outcomes. Nutritional planning may provide benefit in disease-specific outcome and can also be used to decrease common side effects of systemic therapy, such as nausea and vomiting. While many of these skills are not necessarily widely discussed within the traditional Western medical paradigm, the emerging evidence provides reason for optimism that they can provide benefit to patients while being of minimal, if any, risk.

Still, there are gaps in our knowledge regarding the full extent of benefit that can be provided to patients with metastatic bone disease through the integration of these strategies not only on the disease-specific outcomes but overall quality of life over the course of treatment.

How Do We Get There?

In the pursuit of improving the comprehensive care that is provided to patients with metastatic cancer, our goal should be to integrate cutting-edge medical and surgical therapies with the best available evidence regarding care of the entire individual. Building off the findings reported by Bozzo et al. [1], prospective studies could be designed to investigate the timing for initiation of denosumab and the duration of therapy to optimally mange skeletal metastases. Such studies would, ideally, be integrated into a cost-effectiveness analysis to provide further evidence regarding the benefits of this pharmacologic treatment strategy.

Advances in the fields of systemic and radiation therapy and surgical management can be complemented with the integration of mindfulness, nutrition, and sleep science to achieve this goal. This could be accomplished through the endorsement of the multi-disciplinary team of these holistic skills and referral to appropriate providers or incorporation of such providers within the multidisciplinary team. While the care of the entire individual may not have a direct benefit on disease-specific outcomes, a greater sense of well-being coupled with decreased anxiety and depression and improved coping skills are beneficial in and of themselves. Using currently available evidence [2-7, 9, 10], resources can be put in place to provide these comprehensive services to patients and their families without interfering with provision of the traditional therapies. Educational events and direct sessions in which experts in these holistic skills can teach and develop the strategies with patients and their families can be offered. For instance, while patients are receiving infusions or waiting for tests, they can be provided with additional information or individualized coaching to help develop skills in the realm of mindfulness and gratitude training or provided with nutritional counseling and strategies to improve sleep. Specific individual and/or group training can be offered either in person or through digital platforms to develop these skills among patients and their family members. Payment for these services could be incorporated within a research budget for the corresponding studies of the effectiveness of these interventions or through patient support groups and/or fundraising events.

Future study of the benefits of these complementary strategies should be simultaneously carried out to provide greater understanding and further evidence for their incorporation in the standard therapy strategies used in the management of cancer. For instance, observational studies using health-related quality of life measures as a primary outcome, in conjunction with disease-specific outcomes, should be performed to further elucidate the benefit of mindfulness training programs, gratitude practices, sleep interventions, and nutritional training for patients with metastatic bone disease and their families.

In order to “make people feel better,” we need to emphasize not only the disease-specific treatments traditionally offered by surgery, systemic therapy, and radiation therapy, but also integrate treatment of the entire person through mindfulness, gratitude, sleep, and nutrition. Doing this through an evidence-based approach will allow for not only greater understanding of the benefits of these skills but also provide the basis for their routine integration in the management of patients with cancer.